All Cancers

Current Projects
Yusong R. Guo, PhD

Dr. Guo focuses on the Piezo channel, a molecular machine on the cell membrane that converts mechanical stimuli on the outside of the cell into electric signals inside the cell. Piezo channels are important in human cells to sense touch, maintain balance, and regulate blood pressure. High expression of Piezo channels can promote various types of cancer, including breast and gastric. By studying its atomic structure, she aims to determine the mechanism of how the Piezo channel is regulated, which may provide the framework for novel anti-cancer therapies.

Project title: "Structural and mechanistic characterization of mechanosensitive Piezo channels"
Institution: The Rockefeller University
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Roderick MacKinnon, MD
Cancer Type: All Cancers
Research Area: Structural Biology
Marsha M. Hirschi, PhD
Project title: Molecular engineering of an optically controlled glutamate receptor
Institution: The Scripps Research Institute
Named Award: Dennis and Marsha Dammerman Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Gabriel C. Lander, PhD
Cancer Type: All Cancers
Research Area: Biophysics
Qi Hu, PhD

Dr. Hu is focusing on developing small molecule inhibitors to regulate the activity of Gαs, a subunit of the stimulatory G protein, which is encoded by the GNAS gene. Activating mutations of GNAS have been revealed to contribute to progression and metastasis of several kinds of cancers. About 64% of these mutations result in a single variant called R201C, which keeps Gαs in a constitutively active state. His goal is to design and synthesize small molecules to specifically inhibit the abnormally activated Gαs (R201C). Such inhibitors would be promising tools for treatment of cancer with R201C-mutated GNAS.

Project title: "Design of inhibitors of cancer-associated mutant GNAS"
Institution: University of California, San Francisco
Award Program: Fellow
Sponsor(s) / Mentor(s): Kevan M. Shokat, PhD
Cancer Type: All Cancers
Research Area: Chemical Biology
Victoria Hung, PhD

Dr. Hung focuses on a central question in cell biology: how gene expression is spatially and temporally regulated to give rise to cell types and functions. Historically, the ribosome has been viewed as a molecular machine of invariant composition that passively and constitutively translates mRNA to protein. She is studying how phosphorylation of ribosomal components may endow ribosomes with specificity for certain transcripts and unique cellular functions. This work will also provide insight into how ribosome-mediated gene expression may play a role in cellular transformation for many different cancers, and in particular, lymphomagenesis.

Project title: "Defining the post-translational landscape of ribosomes in control of gene regulation and cell fate"
Institution: Stanford University
Named Award: Fraternal Order of Eagles Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Maria Barna, PhD
Cancer Type: All Cancers
Research Area: RNA (RNA processing, miRNA and piRNA mechanisms, enzymatic RNAs, etc.)
Jeffrey A. Hussmann, PhD

Dr. Hussmann is studying how translation is regulated in healthy cells and how this regulation goes awry in disease. Cells control protein abundance by modulating how frequently messenger RNAs are translated by ribosomes, but the mechanisms that determine how densely ribosomes are packed onto each individual transcript are poorly understood. He is developing experimental approaches to produce transcriptome‐wide single‐molecule measurements of ribosome density in order to advance this understanding. These approaches will provide insights into the the key role that this process plays in the development and progression of many cancers.

Project title: "Genome-wide measurement of ribosome spacing on individual transcripts"
Institution: University of California, San Francisco
Named Award: Rebecca Ridley Kry Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Carol Gross, PhD
Cancer Type: All Cancers
Research Area: Genomics
Nicholas T. Ingolia, PhD

The uncontrolled growth and metastasis of cancer cells is driven by changes in the genes expressed by these cells, relative to cells in healthy tissue. Understanding these gene expression changes provides key insights into the behaviors of cancer cells and guides the design of anti-cancer therapies.

Dr. Ingolia is studying a cellular process called translation, which generates protein from RNA. Important gene expression changes result from differences in the translation of mRNAs into functional proteins, rather than the abundance of these mRNAs in the cell. He has developed innovative techniques to comprehensively profile translation in cells and proposes to apply this approach to understand the gene expression differences between normal and cancerous cells. These gene expression changes will reveal distinctive features of cancer cells that explain their pathological behavior and potentially expose new vulnerabilities of these cells that could be targeted to treat cancer.

Project title: "Cis-regulatory code for the translational control of gene expression"
Institution: University of California, Berkeley
Award Program: Innovator
Cancer Type: All Cancers
Research Area: Genomics
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: All Cancers
Research Area: Stem Cell Biology
Alexander 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: "Surveying the chromatin architecture shaped by HSF1 in cancer"
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
Christopher M. Jewell, PhD

Tumors evade the immune system by suppressing the function of T cells otherwise capable of destroying cancer cells. These T cells develop in lymph nodes - specialized tissues that control responses against cancer, infection, and other disease. As T cells become activated against tumors, the cells differentiate and proliferate at much slower rates. This decreased proliferation dramatically reduces the effectiveness of anti-tumor immune responses. 

Dr. Jewell is uniquely trained in both immunology and materials science. He is harnessing bioengineering, immunology, and polymer design to create degradable vaccine "depots" in lymph nodes. The goal is to use these depots to control how T cells develop, promoting a cell fate specific for attacking tumors that also maintains the ability to proliferate at the extremely high rates needed to clear existing tumors and protect against regrowth. This is the first time these ideas have been explored, and the findings from his research will support development of a new class of cancer vaccines that could clear existing tumors and prevent relapse.

 

Project title: "Harnessing intra-lymph node controlled release to study and enhance tumor immunity"
Institution: University of Maryland
Award Program: Innovator
Cancer Type: All Cancers
Research Area: Biomedical Engineering
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