2017 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.
Title: President and Chief Executive Officer
Institution: The Wistar Institute Cancer Center
Research: Altieri's lab focuses on mechanisms of tumor adaptation (or plasticity) as novel, fundamental drivers of disease heterogeneity and worse patient outcomes. The team identified reprogramming of mitochondrial functions as an obligatory hub for this process, enabling organelle-cytoskeleton dynamics, assembly of novel apoptosis-regulatory complex(es), and retrograde gene expression. His studies will dissect the cellular and molecular requirements of tumor plasticity as a novel hallmark of cancer, credential its relevance in xenograft and genetic mouse models of localized and metastatic disease, and exploit emerging vulnerabilities of these pathways to aid new drug discovery.
Title: Professor of Dermatology and Pathology; Gerson and Barbara Bass Bakar Distinguished Professor in Cancer Research
Institution: University of California, San Francisco
Research: Bastian's group is performing multi-omics studies on primary lesions to study the earliest molecular and cellular events associated with melanoma initiation and evolution to improve risk stratification of early-stage cancers. Characterizing the genetic evolution of main melanoma subtypes as they develop from their respective pre-neoplastic lesions is one goal, as is developing a biomarker-based taxonomy, which will serve as a framework for developing significantly advanced diagnostic and prognostic algorithms. Studies of the tumor genome will be complemented by characterization of the composition and functional state of immune cell infiltrates during melanoma evolution.
Title: Director, Division of Cancer Imaging Research, Department of Radiology
Institution: Johns Hopkins University School of Medicine
Research: Bhujwalla will apply molecular imaging in three interactive research areas of the tumor microenvironment, the tumor macroenvironment, and theranostics. She will investigate the role of mechanotransduction and focal adhesion kinase in the metastatic cascade, and examine PDAC-induced cachexia that results in a wide range of symptoms affecting the function of organs. In addition, she will focus on characterizing the tumor interstitial fluid (TIF) in preclinical PDAC xenograft models to develop biomarkers of cachexia and identify potential metabolic targets that will be pursued through the Theranostic focus.
Title: Gustavus Adolphus Pfeiffer Professor and Chair, Department of Biological Chemistry and Molecular Pharmacology
Institution: Harvard Medical School
Research: In T cell acute lymphoblastic leukemia (T-ALL), there are frequent Notch receptor mutations that result in aberrant signaling activity. This research program will focus on the molecular mechanisms of both normal and aberrant Notch signaling, emphasizing structural, biochemical, molecular, and cell-based approaches. Key objectives of the program will be to illuminate the structural basis for normal and oncogenic activation of Notch receptors by ADAM metalloproteases, and to deduce the role of important Notch cofactors and negative feedback regulators in the response of cancer cells to aberrant Notch activity.
Title: Professor, Children's Medical Center Research Institute; Director, Genetics and Metabolic Disease Program; Joel B. Steinberg, M.D. Chair in Pediatrics; Sowell Family Scholar in Medical Research
Institution: University of Texas Southwestern Medical Center
Research: Dr. DeBerardinis plans to expand his program in human cancer metabolism by establishing novel computational methods to better report altered fluxes throughout complex metabolic networks. His lab will examine the evolution of metabolic phenotypes during cancer progression in patients and mice, including by sampling metabolic flux before and after conventional and targeted therapies. In addition, he is establishing methods to disentangle the metabolic contributions of distinct cell types comprising the tumor microenvironment in patients and mice.
Title: Professor, Department of Medicine
Institution: Washington University
Research: Dipersio plans to conduct early phase clinical trials to 1) develop novel methods to target the hematopoietic niche for optimal HSPC mobilization and chemosensitization of acute myeloid leukemia (AML), 2) target the interferon gamma receptor (IFNγR) and IL-6R signaling pathways via use of selective and balanced JAK1/2 inhibitors to mitigate GvHD while maintaining graft vs. leukemia (GvL) after allo-HSCT, and 3) design and test novel AML and T cell acute lymphoblastic leukemia (T-ALL) immunotherapeutics. Managing the threat of GvHD while maximizing the beneficial GvL effect would broaden the scope and usefulness of allo-HSCT.
Title: Professor of Pediatrics and Pathology
Institution: Institute for Genetics, Columbia University
Research: Ferrando's lab has demonstrated that NOTCH1 is a critical regulator of cell growth and proliferation, and identified MYC, the PI3K-AKT pathway, and leukemia cell metabolism as critical effectors of the oncogenic program downstream of NOTCH1. The team will test whether leukemia persistence, disease progression, and relapse are driven by signaling, genetic, epigenetic, and metabolic circuits that bypass the antileukemic effects of NOTCH1 signaling. Specifically, the team will dissect molecular mechanisms wiring NOTCH1 with oncogenic transcriptional programs; functionally analyze the role of long-range enhancers in NOTCH1-induced transformation; and explore the role of tumor microenvironment signals.
Title: Director, Pathogen Associated Malignancies Integrated Research Center
Institution: Fred Hutchinson Cancer Research Center
Research: Galloway's overall goal has been, and will continue to be, to find new ways to better prevent, diagnose, and treat HPV and HPyV infections that can lead to cancer. Her lab will explore new data showing that the Small T antigen can transform primary human fibroblasts and cooperate with Ras. By developing novel mouse models, the team can determine other genetic alterations that cooperate with the viral oncogenes to promote tumorigenicity. These models will be used in innovative ways to test new therapies.
Title: Robert E. Hunter Professor of Therapeutic Radiology and Professor of Genetics
Institution: Yale University
Research: Glazer's team has developed novel DNA repair inhibitors that target key factors in DNA double-strand break repair to sensitize tumors to radiation and chemotherapy and to achieve synthetic lethality in DNA repair deficient cancers. They will advance these agents to the clinic through mechanistic studies and molecular optimization. They have also discovered that tumor hypoxia and alterations in cancer cell metabolism, such as those caused by mutations in isocitrate dehydrogenase genes, can suppress DNA repair and confer previously unsuspected vulnerabilities that can be selectively exploited for cancer therapy.
Title: Howard M. Temin Professor and Chair of Oncology; Director, McArdle Laboratory for Cancer Research
Institution: University of Wisconsin-Madison School of Medicine and Public Health
Research: Using genetically engineered mouse models, patient-derived xenografts, and associated cell strains, Lambert's team will explore new therapeutic targets for the prevention and treatment of HPV-associated diseases. Of particular relevance to HIV-associated neoplasia, PDX models for anal cancer will be used to compare responses to targeted therapies between cancers arising in HIV- infected versus uninfected patients to learn if there are differences of potential clinical importance. The proposed studies build upon insights gained from decades of studying GEM and PDX models for HPV-associated cancers.
Title: Giulio D'Angio Professor of Pediatrics
Institution: Children's Hospital of Philadelphia and University of Pennsylvania
Research: Maris' lab seeks to discover the fundamental mechanisms that subvert normal neural development and orchestrate NB tumorigenesis, and then to translate this knowledge into patient-specific therapies that will be more effective and less toxic. His integrated research efforts include defining the mechanisms by which DNA variation causes malignant transformation via epistatic deregulation of normal developmental pathways using epigenomics approaches; defining how tumors adapt to the selective pressure of therapy; and defining mechanisms of therapy resistance to both standard of care agents and the targeted therapies in development.
Title: Director, Tisch Cancer Institute; Director, Mount Sinai Cancer; and Professor & Chair, Department of Oncological Sciences
Institution: Icahn School of Medicine at Mount Sinai; Mount Sinai Health System
Research: Dr. Parsons' lab will explore the tumor suppressor functions of PTEN and PTEN-L, and how they are they regulated. The goals of this application are to define mechanisms of PTEN regulation, determine the consequences of inactivation in tissue and on cell proliferation and metabolism, and to develop approaches for targeting tumor cells based upon their PTEN status. A greater understanding of PTEN's inactivation and regulation may lead to improved therapy for cancer.
Title: Director, Salk Institute Cancer Center; Professor, Molecular and Cell Biology Laboratory; Dr. William R. Brody Endowed Chair
Institution: Salk Institute for Biological Studies
Research: The central focus of Shaw's laboratory has been to decode the molecular connections between cancer and metabolism, and then, based on these insights, to develop new therapeutic approaches for targeting metabolic vulnerabilities in different cancers. Here we identify and investigate the role in cancer development and therapy for novel components of the LBK1-AMPK pathway that govern the catabolic, low energy state.
Title: Professor, Cell Biology Department, Harvard Medical School, Merton Bernfield Professor of Neonatology, Newborn Medicine Division, Boston Children's Hospital and American Cancer Society Research Professor
Institution: Boston Children's Hospital and Harvard Medical School
Research: Shi's lab will interrogate the epigenetic basis of AML and HGG cancer cell fate using a number of approaches: integrative epigenomic profiling of induced differentiation programs, high throughput CRISPR-Cas9-based screening of these cellular models to identify chromatin factors that regulate differentiation, biochemical analyses to identify the molecular mechanisms by which existing screen hits and those found in future screens manipulate chromatin to influence cancer cell fate, and validation of findings in preclinical animal models and clinical sample analyses.
Title: Arthur H. Rubenstein, MBBCh Professor
Institution: University of Pennsylvania Perelman School of Medicine
Research: Simon will investigate the unprecedented, non-catalytic roles of specific enzymes in clear cell renal carcinoma (ccRCC) and other cancers. Further, by delineating the molecular mechanisms by which changes in gluconeogenesis, the urea cycle, and lipid homeostasis alter ccRCC tumor metabolism may provide new therapeutic avenues to target a majority of patients diagnosed with this kidney cancer subtype. The results obtained from ccRCC will also be applied to other malignancies, including soft-tissue sarcoma, hepatocellular carcinoma, and Burkitt's lymphoma, which appear to engage in highly similar metabolic reprogramming.
Title: Professor, Departments of Gynecologic Oncology & Reproductive Medicine and Cancer Biology, co-director of the Center for RNA Interference and Non-Coding RNA, director of the Blanton-Davis Ovarian Cancer Research Program
Institution: The University of Texas MD Anderson Cancer Center
Research: Despite the promise of synthetic delivery systems, novel and biocompatible delivery strategies that are independent of reliance on vascular leakiness are highly desirable. In this project, Sood proposes to develop a biomimetic exosomal system that will enable active delivery of cancer therapeutics to the tumor microenvironment. These naturally occurring particles represent a promising and safe alternative approach for delivering RNAi therapeutics.
Title: Member, Whitehead Institute; Professor, Massachusetts Institute of Technology
Institution: Whitehead Institute for Biomedical Research
Research: Relatively little is known about how non-genetically determined traits of cancer cells are acquired and disrupted during tumor formation. Super-enhancers (SEs) represent large aggregations of transcription factors (TFs) associated with a relatively small number (several hundred) of gene promoters in both normal cells and cancer cells. Weinberg's lab will examine the disruptive effects of specific oncogene-encoded proteins (and/or loss of tumor suppressor gene proteins) on the spectrum of SEs within experimentally transformed human cells from a variety of normal cell lineages.
Title: Director, Institute for Stem Cell Biology and Regenerative Medicine, and Director, Ludwig Center for Cancer Stem Cell Research and Medicine
Institution: Stanford University
Research: Weissman will test whether accumulation of mutations occurs in a central nervous system stem cell [CNS SC] clone that gives rise to a brain cancer stem cell [CSC]. Analysis of these precancers and cancers may identify new therapeutic targets. His lab showed that phagocytosis of cancer cells by macrophages depends on the balance between pro and anti phagocytic signals, and identified calreticulin, an ‘eat me’ signal on all cancers. They will study how cancer cells are labeled with calreticulin for elimination by macrophages, and how phagocytosis is harnessed to remove harmful cells.