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NCI Outstanding Investigator Award Recipients

2019 Outstanding Investigator Award (R35)

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.


 
Joan Brugge - 2019 OIA Recipient
Joan S. Brugge, Ph.D.
Title: Director of the Ludwig Center, Louise Foote Pfeiffer Professor of Cell Biology
Institution: Harvard Medical School
Research: The objective of this study is to identify and characterize early premalignant changes in breast tissues from women that carry genetic alterations associated with high risk of breast cancer to develop strategies to detect and prevent the development of breast cancer. Thus far, there have been 30 women with wild-type or mutant breast cancer gene 1 (BRCA1) or breast cancer gene 2 (BRCA2) whose breast tissue has been studied using mass cytometry (CyTOF). The outcome of these studies was the discovery of previously unrecognized subpopulations of cells that are enriched in breast tissues from BRCA1 and/or BRCA2 carriers. Future steps of this study by Dr. Brugge and her team include discovering ways to interfere with tumor progression, and to develop novel diagnostic strategies to inform on the timing of prophylactic interventions.

 
James Decaprio - 2019 OIA Recipient
James A. DeCaprio, M.D.
Title: Professor of Medicine, Harvard Medical School and Brigham and Women’s Hospital
Institution: Dana-Farber Cancer Institute
Research: Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine carcinoma of the skin with two distinct etiologies. Virus-negative MCC is caused by sunlight induced ultraviolet damage to the tumor DNA, while virus-positive MCC is caused by integration of the Merkel cell polyomavirus DNA with continuous expression of a truncated form of Large T antigen and an intact Small T antigen. Dr. DeCaprio and his team propose that by comparing the oncogenic signaling pathways activated in virus-negative MCC and virus-positive MCC, we will gain important new insights into MCC as well as other neuroendocrine carcinomas.

 
Michael Eck- 2019 OIA Recipient
Michael J. Eck, M.D., Ph.D.
Title: Professor of Biological Chemistry and Molecular Pharmacology, Harvard Medical School
Institution: Dana-Farber Cancer Institute
Research: Dr. Eck and his team are using biochemical and biophysical tools to study the regulation of BRAF and its partners in the RAS/MAP kinase pathway. Using X-ray crystallography and cryo-electron microscopy, they are working to understand at a structural level how BRAF is maintained in its quiescent state, how it is normally activated by RAS, and how it is aberrantly activated by cancer-causing mutations. A major goal of their work is to use structural insights to discover new pharmacologic agents that target BRAF in a mutant-selective manner.

 
Todd Golub - 2019 OIA Recipient
Todd R. Golub, M.D.
Title: Core Institute Member, Chief Scientific Officer, Director of the Cancer Program
Institution: Broad Institute
Research: A number of scientific challenges must be overcome before cancer precision medicine can become a reality for all patients. These challenges are the primary focus of Dr. Golub and his team. Some examples of these challenges include but are not limited to, using gene expression in addition to DNA analysis for predicting drug sensitivity. Therefore, Dr. Golub believes it is imperative to develop methods suitable for quantitative RNA-based diagnostics, using, for example, single cell and in situ sequencing methods. The present proposal aims to address these challenges over the next 7 years ahead by developing new methods and datasets that will accelerate cancer precision medicine research throughout the research community.

 
Richard Gregory- 2019 OIA Recipient
Richard I. Gregory, Ph.D.
Title: Professor, Department of Pediatrics Stem Cell Biology Chair, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School
Institution: Boston Children’s Hospital
Research: One limitation to treating cancer is the lack of “druggable” targets for therapeutic intervention. Over the last thirty years, a lot of work has been done in an attempt to understand how epigenetic changes, including DNA methylation and histone modifications, influence gene expression and contribute to cancer. The goal of Dr. Gregory and his team is to explore the relevance of messenger ribonucleic acid (mRNA) methylation in cancer to establish the “epitranscriptome” as a new and effective cancer therapeutic target. Their work will ultimately alter the field of cancer medicine by creating the epitranscriptome as a novel therapeutic target and could lead to more effective treatments for lung, colon and other types of tumors.

 
Tony Hunter - 2019 OIA Recipient
Tony Hunter, Ph.D.
Title: American Cancer Society Professor, Molecular and Cell Biology Laboratory, Renato Dulbecco Chair
Institution: Salk Institute for Biological Studies
Research: Phosphorylation of histidine (His) in proteins has a 60-year history. Initially identified as a phospho-enzyme intermediate, His phosphorylation of proteins serves as a regulatory mechanism in bacteria that is essential for signal transduction by surface receptors that sense nutrients. It also occurs in mammalian cells with evidence for a role in liver cancer. Dr. Hunter and his team will investigate whether increased His phosphorylation plays a broader role in human cancer. Overall, it is anticipated that comparative studies on hepatocellular carcinoma (HCC), neuroblastoma, and pancreatic ductal adenocarcinoma (PDAC) will shed light on the general role of His phosphorylation in cancers, common mechanisms of this process, and if targeting His phosphorylation could be a viable, new therapeutic approach.

 
Anthony Letai - 2019 OIA Recipient
Anthony Letai, M.D., Ph.D.
Title: Professor of Medicine, Harvard Medical School
Institution: Dana-Farber Cancer Institute
Research: Dr. Letai and his team are working in a lab dedicated to identifying therapies that selectively induce apoptosis in cancer cells. Through research, they have learned that by using certain selectively-interacting BH3 peptides, they could use BH3 profiling to identify cells that were especially sensitive to BCL-2, MCL-1 or BCL-XL inhibition via BH3 mimetic drugs. The Letai Lab is exploring Dynamic BH3 Profiling (DBP) as a discovery tool and predictive biomarker in many liquid and solid tumors, identifying drugs that selectively induce apoptotic signaling in an individual patient’s tumor. This program also uses the information gathered from their research as a tool to identify drugs that can make target tumor cells more sensitive to immuno-oncology therapies.

 
Jason Lewis - 2019 OIA Recipient
Jason S. Lewis, Ph.D.
Title: Emily Tow Jackson Chair in Oncology; Member and Laboratory Head, MSKCC Institute; Vice Chair for Research, Department of Radiology; Chief, Radiochemistry and Imaging Sciences Service
Institution: Memorial Sloan Kettering Cancer Center
Research: The need for molecular imaging arose from the need to better understand the fundamental molecular pathways inside organisms in a noninvasive manner. Dr. Lewis and his team are situated at the intersection of various disciplines that non-invasively and quantitively measure target biology within cancer. Building on past successes, the hope is to continue expanding their knowledge into three other realms; (1) determining if the imaging agents can be transformed into theranostic agents with the ability to quantify the target through non-invasive imaging while providing concomitant lethality, (2) can the theranostic agents be optimally deployed to treat tumor heterogeneity, and (3) can imaging cancer-specific pathways provide immediate and real-time predictors of response. By answering these questions, the Lewis Lab can begin developing new and transformative concepts related to the interactions between imaging, therapy and treatment response.

 
David Livingston - 2019 OIA Recipient
David M. Livingston, M.D.
Title: Charles A. Dana Chair in Human Cancer Genetics, Emil Frei III Distinguished Professor of Medicine, Harvard Medical School
Institution: Dana-Farber Cancer Institute
Research: Inherited BRCA1 mutations often result in breast and ovarian cancer in affected families. The goal of the Dr. Livingston and his team is to illuminate the key molecular steps that occur after menarche in tumor-free, BRCA1-mutated mammary epithelium and contribute, powerfully, to future BRCA1 breast cancer (BrCa) development. His current research shows that, when interrupted, a series of defined biochemical events leads to a conversion of normal, BRCA1-mutated breast epithelial cells into a DNA- damaged, dedifferentiated and, subsequently, a tumorigenic state. This research includes the analysis of single cell RNAseq data to assess key cell lineage relationships and mammary epithelial gene, protein expression, and function screens to detect those processes that promote, sustain, and suppress BRCA1 tumorigenesis.

 
Thomas Roberts - 2019 OIA Recipient
Thomas M. Roberts, Ph.D.
Title: Professor of Biological Chemistry and Molecular Pharmacology, Harvard Medical School
Institution: Dana-Farber Cancer Institute
Research: While studying the PI3 Kinase isoform dependence of different tumor types, Dr. Roberts and his team discovered that tumors driven by the loss of the phosphatase and tensin homolog (PTEN) tumor suppressor are uniquely dependent on the p110β isoform of phosphoinositide 3-kinase (PI3K). This finding possibly explains why PI3K inhibitors first tested on PTEN null tumors were unsuccessful in the clinic, as they were poor p110β inhibitors. Fortunately, new p110β specific compounds are now showing clinical potential. This research will focus more intensely on testing new drug combinations while also continuing to refine the mechanistic understanding of the effects of PTEN loss on PI3K signaling to generate even better combination therapies.

 
Davide Ruggero - 2019 OIA Recipient
Davide Ruggero, Ph.D.
Title: Professor of Urology and Helen Diller Family Endowed Chair in Basic Research
Institution: University of California, San Francisco
Research: Oncogenic lesions directly highjack the cell’s translation apparatus to make a tailored proteome that directs specific steps in cancer development. This is molecularly achieved through translationally regulated networks of mRNAs that direct cancer initiation and progression. Dr. Ruggero and his team have been at the forefront of this research by developing modern tools to study the cancer cell translatome and developing the first mouse models for translation components. They will work to leverage long-standing interests in translational control in cancer to identify synthetic lethal interactions driven by alterations in the translation machinery during cancer evolution. They will also employ new pharmacogenomic approaches to study how translation control modulates metabolic programs in cancer cells. Ruggero will further characterize the mechanisms by which oncogenes direct the formation of “cancer ribosomes”, which selectively establish an oncogenic translation program. This research may lead to the design of new therapeutic interventions that erase unwanted post-transcriptional changes in cancer.

 
Julien Sage - 2019 OIA Recipient
Julien Sage, Ph.D.
Title: Professor of Pediatrics (Hematology/Oncology) and of Genetics
Institution: Stanford University
Research: Dr. Sage and his team are interested in the mechanisms that control the identity and the fate of cancer cells during tumor evolution, including in response to treatment. Dr. Sage’s work on Rb-mutant small cell lung cancer (SCLC) has provided fundamental novel insights into the biology of this neuroendocrine cancer. SCLC is the most lethal form of lung cancer and over the past 30 years treatment options have remained virtually unchanged. In the next 7 years, the Sage Lab will continue to use SCLC as a paradigm to elucidate the mechanisms that determine the identity of cancer cells, their plasticity and their fate.

 
Frank Slack - 2019 OIA Recipient
Frank J. Slack, Ph.D.
Title: Professor, Medicine, Harvard Medical School; Professor, Pathology, Beth Israel Deaconess Medical Center
Institution: Beth Israel Deaconess Medical Center/Harvard Medical School
Research: MicroRNAs (miRNAs) are regulatory ribonucleic acid (RNA) molecules that control a large variety of cancer processes, including proliferation/cell cycle, survival, metabolism and metastasis, as well as have led the charge in the non-coding RNA (ncRNA) revolution. Dr. Slack and his lab have demonstrated that they regulate cancer genes and that their mis-expression can be informational and causal in cancer. From this, there is a unique opportunity to use this information as effective biomarkers and therapeutics in cancer. In his research, Dr. Slack will use a three-pronged approach that includes; comprehensive discovery and functional validation in the miRNA space in cancer, overcoming delivery barriers to cancer tissue and target engagement, and advancing miRNA therapeutics and targeting immune checkpoints.

 
Patrick Sung - 2019 OIA Recipient
Patrick Sung, Ph.D.
Title: Professor of Biochemistry and Structural Biology; Robert A. Welch Distinguished Chair in Biochemistry
Institution: University of Texas Health Science Center
Research: Homology-directed DNA repair (HDR) is reliant on the tumor suppressors BRCA1-BARD1, breast cancer gene 2 (BRCA2), and partner and localizer of breast cancer gene (PALB2), mutations in these tumor suppressors cause breast, ovarian and other cancers. Progress in understanding how these tumor suppressors help mediate HDR and how their mutational inactivation impacts genome integrity has been hampered by the challenge of purifying them for mechanistic studies. Dr. Sung and his team will dissect the underlying mechanisms of different stages of HDR to specifically furnish insights regarding the roles of the aforementioned tumor suppressors therein. They also plan to pursue chemical screens and synthesis with the Cancer Prevention and Research Institute of Texas (CPRIT)-supported Center for Innovated Drug Discovery to develop inhibitors of HDR to use as a chemical biology tool and for preclinical studies.

 
Jenny Ting - 2019 OIA Recipient
Jenny Ting, Ph.D.
Title: Director, Center for Translational Immunology School of Medicine, William Rand Kenan Professor of Genetics
Institution: University of North Carolina at Chapel Hill
Research: Colorectal cancer (CRC) remains a leading cancer worldwide that is resistant to many treatments. Two risk factors for CRC are a history of chronic colitis or inflammatory bowel disease (IBD) and obesity. Unfortunately, the mechanisms linking these predisposing factors to CRC are not well understood. Consequently, there is a pressing need to clarify these basic mechanisms. Dr. Ting and her team plan to examine the roles of NLRs (nucleotide-binging domain, leucine-rich repeat containing proteins, or nucleotide-oligomerization domain receptor) in humans and in murine models of cancers. These studies aim to elucidate the complex interaction of NLRs with the microbiome and cellular transformation, as well as to harness NLRs to enhance cancer immunotherapy.

 
Matthew Vanderheiden - 2019 OIA Recipient
Matthew Vander Heiden, M.D., Ph.D.
Title: Associate Professor of Biology; Associate Director, Koch Institute for Integrative Cancer Research
Institution: Massachusetts Institute for Technology
Research: Cancer cells have metabolic requirements that differ from most normal, non-proliferating cells. To proliferate, cancer cells must transform available nutrients into the varied array of macromolecules that are needed to build a new cell. How specific cancers integrate cancer cell-intrinsic and extrinsic factors to rewire metabolism and support cancer progression is a major unanswered question. The Vander Heiden Lab endeavors to understand how cancer cell metabolism is adapted to support tumor initiation and progression. They aim to advance the understanding of metabolic pathway biochemistry and its relationship to cancer and mammalian physiology, as well as to identify how best to target metabolism for therapy.

 
David Weinstock - 2019 OIA Recipient
David Weinstock, M.D.
Title: Professor of Medicine, Harvard Medical School
Institution: Dana-Farber Cancer Institute
Research: The outcomes for patients with high-risk lymphoid malignancies, including T-cell lymphomas, mantle cell lymphoma and acute lymphoblastic leukemia that harbor cytokine receptor-like factor 2 gene (CRLF2) rearrangements, remain poor. The long-term goal of Dr. Weinstock and his team is to build on models and collaborations to iteratively define aspects of lymphoid tumor biology and translate these discoveries into therapeutic approaches for patients. The goal of Dr. Weinstock’s proposal is to develop and utilize innovative and faithful models of lymphoid malignancies, interrogate in situ microenvironmental and immune responses, define mechanisms of therapeutic response and target adaptive in vivo resistance.

 
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