All Cancers

Current Projects
Andrew M. Intlekofer, MD, PhD

New drugs that target metabolic pathways have shown promise for the treatment of cancer, but the benefits of these drugs have been restricted to rare patients whose cancers have mutations in specific metabolic enzymes. Dr. Intlekofer identified a metabolic pathway whereby subpopulations of genetically identical cancer cells produce a metabolite called L-2-hydroxyglutarate (L-2HG) that induces stem cell-like properties associated with resistance to anti-cancer therapies. He is investigating the mechanisms by which L-2HG regulates the identity and function of cancer stem cells in order to determine whether targeting the L-2HG pathway represents a broadly applicable strategy for treating cancer.

Project title: "Metabolic coupling of the hypoxic niche to stemness"
Institution: Memorial Sloan Kettering Cancer Center
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Ross L. Levine, MD
Cancer Type: Blood, All Cancers
Research Area: Stem Cell Biology
Alexander M. Jaeger, PhD

Dr. Jaeger is investigating how a protein called the Heat Shock Transcription Factor 1 (HSF1), a potent pro-survival transcription factor, orchestrates changes in the three-dimensional architecture of chromosomes to activate tumor supportive gene expression programs in diverse cancer types. Increasing evidence suggests that the three dimensional architecture of chromosomes can influence the unique gene expression programs that support tumor growth. He aims to determine how gene expression is significantly altered in cancer cells when compared to normal cells.

Project title: "Targeting protein folding mechanisms to stimulate anti-tumor immune responses"
Institution: Koch Institute for Biomedical Research
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Tyler E. Jacks, PhD
Cancer Type: All Cancers
Research Area: Chromatin Biology
John C. Janetzko, PhD

Dr. Janetzko studies G protein-coupled receptors (GPCRs), a class of membrane-embedded proteins that relay signals about hormone and neurotransmitter binding to the inside of the cell. Several types of cancer cells hijack these proteins by keeping them in an active state (constitutively turned “on”) in order to promote their growth and allow them to metastasize. The activated GPCR often becomes a target for another set of proteins, called GRKs (GPCR kinases). GRKs chemically modify active receptors, which changes the type of signals the GPCR sends and simultaneously marks them to be turned off. His research will use structural and biophysical methods to understand how activated GPCRs are recognized by GRKs, and how these kinases might be exploited as new therapeutic targets in cancer.

Project title: "A biophysical approach to studying GRK-GPCR complexes"
Institution: Stanford University
Award Program: Fellow
Sponsor(s) / Mentor(s): Brian K. Kobilka, MD
Cancer Type: All Cancers
Research Area: Biophysics
Zhejian Ji, PhD

Dr. Ji studies the function of a critical ATPase protein called p97 in an important cellular process called protein degradation, which regulates proteins and can promote cancer cell proliferation and survival. His goal is to understand the molecular mechanism of how p97 functions. A better understanding of p97 could ultimately benefit the development of anti-cancer drugs based on p97 inhibition.

 

Project title: "Function of the Cdc48 ATPase in protein degradation"
Institution: Harvard Medical School
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Tom A. Rapoport, PhD
Cancer Type: All Cancers
Research Area: Biochemistry
Whitney Johnson, PhD

Dr. Johnson is studying how genome rearrangements occur in cancer, using artificial pancreatic cancer organoids—clusters of cells that act as a model system. Cancer cells have unstable genomes that mutate and rearrange at a high rate compared to normal cells. Ultimately, Dr. Johnson hopes to understand how genome instability may be exploited to improve cancer treatments, including immunotherapy.

Project title: "Using organoid cancer models to identify genome catastrophe mechanisms"
Institution: Dana-Farber Cancer Institute
Award Program: Fellow
Sponsor(s) / Mentor(s): David Pellman, MD
Cancer Type: Pancreatic, All Cancers
Research Area: Cell Biology
Yunsik Kang, PhD

Dr. Kang aims to identify mechanisms that eliminate unneeded cells in the brain. During animal development, extra neurons and neuronal connections are produced, but these unneeded neurons are selectively “eaten” by glia (another type of cell in the brain) in a process called phagocytosis. He will use the nervous system of the fruit fly Drosophila melanogaster as a model system to perform rapid genetic screens and cell type-specific manipulations, allowing him to quickly find new mechanisms that regulate phagocytosis.  Understanding how cells are targeted for phagocytosis during development will help us learn how to harness these targeting mechanisms to eliminate cancer cells for therapeutic purposes. This research will also help to understand how cancer cells evade immune detection and clearance, and may aid in the development of new kinds of cancer treatments. 

Project title: "Molecular mechanisms regulating phagocytosis of neurons"
Institution: Oregon Health & Science University
Award Program: Fellow
Sponsor(s) / Mentor(s): Marc R. Freeman, PhD
Cancer Type: All Cancers
Research Area: Neuroscience
Grace E. Kenney, PhD

Dr. Kenney studies how microbes make natural products, a major source of new chemotherapy drug candidates. Dr. Kenney is identifying the chemical reactions used by microbes in nature to synthesize compounds that have the potential to act as chemotherapeutic drugs. Once the biological synthesis of these compounds is understood, this information can be used to identify, investigate, and ultimately re-engineer new families of natural products that can be evaluated for their potential as novel drugs.

 
Project title: "Two enzymatic routes towards diazo biosynthesis in cytotoxic natural products"
Institution: Harvard University
Named Award: Merck Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Emily P. Balskus, PhD
Cancer Type: All Cancers
Research Area: Biochemistry
Thomas R. LaBar, PhD

Dr. LaBar is using budding yeast and computational modeling to study the basic processes that determine how cancer cell populations evolve in response their environment. Dr. LaBar aims to understand how the number of cells in a tumor may drive the evolution of cancer cells based on their supply of new mutations. His research has the potential to shed light on specific mutations that appear in certain cancers, alterations that allow cancer cell populations to grow abnormally, and strategies that will help predict the evolution of cancer cell populations and patient prognosis.

Project title: "Elucidating the mechanisms of cellular evolution with experimental evolution"
Institution: Harvard University
Award Program: Fellow
Sponsor(s) / Mentor(s): Andrew W. Murray, PhD
Cancer Type: All Cancers
Research Area: Evolution
Jamie Lahvic, PhD

Dr. Lahvic is investigating how neighboring normal cells will try to impede the growth of cancer cells, and how a tumor escapes these controls. Dr. Lahvic aims to understand the genetic predispositions to cancer and find clues to a new way of preventing and treating cancer: activation of normal cells to directly fight a nearby tumor. While this work could hold relevance for all carcinomas, she is focusing on Ras mutations, which are especially common in pancreatic and colon cancers.

Project title: "Uncovering cell non-autonomous mechanisms of tumor suppression"
Institution: University of California, Berkeley
Named Award: The Mark Foundation for Cancer Research Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Iswar Hariharan, MBBS, PhD
Cancer Type: All Cancers
Research Area: Cancer Genetics
Brian J. Laidlaw, PhD

Dr. Laidlaw is investigating the mechanisms underlying immune cell positioning following viral infection and tumor challenge. Localization of immune cells to particular sites within the tissue is critical for their maintenance and protective capacity upon reencountering an antigen. How immune cell migration within the tissue is regulated remains poorly understood. His studies should significantly enhance our understanding of immune cell trafficking and inform the development of new immunotherapies against cancer that modulate these pathways to promote tumor regression.

Project title: "Role of EBI2 in the regulation of lymphocyte migration during viral infection and cancer"
Institution: University of California, San Francisco
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Jason Cyster, PhD
Cancer Type: All Cancers
Research Area: Basic Immunology
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