Olivera (Olja) Finn
Olivera (Olja) Finn, PhD, a native of the former Yugoslavia, is the University of Pittsburgh Distinguished Professor of Immunology and Surgery, and Founding Chair of the Department of Immunology, a position she held from 2001 to 2013. She was Program Leader of the Cancer Immunology Program at the University of Pittsburgh Cancer Institute from 1991 to 2014. Dr. Finn received her PhD in Immunology at Stanford University in 1980 under the mentorship of Dr. Henry S. Kaplan. She then completed her postdoctoral training at Stanford in 1982 under the mentorship of Dr. Ronald Levy. Dr. Finn then assumed positions at Duke University, and in 1991 moved to the University of Pittsburgh.
Dr. Finn gained prominence through her original focus on transplantation biology and later through her basic and applied research focused on tumor antigens and the development of cancer vaccines. She is the discoverer of the MUC1 tumor antigen, and for the last 25 years has published extensively and continuously on her basic and preclinical work on the development and evaluation of MUC1 cancer vaccines. She has been a coinvestigator on a dozen clinical trials of various MUC1 vaccines in pancreatic, colon, breast, prostate, and lung cancer. Dr. Finn and her team also identified cyclin B1 as a tumor antigen and published several papers on its excellent potential as a cancer vaccine. Her current efforts are focused on the development of preventative cancer vaccines.
She has an extensive track record of research accomplishments reported in over 170 peer-reviewed papers as well as numerous reviews and book chapters. Dr. Finn is on editorial boards of many cancer journals, including Cancer Immunology Research, and is on the advisory boards of many cancer centers and several companies. She has served on NCI study sections and was a member of the NCI Board of Councilors. She has been a member of the American Association for Cancer Research since 1983 and is Past Chair of the Steering Committee of the AACR Cancer Immunology (CIMM) Working Group. Dr. Finn was President of the American Association of Immunologists from 2007 to 2008 and in 2016 she received the AAI Lifetime Achievement Award. In 2017, Dr. Finn received the AACR-CRI Lloyd J. Old Award in Cancer Immunology, honoring her groundbreaking work identifying the first tumor-associated T-cell target antigen, MUC1.
Cancer Immunol Res May 1 2017 5:347-354; DOI:10.1158/2326-6066.CIR-17-0112
Dr. Lonberg is Senior Vice President, Oncology Discovery Biology, at Bristol-Myers Squibb, where he leads drug discovery efforts for both targeted and immuno-oncology agents. Dr. Lonberg began his career in the biotechnology/pharmaceutical industry, leading the GenPharm International research group that developed genetically engineered strains of mice with germline configuration human immunoglobulin genes. These transgenic animals have been used to discover more than three dozen clinical-stage human sequence antibodies, including 10 FDA-approved products (golimumab, ustekinumab, ofatumumab, canakinumab, ipilimumab, nivolumab, secukinumab, daratumumab, bezlotoxumab, and olaratumab). GenPharm International was acquired by Medarex in 1997, and then by Bristol-Myers Squibb in 2009. In 1998, the Medarex drug discovery group began to focus on antibody therapies that target and modulate immune-attenuating pathways to activate patient immune responses to cancer cells (so-called “checkpoint blockade” therapies). Ipilimumab, which began clinical testing in 2000, was the first-ever checkpoint blockade cancer therapy to enter clinical development and to gain regulatory approval. Ipilimumab, approved in 2011, was also the first drug to demonstrate, in a randomized clinical trial, a survival benefit for patients with metastatic melanoma. A second checkpoint blockade cancer therapeutic, nivolumab, entered clinical development in 2006 and gained regulatory approval in 2014. Dr. Lonberg received his PhD in Biochemistry and Molecular Biology from Harvard University (Cambridge, MA) in 1985, where he studied under Dr. Walter Gilbert. He was a postdoctoral fellow at Memorial Sloan Kettering Cancer Center (New York, NY) and was elected to the National Academy of Engineering in 2015.
Cancer Immunol Res April 2017 4:275-281; doi: 10.1158/2326-6066.CIR-17-0057
Alan J. Korman
Dr. Korman is currently Vice President, Immuno-Oncology, at Bristol-Myers Squibb, where he leads a group dedicated to the development of biologics in tumor immunotherapy. Dr. Korman started his career in the biotechnology industry at Supragen in Colorado in 1993, which became part of NeXstar Pharmaceuticals. At NeXstar, he initiated the development of therapeutics targeting CTLA4. In 2000, he joined Medarex (Bristol-Myers Squibb since 2009) and continued the development of antibody therapeutics in tumor immunotherapy with programs targeting PD-1 and PD-L1 along with the preclinical development of combinations in immunotherapy. Five additional antibodies in immuno-oncology (anti-LAG-3, anti-GITR, anti-OX40, anti-CD73, and anti-TIGIT) are currently in clinical development. Dr. Korman received his PhD in Cellular and Developmental Biology from Harvard University (Cambridge, MA) in 1984, where he studied molecular immunology in the laboratory of Dr. Jack Strominger. From 1984 to 1989, he was a Whitehead Fellow at the Whitehead Institute, Massachusetts Institute of Technology (Cambridge, MA), where he continued his work in molecular immunology in association with the laboratory of Dr. Richard Mulligan. He was also a Chargé de Recherche at the Institut Pasteur (Paris, France) from 1990 to 1993, where he studied viral superantigens.
Cancer Immunol Res January 2017 5:3-8; doi:10.1158/2326-6066.CIR-16-0297
Dmitry I. Gabrilovich
Dmitry I. Gabrilovich, MD, PhD, is currently the Christopher M. Davis Professor in Cancer Research and Program Leader, Translational Tumor Immunology, at the Wistar Institute in Philadelphia and Wistar Professor, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania (Philadelphia, PA). Dr. Gabrilovich graduated from the Medical School of Kabardino-Balkarian State University, USSR, and in 1989 received his PhD in epidemiology from the Central Institute of Epidemiology, Moscow, USSR, after which he worked as the head of the cellular immunology group at the HIV Reference Center in Moscow. During those years, his group demonstrated the activation of neutrophils in HIV-infected individuals.
Based on this work, in 1992, he was awarded the Wellcome Trust Fellowship to study dendritic cell (DC) biology in experimental retroviral infection under Dr. Stella C. Knight at the Imperial College of London in the United Kingdom. He was trained in cancer research at University of Texas Southwestern Medical School (Dallas, TX) and Vanderbilt University (Nashville, TN) in the laboratory of Dr. D. Carbone.
Dr. Gabrilovich obtained his first independent faculty position at Loyola University Medical School in Chicago, IL, in 1999. In 2000, Dr. Gabrilovich moved to H. Lee Moffitt Cancer Center in Tampa, FL, where he progressed through the ranks and eventually became Robert Rothman Endowed Chair in Cancer Research and Head, Section of Dendritic Cell Biology.
While at Vanderbilt, he demonstrated that DCs in tumor-bearing mice (and later in cancer patients) were functionally impaired. He has described the first tumor-derived factor directly implicated in DC defects in cancer, VEGF, and suggested that myeloid progenitor cells were the main targets for this negative effect. In subsequent work at Loyola University and Moffitt Cancer Center, he described and characterized immature myeloid cells with immunosuppressive activity, making him one of the first to discover the cells now called myeloid-derived suppressor cells (MDSC). His group characterized a number of molecular mechanisms regulating expansion and function of these cells. Dr. Gabrilovich established the role of antigen-specific mechanisms in the regulation of T-cell tolerance mediated by MDSCs and described the critical contribution of peroxynitrite to this effect. Dr. Gabrilovich's group also provided some of the first evidence that MDSCs can be therapeutically targeted in patients. His group established lipid accumulation as one of the mechanisms negatively regulating DC function in cancer. Currently, his group is a world leader in the evaluation of DC accumulation and function and in determining which mechanisms make the most suitable targets for therapeutic enhancement of antitumor responses.
Cancer Immunol Res January 2017 5:3-8; doi:10.1158/2326-6066.CIR-16-0297
Laurence Zitvogel is the Scientific Director of the Immuno-Oncology Programme of Gustave Roussy, as well as Research Director, Institut National de la Santé et Recherche Medicale and Head of the Center for Clinical Investigations for Biotherapies of Cancer, located at Institut Gustave Roussy, Villejuif-Grand, Paris, France.
Prof. Zitvogel earned her MD in medical oncology in 1992 and her PhD in tumor immunology in 1995 from the Ecole de Médecine, Université Paris (Paris, France). She was a junior associate at the University of Pittsburgh (Pittsburgh, PA) in the laboratory of Michael Lotze, where she worked on antitumor vaccines that utilized dendritic cells.
After returning to France in 1995, Prof. Zitvogel was appointed to the faculty of the Institut Gustave Roussy, where her interest in the use of dendritic cells and other novel substances for therapeutic exosome-based vaccines continued. In 2005, she became Professor and Director of the center, where she currently works. Prof. Zitvogel has merged her interests in fundamental science and translational research in her work on cancer therapies like those based on dendritic cells and innate effectors and the resultant phase I patient studies. As her research widened and deepened, she investigated how chemotherapies and radiotherapy interacted with the immune system and made fundamental contributions that altered our understanding of how these approaches interacted with antitumor responses. She pioneered the concept of immunogenic cell death and is currently unraveling the role of gut microbiota in cancer immunosurveillance and responses.
Prof. Zitvogel has been the recipient of several prestigious prizes, including Chevalier de l’Ordre de la Légion d’Honneur and the INSERM Grand Prix for translational research, and is an elected member of the French Academy of Medicine.
Cancer Immunol Res November 2016 4:895-902; doi:10.1158/2326-6066.CIR-16-0197
Guido Kroemer is Professor, Faculty of Medicine of the University of Paris Descartes (Paris V); Director, Institut National de la Santé et de la Recherche Médicale (INSERM) Unit “Apoptosis, Cancer and Immunity”; Director, Metabolomics and Cell Biology platforms of the Gustave Roussy Cancer Campus (Villejuif-Grand Paris, France); and a practitioner at the Hôpital Européen George Pompidou in Paris (France). He is also the Director of the Paris Alliance of Cancer Research Institutes (PACRI) and the LabEx “Immuno-Oncology.”
Dr. Kroemer earned his MD in 1985 from the University of Innsbruck (Innsbruck, Austria). He received his PhD (1992) in molecular biology at the Autonomous University of Madrid (Madrid, Spain), where he investigated immune tolerance, regulating autoimmune responses, and T-cell clonal deletion.
After his recruitment to the French Medical Research Council (INSERM), Dr. Kroemer has made fundamental contributions to our understanding of regulated cell death (apoptosis) with his discovery that mitochondrial membrane permeabilization is a decisive step in apoptosis. His research took him into the adjacent field of autophagy and where his laboratory's work showed that autophagy is a cytoprotective mechanism with lifespan-extending effects. How cells die, refuse to die, or protect themselves from being killed are major questions in cancer biology. Dr. Kroemer's laboratory has also provided evidence that the success of anticancer therapies is dependent on stimulating tumor-targeting immune responses.
Dr. Kroemer has received the Descartes Prize of the European Union, the Carus Medal of the Leopoldina, the Dautrebande Prize of the Belgian Royal Academy of Medicine, the Léopold Griffuel Prize of the French Association for Cancer Research, the Mitjavile prize of the French National Academy of Medicine, and a European Research Council Advanced Investigator Award.
Cancer Immunol Res November 2016 4:895-902; doi:10.1158/2326-6066.CIR-16-0197
Alexander Y. Rudensky
Alexander Rudensky is the chair of the Immunology Program and director of the Ludwig Center at Memorial Sloan Kettering Cancer Center (MSKCC) in New York, with which he has been affiliated since 2009. He has also served as an investigator with the Howard Hughes Medical Institute since 1993 and as a Tri-Institutional Professor at MSKCC, Rockefeller University, and Cornell University.
Dr. Rudensky graduated from the Medical Biology School of the State Medical Institute in Moscow, USSR. He received his PhD in 1986 from the Gabrichevsky Research Institute of Epidemiology and Microbiology, Moscow, after which he served as a senior research scientist at the Institute for Genetics of Microorganisms in Moscow. In 1990 he joined Charles Janeway Jr at Yale for his postdoctoral studies.
In 1992, Dr. Rudensky joined the faculty at the University of Washington, Seattle, focusing on the functions of CD4 T cells in T cell–mediated immunity. In Seattle, one of his main interests was the molecular mechanisms underlying the presentation of antigens to T cells and the effect of recognition of the antigen on the developing thymocytes. His laboratory's interests broadened as the secrets of efficient peptide loading became clearer. One end result was the realization that to have a normal peripheral T-cell population, the thymus needed a small number of a wide diversity of peptides to be available for presentation. This work led to Rudensky's interest in how the T-cell repertoire is fine-tuned through exposure to self-peptides in the thymus, and how manipulation of the environment can alter what slips through the thymic “barrier.”
Focusing more attention on how mildly self-reactive T cells can be controlled in the periphery, Rudensky and his colleagues zeroed in on the regulatory T cell and defined it as a CD25-expressing cell that also expressed the Foxp3 gene. The Rudensky laboratory is currently the world leader in examining the mechanisms underlying the differentiation and functions of regulatory T cells, making continual progress in regulatory T-cell developmental requirements, how their suppressive activities are regulated, and how tweaking their functional sensitivities can provide new approaches to the many programs with which they interact, including autoimmunity, allergy, and cancer.
Focusing more attention on how mildly self-reactive T cells can be controlled in the periphery, Rudensky and his colleagues zeroed in on the regulatory T cell and defined it as a CD25-expressing cell that also expressed the Foxp3 gene. The Rudensky laboratory is currently the world leader in examining the mechanisms underlying the differentiation and functions of regulatory T cells, making continual progress in regulatory T-cell developmental requirements, how their suppressive activities are regulated, and how tweaking their functional sensitivities can provide new approaches to the many programs with which they interact, including autoimmunity, allergy, and cancer.
Dr. Rudensky is a member of the American Academy of Arts and Sciences, The National Academy of Sciences, and the National Academies’ Institute of Medicine. He has won numerous awards, including the 2015 William B. Coley Award for Distinguished Research in Basic Immunology.
Cancer Immunol Res September 2016 4:721-725; doi:10.1158/2326-6066.CIR-16-0193
Ellen Puré, PhD, is the Grace Lansing Lambert Professor of Biomedical Science and Chair of the Department of Biomedical Sciences at the University of Pennsylvania School of Veterinary Medicine, in Philadelphia. Dr. Puré received her baccalaureate degree from Washington University in St. Louis, MO, where she conducted research on the vascular biology of arachidonic acid metabolites in the laboratory of Philip Needleman. She obtained her doctorate at the University of Texas Southwestern Medical School in Dallas. Her dissertation on antigen receptor and T cell–derived cytokine-mediated activation of B lymphocytes was conducted under the auspices of Ellen Vitetta. She trained as a Damon Runyon–Walter Winchell Postdoctoral Fellow and Leukemia Society Special Fellow and then joined the faculty at the Rockefeller University in New York. In 1992 Dr. Puré moved to Philadelphia, where she was on the faculty of the Wistar Institute until moving to the University of Pennsylvania in 2013.
Dr. Puré’s research focuses on the cellular and molecular basis of inflammation and fibrosis. She studies the basic mechanisms involved in these processes and the contribution of these processes to disease, with an emphasis on cancer in preclinical animal models. A major focus of her laboratory’s work is to define the role of stromal cells, extracellular matrix (ECM), and matrix remodeling in cancer initiation, progression, and metastasis; and to develop novel therapeutic approaches that target the stromal compartment of tumors to use in combination with more conventional therapies that target malignant cells and antiangiogenic therapies.
Two pathways of focus in Dr. Puré’s lab are (i) hyaluronan, a prominent provisional and tumor-associated matrix glycosaminoglycan, and the principle hyaluronan receptor, CD44; and (ii) the cell surface serine protease fibroblast activation protein and the role of this protease in remodeling of collagen-rich provisional and tumor-associated matrix. Her lab established that CD44 promotes atherosclerosis, and they have defined multiple mechanisms by which CD44 promotes inflammation by mediating leukocyte recruitment and leukocyte and mesenchymal cell activation and migration. Her group also established that CD44 is required for intratumoral migration of tumor antigenspecific T cells and optimal antitumor immunity.
Dr. Puré and her colleagues defined fibroblast activation protein, FAP, as a marker of stromal cells and a subset of M2-like macrophages associated with active matrix remodeling in settings of chronic inflammation, tissue fibrosis, and virtually all epithelial-derived solid tumors. They demonstrated that, in human breast cancer, FAPþ stromal cells exhibit subtype-specific gene expression profiles consistent with the coevolution of tumor cells and stromal cells in the tumor microenvironment. Using an adoptive immunotherapy approach to target tumor stromal cells for deletion, her research group has established that FAPþ stromal cells are required for the generation and maintenance of the desmoplastic response that characterizes many solid human tumors. Dr. Puré’s lab established that disrupting tumor-associated matrix by targeting the stromal compartment at either the molecular or cellular level effectively inhibits tumor growth through both immune-dependent and immune-independent mechanisms as a function of tumor immunogenicity and degree of desmoplasia associated with various tumor types. A current focus of her research is to understand what is emerging as a critical role for ECM composition, organization, and biomechanical signaling in tumor initiation, progression and metastasis, chronic inflammation, and fibrosis.
Dr. Puré was a Pew Scholar, an American Heart Established Fellow, the Crawford- Maynard Established Fellow of the American Heart Association, and recipient of a Distinguished Alumnus Award from the University of Texas Southwestern Medical School, an Asthma and Allergy Foundation of America Investigator Award, and the Arthritis Foundation-Stewart J. McCracken Chapter Award for Research. She has trained numerous undergraduates, predoctoral students, postdoctoral fellows, medical students, and clinical fellows.
Cancer Immunol Res April 2016 4:269-278; doi:10.1158/2326-6066.CIR-16-0011
Eric Vivier, DVM, PhD, is a professor of immunology at Aix-Marseille University who was born in Clamart, France. He graduated with the highest honors (silver medal) from the Ecole Nationale Vétérinaire de Maisons-Alfort and received his doctoral degree in immunology from Paris XI University. He began his postdoctoral training as a Fogarty International Center Research Fellow at Harvard Medical School with Paul J. Anderson and Stuart F. Schlossman (the Dana-Farber Cancer Institute). He joined Aix-Marseille University as a professor at the Centre d'Immunologie de Marseille-Luminy (CIML) in 1993 and became its director in 2008. In 1999, Dr. Vivier cofounded the biotech company Innate-Pharma. In 2014, he was one of the founders of the Marseille-Immunopole, an immunology cluster linking fundamental research, therapeutic innovation, and industrial development in the Aix-Marseille region.
Dr. Vivier has made seminal contributions to our understanding of the molecular basis of the ontogeny, function, and therapeutic manipulation of natural killer (NK) cells, and the identification of innate lymphoid cells (ILCs) in mice and humans. His research has had a profound influence on the field of innate immunology. His early work determined the mode of action of the inhibitory MHC class I receptors expressed on NK cells and extended the concept of ITIM-bearing molecules to multiple cell types and multiple biologic functions. In parallel, his group identified the ITAM-bearing polypeptide, KARAP/DAP12. The Vivier laboratory has since been a world leader in the generation of transgenic mouse models for the dissection of NK-cell function in vivo. Building on these basic research results, the Vivier laboratory has also been involved in the development of innovative treatments for cancer. This translation of basic research discoveries into clinical applications led to the development, in 2009, of a first-in-class therapeutic monoclonal antibody to KIR (lirilumab), the efficacy of which against various cancers is currently being assessed. These studies on NK cells led to the involvement of the Vivier laboratory in the discovery of ILCs through the detection and characterization of the ILC3 cell subset in human and mouse intestine.
Dr. Vivier has published more than 270 scientific articles and is on the editorial boards of leading peer-reviewed journals. He serves on the expert panel of the European Research Council and on the committees of pharmaceutical and biotechnology companies. In recognition of his scientific achievements, Dr. Vivier has received awards from the French National League against Cancer (1996, 2004, and 2013), the National Award and Tremplins Rhône-Poulenc Award for Biotech start-ups (1999), the Lucien Tartois Award from the Fondation pour la Recherche Médicale (1999), the Jacques Oudin Award from the French Society for Immunology (2003), the Deutsche Gesellschaft für Immunologie/EFIS Award (2004), the Grand Prix Turpin in Oncology (2008), and the Grand Prix Charles Oberling in Oncology (2010). In 2007, Dr. Vivier became a senior fellow of the Institut Universitaire de France, and, in 2013, he was elected to the French National Academy of Medicine.
Cancer Immunol Res October 2015 3:1109-1114; doi:10.1158/2326-6066.CIR-15-0222
Pramod Kumar Srivastava
Pramod Kumar Srivastava, PhD, MD, is the Northeast Utilities Chair Professor in Experimental Oncology, professor of immunology and medicine, and director of the Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut School of Medicine in Farmington, CT. Dr. Srivastava has championed the cause of personalized immunotherapy of human cancer for over 25 years. He was the first to demonstrate that immunization of mice with heat-shock proteins (HSP) hsp70 and hsp90 isolated from tumors elicited tumor-specific immunity, and that immunogenicity of tumor-derived HSPs comes from HSP-associated peptides, which include any antigenic peptides. He suggested and showed that hsp70 and hsp90 members play a critical role in antigen processing and presentation by MHC class I molecules. Dr. Srivastava showed that endogenous HSP-peptide complexes are the essential vehicles of antigen transfer from antigen-donor cells to antigen-presenting cells (APC) during cross-priming. To explain the powerful adjuvant-like properties of hsp70 and hsp90, he hypothesized and later showed that these HSPs interact with APCs through HSP receptors, such as CD91. Dr. Srivastava developed the HSP-peptide cancer vaccine vitespen or Oncophage, which was approved in Russia in 2008 for treatment of patients with nonmetastatic renal cell carcinoma. Oncophage is the first therapeutic cancer vaccine to be approved for clinical use in the world. An NIH/CTEP (Cancer Therapy Evaluation Program)–approved large randomized study testing Oncophage in patients with recurrent glioblastoma multiforme is ongoing at multiple U.S. centers.
Dr. Srivastava hypothesized in 1993 that cancers are individually antigenically distinct because of random passenger mutations, a proportion of which become immunogenic in any given patient. With the availability of high-throughput genomics and bioinformatics capabilities, he and others have demonstrated that this is indeed the case. Dr. Srivastava is now pursuing genomics-driven personalized immunotherapy for the treatment of human ovarian and other cancers.
Dr. Srivastava has had continuous research support from the NIH for 25 years. He was a member of the NIH Experimental Immunology Study Section and several study sections of the U.S. Department of Defense. He has been a member of the Scientific Advisory Council of the Cancer Research Institute since 1995. In 1997 he was inducted into the Roll of Honor of the Union Internationale Contre le Cancer and became a founding member of the Academy of Cancer Immunology. Dr. Srivastava is an inventor on over 200 awarded patents and has cofounded a number of biotechnology companies, including Antigenics (AGEN), Ikonisys, and Life Science Pharmaceuticals. Dr. Srivastava obtained his bachelor's degree in biology and chemistry and a master's degree in botany (paleontology) from the University of Allahabad, India. He studied yeast genetics at Osaka University, Japan, and completed his PhD in biochemistry at the Center for Cellular and Molecular Biology, Hyderabad, India. He also trained at Yale University and Sloan Kettering Institute for Cancer Research. He obtained his MD degree from the University of Connecticut School of Medicine. He has previously held faculty positions at the Mount Sinai School of Medicine and Fordham University, both in New York City.
Cancer Immunol Res 2015. 3:969-977; doi:10.1158/2326-6066.CIR-15-0134
Martin C. Mihm Jr
James J. Mulé
Dr. Mihm is a professor of pathology and dermatology at Harvard Medical School (HMS) and the associate director of the melanoma program at the Dana-Farber Brigham and Women's Cancer Center. Dr. Mulé is the associate center director for translational science, the Michael McGillicuddy Endowed Chair for Melanoma Research and Treatment, and the scientific director of Cell-based Therapies at the Moffitt Cancer Center in Tampa, Florida.
Dr. Mihm was named the 2003 Legend in Dermatopathology of the American Society of Dermatopathology. His research interests have principally been related to malignant melanoma. He began his studies on melanomas with Wallace Clark in 1965 and coauthored the first publication of the classification of malignant melanoma into subtypes. For two decades, Dr. Mihm codirected the WHO melanoma pathology program, which was devoted mainly to the study of TILs in melanoma and has made significant contributions to establishing the importance of TILs as a prognostic factor in primary and metastatic melanoma. In the late 1970s, Dr. Mihm studied delayed hypersensitivity reactions in animals and humans with Harold F. Dvorak, author of the January 2015 Masters primer entitled “Tumors: Wounds That Do Not Heal—Redux.” Dr. Mihm's collaboration with Dr. Dvorak led to the discovery of the role of basophils in human hypersensitivity reactions, and a definitive description of delayed hypersensitivity in humans that, in turn, led to the first description of the role of the vasculature in human allograft rejection. In the past decade, along with physician-scientist Paula North, Dr. Mihm has begun to study the pathogenesis of vascular anomalies in children and adults. The two researchers discovered a specific phenotype in infantile hemangiomas, and they are investigating the pathogenesis of these lesions. In 1994, Dr. Mihm began collaborations with Glenn Dranoff and F. Stephen Hodi to study vaccine reactions to autologous melanoma cells and the various factors affecting host immune response and survival. This work has led to critical insights in the dynamics of immune function and its regulation. Dr. Mulé began his studies in tumor immunology and immunopathology under the mentorship of Karl Erik and Ingegerd Hellstrom at the Fred Hutchinson Cancer Research Center (FHCRC) in Seattle, Washington, soon after it opened its doors in 1975. There, he showed for the first time that lymphocytes could selectively localize in tumors in vivo. In 1981, Dr. Mulé moved to the Surgery Branch of NCI to study under Steven A. Rosenberg, publishing a series of studies on the antitumor effect of lymphokine-activated killer cells plus recombinant IL2, the mechanisms operative in high-dose IL2 therapy, and the enhancement of therapeutic potency of cytokine gene-modified tumor cells and TILs. Dr. Mulé's research group is now involved in characterizing and validating genomic signatures of immunotherapy response, as well as designing and testing novel dendritic cell–based vaccine and adoptive T-cell transfer strategies in preclinical animal tumor models. The aim of their work is to improve these approaches through a focus on breaking tolerance to tumor self-antigens by inhibiting regulatory cells, boosting T-cell costimulation, and administering combinations of recombinant cytokines and other defined molecules with immune-enhancing activities.
Drs. Mihm and Mulé have received numerous awards and recognitions. Dr. Mihm is particularly proud of his teaching and mentoring awards and Dr. Mulé of his trainees who now hold research and teaching positions world-wide. Drs. Mihm and Mulé serve on the editorial boards of leading peer-reviewed journals and on the scientific advisory boards of various academic and health institutions as well as biotechnology and pharmaceutical companies. Dr. Mihm was born in Pittsburgh, Pennsylvania and graduated summa cum laude from Duquesne University. He obtained his MD from the University of Pittsburgh Medical Center. He completed his residency in dermatology and pathology at the Massachusetts General Hospital (MGH) and subsequently joined the MGH staff. In 1976, he founded one of the first five U.S. residency training programs in dermatopathology. In 1993, he joined the faculty of Albany Medical Center to establish a dermatology and dermatopathology training program. He returned to MGH in 1996 as a clinical professor to continue work in melanoma and to establish a vascular malformation clinic. Dr. Mihm holds five adjunct professorships at different schools in the United States. He cofounded the Rare Tumor Institute of the WHO in Milan, Italy, and was its external coordinator for 5 years. He is currently the codirector of the melanoma pathology program of the European Organisation for the Research and Treatment of Cancer. He has written over 500 articles and authored or coauthored 12 books. Dr. Mulé was born in Kearny, New Jersey, and graduated from the New Jersey City University; he received a special individual PhD from the FHCRC and the University of Washington, Seattle. He is a long-standing special government employee with the FDA (CBER) and NCI. He chaired the Cellular, Tissue, and Gene Therapy Advisory Committee of CBER, FDA, and was a member of the NCI Director's Board of Scientific Counselors (BSC-A). He has written over 200 articles and has been a continuously funded investigator for nearly 25 years. Dr. Mulé received postgraduate training at the Surgery Branch of NCI, where he became a senior investigator with tenure. After helping to launch and scientifically direct two biotechnology companies in Palo Alto, California, Dr. Mulé was named the inaugural director of the Graduate Program in Immunology and director of the Tumor Immunology and Immunotherapy Program at the University of Michigan, where he was also the Maude T. Lane Endowed Professor of Surgery and a professor in the Department of Internal Medicine.
Cancer Immunol Res 2015; 3:827-835; doi:10.1158/2326-6066.CIR-15-0143
Jeffrey V. Ravetch
Jeffrey V. Ravetch, MD, PhD, is the Theresa and Eugene M. Lang Professor at The Rockefeller University and head of the Leonard Wagner Laboratory of Molecular Genetics and Immunology. Dr. Ravetch and his laboratory have made major discoveries contributing to our understanding of the biology of the Fc receptors (FcR) and their critical roles in inflammation and in shaping the immune response. Even though the existence of the FcRs was suggested decades earlier, the structures and functions of these receptors were not defined until Dr. Ravetch and his colleagues cloned and characterized two murine FcRs for the immunoglobulin G (IgG) isotype (FcR) in 1986. In that seminal article they described the near homologous extracellular domains of these FcRs with distinct cytoplasmic tails, including the discovery of the immune-tyrosine inhibitory motif, thus providing the molecular basis for the functional heterogeneity of FcRs. Based on the cellular distribution and preferential expression patterns, they hypothesized that FcRs bind the same ligands but transmit different signals. Since then, using elegant biochemistry and mouse strains they generated with various components of the FcRs genetically modified, the Ravetch laboratory has defined mechanisms by which antibodies mediate their diverse biologic activities in vivo, establishing the preeminence of FcR pathways in host defense, inflammation, and tolerance. They have identified and described novel inhibitory signaling pathways to account for the paradoxical roles of antibodies as promoting and suppressing inflammation. The focus of the Ravetch laboratory is to continue to define the function and regulation of the IgG Fc domain and the diverse FcRs to which they bind. He has extended his studies into clinical applications for the treatment of neoplastic, inflammatory, and infectious diseases through collaborations with industry partners.Dr. Ravetch has received numerous awards, including the Burroughs-Wellcome Scholar Award in molecular parasitology, the Pew Scholar Award, the Lee C. Howley Sr. Prize, the AAI-Huang Foundation Meritorious Career Award, the William B. Coley Award for distinguished research in basic and tumor immunology, the Sanofi-Institut Pasteur Award, the Canada Gairdner International Prize, and the Wolf Prize in Medicine. He received an honorary doctorate from Freidrich-Alexander University, Nuremberg/Erlangen. Dr. Ravetch was elected as a member of the U.S. National Academy of Sciences and the Institute of Medicine, as a Fellow of the American Academy of Arts and Sciences, and of the American Association for the Advancement of Science. He serves as a consultant or a member on the scientific advisory boards of numerous organizations, including charitable foundations that support scientific research and training, such as the Cancer Research Institute, the Irvington Institute for Medical Research, and the Damon Runyon Foundation, and various biotechnology and pharmaceutical companies. He has published more than 200 research articles, book chapters, and reviews and serves on the editorial boards of leading peer-reviewed journals.
Dr. Ravetch is a native of New York City. He received his BS degree, cum laude, in molecular biophysics and biochemistry from Yale University, where he worked with Donald M. Crothers on the thermodynamic and kinetic properties of synthetic oligoribonucleotides. He earned his PhD in genetics from The Rockefeller University under the tutelage of Norton Zinder and Peter Model, investigating the genetics of viral replication and gene expression for the single-stranded DNA bacteriophage f1, and his MD from Cornell University Medical School. Dr. Ravetch pursued postdoctoral training with Philip Leder at the NIH, identifying and characterizing the genes encoding human antibodies and the DNA elements involved in switch recombination. He was a member of the faculty of Memorial Sloan Kettering Cancer Center and Cornell Medical College before joining The Rockefeller University. Dr. Ravetch is an avid fan of poetry, dating back to his undergraduate days at Yale, where he earned a BA in English literature simultaneously with his BS degree. He is a passionate collector of 20th century American poetry, focusing on the works of Wallace Stevens, Robert Penn Warren, and Mark Strand. He served on the board of the American Academy of Poets and is currently a board member of the National Poetry Series. When not in the lab or on the road, Dr. Ravetch can be found at the opera or tending to his gardens in the Hudson Valley.
Cancer Immunol Res. 2015; 3 (7) 704-713. doi:10.1158/2326-6066.CIR-15-0120
Lewis L. Lanier
Lewis L. Lanier, PhD, is an American Cancer Society Professor and the J. Michael Bishop Distinguished Professor and chair of Microbiology and Immunology at the University of California San Francisco (UCSF). He leads the Cancer, Immunity, and Microenvironment Program of the UCSF Helen Diller Comprehensive Cancer Center. Dr. Lanier is a pioneer in the study of natural killer (NK) cells. He identified a subset of human lymphocytes with the innate capacity to kill tumor cells and infected cells, which he hypothesized as a third lymphocyte lineage, and began to study their biology before NK cells were fashionable. He showed that these cells express surface markers CD56 and CD16, and that the CD16 Fc receptor mediates antibody-dependent cellular cytotoxicity. The Lanier group has identified and characterized many of the activating and inhibitory NK-cell surface receptors and their ligands. In addition, they discovered the immunotyrosine-based activation motif (ITAM)-bearing DAP12 adaptor molecule that signals for NK-cell receptors and the NKG2D/DAP10 receptor complex in mice and humans. They also showed that many of these NK receptors are present on T cells and modulate T-cell function. Dr. Lanier and his research group continue to study NK cells, a component of innate immune surveillance that recognizes and eliminates cells that have become transformed or infected by viruses.In recognition of his scientific contributions, Dr. Lanier was awarded the William B. Coley Award for Distinguished Research in Basic Tumor Immunology from the Cancer Research Institute in 2002. In 2005 he received the Rose Payne Award for his contributions to immunogenetics from the American Society for Histocompatibility and Immunogenetics. In 2010 he was elected to the U.S. National Academy of Sciences; in 2011 he became a fellow of the American Academy of Microbiology and was elected to the American Academy of Arts and Sciences. He received the 2001 Distinguished Service Award from the American Association of Immunologists (AAI) and served as AAI president from 2006 to 2007. He has published more than 400 scientific articles and is on the editorial boards of leading peer-reviewed journals. Dr. Lanier serves on the Scientific Advisory Board of several pharmaceutical and biotechnology companies and research institutes.
Dr. Lanier was born in Memphis, Tennessee. He graduated with high honors in biology (microbiology) from Virginia Polytechnic Institute and State University and received his PhD in microbiology and immunology from the University of North Carolina (UNC) Chapel Hill. He began his postdoctoral training at the Lineberg Cancer Center at UNC Chapel Hill and continued as a Damon Runyon-Walter Winchell Cancer Research Fellow at the University of New Mexico. He joined the Research and Development Department at the Becton Dickinson Monoclonal Center in Mountain View, California, where he advanced to Associate Director of Research. In 1990, he joined the DNAX Research Institute of Molecular and Cellular Biology in Palo Alto and later became its Director of Immunobiology. In 1999, he joined the faculty of UCSF, where he became chair of Microbiology and Immunology in 2010. Dr. Lanier is an avid sailor who skippers a sailboat racing team on San Francisco Bay. He is also a music aficionado. As the keynote speaker at the Harvard Medical School (HMS) Immunology program retreat in 2014, he impressed young immunologists with his performance of a rap version of The Band's 1968 classic hit song “The Weight” accompanied by the HMS Immunology house band, Captain Fred and The Pogies.
Cancer Immunol Res. 2015; 3 (6) 575-582. doi:10.1158/2326-6066.CIR-15-0098
Vincenzo Cerundolo, MD, PhD, is the director of the United Kingdom Medical Research Council (MRC UK) Human Immunology Unit and professor of immunology at the Weatherall Institute of Molecular Medicine, University of Oxford, UK. In the early 1990s Dr. Cerundolo made key discoveries characterizing the cellular mechanisms involved in the presentation of intracellular peptides to MHC class I–restricted T lymphocytes, which have had a great impact on the field. In particular, he was instrumental in the identification of genes within the MHC locus that are critical for the generation of peptides presented by MHC class I molecules. Dr. Cerundolo described the first human antigen processing-deficient cells, leading to the cloning and characterization of the transporter associated with antigen-processing 1 and 2 (TAP1, TAP2) genes and the identification of several families of TAP1/2-deficient patients with necrotizing granulomatous skin lesions and small vessel vasculitis. He was the first to determine the relationship between the length of peptides and their binding affinity to MHC class I molecules, hence explaining the homogenous length of peptides isolated from MHC class I molecules. He showed the proteasome-dependent processing of defined melanoma antigenic proteins into epitopes for antitumor T cells and thus the direct role of immunoproteasomes in cross-presentation of exogenous proteins.
Dr. Cerundolo was born in Lecce, Italy. He was a graduate in medicine and completed his PhD in immunology at the University of Padua, Italy, where he also received training in clinical and experimental oncology. He moved to the UK as an EMBO Fellow in 1988 to work with Professor Alain Townsend. Dr. Cerundolo was appointed professor of immunology at the University of Oxford in 2000, director of the MRC Human Immunology Unit in 2010, and head of the Investigative Medicine Division of the Radcliffe Department of Medicine in 2012. Dr. Cerundolo enjoys running and is a member of one of the Oxford Road Runner Clubs. He is a fellow of Merton College at the University of Oxford, the Academy of Medical Sciences, UK, and the Royal College of Pathologists, and is the Batsheva Fellow of the Israeli Academy of Medical Sciences. He serves on the scientific advisory boards of numerous institutions and charitable organizations, and on the editorial boards of leading peer-reviewed journals.
Cancer Immunol Res. 2015; 3 (5) 425-435. doi:10.1158/2326-6066.CIR-15-0062
Ellis L. Reinherz
Ellis L. Reinherz, MD is a professor of medicine at Harvard Medical School (HMS) and chief of the Laboratory of Immunobiology and codirector of the Cancer Vaccine Center at the Dana-Farber Cancer Institute (DFCI). Dr. Reinherz is known for his basic research that has revealed key functional and structural discoveries about T-cell receptors (TCR), including their CD3 signaling subunit components, and how the TCRs, along with the CD4 and CD8 coreceptor molecules that he identified, bind to the peptide–major histocompatibility complex (MHC). More recently he and his colleagues have defined the TCR as an anisotropic mechanosensor, offering a physical solution to the longstanding question of how T cells can achieve rapid and specific sensing of a single peptide bound to an MHC molecule among a sea of unrelated peptides arrayed on the surface of an antigen-presenting cell with exquisite specificity and dynamic range. His findings on the molecular basis of adaptive immunity have implications for rational vaccine design and human immunotherapy efforts in the clinic. He has authored more than 400 research publications in human and murine immunology, spanning areas in basic and translational research. The development of OKT3, the first FDA-approved monoclonal antibody (mAb) in humans, resulted from his studies demonstrating the ability of the mAb to inhibit antigen-specific T-cell responses.
Dr. Reinherz was born in Malden, MA, and is a distinguished alumnus of the Middlesex School in Concord, MA. He entered Harvard College in 1968 and graduated summa cum laude in 1971 with an AB degree. He received his medical degree from HMS in 1975. After completing his internship and residency at the Massachusetts General Hospital and a hematology fellowship at the Brigham and Women's Hospital, Dr. Reinherz pursued research training as a postdoctoral fellow in the laboratory of Stuart Schlossman. Subsequently he was recruited to join the faculty of DFCI and HMS as an assistant professor of medicine, and he has held the rank of HMS professor of medicine since 1994. Dr. Reinherz is a member of the editorial boards of several basic and clinical immunology journals; he is the coeditor of the T-cell biology section of Frontiers in Immunology. Currently he chairs the steering committee of the NIH Human Immunology Project Consortium. Dr. Reinherz is a member of the American Federation for Clinical Research, the American Society of Hematology, the American Society of Clinical Investigation, and the American Association of Immunologists (AAI). He is the recipient of the 2011 AAI Human Immunology Award.
Cancer Immunol Res. 2014; 3 (4) 305–12. doi:10.1158/2326-6066.CIR-15-0042
Thomas A. Waldmann
Thomas A. Waldmann, MD, is an NIH Distinguished Investigator and the chief of the Lymphoid Malignancies Branch of the National Cancer Institute (NCI) at the NIH. Dr. Waldmann is known for his seminal translational work on the IL2/IL2R system and the clinical application of IL2R-directed monoclonal antibody–mediated therapy for certain lymphoid malignancies and autoimmune diseases, including multiple sclerosis. He codiscovered IL15 and has translated this insight into the use of IL15 for treatment of metastatic malignancy.Dr. Waldmann was born in New York, NY. He received his AB degree from the University of Chicago, his MD degree from Harvard Medical School, and served his residency in internal medicine at the Massachusetts General Hospital. Dr. Waldmann joined the NCI in 1956, where he became chief of the Metabolism Branch (now termed Lymphoid Malignancies Branch) in 1973. In studies with NIH colleagues at that time, Stanley Korsmeyer and Philip Leder, Dr. Waldmann introduced molecular genetic analysis of immunoglobulin and T-cell receptor gene rearrangements in the analysis of lymphoid neoplasms. His early research focus was on the critical immunologic role played by the IL2R on the growth, differentiation, and regulation of normal and neoplastic T cells. He defined two of the three IL2R elements including IL2Rα and IL2Rβ using the first monoclonal antibody to a cytokine receptor termed anti-Tac (anti-CD25, daclizumab) that he developed. Dr. Waldmann demonstrated the effectiveness of daclizumab in the treatment of multiple sclerosis and in the reduction of renal transplant rejection episodes, an application for which this agent has been approved by the FDA. In a pivotal recent finding, Dr. Waldmann demonstrated that many patients with refractory and relapsed Hodgkin lymphoma could be effectively treated with daclizumab armed with the β-emitting radionuclide Yttrium-90.
Furthermore, Dr. Waldmann codiscovered IL15, a cytokine that inhibits activation-induced cell death, stimulates T-cell proliferation, promotes survival of CD8-memory T cells, and supports the development and maintenance of natural killer cells. IL15 binds to the β and γ chains that are common to both the IL15R and IL2R. Dr. Waldmann has recently completed a study of IL15 in the treatment of patients with metastatic malignancy. The shared and contrasting roles of IL2 and IL15 in the life and death of normal and neoplastic lymphocytes is the focus of Dr. Waldmann's Masters primer in this issue of Cancer Immunology Research.
Dr. Waldmann's scientific efforts have been recognized with numerous honors, including the Henry Stratton Medal, the Paul Ehrlich Medal, the Lila Gruber Prize, the Simon Shubitz Prize, the Ciba-Geigy Drew Award, the Abbott Prize in Immunology, the Milken Family Medical Foundation Distinguished Scientist Award, the Artois-Baillet Latour Health Prize, the Bristol-Myers Squibb Award, and the American Association of Immunologists–Dana Foundation Award in Human Immunology Research. As a tribute for his many seminal contributions to human immunology, including the landmark studies of catabolism of immunoglobulins and immunoglobulin gene rearrangement, the Foundation of Primary Immunodeficiency has established the annual Thomas Waldmann Award for Excellence in Human Immunology. Dr. Waldmann is an elected member of the U.S. National Academy of Sciences (NAS), the American Academy of Arts and Sciences, the Institute of Medicine of the U.S. NAS, the Association of American Physicians and American Society for Clinical Investigation, the UK Royal Society of Medical Sciences, and the Hungarian Academy of Sciences.
Cancer Immunol Res. 2015; 3 (3) 219–27. doi: 10.1158/2326-6066.CIR-15-0009
Eva Fischer Klein, MD, PhD, is a professor emeritus and group leader in the Microbiology, Tumor and Cell Biology Center (MTC) of the Karolinska Institute, Stockholm, Sweden. Her pioneering contributions in experimental and clinical studies cover several aspects of malignancy including tumorigenesis, host immune responses, and the microenvironment. Guided by her work on virus-induced lymphomas in mice she began studies on Burkitt lymphoma in its initial stages when the Epstein–Bar virus (EBV) was discovered in Burkitt lymphoma tissues. EBV continues to be her main research focus. She has established a number of cell lines derived from African Burkitt lymphoma that are in use today. Dr. Klein was born in Budapest, Hungary, in 1925. With the help of friends she survived the Holocaust (miraculously on a few occasions); immediately after the war she began medical studies at the University of Budapest, where she met Georg Klein, who became her husband.
In the last days before the Iron Curtain descended on Hungary the couple moved to Stockholm. They both obtained positions as research students in the department of cell biology and genetics at the Karolinska Institute in 1948 under the tutelage of Professor Torbjörn Caspersson. The black and white photograph was taken in 1948 upon their arrival at the Karolinska. (For more details, see the article by G. Klein and E. Klein in Ann Rev Immunol 1989;7:1–33.)
Professor Klein received her MD in 1955 and her PhD in 1965. Her PhD thesis work was on the transformation of solid tumors into ascites tumors, focusing on the evolution of tumor cell populations based on variation and selection. This theme recurs in her present studies in chronic lymphocytic leukemia. Dr. Klein became a professor of tumor biology in 1979 and professor emeritus in 1993.
She has mentored many students, some of whom have reached top positions in Sweden and internationally.
Dr. Klein has published over 500 papers. She has served as an editor for Seminars in Cancer Biology. She is a member of the Royal Swedish Academy of Sciences, a foreign member of the Hungarian Academy of Sciences and the Hungarian Immunological Society, the first honorary member of the Israel Immunological Society, and a fellow of the European Union Contra Cancer. She was elected as a fellow of the American Association for Cancer Research Academy in 2013.
Professor Eva Klein has received many awards and honors, including honorary doctorates from the University of Nebraska and the Ohio State University; the Bertha Goldblatt Teplitz Award from the Ann Langer Cancer Research Foundation; the inaugural William B. Coley Award in Tumor Immunology from the Cancer Research Institute; the Björken Prize from Uppsala University; the Nordic Prize of the Erik Fernström Foundation of Lund University; the Thomas P. Infusino Prize and Lectureship in Cancer Causation and Epidemiology from the Lautenberg Center for General and Tumor Immunology; the Orden Nacional al Mérito de la República de Colombia; and the Mendel Honorary Medal for Merit in the Biological Sciences from the Academy of Sciences of the Czech Republic. She was declared the 2006 MTC Scientist of the Year, and in 2010 she received the Karolinska Institute's 200-Year Anniversary Silver Medal for Medical Research. The Kleins have one son, who is a mathematician, and two daughters, one an MD and the other a playwright.
Cancer Immunol Res. 2014; 3 (2) 97–102. doi:10.1158/2326-6066.CIR-14-0238
Harold F. Dvorak
Harold Fisher Dvorak, MD, was the chief of pathology at the Beth Israel Deaconess Medical Center (BIDMC) and the Mallinckrodt Professor of Pathology atHarvard Medical School (HMS) from 1979 to 2005. He received the 2014 Canada Gairdner International Award for discovering vascular endothelial growth factor (VEGF), a protein that has been effectively targeted in cancer and wet macular degeneration. Dr. Dvorak is a superb classic scientist who enjoys research and pursues science diligently and elegantly. In the early 1970s, Dr. Dvorak and colleagues demonstrated that delayed-type hypersensitivity reactions are heterogeneous, involving various immune-cell populations, and are associated with increased vascular permeability to plasma proteins due to the secretion by macrophages and mast cells of a new factor, which they characterized as the vascular permeability factor (VPF, renamed VEGF).
In 1983, Dr. Dvorak and his colleagues were the first to demonstrate that tumor cells secreted VEGF. This seminal discovery provided the molecular basis for the field of angiogenesis. His research has helped elucidate the nature and composition of tumor stroma and the pathogenesis of its generation. Dr. Dvorak made the critical observation that tumors behave like "wounds that do not heal" in that the vascular and stromal responses they induce closelymimic those of healing wounds. In both settings, and also in chronic inflammatory reactions, the initial sequence of events includes vascular hyperpermeability resulting in plasma fibrinogen extravasation, extravascular fibrin deposition, induction of angiogenesis, and progression to desmoplasia or scar formation. Based on Dr.Dvorak's work and the work of others, VEGF is regarded as the key angiogenic factor contributing to the neovascularization associated with tumor growth and other adaptive or pathologic angiogenic responses. More recently, his work has characterized the different types of blood vessels that tumors generate and the molecular mechanisms by which they form.
Dr. Dvorak has published over 300 original papers and review articles. He is a fellow of the American Association for the Advancement of Science and of the National Foundation for Cancer Research (NFCR). He has served as president of the American Society for Investigative Pathology, which awarded him the 2002 Rous-Whipple award, and in 2013, the Gold-headed Cane award for his scientific accomplishments. In addition to the 2014 Gairdner Award, Dr. Dvorak's many honors include the 2005 Lefoulon-Delalande Grand Prix from the Institut de France and the 2006 inaugural Albert Szent-Gyorgyi Prize for Progress in Cancer Research from the NFCR.
Cancer Immunol Res. 2015; 3 (1) 1–11. doi:10.1158/2326-6066.CIR-14-0209
Andrew D. Luster
Andrew D. Luster, MD, PhD, is the Persis, Cyrus, and Marlow B. Harrison Professor of Medicine at Harvard Medical School (HMS) and the E. Alexandria and Michael N. Altman Chair in Immunology at Massachusetts General Hospital (MGH). He received his BS in Biology summa cum laude from Duke University, his PhD in molecular genetics and immunology from the Rockefeller University, and his MD from Cornell University Medical College. Dr. Luster was a medical resident and infectious disease fellow in the Department of Medicine at MGH and a research fellow in the HMS Department of Genetics. In 1994, Dr. Luster established his independent laboratory at MGH. He was appointed chief of a new MGH division, the Division of Rheumatology, Allergy, and Immunology, and was named director of the new Research Center for Immunology and Inflammatory Diseases in 2000.
Dr. Luster is a quintessential medical scientist–a clinician with solid training in basic science. Over the past three decades, he has been intimately associated with the birth, growth, and development of the chemokine field. He performed his PhD research in the laboratories of Drs. Jeffrey Ravetch and Zanvil Cohn, identifying the interferon-g inducible cytokine IP-10 and characterizing its molecular regulation. He continued his training in the fundamentals of basic science research as a postdoctoral fellow in Dr. Philip Leder's laboratory (HMS), studying the in vivo antitumor activity of the CXC chemokine IP-10 and defining the biologic activity of the CC chemokine eotaxin, an eosinophil chemoattractant.
Dr. Luster has made multiple seminal contributions to our understanding of the roles of the chemokine family of immunoregulatory chemotactic cytokines in health and diseases since his initial discovery of the T-cell chemoattractant IP-10 (now also called CXCL10). His laboratory has helped define the chemokine family and its functions in immune-cell trafficking, which is necessary to generate innate and adaptive immune responses, and in the pathogenesis of immune and inflammatory diseases.
Dr. Luster is an outstanding teacher; he has taught many medical and immunology classes and has mentored over 60 clinical and basic science trainees from around the world. He is a reviewer for numerous peer-review journals and a member of various scientific advisory boards.
Dr. Luster has received numerous awards and honors, including a Damon Runyon–Walter Winchell Postdoctoral Fellowship, a Cancer Research Institute Investigator Award, a Culpeper Medical Scientist Award, an NIH MERIT Award, and the 2011 Lee C. Howley Sr. Prize for Arthritis Research from the Arthritis Foundation. He is an elected member of the American Society for Clinical Investigation, the Interurban Clinical Club, and the American Association of Physicians.
Cancer Immunol Res. 2014; 2 (12) 1125–1131. doi:10.1158/2326-6066.CIR-14-0160
Michael L. Dustin
Michael L. Dustin, PhD, is a professor of molecular immunology at the Nuffield Department of Orthopedic, Rheumatology and Musculoskeletal Sciences, and the head of immunology at the Kennedy Institute of Rheumatology at the University of Oxford, UK. He was born in Poughkeepsie, NY, where he was inspired to study biology by looking at pond water through a microscope. He received a BA in biology with honors from Boston University and a PhD in cell and developmental biology from Harvard University. After his PhD work on T-cell adhesion molecules in Timothy Springer's lab, Dr. Dustin joined the laboratory of Stuart Kornfeld at the Washington University School of Medicine, St. Louis (WUStL) to expand his studies in cell biology and microscopy. In 1993, he established his independent laboratory as Assistant Professor of Pathology at WUStL, where he led a collaborative group in discovering the requirements for the T-cell immunological synapse. He moved to the Skirball Institute of Biomolecular Medicine at the New York University School of Medicine in 2001 as the Irene Diamond Professor in Immunology, and then the Muriel G. and George W. Singer Chair Professor of Molecular Immunology.
In 2013, Dr. Dustin joined the University of Oxford as a Wellcome Trust Principal Research Fellow. The Dustin laboratory has made substantial contributions to our understanding of T-cell surface molecules, the mechanism and regulation of T-cell migration in the lymph node and spleen, the mechanism of T-cell tolerance and activation in vivo by dendritic cells, and the modulation of T-cell immunological synapses.
He has collaborated on intravital microscopy studies on breast and pancreatic cancers. The Dustin team in Oxford is developing new approaches to harness the immunological synapse as a therapeutic target in autoimmune disease and cancer.
Dr. Dustin has served on various scientific advisory boards and journal editorial boards. He is a fellow of the American Association for the Advancement of Sciences. He has received numerous awards, including a Presidential Early Career Award in Science and Engineering and the DART-NYU Biotechnology Award. He was also included in Esquire magazine's Best and Brightest in 2001. Dr. Dustin has organized various conferences on imaging of immunoreceptors and the immune system and authored over 250 peer-reviewed, original research papers, review articles, and book chapters. He is an enthusiastic teacher and has mentored over 40 graduate and postgraduate trainees. In addition, His lab has hosted over 20 visiting scientists from around the world. In keeping with his upbringing in the picturesque Hudson Valley, Dr. Dustin enjoys birding, cycling, and nature photography.
Cancer Immunol Res. 2014; 2 (11) 1023–1033. doi:10.1158/2326-6066.CIR-14-0161
Inder Mohan Verma
Inder Mohan Verma, PhD, is the Irwin and Joan Jacobs Chair Professor in Exemplary Life Science, Professor and Director of the Laboratory of Genetics at The Salk Institute for Biological Sciences (La Jolla, CA), and an American Cancer Society Professor of Molecular Biology. He is also an adjunct professor in the department of biology at the University of California, San Diego, and a distinguished adjunct professor in the Biotechnology Research Group at the King Abdulaziz University (Jeddah, Saudi Arabia). Dr. Verma was educated at the Lucknow University in India, and received his PhD in Biochemistry from the Weizmann Institute of Science (Rehovot, Israel), characterizing mitochondrial ribosomal RNA from the fungus Aspergillus nidulans, under the mentorship of Professor Uri Littauer. In 1971 he joined the laboratory of Nobel laureate David Baltimore at the Massachusetts Institute of Technology (Cambridge, MA), where he studied reverse transcriptase from RNA tumor viruses, including avian myeloblastosis virus, mouse leukemia virus, and hamster leukemia virus. Dr. Verma established his independent laboratory at The Salk Institute in 1974, and at the age of 26, he was one of the youngest faculty members.
Dr. Verma's work on RNA tumor viruses and reverse transcriptase led to his identification and/or characterization of several oncogenes, including c-fos, c-rel, and the breast cancer genes (BRCA1, BRCA2). The Verma laboratory has contributed significantly to the delineation of the regulation and expression of c-fos during prenatal and postnatal development, growth, and differentiation. These investigators have characterized the mechanism of BRCA1 tumor suppression. C-rel is a member of the nuclear factor-κB (NF-κB) family of master transcription factors, the subject of this Masters primer.
With expertise in molecular biology and retrovirology, Dr. Verma developed viral expression vectors for gene transfer to replace missing or defective cellular proteins, and this work has become the foundation for cell and gene therapy. The Verma laboratory has used the gene therapy technology to generate a mouse model of glioblastoma, from which they have identified neural cancer stem cells, as few as ten of which can induce tumors in immunodeficient mice. They are using the same technique to investigate the initiation and treatment of lung and prostate cancers.
Dr. Verma was born in Sangrur, Punjab, India. He has received many honors, including an Outstanding Investigator Award from the NIH (1988), and he was elected as a member of the Third World Academy of Sciences (1995), the National Academy of Sciences, India (1997), the U.S. National Academy of Sciences (NAS; 1997), the U.S. NAS Institute of Medicine (1999), the American Academy of Arts and Sciences (2000), the European Molecular Biology Organization (1998), and the American Philosophical Society (2006). Dr. Verma was elected as a Foreign Fellow of the Indian National Science Academy (2005). He was awarded the Vilcek Foundation Prize (2008), the ASGT Outstanding Achievement Award (2009), the Spector Prize (2010), and the Pasarow Award in Cancer Research (2010). Dr. Verma now serves as the Editor-in-Chief of the Proceedings of the National Academy of Science of the United States.
Cancer Immunol Res. 2014; 2 (9) 823–30. doi:10.1158/2326-6066.CIR-14-0112
Melody A. Swartz
Melody A. Swartz, PhD, is the William B. Ogden Professor of Molecular Engineering at the University of Chicago, and Professor of Bioengineering at the Ecole Polytechnique Fédérale de Lausanne (EPFL) in the Institute for Bioengineering and the Swiss Institute for Experimental Cancer Research. Dr. Swartz was trained in chemical engineering; she earned a BS at The Johns Hopkins University in 1991, and a PhD at MIT in 1998. Her PhD thesis was completed in the laboratory of Dr. Rakesh Jain at the Massachusetts General Hospital, where she investigated how the transport functions of lymphatic vessels were coupled to the local tissue biomechanics, developing mathematical and experimental models to understand how the lymphatics respond to edema and how they restore homeostatic fluid balance. Dr. Swartz performed her postdoctoral studies in airway biomechanics at the Brigham and Women's Hospital and Harvard Medical School in the laboratory of Dr. Jeffrey Drazen, where she investigated how mechanical stresses are communicated between cells to instigate stress-dependent remodeling of the extracellular matrix.
She was attracted to the discipline of engineering because of its quantitative and systems-level approaches to problem-solving that can be used to address fundamental biological questions. After completing her training, Dr. Swartz joined the Department of Biomedical Engineering at Northwestern University as an assistant professor in 1999. She moved to the EPFL in 2003, where she was promoted to associate professor in 2006, and then full professor in 2010. Dr. Swartz joined the newly founded Institute for Molecular Engineering at the University of Chicago in 2014, as she returned to her hometown.
With her training as a bioengineer, coupled with strong interests in cancer immunology, Dr. Swartz uses quantitative and multidisciplinary approaches to investigate the roles of the lymphatic system in immunophysiology and pathophysiology, focusing efforts on the interface between vascular biology, transport-biomechanics, and immunology. Her laboratory is currently exploring the function of lymphatic drainage in maintaining local immunologic tolerance, and the roles of lymphangiogenesis in inflammatory diseases including cancer. They are applying the cumulated knowledge of systems immunology of the lymphatic system to develop novel immunotherapeutic approaches in cancer, including lymph node-targeting vaccine approaches.
Dr. Swartz was elected a fellow of the American Institute for Medical and Biological Engineering in 2007 and a fellow of the Biomedical Engineering Society in 2012. She has received numerous awards including the Arnold and Mabel Beckman Young Investigator Award in 2002, the Biomedical Engineering Society's Rita Schaffer Young Investigator Award in 2001, the European Research Council Investigator Awards in 2008 and in 2013; and the 2010 Robert Wenner Prize for Cancer Research from the Swiss Cancer League. In recognition of her creativity in research, she was named a MacArthur Foundation Fellow in 2012.
Cancer Immunol Res. 2014; 2 (8) 700–707. doi:10.1158/2326-6066.CIR-14-0115
Harald von Boehmer
Harald von Boehmer, MD, PhD, is a professor emeritus at the Dana-Farber Cancer Institute (DFCI) and Harvard Medical School (HMS), an adjunct professor at the University of Florida, and a visiting professor in the Institute for Immunology at the Ludwig-Maximilian University of Munich, Germany, where he received his MD in 1968. He subsequently earned a PhD in 1974 from the University of Melbourne, Australia, under the tutelage of Dr. Ken Shortman. Dr. von Boehmer was a member of the Basel Institute for Immunology in Switzerland until 1996, before becoming the director of Unité INSERM 373 at the René Descartes University in Paris, France. He was recruited to join the faculty at DFCI-HMS in 1999, where he served as chief of the Laboratory for Lymphocyte Biology in the DFCI Department of Cancer Immunology and AIDS and a faculty member of the HMS Department of Microbiology and Immunobiology.
The von Boehmer laboratory has contributed significantly to our understanding of T-cell development and its roles in immune responses. Dr. von Boehmer discovered the pre-TCR, cloned the pre-TCRα gene, and defined its role in TCRβ allelic exclusion. Using gene transfer of the TCR, he characterized TCR contribution to recognition by T cells of peptide–MHC complexes. Through analysis of TCR transgenic mice, his favorite experiments, he delineated the role of negative selection in the thymus of developing T cells by peptide–MHC complexes to generation of self-tolerance. He elucidated mechanisms of positive selection in intrathymic generation of CD8+ killer cells, CD4+ helper cells, and FoxP3-expressing CD4+ regulatory cells.
His studies on TCR-signaling pathways that permit conversion of naïve T cells into regulatory T cells in vivo have been used to establish antigen-specific tolerance to insulin and prevention of type 1 diabetes. He described the contribution of T-cell development to acute lymphoblastic T-cell leukemia. In particular, his studies of TCR signaling and Notch signaling revealed that T-cell lineage commitment is instructed by the intensity of TCR signals, and that Notch signaling is mandatory for the generation of α β but not γ δ lineage T cells.
Dr. von Boehmer was born in Guben, Germany; he is an accomplished cellist and has performed with orchestras in Goettingen and Freiburg. His many honors include the Louis- Jeantet Prize for Medicine, jointly with Nicole Le Douarin and Gottfried Schatz (1990), the Avery- Landsteiner prize of the German Society for Immunology (1990), the Paul Ehrlich and Ludwig Darmstadter Prize for Immunology (1993), the Kurt A. Korber Prize for European Science (1997), and most recently the Helmholtz International Fellow Award (2013). He also received an honorary medical degree from the Technical University of Munich (2002). Dr. von Boehmer is an elected member of the Academia Europaea (1990), the Institut Universitaire de France (1997), and the German Academy of Sciences Leopoldina (2003).
Cancer Immunol Res. 2014; 2 (7) 592–597. doi:10.1158/2326-6066.CIR-14-0070
William E. Paul, MD, is an NIH Distinguished Investigator, and Chief of the NIAID Laboratory of Immunology. Dr. Paul is best known for his path-breaking work on cytokine biology including the discovery of interleukin-4, and its role as the key regulator of allergic inflammatory diseases. He delineated the mechanisms of differentiation of naïve CD4 T cells into T-helper effector cells, a subject that remains one of the dominant themes of contemporary immunology.
Dr. Paul was born in Brooklyn, NY. He received his BA degree, summa cum laude, from Brooklyn College, and MD, cum laude, from the State University of New York Downstate Medical Center. He served internship and residency in medicine at the Boston Medical Center, MA. He was a research fellow in the laboratory of Nobel laureate Dr. Baruj Benacerraf at the New York University School of Medicine. In 1968, Dr. Paul joined the NIAID and became chief of the Laboratory of Immunology in 1970. From 1994 to 1997, during his tenure as assistant surgeon general of the United States, he served as the Director of the NIH Office of AIDS Research (OAR), and the associate NIH director for AIDS. As OAR director, Dr. Paul was responsible for, at that time, a new emphasis on HIV vaccine research and development, and the creation of the Vaccine Research Center on the NIH campus. Dr. Paul was elected to the U.S. National Academy of Sciences, the Institute of Medicine, and the American Academy of Arts and Sciences.
He was president of the American Association of Immunologists (AAI) and of the American Society of Clinical Investigation. Dr. Paul has received numerous honorary degrees, awards and recognitions, including the 1980 Founder's Prize of the Texas Instruments Foundation, the 1988 Life Sciences Award from the Federation of American Societies for Experimental Biology, the Tovi Comet-Wallerstein Prize of Bar-Ilan University, Lifetime Achievement Awards from the AAI and the International Cytokine Society, the 2008 Max Delbruck Medal, and the 2009 Clemens von Pirquet Medal. He is a Raymond and Beverly Sackler Senior Professor by Special Appointment at Tel Aviv University, and an Adjunct Professor of Pathology and Laboratory Medicine at the University of Pennsylvania Medical School. Dr. Paul is a prolific researcher and educator. He has authored more than 600 scientific articles and has edited two of the most influential immunology text and reference books. He served as founding editor-in-chief of the Annual Review of Immunology for its first 31 editions. He is the editor of the advanced textbook, Fundamental Immunology now in its seventh edition. He has mentored many prominent immunologists including the late Charles Janeway, Jr., Ron Schwartz, Laurie Glimch er, Mark Davis, and Tony DeFranco.
Cancer Immunol Res. 2014; 2 (6) 503–509; doi:10.1158/2326-6066.CIR-14-0046
Herman N. Eisen, MD, is a professor emeritus in the department of biology at the Massachusetts Institute of Technology (MIT). Dr. Eisen joined the faculty at MIT in 1973 as one of the founding members of the MIT Center of Cancer Research, later named the Koch Institute for Integrative Cancer Biology. He is also affiliated with the Ragon Institute of Massachusetts General Hospital (MGH), MIT, and Harvard University. His early interest was in chemistry. Inspired by the work of Karl Landsteiner, who generated antibodies from hapten-linked proteins, and a seminar by Fred Sanger, who described how he deduced the amino acid sequence of insulin, Dr. Eisen began his distinguished research career in immunology, focused on antibody development and antigen recognition. Benefiting from the post–World War II expansion of NIH-supported research, Dr. Eisen received one of the first physician–scientist awards to study sulfonamide-induced antibodies at New York University (NYU). Using equilibrium dialysis he and his bench-mate, Fred Karush, determined the number of antigen-binding sites on antibodies (Eisen and Karush, J Am Chem Soc 1949;71:363–4).
At Washington University in St. Louis (WUStL), Eisen and his colleagues discovered that the affinity of serum antibodies increases progressively with time after encountering antigen (later called affinity maturation of antibodies, and the subject of the Master primer in this issue). At MIT, the Eisen lab focused on CD8 T cells and their killing of cells that display peptide–MHC complexes recognized by the T cells' antigen-binding receptor.
Dr. Eisen was born in Brooklyn, New York, in 1918. He entered the NYU honors program in 1934 and was the free-swinging, left-handed first baseman for the college's baseball team until he developed tuberculosis and had to leave school for a year. He received hisMDfrom NYU in 1943 and served residencies in pathology at the Columbia- Presbyterian Hospital and in medicine at the Bellevue Hospital. After brief stints at the Memorial Sloan-Kettering Institute and NYU Medical School, including part-time medical practice, he moved to WUStL in 1955, first as professor of medicine and then as professor and chairman of the department of microbiology. Dr. Eisen has received numerous honors, including a National Cancer Institute Outstanding Investigator award, the von Behring-Heidelberger Award, and the American Association of Immunologists (AAI) Lifetime Service/Achievement award. He has served on the scientific advisory boards of the Howard Hughes Medical Institute, Yale Medical School, Harvard School of Public Health, MGH, the Children's Hospital of Boston, the National Institute for Arthritis and Metabolic Diseases, the Roche Institute for Molecular Biology, and the Merck Institute. He was the vice president of the American Society for Clinical Investigation (1965) and the president of the AAI (1968). Dr. Eisen was elected to the American Academy of Arts and Sciences (1965), the U.S. National Academy of Sciences (1969), and the Institute of Medicine (1974).
Cancer Immunol Res. 2014; 2 (5) 381–392; doi:10.1158/2326-6066.CIR-14-0029
Tadamitsu Kishimoto, MD, PhD, is an endowed chair professor at the Immunology Research Center of the Osaka University Graduate School of Frontier Biosciences. He is currently Japan's leading scientist in the life sciences, specifically in immunology. Dr. Kishimoto has made fundamental contributions to our understanding of cytokine functions through a comprehensive and elegant series of studies on interleukin (IL)-6, its transcription regulatory factors, its receptor and signal-transduction system, and their utilization by the IL-6 family of cytokines. He has developed humanized monoclonal antibodies to the IL-6 receptor and treatments for immune disorders, including Castleman disease, rheumatoid arthritis, and juvenile idiopathic arthritis.
Dr. Kishimoto was born in Osaka, Japan, in 1939 and was named an honorary citizen of Tondabayashi City in the Osaka Prefecture in 1992. He received an MD (1964) and a PhD in medicine (1969) from Osaka University. During this period, inspired by Dr. Yuichi Yamamura's work on immunology and medicine, Dr. Kishimoto purified and characterized the structure of human IgM from a patient with Waldenstrom macroglobulinemia. He was a research fellow in Dr. Kimishige Ishizaka's laboratory at the Johns Hopkins University, where he studied the regulation of antibody response in an in vitro rabbit lymphocyte system and demonstrated the presence of soluble factors in primed rabbit lymphocytes that enhance antibody production.
He showed that the activity inducing the different classes of antibodies is distinct. Dr. Kishimoto returned to his alma mater as a professor and chair of the Department of Medicine, where he discovered and cloned the genes encoding IL-6 and its receptor and delineated the signaling pathway used by the IL-6 family of cytokines. He became the dean of faculty of Osaka University Medical School in 1995. Dr. Kishimoto was the president of Osaka University from 1997 to 2003 and a cabinet member of the Council for Science and Technology Policy Office from 2004 to 2006.
Dr. Kishimoto has received numerous awards, which include the Imperial Prize of the Japan Academy, the Sandoz Prize for Immunology from the International Union of Immunological Society, the Avery-Landsteiner Prize from the German Immunology Society, the Robert Koch Gold Medal, the Crafoord Award from the Royal Swedish Academy of Sciences, and the Japan Prize. He was elected as a Foreign Associate member of both the Institute of Medicine and the U.S. National Academy of Sciences. He is also a member of the Japan Academy and the Deutsche Akademie der Naturforscher Leopoldina and an honorary member of the American Association of Immunologists and the American Society of Hematology. In 1998, Dr. Kishimoto was awarded the Order of Culture from the Emperor of Japan.
Cancer Immunol Res. 2014; 2 (4) 288–294; doi:10.1158/2326-6066.CIR-14-0022
Douglas T. Fearon
Douglas T. Fearon, MD, FRS, is the Emeritus Sheila Joan Smith Professor of Immunology at the University of Cambridge, UK, and senior group leader at the Cancer Research UK Cambridge Institute. He received his medical degree at the Johns Hopkins University School of Medicine, followed by internship and residency in internal medicine at the Johns Hopkins Hospital (Baltimore, MD). His scientific training began in 1972 when he joined Dr. Frank Austen's laboratory at Harvard Medical School (HMS) and the Robert bent Brigham Hospital (now part of the Brigham and Women's Hospital) in Boston, MA, as a clinical research fellow in rheumatology and immunology. During this time, Dr. Fearon learned the fundamentals of basic research; he studied innate immunity, identifying and characterizing components of the complement system that enhance immune responses and support antibody functions. He became a full professor at HMS in 1984.
Dr. Fearon returned to Johns Hopkins School of Medicine in 1987, where he developed and directed the graduate program in immunology. During this period, the Fearon laboratory studied various aspects of adaptive immunity and B-cell and T-cell biology, culminating in the identification of complement C3d as a molecular adjuvant that bridges the innate and adaptive immunity. In 1993, ending his dual role as clinician and scientist, Dr. Fearon moved
his laboratory to the University of Cambridge to work as a full-time researcher. The Fearon laboratory has been exploring the means by which tumors escape control by the immune system. Currently they focus on the role of the carcinoma-associated fibroblast that is identified by its expression of fibroblast activation protein in the tumor microenvironment and immune control of tumor growth.
Dr. Fearon received his BA cum laude with honors in English literature from Williams College (Williamstown, MA) while quarterbacking for the college's football team. After completing his medical training at Johns Hopkins in 1970, Dr. Fearon served as a major in the U.S. Army Medical Corps for two years, one of which was spent in Vietnam, and he received the Bronze Star for his efforts at helping soldiers overcome heroin addiction. He was elected a fellow of both the UK Royal Society and the Academy of Medical Sciences and a member of both the U.S. National Academy of Sciences and the American Academy of Arts and Sciences. Dr. Fearon has published over 140 peer-reviewed research papers and 78 reviews.
Cancer Immunol Res. 2014; 2 (3) 187–193; doi:10.1158/2326-6066.CIR-14-0002
Harvey Cantor, MD, is the Baruj Benacerraf Professor of Microbiology and Immunobiology at Harvard Medical School and chair of the Department of Cancer Immunology and AIDS at the Dana-Farber Cancer Institute. Dr. Cantor's educational and practical training includes a BA from Columbia University and an MD from the New York University School of Medicine, 2 years of fellowship training at the NIH campus in Bethesda, Maryland, 2 years as an NIH Special Fellow at the National Institute for Medical Research in Mill Hill, London, and a residency in medicine at the Stanford University Hospital.
In the early 1970s, T cells were thought to be a homogenous population of lymphocytes that were not B cells. Dr. Cantor's studies indicated that the thymus gave rise to two major lineages of T cells (T-helper [TH] and T-cytotoxic [T,C]), which recognized the MHC class II and class I molecules, respectively, and which were equipped to mediate distinct immunologic functions before overt encounter with antigen. These experiments were based on the idea that the pattern of proteins expressed on the cell surface could be used to separate and define the developmental and functional components of the immune system. The Cantor laboratory used this approach to dissect cell-mediated immunity into its cellular components, to isolate natural killer (NK) cells, and to correlate T-cell surface phenotype with function and MHC restriction at the clonal level.
Recent studies from the Cantor lab have begun to define a lineage of CD8+ regulatory T cells (Treg) that are genetically programmed to inhibit the development of autoimmune disease and to regulate antitumor immunity via suppression of the activation and expansion of follicular helper T cells (TFH). The Cantor lab has defined an interaction between dendritic cells and T cells that regulates the differentiation of TH cell subsets after infection and have defined an inhibitory interaction between NK cells and autoreactive T cells that may regulate autoimmune disease.
Dr. Cantor is a member of the U.S. National Academy of Sciences and the American Academy of Arts and Sciences and a fellow of the American Association for the Advancement of Science. Many of the individuals he has mentored are now prominent immunologists, and several are members of the U.S. National Academy of Sciences and/or Institutes of Medicine, including Laurie Glimcher, professor of medicine and dean and provost of the Weill Cornell Medical College, Anjana Rao, professor at the La Jolla Institute for Allergy and Immunology, and Gary Nabel, past director of the NIH Vaccine Research Center and current Senior Vice President and Chief Scientific Officer of Sanofi.
Cancer Immunol Res. 2014; 2 (2) 91–98; doi:10.1158/2326-6066.CIR-13-0216
Marc E. Rothenberg
Marc E. Rothenberg, MD, PhD, is a professor of pediatrics at the University of Cincinnati College of Medicine and the director of the Division of Allergy and Immunology at the Cincinnati Children's Hospital Medical Center. He graduated summa cum laude in chemistry and biochemistry from Brandeis University and received his MD/PhD degree from Harvard Medical School (HMS). His PhD thesis work was on eosinophil hematopoiesis in Dr. Frank Austen's laboratory, where he developed the first culture system for human eosinophils. Dr. Rothenberg completed residency training in pediatrics and a combined fellowship in allergy/immunology and hematology at the Boston Children's Hospital and HMS. His postdoctoral training was in Dr. Philip Leder's laboratory, where he cloned the gene encoding the eotaxin chemokine. At the University of Cincinnati Children's Hospital, he has helped to build a premier program in pediatric research, with his division a leader in pediatric allergy and immunology.
Dr. Rothenberg's research program is focused on the molecular mechanisms of allergic disorders. He directs the Cincinnati Center for Eosinophilic Disorders, where he sees patients with allergic and immunologic diseases from around the world.
Dr. Rothenberg has received many honors, including the Pharmacia Allergy Research Foundation Award for the best young investigator in the allergy field; the American Academy of Allergy, Asthma, and Immunology Young Investigator and Scholar in Allergy Awards; the Ohio Governor's Recognition Award; and the 2007 Society of Pediatric Research E. Mead Johnson Award. He is an elected member of the American Society of Clinical Investigation, the Association of American Physicians, and the Society for Pediatric Research and a Diplomate of the American Academy of Allergy, Asthma, and Immunology. Dr. Rothenberg has published over 250 articles on the molecular mechanisms of allergic responses and edited a book entitled Chemokines in Allergic Disease. He has served on various review panels for journals and funding agencies, including the Advisory Council of the NIAID, the Burroughs Trust, and the Medical Research Council of the UK. His research has been supported by the NIH, the U.S. Department of Defense, the Human Frontier Science Program Organization, the Burroughs Wellcome Fund, the Dana Foundation, and the Food Allergy and Anaphylaxis Network.
Cancer Immunol Res. 2014; 2 (1) 1–8; doi:10.1158/2326-6066.CIR-13-0196
Donald Metcalf completed a BSc(Med) in virology and an MD at Sydney University (Sydney, Australia). After an internship at the Royal Prince Alfred Hospital in Sydney, he joined The Walter and Eliza Hall Institute (WEHI) of Medical Research in Melbourne as the Carden Fellow in Cancer Research, a position he has continued to hold since 1954. His work at the WEHI has been interspersed with periods of 1 to 2 years as a visiting scientist at Harvard Medical School (Boston, MA), Roswell Park Memorial Institute (Buffalo, NY), the Swiss Institute for Experimental Cancer Research (Lausanne, Switzerland), the Radiobiological Institute (Rijswijk, the Netherlands), and the University of Cambridge (United Kingdom).
Dr. Metcalf is distinguished for his work on the control of blood cell formation. He discovered the function of the thymus in directing lymphocyte development and, beginning in 1965, developed a series of specialized culture techniques permitting the growth of the various types of blood cells. These cultures led to the discovery of the colony-stimulating factors (CSF), hormones that control the formation of immune cells and the defense against infections. Dr. Metcalf's team purified all four CSFs and characterized their complex functions. His work, along with that of others, led to the cloning of both mouse and human genes encoding the four CSFs and the mass production of these hormones in culture. They showed that the CSFs, when injected into animals,
stimulated the formation and activity of immune cells. Metcalf and his colleagues demonstrated the effectiveness of granulocytemacrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) in humans. These CSFs have been used in 10 to 20 million patients around the world as reagents in accelerating the regrowth of blood cells following anticancer treatment, in permitting improved methods for blood cell transplantation, and for increasing resistance to infections.
Dr. Metcalf has published more than 730 scientific papers and nine books on his research, received the highest honors and awards from every industrial nation, and is recognized internationally as the leader in his field. Just to name a few of these accomplishments, Dr. Metcalf is a Fellow of the Australian Academy of Science, a Fellow of the Royal Society London, a Foreign Associate of the U.S. National Academy of Sciences, and a Companion of the Order of Australia. Yet, at the age of 84, Dr. Metcalf continues to work at the bench 8 hours each day. His recent work analyzes the mechanisms by which lineage commitment occurs in hematopoietic populations and the cellular events in oncogene-induced myeloid leukemogenesis.
Cancer Immunol Res. 2013; 1 (6) 351–356; doi:10.1158/2326-6066.CIR-13-0151
Stephen J. Galli
Stephen J. Galli, MD, has been chair of the Department of Pathology, the Mary Hewitt Loveless, MD Professor, and a professor of pathology and of microbiology and immunology at Stanford University School of Medicine since February 1999. He received his BA in biology in 1968 from Harvard College, a BMS in 1970 from Dartmouth Medical School (then a two-year school), and the MD in 1973 from Harvard Medical School (HMS) and completed a residency in Anatomic Pathology at Massachusetts General Hospital (MGH) in 1977. After postdoctoral training with Harold F. Dvorak at MGH, he joined the HMS faculty in 1979 as assistant professor of pathology, became professor of pathology in 1993, and, until moving to Stanford in 1999, served as director of the Division of Experimental Pathology at Beth Israel Deaconess Medical Center and a faculty member of the HMS Graduate Program in Immunology.
Steve Galli's research focuses on the development and function of mast cells and basophils (the major effector cells of asthma and anaphylaxis) and the development of new animal models for studying the roles of these cells in health and disease. These models include so-called mast cell knock-in mice (i.e., genetically
mast cell-deficient mice, bearing mutations affecting c-kit structure or expression, which have been selectively engrafted with wild type or genetically altered mast cells generated in vitro) and, more recently, mice rendered genetically deficient in mast cells and basophils by a mechanism that does not involve mutations affecting c-kit. The Galli group has used these models extensively in efforts to elucidate the roles of mast cells in health and disease.
Dr. Galli was president of the American Society for Investigative Pathology (ASIP; 2005–2006) and has been elected to the Pluto Club (Association of University Pathologists), the Collegium Internationale Allergologicum (for which he serves as president from 2010–2014), the American Society for Clinical Investigation, the Association of American Physicians, and the Institute of Medicine of the U.S. National Academies. He is also a foreign member of the Accademia Nazionale dei Lincei (National Academy of the Lynxes) in Rome, regarded as the oldest secular scientific society in the Western World.
Cancer Immunol Res. 2013; 1 (5) 269–279; doi:10.1158/2326-6066.CIR-13-0119
Miriam Merad, MD, PhD, is Professor of Oncological Science in the Department of Medicine and Immunology and a member of the Immunology Institute and The Tisch Cancer Institute at the Mount Sinai School of Medicine in New York. Dr. Merad received her MD from the University of Algiers, Algeria. She did her residency in hematology and oncology in Paris, France, and obtained her PhD in immunology in collaboration between Stanford University and University of Paris VII. She was recruited to Mount Sinai School of Medicine in 2004 and was promoted to the rank of associate professor with tenure in 2007 and to full professor in 2010.
In 2010, Dr. Merad became the program leader of the Cancer Immunology Immunotherapy Group at The Tisch Cancer Institute and the director of the Human Immunomonitoring Center. Dr. Merad also serves as the associate director for the MD/PhD Program at Mount Sinai Medical School. Dr. Merad's laboratory studies the mechanisms that regulate the development and function of innate myeloid cells, including dendritic cells, Langerhans cells, and macrophages.
The Merad laboratory has made seminal discoveries in Langerhans cells and macrophage biology revealing their embryonic origin and their local maintenance in situ. Dr. Merad's laboratory has also extensively studied the mechanisms that control dendritic cells and macrophage homeostasis and function in barrier tissues such as the skin, lung, and gut. More recently she joined the ImmGen Consortium to help decipher the transcriptional regulation of the tissue dendritic cell and macrophage lineage. Currently, one of the major goals of the Merad laboratory is to identify the contribution of innate myeloid cells to disease outcome, including cancer and microbial immunity.
Dr. Merad has authored more than 100 primary papers and reviews in high-profile journals and obtained extensive NIH funding for her studies on dendritic cells and macrophage biology in mice and humans.
Cancer Immunol Res. 2013; 1 (4) 201–209; doi:10.1158/2326-6066.CIR-13-0117
Ira Mellman received his AB degree from Oberlin College and his PhD degree in genetics from Yale University School of Medicine. He was a postdoctoral fellow and later assistant professor at The Rockefeller University, working with the late Ralph M. Steinman, the 2011 Nobel Prize winner in Physiology or Medicine. Dr. Mellman joined the Yale Department of Cell Biology, which was then headed by Nobel Laureate Dr. George E. Palade, whom he eventually succeeded as chair. Dr. Mellman has been a long-time member of the Ludwig Institute for Cancer Research and served as Scientific Director of the Yale Comprehensive Cancer Center. He is a member of the U.S. National Academy of Sciences, a fellow of the American Academy of Arts and Sciences, and an elected foreign member of the European Molecular Biology Organization. Dr. Mellman is the founder of CGI Pharmaceuticals, Inc. (now owned by Gilead) and Athersys, Inc., and an advisor to research institutes and foundations around the world.
Dr. Mellman's work has contributed numerous fundamental concepts to our current understanding of cell biology and
immunology, beginning with the discovery, definition, and naming of a new organelle, the endosome. Extending this work, his laboratory helped to elucidate the mechanisms by which epithelial cells polarize to form tissues and initiate cancer and revealed the various specializations responsible for the ability of dendritic cells to initiate immune responses.
Dr. Mellman joined Genentech in 2007 as the Vice President of Research Oncology. Placed in charge of the largest therapeutic area in Genentech's research organization, Dr. Mellman is responsible for leading all aspects of oncology research and advancing both antibody and small-molecule drug candidates into the clinic. The development of immunotherapeutic approaches to cancer is now a key feature of Genentech's activities. Dr. Mellman also serves as Professor of Biochemistry and Biophysics at the University of California, San Francisco.
Cancer Immunol Res. 2013; 1 (3) 145–149; doi:10.1158/2326-6066.CIR-13-0102
Richard A. Flavell
Richard A. Flavell is Sterling Professor of Immunobiology at Yale School of Medicine, New Haven, Connecticut, and an Investigator of the Howard Hughes Medical Institute, Home Institution. He received his B.Sc. (Honors) and Ph.D. in biochemistry from the University of Hull, England, and performed postdoctoral work with Piet Borst in Amsterdam and Charles Weissmann in Zurich. Before joining Yale, Flavell was Assistant Professor at the University of Amsterdam; Head of the Laboratory of Gene Structure and Expression at the National Institute for Medical Research, Mill Hill, London; and President and Chief Scientific Officer of Biogen Research Corporation, Cambridge, Massachusetts. Dr. Flavell is a fellow of the British Royal Society and a member of both the US National Academy of Sciences and the Institute of Medicine.
Richard Flavell is co-discoverer of introns in cellular genes; he showed DNA methylation correlates inversely with, and prevents, gene expression. He was the first to develop reverse genetics, with Weissmann, and pioneered the approach in vivo to study function. The Flavell laboratory uses mouse genetics to study activation in immunity and autoimmunity, apoptosis, and T-cell tolerance.
Flavell was instrumental in discovering the molecular basis of T-cell differentiation from precursor cells into differentiated subsets, which led to the discovery of GATA3 as a critical regulator of the Th2 response and the first example of such a molecule in Th cell differentiation. He demonstrated the first case of regulation of gene expression in trans, via chromosome kissing. The Flavell laboratory has elucidated the role of TGF-β in the regulation of immune response, which has relevance both to the control of autoimmune diseases and to the evasion of immune response by tumors.
The Flavell laboratory has discovered the role of several Toll-like receptors and intracellular Nod-like receptor families in innate immune response, which led to the elucidation of function of Nod2 in inflammatory bowel diseases (IBD) and Nlrp proteins in the production of IL-1. Most recently, he has established a connection between inflammasomes, microbial homeostasis, and chronic diseases. He showed that inflammasome dysfunction causes dysbiosis of the microbiota, which, in conjunction with a susceptible diet, leads to IBD and various metabolic syndromes.
Cancer Immunol Res. 2013; 1 (2) 77–84; doi:10.1158/2326-6066.CIR-13-0081
Hidde L. Ploegh
Hidde L. Ploegh is a professor of biology at Massachusetts Institute of Technology and a member of the Whitehead Institute for Biomedical Research in Cambridge, MA; prior to this appointment, he directed the immunology graduate program (1997–2005) at Harvard Medical School. He received his PhD in 1981 from the University of Leiden, the Netherlands, and performed the research for his doctoral thesis in Jack Strominger's lab at Harvard. Prior to his affiliation with Harvard, Dr. Ploegh served as a junior group leader in the immunology division led by Klaus Rajewsky at the University of Cologne in Germany.
Dr. Ploegh has published over 400 papers, with topics spanning the range from how viruses evade immune surveillance to how the host innate and adaptive immune responses distinguish self from non-self and how professional antigen-presenting dendritic cells sense the presence of antigens and instruct the immune response. The Ploegh lab has contributed significantly to research on how products of the major histocompatibility complex are assembled and delivered to help initiate immune responses.
Cancer Immunol Res. 2013; 1 (1) 5–10; Published OnlineFirst April 7, 2013; doi:10.1158/2326-6066.CIR-13-0023