2020 NCI Outstanding Investigator Award Recipients
NCI’s Outstanding Investigator Award supports accomplished leaders in cancer research, who are providing significant contributions toward understanding cancer and developing applications that may lead to a breakthrough in biomedical, behavioral, or clinical cancer research. Below are profiles of the most recent NCI Outstanding Investigator Award recipients.
2023 | 2022 | 2021 | 2020 | 2019 | 2018
Andrew T. Chan, M.D., M.P.H.
Title: Professor of Medicine, Harvard Medical School; Chief, Clinical and Translational Epidemiology Unit, Massachusetts General Hospital; Director of Epidemiology, MGH Cancer Center
Institution: Massachusetts General Hospital
Research: Building on expertise in molecular epidemiology, clinical trials, the gut microbiome, and clinical cancer prevention, Dr. Chan and his team propose a comprehensive Precision Prevention Research Program. The Program will leverage complementary sources of human data, including population-based studies and clinical cohorts, to study the role of cancer prevention agents across the continuum from healthy individuals to patients with advanced cancer. Enhancing understanding of the molecular underpinnings and mode-of-action of prevention agents may lead to novel mechanistic biomarkers to improve risk stratification of individuals for chemopreventive strategies.
Fergus J. Couch, Ph.D.
Title: Professor and Chair, Division of Experimental Pathology, Department of Laboratory Medicine and Pathology
Institution: Mayo Clinic Rochester
Research: Breast cancer has a strong heritable component with approximately 15% of patients exhibiting a family history of the disease. Dr. Couch and his team recently established that inherited variants in 12 genes make some individuals more susceptible to breast cancer, that variants in all 12 genes increase risk of breast cancer in minority populations, and that variants in certain genes predispose only to estrogen receptor (ER) positive (ATM and CHEK2) or ER negative and triple negative breast cancer. Despite these major advances, clinical application of the information is still lacking. Dr. Couch and his team plan to address clinically relevant issues, including improved application of genetic testing results for risk management of patients and improved selection of breast cancer therapy. In addition, Dr. Couch and his lab aim to identify new breast cancer predisposition genes that account for the missing heritability.
Daniel DiMaio, M.D., Ph.D.
Title: Waldemar Von Zedtwitz Professor of Genetics and Professor of Molecular Biophysics and Biochemistry and of Therapeutic Radiology; Deputy Director, Yale Cancer Center
Institution: Yale University School of Medicine
Research: HPV is responsible for 5% of human cancers, millions of cases of genital warts, and countless cases of other types of papillomas. Despite effective vaccines, HPV infection and the cancers it causes will remain a major public health problem for decades. The DiMaio lab recently discovered that HPV traffics via the retrograde transport pathway during infection. They found that retromer, a protein complex important for recycling transmembrane receptors, is required for sorting of the incoming virus particle into this pathway. The DiMaio lab also discovered a cell-penetrating peptide (CPP) that drives the HPV L2 capsid protein into the cytoplasm to engage retromer. Dr. DiMaio and his team will further characterize the mechanism of CCP and retromer action during papillomavirus infection, exploit HPV CPPs as tools to deliver bioactive agents into the cell, develop novel genetic approaches to study virus infection, and discover new aspects of cell biology relevant to virus infection and cancer.
Benjamin L. Ebert, M.D., Ph.D.
Title: George P. Canellos, M.D., and Jean S. Canellos Professor of Medicine at Harvard Medical School, Chair of Medical Oncology at the Dana-Farber Cancer Institute, a Howard Hughes Medical Institute Investigator, and an Institute Member of the Broad Institute.
Institution: Dana-Farber Cancer Institute
Research: Clonal hematopoiesis of indeterminate potential (CHIP) is a common, age-associated condition in which the blood-forming cells in otherwise healthy people acquire a mutation that could increase their risk of developing cancer. Dr. Ebert and his lab propose to examine the biology of individual mutations and to understand cell-autonomous and cell non-autonomous mechanisms of clonal dominance. Dr. Ebert and his lab will examine progression from CHIP to malignancy and the ongoing addiction of the malignant cells to the truncal mutations. They will also integrate these biological studies with large-scale genetic studies to examine the risk of malignant transformation and clinical consequences of specific mutations. Finally, in the context of solid tumors, they will examine how CHIP generates tumor- infiltrating macrophages with aberrant function, and how these somatically mutated macrophages influence solid tumor biology, immune response, and response to immunotherapy.
Dean W. Felsher, M.D., Ph.D.
Title: Professor, Medicine – Oncology, Pathology. Director, Translational Research and Applied Medicine (TRAM) and Advanced Residency Training at Stanford (ARTS). Member, Bio-X, Maternal & Child Health Research Institute (MCHRI), Stanford Cancer Institute, Faculty Fellow, Stanford ChEM-H, Molecular Imaging Program (MIPS) and Canary Institute
Institution: Stanford University
Research: MYC is the most commonly activated oncogene in human cancer. However, to date, no existing therapies have been able to successfully directly target MYC or the MYC pathway. Dr. Felsher and his lab will target the MYC oncogene pathway to treat human cancer using recent fundamental insights into how MYC initiates and maintains tumorigenesis. Dr. Felsher and his team will build their future research on recent observations that have used a CRIPSR synthetic lethal screen and combined RNA, ChIP, and metabolomic analysis to identify nuclear transport and lipogenesis, respectively, as examples of otherwise unknown MYC-regulated gene pathways that can be targeted to block and reverse MYC- driven cancer. Dr. Felsher and his team also propose the use of his library of conditional transgenic mouse models and human PDX models to identify targetable genes and pathways in the MYC oncogene pathway.
Maria Jasin, Ph.D.
Title: Member, Developmental Biology Program, and William E. Snee Chair
Institution: Memorial Sloan Kettering Cancer Center
Research: Homology-directed repair (HDR), is a major repair pathway for DNA double-strand breaks (DSBs), including lesions arising during DNA replication and from exogenous sources. Dr. Jasin and her lab have an overarching goal of integrating their understanding of how HDR proteins act to maintain genomic stability and cell and tissue homeostasis, with a particular focus on breast cancer gene 2 (BRCA2), how HDR proteins come to be “lost” in cells, and how their function can be restored, thus impacting our understanding of tumor initiation, therapy response, and therapy resistance.
Craig T. Jordan, Ph.D.
Title: Professor, Medicine-Hematology
Institution: University of Colorado Denver
Research: Acute myeloid leukemia (AML) is driven by a biologically distinct leukemia stem cell (LSC) population. While the conceptual importance of targeting leukemic disease at its root is clear, studies in recent years have demonstrated that the inherent intra-patient heterogeneity of LSC populations makes complete eradication a very challenging objective for most patients. The studies by Dr. Jordan and his lab have therefore attempted to identify common foundational properties of primary human LSCs that can be employed in the development of therapeutic strategies in the hope that intrinsic heterogeneity can be overcome. The focus of these studies will be to understand and exploit novel aspects of LSC biology towards the goal of improved outcomes for AML patients.
Thirumala-Devi Kanneganti, Ph.D.
Title: Member, St. Jude Faculty, Vice-Chair, Immunology Department, Rose Marie Thomas Endowed Chair
Institution: St. Jude Children’s Research Hospital
Research: Innate immunity, inflammasome activation, and cell death are essential for host defense against infection, but dysregulation of these processes often leads to disease. Dr. Kanneganti and her team have made seminal discoveries elucidating molecular mechanisms of inflammasome activation and cell death, characterizing upstream regulators and critical signaling pathways. These studies have led them to discover extensive crosstalk among the cell death pathways pyroptosis, apoptosis, and necroptosis, establishing the fundamental concept of PANoptosis: a unique inflammatory programmed cell death regulated by the PANoptosome complex, which provides a molecular scaffold for the machinery required for the inflammasome/pyroptosis, apoptosis, and necroptosis to interact. PANoptosis is implicated in infectious, autoinflammatory, metabolic, and neurologic diseases and cancer. This research will identify the key mechanisms of novel innate immune sensors and inflammasome regulators recently discovered in Dr. Kanneganti’s lab and their crosstalk with cell death regulators in the development of colorectal cancer and beyond.
Joan Massagué, Ph.D.
Title: Director, Sloan Kettering Institute; Member, Cancer Biology & Genetics Program
Institution: Memorial Sloan Kettering Cancer Center
Research: Phenotypic plasticity and its regulation by contextual signals is of central importance to tumor biology. Transforming growth factor beta (TGFβ) is a major regulator of cell phenotype during development, tissue homeostasis, regeneration, and cancer. The long-term goal of Dr. Massague and his lab is to elucidate TGFβ signaling and the principles that govern its effects on normal and neoplastic cells. Dr. Massagué and his lab will also elucidate the role of EMT-linked intra-tumoral fibrosis in tumor growth and metastasis. Focusing on metastasis- initiating cells, Dr. Massagué and his team will follow recent evidence that TGFβ imposes a quiescent, immune evasive state that provides long-term survival to dormant metastastic cells and potentially resistance to immunotherapy. Collectively, their studies will provide knowledge and experimental models to delineate the role of TGFβ in fibrosis, tumor invasion, and metastasis, and will better define how and when to target TGFβ in cancer.
Mark R. Philips, M.D.
Title: Professor, Departments of Medicine, Cell Biology and Biochemistry & Molecular Pharmacology at NYU Grossman School of Medicine, Director, Medical Scientist Training Program, Associate Director for Education, Perlmutter Cancer Center.
Institution: New York University Grossman School of Medicine
Research: Mutant RAS genes drive cancer more frequently than any other oncogene. For more than two decades Dr. Philips and his laboratory have focused on the post-translational modification and membrane targeting of RAS and related small GTPases. They have made paradigm-shifting contributions to the field including the discovery that RAS traffics to and signals from endomembranes as well as the plasma membrane. These observations established the field of compartmentalized signaling of RAS. Dr. Philips and his lab hope to address the overarching scientific question about whether the differential modification and membrane trafficking of RAS proteins can reveal new therapeutic vulnerabilities. They expect the work proposed will lead to new insights into basic RAS biology and reveal vulnerabilities that can be exploited therapeutically.
David A. Scheinberg, M.D., Ph.D.
Title: Chairman, Molecular Pharmacology Program; and, Chairman, Center for Experimental Therapeutics
Institution: Memorial Sloan Kettering Cancer Center
Research: The goals of Dr. Scheinberg’s research since 1978 have been to distinguish the features of cancer cells from healthy cells in order to be able to discover and develop safe and selective innovative immunotherapies. Since then, Dr. Scheinberg and his lab have discovered and developed therapies ranging from humanized antibodies, to various potent conjugates of these antibodies, to T-cell receptor mimic antibodies, to bispecific T-cell engage (BiTE) forms and chimeric antigen receptor (CAR) forms to create the generation of agents and experiments now proposed. Building off the research they have done, Dr. Scheinberg and his lab will begin innovative research to exploit the immune response to cancer specific targets.
Alex Toker, Ph.D.
Title: Professor, Pathology, Harvard Medical School, Beth Israel Deaconess Medical Center
Institution: Beth Israel Deaconess Medical Center
Research: The phosphoinositide 3-kinase (PI3K) pathway is one of the most frequently deregulated signaling cascades in human cancers, regulating virtually all aspects of tumorigenesis in humans, including initiation and progression. In spite of extensive efforts aimed at decoding the function of PI3K/AKT signaling in cancer, and a multitude of small molecule inhibitors developed and aimed at interrupting one or more enzymes in this pathway, robust therapeutic responses to PI3K or AKT inhibition have to date remained elusive. There is therefore an urgent need to identify previously unappreciated vulnerabilities associated with PI3K/AKT pathway addiction. Over the past two decades, Dr. Toker and his group have been at the forefront of discoveries on the regulation of AKT downstream of PI3K, as well as identifying mechanisms by which AKT mediates signal relay to cellular phenotypes associated with malignancy. The Toker lab builds on their collective experience at deciphering the contribution of PI3K and AKT in cancer with emphasis on discovering, identifying and characterizing vulnerabilities associated with PI3K/AKT pathway addiction.
Valerie M. Weaver, Ph.D.
Title: Professor & Director, Center for Bioengineering and Tissue Regeneration, Department of Surgery
Institution: University of California San Francisco Helen Diller Family Comprehensive Cancer Center
Research: Although breakthroughs have been made that have improved the five-year survival of many cancer patients, the long-term prognosis for many remains unchanged. Dr. Weaver and her lab have been studying the role of the extracellular matrix (ECM) and tissue tension in malignant transformation and progression. Their findings argue that malignancy is fostered by loss of tensional homeostasis induced by genetic modifications and a stiffened ECM that synergistically stimulate actomyosins to alter the cytoskeleton, cell signaling and gene expression. The research by Dr. Weaver and her team aims to identify conserved molecular mechanisms whereby tension initiates and promotes malignancy and metastasis to identify predictive biomarkers of tumorigenesis for risk stratification and to develop drug targets for chemoprevention and anti-tumor therapies.
Wenyi Wei, Ph.D.
Title: Professor of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School
Institution: Beth Israel Deaconess Medical Center
Research: A vast majority of the 25,000 genes identified in the human genome are subjected to alternative splicing, and their protein products are often heavily modified with posttranslational modifications including but not limited to ubiquitination, phosphorylation, methylation, and acetylation, thereby vastly increasing the functional diversity of the human proteome. Aberrant cell signaling events caused by dysregulation of protein modifications often lead to altered protein homeostasis and cellular function that facilitate the development of human diseases including cancer. The long-term goals of Dr. Wei’s research program are to understand how aberrant protein posttranslational modifications including phosphorylation and ubiquitination influence tumorigenesis, which could guide the identification of novel drug targets for treating human cancers.
Hans-Guido Wendel, M.D.
Title: Member, Memorial Sloan Kettering Cancer Center
Institution: Memorial Sloan Kettering Cancer Center
Research: Follicular lymphoma (FL) is the second most common and still incurable form of B cell lymphoma. FL is a slow growing cancer that shows a unique dependence on a supportive microenvironment. Dr. Wendel and his lab speculate that the FL microenvironment protects and sustains the malignant B cells and contributes to FL development, progression, and resistance to therapy. Additionally, they propose that disrupting interactions in the FL niche will be especially effective against FL. The goal of Dr. Wendel’s lab is to identify opportunities to disrupt the supportive niche and to exploit this for new therapies. They have already had some success in this regard: they engineered bi-functional antibodies and modified chimeric antigen receptor T cells (CAR-T cells) that target interactions between malignant B cells and supportive niche elements.