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
Jean Zhao, Ph.D.
Title: Professor of Biological Chemistry and Molecular Pharmacology, Harvard Medical School
Institution: Dana-Farber Cancer Institute
Research: The Zhao Lab investigates the signaling networks regulating cellular processes in cancer, examining how these signals affect tumor, immune, and stromal cells. Their research aims to elucidate mechanisms of immune evasion, therapy resistance, and metastasis. Ongoing projects focus on deciphering how PI3K/PTEN signals control immune responses in prostate and breast malignancies. They are also unraveling how immune activity influences targeted therapy effectiveness in cancer. Additionally, they investigate how breast tumors spread to the brain and pursue therapeutic approaches to treat brain metastases. By applying their expertise in signal transduction and pharmacology to genetically engineered mouse models (GEMMS) and patient-derived xenografts (PDXs), the Lab conducts multi-omics and mechanistic analyses. This enables comprehensive understanding of tumorigenesis, immune evasion, and therapeutic resistance to significantly advance cancer biology and immuno-oncology.
Craig B. Thompson, M.D.
Title: Member, Cancer Biology and Genetics Program and Department of Medicine
Memorial Sloan Kettering Cancer Center, New York, NY
Institution: Memorial Sloan Kettering Cancer Center
Research: There has been a renewed interest in how oncogenic driver mutations and tumor suppressor losses contribute to cancer-associated alterations in cellular metabolism. Through their research, the Thompson Lab is exploring the hypothesis that glutamine-dependent mitochondrial glutamate accumulation provides the cell with an intracellular reserve of reduced nitrogen that can be directed toward mitochondrial support of de novo polyamine production, amino acid biosynthesis, and glutathione generation. In addition, the Thompson Lab is studying how the differential fates of mitochondrial glutamate are regulated by growth factors, as well as by oncogenes and tumor suppressors. While the normal pool of mitochondrial glutamate is fed by extracellular glutamine uptake, the Thompson Lab plans to test whether the combination of lactate and ammonia that accumulates in the tumor microenvironment (TME) under nutrient-poor conditions can be utilized to restore mitochondrial glutamate and cytosolic glutamine to levels that support adaptive translation and cell survival. The results will aim to clarify how cancer cell avidity for nitrogen is satisfied based on nutrient availability and the presence of specific oncogenic mutations and tumor suppressor losses. The insights gained will help to shape new approaches for the diagnosis and treatment of cancer.
Kimberly Stegmaier, M.D.
Title: Professor of Pediatrics, Harvard Medical School; Vice Chair of Pediatric Oncology Research, Dana-Farber Cancer Institute; Co-Director of the Pediatric Hematologic Malignancy Program, Boston Children's Hospital and Dana-Farber Cancer Institute; Ted Williams Chair, Dana-Farber Cancer Institute
Institution: Dana-Farber Cancer Institute
Research: Despite progress in understanding the molecular basis of childhood malignancies, cancer remains a leading cause of disease-related death in children. Moreover, childhood cancers continue to be treated with old approaches, including cytotoxic chemotherapy, radiation, and surgery, each with associated morbidities. The Stegmaier laboratory will address the fundamental challenge of improving treatments for children with cancer with more tumor targeted drugs. They will focus primarily on fusion-driven pediatric cancers of high unmet need, such as acute myeloid leukemias (AMLs) and the solid tumor Ewing sarcoma. Dr. Stegmaier and her team propose a multi-pronged strategy – the direct targeting of oncogenic fusions, the targeting of highly vetted non-oncogene liabilities, and the discovery and targeting of regulators of immunotherapies. They will focus on targets involved in gene regulation such as transcription factor fusions, transcriptional co-activators/repressors, and chromatin regulating complexes, which have emerged from their screening efforts. They will pioneer strategies of targeted protein degradation to validate and mechanistically dissect the role of these targets in tumor maintenance and to develop inhibitors/degraders that will ultimately inform new therapies.
Ross L. Levine, M.D.
Title: Senior VP for MH Translational Research, Laurence Joseph Dineen Chair in Leukemia Research, Member of the Human Oncology and Pathogenesis Program, Attending Physician at Memorial Sloan Kettering Cancer Center
Institution: Memorial Sloan Kettering Cancer Center
Research: Genetic and functional data have demonstrated the importance of somatic mutations in signaling effectors and in epigenetic modifiers in the pathogenesis of myeloproliferative neoplasms (MPN) and acute myeloid leukemia (AML). However, the mechanisms by which these two classes of leukemia disease alleles cooperate to induce transformation, and how coordinated mutations in signaling pathways and in epigenetic regulators affect the response to targeted therapy, has not been fully explored. Through their work, the Levine Lab plans to investigate how mutations in signaling effectors cooperate with mutations in epigenetic regulators to induce myeloid transformation, and how these mutations influence the response to targeted therapies. The Levine Lab will then extend their studies to investigate whether combination therapeutic approaches can achieve increased efficacy in models of MPN and AML. The long-term goal of their research is to characterize novel mechanisms by which oncogenic disease alleles cooperate to induce leukemogenesis, and to create novel combination strategies that can be investigated in the clinical context. The Levine Lab will use a combination of genetically accurate animal models, epigenomic studies in murine models and patient samples, and preclinical therapeutic studies aimed at rational design of combination therapeutic strategies.
Timothy C. Wang, M.D.
Title: Chief, Division of Digestive and Liver Diseases, Silberberg Professor of Medicine, Co-leader of the Tumor Biology and Microenvironment Program, Herbert Irving Comprehensive Cancer Center
Institution: Columbia University
Research: The Wang Lab seeks to investigate the role of nerves and other stromal cells in the development of digestive cancers, including stomach, esophageal, colon, and pancreas. The Wang Lab will build on previous work that suggests that GI cancers arise from tissue stem cells, and that stromal niche elements can regulate stem cells, and that by inhibiting stromal cells in the microenvironment, it may be possible to inhibit the development of tumors.
Marcel R.M. van den Brink, M.D., Ph.D.
Title: Principal Investigator – Medical Oncologist; President and Deana and Steve Campbell Chief Physician Executive Distinguished Chair
Institution: City of Hope National Medical Center
Research: The gut microbiota consists of a community of diverse microbes and has many effects on human (patho)physiology. Microbiome composition has been associated with many diseases, but causal inference is often lacking. Over the last several years, the van den Brink Lab has focused on the role of gut microbiota in outcomes of allogenic hematopoietic cell transplantation (allo-HCT) and immunotherapy. In their new research, the van den Brink Lab plans to improve cancer immunotherapy by targeting the intestinal microbiome based on preclinical and clinical studies. The van den Brink Lab will accomplish this through the development of a new pipeline for microbiome analysis, as well as preclinical and clinical projects regarding intestinal microbiome and CAR T-cell therapy, new techniques to analyze the effects of diet and drugs on the intestinal microbiome, and preclinical and clinical studies regarding immune modulation by bile acids. Results from the research will aim to inform the future development of clinical trials to test therapeutic strategies to enhance efficacy and decrease toxicity in patients receiving cancer immunotherapy, such as CAR T-cell therapy and allo-HCT.
Jeffrey S. Miller, M.D.
Title: Deputy Director; Co-Leader Immunology Program, Masonic Cancer Center
Institution: University of Minnesota
Research: During the last 25 years, the Miller Lab has led clinical efforts to develop novel natural killer (NK) cell immunotherapy strategies to treat cancer by advancing lab-based discoveries in the areas of NK cell and interleukin (IL)-15 biology. The Miller Lab has found that exposure to cytomegalovirus (CMV) induces a population of NK cells with potent immune and anti-tumor function that are marked by the expression of the NKG2C activating receptor that recognizes HLA-E, which is overexpressed on many solid tumor cancers. Through their work, the Miller Lab plans to develop novel strategies to specifically target solid tumor malignancies by testing new induced pluripotent stem cells (iPSC) edits that facilitate homing and migration, overcome hypoxia, and promote survival after adoptive transfer in patients with solid tumor malignancies. To enhance the specificity and anti-tumoral activity of iPSC derived NK cells (iNK) cells, the Miller Lab has developed a camelid nanobody specific for B7-H3, an immune checkpoint protein, that serves as the engager of a novel chimeric antigen receptor (CAR). In addition, the Miller Lab will compare these CAR iNK cells using the same CAR edited into an iPSC-derived T cell. The impact of these investigations is to develop novel off-the-shelf immune cell therapies with the potential to change standards of cancer care.
M. Celeste Simon, Ph.D., M.S.,B.A.
Title: Arthur H. Rubenstein, MBBCh Professor, Scientific Director, Abramson Family Cancer Research Institute, Associate Director, Shared Resources, Abramson Cancer Center
Institution: University of Pennsylvania
Research: The most common kidney cancer subtype is clear cell renal cell carcinoma (ccRCC), which accounts for approximately 75% of all cases. Multiple therapies are now available to ccRCC patients, including anti-angiogenic VEGF/receptor tyrosine kinase inhibitors, immune checkpoint blockade, mTORC1-based drugs, and a novel HIF-2a inhibitor. However, not all patients respond to these treatments and five-year relapse rates now approach 40%, where many of these cases develop metastases. Through their work, the Simon Lab has generated copy number variation, transcriptomic, and metabolomic data to identify multiple metabolic pathways that are universally altered in ccRCC tumors. The findings of the research conducted by the Simon Lab have been extended to other cancers such as hepatocellular carcinoma (HCC) and soft tissue sarcoma (STS), which appear to engage in highly similar metabolic reprogramming. To continue these advancements, Dr. Simon and her team will investigate how consistent metabolic adaptations within the tumor parenchyma impact stromal components. A principal conceptual innovation of their recent work is the demonstration that multiple metabolic networks are consistently altered (approximately 100%) in genetically diverse cancers like ccRCC, HCC, and STS, and the identification of novel, highly feasible therapeutic strategies.
Ralph J. DeBerardinis, M.D., Ph.D.
Title: Professor, Children’s Research Institute, and Howard Hughes Medical Institute Investigator
Institution: UT Southwestern Medical Center
Research: Metabolic reprogramming is a hallmark of malignancy and potential source of therapeutic targets. Recent studies indicate that metabolic liabilities change as cancer progresses, meaning pathways most relevant to advanced cancers may not be apparent in locally invasive, treatment-naïve tumors at the site of origin. With this knowledge, the DeBerardinis Lab developed an approach to probe the metabolic network of intact human tumors by infusing patients with stable isotope-labeled nutrients during tumor resection or biopsy. To aid in their work, Dr. DeBerardinis and his team propose three directions. First, examine how mitochondrial metabolism stimulates metastasis to identify discrete metabolic dependencies that could be safely targeted in patients. Second, develop a series of approaches to discover new metabolic liabilities in human tumors. Third, use the orthogonal approach of studying human inborn errors of metabolism (IEMs) to discover why some metabolic anomalies prime cells to become malignant. Altogether, Dr. DeBerardinis and his team hope these efforts will build on their long-standing productivity in human cancer metabolism by uncovering new mechanisms governing the metabolic basis of cancer progression and producing new methodologies to understand and treat lethal malignancies.
Paul J. Hergenrother, PhD
Title: Kenneth L. Rinehart Endowed Chair in Natural Products Chemistry; Professor, Department of Chemistry and Carl R. Woese Institute for Genomic Biology; Deputy Director, Cancer Center at Illinois; Director, NIH Chemistry-Biology Interface Training Program
Institution: University of Illinois at Urbana-Champaign
Research: The clinical success of Gleevec (imatinib) two decades ago appeared to usher in a new era for cancer treatment, whereby a molecular defect in a patient’s tumor was known and could be exploited with a selective drug. However, the progress of traditional drug discovery in this realm suggests new approaches are needed to fully realize the potential of targeted therapy for oncology. Through their work, Dr. Hergenrother and his team have developed a discovery platform -- from compound synthesis, to cell culture evaluation, target identification, sophisticated animal models, and translation -- that has resulted in four novel cancer drugs licensed and moving toward cancer patients in 15 years. In their continued research, the Hergenrother Lab will create an unprecedented collection of compounds biased for anticancer activity. In doing this work, Dr. Hergenrother and his team will help the field realize the full potential of personalized medicine for cancer.
Charles G. Mullighan, MBBS (Hons), MSc, MD
Title: Member, St. Jude Faculty, Deputy Director, Comprehensive Cancer Center, Co-Leader, Hematological Malignancies Program, Medical Director, St. Jude Biorepository, William E. Evans Endowed Chair
Institution: St. Jude Children’s Research Hospital
Research: Acute leukemia is the commonest childhood tumor and a leading cause of cancer death in the young. The goal of research of the Mullighan laboratory is to use integrated genomic discovery, experimental modeling and therapeutic development to identify and characterize the genomic drivers of disease, mechanisms of resistance to therapy, and to develop new treatment approaches. The research program will build upon prior discoveries to pursue several conceptually and technically innovative areas central to advancing cure rates for these diseases, including: the mechanistic basis of enhancer deregulation in leukemia; the role of genomic drivers such as activation of BCL11B in lineage ambiguous leukemia; the mechanistic role and potential for therapeutic targeting of LMO2/STAG2 alterations in leukemia; and the mechanistic role and potential for therapeutic targeting of fusion oncoprotein-mediated liquid-liquid phase separation. The Mullighan laboratory will develop innovative protein degradation approaches using molecular glues to degrade hitherto intractable cancer drivers of high-risk leukemia.
Titia de Lange, Ph.D.
Title: Leon Hess Professor, American Cancer Society Professor, Head of Laboratory of Cell Biology and Genetics, Director, Anderson Center for Cancer Research
Institution: Rockefeller University
Research: Numerous recent whole-genome sequencing (WGS) studies have revealed that most cancer genomes carry a remarkable level of structural changes, affirming the need to understand how this genome instability arises. In their work, the De Lange Lab will focus on how telomeres affect tumorigenesis with emphasis on the two major contributions of telomeres in cancer: the telomere tumor suppressor pathway and telomere-driven genome instability. To gain deeper insights into the telomere tumor suppressor pathway, Dr. De Lange and her team will determine how telomere length is regulated. Following a recent demonstration that cancer cell lines with short telomeres are exceptionally sensitive to loss of the telomeric factors CST and TRF1, Dr. De Lange and her team will determine the mechanistic basis of these vulnerabilities in hopes that their insights may point to new treatments. The De Lange Lab aims to derive deep insights into how cancer genomes are altered, with the overarching goal of providing oncologists with information that can inform their decisions on diagnosis, treatment, and prevention.
Jeanne S. Mandelblatt, M.D., MPH
Title: Professor of Oncology
Institution: Georgetown University
Research: By 2030, three-quarters of the 22 million U.S. cancer survivors will be 65 years and older, and the number of older Hispanic and Black survivors will have grown three times faster than White survivors. These shifting demographics are a driving crisis in cancer care due to a lack of evidence to guide care for older survivors. The Mandelblatt Lab plans to shift how cancer disparities are approached by providing a mechanistic understanding of the role of cellular aging in the relationships between social determinants of health and survivorship outcomes. The Mandelblatt Lab will use a conceptual model that integrates a multi-level disparities framework with oncology and geroscience. The primary goals of the Mandelblatt Lab are to discover cellular aging processes in large cohorts of older Black, Hispanic and White survivors that explain relationships between health determinants and quality of life; define mechanistic pathways suggested by cohort results; and test the impact of interventions targeting those pathways in a preclinical model of cancer survivorship. The work of Dr. Mandelblatt and her team will support efforts to tailor clinical care for the burgeoning older minority survivor population and will aim to transform how we approach cancer disparities in the context of aging.
Thomas F. Gajewski, M.D., Ph.D.
Title: AbbVie Foundation Professor of Pathology, Professor of Medicine, Professor of Ben May Department of Cancer Research
Institution: University of Chicago
Research: Novel immunotherapies for cancer are having a major clinical impact, in particular anti-PD-1 monoclonal antibodies (mAbs). However, our understanding of the mechanisms that explain why a subset of patients responds to these therapies while other patients do not remain incomplete. Prior data discovered by the Gajewski Lab suggested that a baseline T cell-inflamed tumor microenvironment is a predictive biomarker for response to anti-PD-1. The overall hypothesis of the Gajewski Lab is that germline polymorphisms in the host, genomic features of the tumor cells, and the composition of intestinal microbiota can influence the extent of a spontaneous T cell response against a patient's tumor, which in turn will determine the likelihood of response to immunotherapy. While the work of the Gajewski Lab thus far has focused on melanoma, genomic data have indicated that many of the same principles apply to multiple additional cancer types. Dr. Gajewski and his team identify candidate therapeutic targets from patient material, create mouse preclinical models to study mechanism, then use those data to prioritize new treatment strategies to expand immunotherapy efficacy further.
Riccardo Dalla-Favera, M.D.
Title: Percy and Joanne Uris Professor of Clinical Medicine, Professor of Pathology and Cell Biology, Genetics and Development and Microbiology and Immunology (in the Institute for Cancer Genetics), Director, Institute for Cancer Genetics
Institution: Columbia University
Research: Diffuse large B cell lymphoma (DLBCL), the most common lymphoma, is incurable in approximately 30% of patients and, despite recent advances in CAR T-cell therapies, remains a significant clinical challenge. One barrier to rationally targeted new therapies is the remarkable heterogeneity of these tumors, which leaves as many as 20% to 50% of cases unclassified based on cell-of-origin or more recent genetic-based classifications. In their recent work, the Dalla-Favera Lab found that regions corresponding to active super-enhancers (SEs) are highly and specifically hypermutated in 97% of DLBCL cases, as compared to the same loci when not active as SEs. Through their research, Dr. Dalla-Favera and his team hope to identify and mechanistically dissect the top recurrently mutated/functionally relevant SEs and associated target genes. In addition, Dr. Dalla-Favera and his team aim to gain a better understanding of the role of the glucocorticoid receptor pathway, which appears to be commonly targeted by the SE hypermutation mechanism, as well as by direct coding mutations, in normal B cell biology and lymphomagenesis. The Dalla-Favera Lab anticipates that this new layer of genetic alterations will identify novel mechanisms of dysregulation for known oncogenes, as well as new dysregulated genes and pathways, with implications for precision classification and therapeutic targeting of DLBCL.
Peter A. Jones, Ph.D., D.Sc. (hon)
Title: Chief Scientific Officer
Institution: Van Andel Institute
Research: The mammalian de novo DNA methyltransferase, DNMT3A, is essential for postnatal development of the brain, control of body size and regulation of hematopoiesis. Mutations in the DNMT3A gene are commonly found in age-associated clonal hematopoiesis of indeterminant potential and are drivers for certain leukemias, which reinforces the importance of understanding how the enzyme functions in living cells. Although we know how DNMT3A methylates naked DNA, less is known about how this occurs in the context of nucleosomes. The Jones Lab will utilize biochemical, cryo-EM, cellular and mouse studies to gain a more precise understanding of how DNA methylation works in the context of chromatin. They also will leverage recently developed techniques to explore the role of a truncated isoform, DNMT3A2. In addition, the Jones Lab will study the prevalence of hemimethylation in cancer cells and investigate its effects on binding of other transcription factors and chromatin structure, due to differential binding in asymmetric cell divisions in cancer cells. Through their work, the Jones Lab hopes to answer critical questions that will advance cancer research and inform improved treatments.
William G. Kaelin Jr., M.D.
Title: Sidney Farber Professor of Medicine, Harvard Medical School, Investigator, Howard Hughes Medical Institute
Institution: Dana-Farber Cancer Institute
Research: VHL tumor suppressor protein (pVHL) inactivation is the usual initiating truncal event in clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer. pVHL forms a ubiquitin ligase that targets the hypoxia-inducible factors (HIF) transcription factor for degradation. The work of the Kaelin Lab has contributed to the development of vascular endothelial growth factor (VEGF) inhibitors/HIF-2 inhibitors for ccRCC, and 2-HG inhibitors for IDH mutant leukemia. In addition, the Kaelin Lab has identified new potential SL interactors for VHL (CDK4/6 and ITGAV) and mutant IDH (DHODH and GSK3b), and plan to conduct further validation and mechanistic studies. Additionally, the Kaelin Lab embarked on SL screens in Drosophila fly cells as paralog compensation may cause false negatives in genetic screens with human cells. The Kaelin Lab created an “up” screen for chemicals and gene knockouts that can degrade a protein of interest and used it to discover that Spautin-1 is a cereblon-independent IKZF1 degrader and are pursuing the underlying mechanism. Research conducted by Dr. Kaelin and his team found that HIF-2 drives the expression of many endogenous retroviruses, some of which can be translated and presented as HLA-bound peptides. However, the researchers plan to continue examining additional ccRCC cell lines and tumors for such peptides and whether they are immunogenic.