All Cancers

Current Projects
Darryl A. Wesener, PhD

Dr. Wesener is studying how food processing by the community of tens of trillions of microbes (microbiota) that resides in the human gut influences nutritional status. Obesity, and its associated metabolic abnormalities, is associated with higher incidence of certain cancers, notably those affecting the colon, uterus, and breast. Transplantation of intact gut microbiota from obese humans into germ-free mice leads to increased fat gain and obesity-associated metabolic abnormalities. He will employ synthetic food particles and mice colonized with human gut microbial communities to uncover biochemical functions and food ingredients that promote establishment of a beneficial microbiota that promotes leanness and metabolic health.

Project title: "Synthetic food particles for studying human gut microbiota function"
Institution: Washington University
Award Program: Fellow
Sponsor(s) / Mentor(s): Jeffrey I. Gordon, MD
Cancer Type: All Cancers
Research Area: Microbiology
Jonathan R. Whicher, PhD

Dr. Whicher [GE Asset Management Fellow] focuses on a cellular structure called the voltage-gated potassium channel Eag1, which can promote tumor growth and is aberrantly expressed in many types of cancer including breast, colon, prostate, lung, and liver. He is determining the structure and mechanism of Eag1 in order to elucidate how Eag1 promotes cancer growth, with the eventual goal of developing Eag1 modulators as potential anti-cancer therapies.

Project title: "Structure and mechanism of the voltage-gated potassium channel hEag1"
Institution: The Rockefeller University
Named Award: GE Asset Management Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Roderick MacKinnon, MD
Cancer Type: All Cancers
Research Area: Structural Biology
Sarah (Sadie) M. Wignall, PhD

[Lau/Palihapitiya Innovator]

Cancer cells exhibit uncontrolled growth and proliferation, leading to the formation of malignant tumors. Therefore, many current cancer therapies are aimed at trying to block cell multiplication, with the goal of killing cancerous cells and halting tumor growth. However, many of these treatments also affect the growth and division of non-cancerous cells in the body, leading to severe side effects. 

Dr. Wignall will investigate a pathway required for the division of cancerous, but not normal cells. This pathway regulates a physical structure in the cell called the centrosome. By learning more about this pathway, she hopes to ultimately contribute to designing therapies that will specifically attack cancer cells, leading to better treatment options for cancer patients.

 

Project title: "Probing centrosome-clustering mechanisms to identify targets for new cancer therapies"
Institution: Northwestern University
Named Award: Lau/Palihapitiya Innovator
Award Program: Innovator
Cancer Type: All Cancers
Research Area: Proliferation/Cell Cycle
Andrew L. Wolfe, PhD

Dr. Wolfe studies KRAS, a cancer-promoting protein that is activated by mutations in most forms of cancer. Tumor cells can become “addicted” to the presence of overactive KRAS protein, such that they die when KRAS is suddenly removed. He will focus his research on an exciting new class of inhibitors that cause active KRAS to be rapidly degraded. He aims to explore the effects of depleting KRAS on cancer cells, understand the mechanism by which these novel KRAS inhibitor drugs cause the protein to be degraded, and optimize the efficacy of these drugs. Understanding which drug combinations are most effective and which patients are most likely to be helped by KRAS depletion are critical steps for improving patient outcomes. The results of this research are expected to have a major positive impact because they will a) expand our knowledge of tumors’ reliance on KRAS, and b) characterize the effects of this novel class of cancer therapeutics against active KRAS, a critical target driving many forms of cancer.

Project title: "The therapeutic potential and biological effects of targeting oncogenic KRAS"
Institution: University of California, San Francisco
Award Program: Fellow
Sponsor(s) / Mentor(s): Frank McCormick, PhD
Cancer Type: All Cancers
Research Area: Cancer Genetics
Sungwook Woo, PhD

Dr. Woo [HHMI Fellow] is using protein structures to illustrate the mechanisms of cancer-related processes. His research aims to overcome limitations of current techniques by using recent breakthroughs in “programmable DNA self-assembly” to develop protein framework structures that contain “pockets” with tunable size and shape for structural studies. If successful, his efforts will provide a general tool for structural biology and in turn benefit the mechanistic studies and therapeutic development for cancer.

Project title: "Crystal-free crystallography using programmable 3D DNA crystal frameworks"
Institution: Harvard University
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Peng Yin, PhD
Cancer Type: Skin, All Cancers
Research Area: Nanotechnology
Jiaxi Wu, PhD

Dr. Wu is investigating the mechanism of dendritic cell (DC) missing-self recognition and migration. DCs recognize and present antigens to lymphocytes, a process that is essential for shaping host immune responses against infection and cancer. How DCs recognize altered self cells (such as cancer cells and pathogen-infected cells) remains poorly understood. These studies should significantly enhance our understanding of DC biology and eventually contribute to the development of new strategies to harness DC function for immunotherapy against cancer.

Project title: "Mechanism of dendritic cell missing-self recognition and migration to activate CD4 T cell responses"
Institution: University of California, San Francisco
Award Program: Fellow
Sponsor(s) / Mentor(s): Jason Cyster, PhD
Cancer Type: All Cancers
Research Area: Basic Immunology
Swathi Yadlapalli, PhD

Dr. Yadlapalli [HHMI Fellow] aims to elucidate the neural and molecular mechanisms involved in the regulation of metabolism. Living organisms from insects to humans have evolved neural mechanisms involving circadian clocks to synchronize their physiology, metabolism and behavior with the external environment. Disruption of these clocks is associated with increased incidence of cancer, diabetes, and heart disease. She has developed an ultra-sensitive calorimeter that allows for precise quantification of metabolic activity, which she will use   to investigate the circadian regulation of metabolism. These studies will provide novel insights into how networks of circadian clock neurons orchestrate daily changes in metabolism, and may be applied to the development of novel treatments for cancers and metabolic disorders, particularly those associated with circadian dysfunction.

Project title: "Neural and genetic basis of metabolic regulation"
Institution: University of Michigan
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Orie T. Shafer, PhD, and Edgar Meyhofer, PhD
Cancer Type: Brain, All Cancers
Research Area: Neuroscience
Yi Yin, PhD

Dr. Yin is using newly developed state-of-the-art single cell sequencing technology to examine how DNA repair mechanisms go awry and contribute to cancer initiation and progression, as well as response to chemotherapy. Cancer cells usually have characteristic loss-of-heterozygosity, copy number variation and other types of genome rearrangements. A better understanding of the molecular mechanisms, genomic and cell contexts and effects from different allele variants in DNA repair genes of each individual may help guide treatment approaches for many cancer types, including breast, skin, and blood cancers.

Project title: "Global analysis of DNA break repair by single-cell sequencing"
Institution: University of Washington
Award Program: Fellow
Sponsor(s) / Mentor(s): Jay A. Shendure, MD, PhD
Cancer Type: Blood, Breast, Skin, All Cancers
Research Area: Chromosome and Telomere Biology
Ziyang Zhang, PhD

Dr. Zhang is developing a new form of cancer immunotherapy with improved safety and controllability. Redirecting the immune system to launch attacks on tumor cells has emerged as an extremely promising approach to fight cancer. One such strategy, named bispecific T cell engager antibody (BiTE) has shown remarkable efficacy against blood cancers, but it is also associated with severe toxicity. Using tools of synthetic organic chemistry, he aims to build a “chemical switch” that can be used to rapidly tune the activity of BiTE, thus allowing the circumvention of toxic side effects without diminishing therapeutic potential. The ultimate goal of this project is develop a cancer immunotherapy that can be safely employed at doses effective for the treatment of solid tumors.

Project title: "Controlling the activity of bispecific T cell engagers with a chemically cleavable molecular switch"
Institution: University of California, San Francisco
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Kevan M. Shokat, PhD
Cancer Type: All Cancers
Research Area: Chemical Biology
Chuchu Zhang, PhD

Dr. Zhang aims to understand how the sensory organ called Area Postrema (AP) detects and generates nausea. Intense and protracted nausea and vomiting are major side effects of cancer therapy, with current anti-emetic drugs demonstrating only limited efficacy. She will use molecular and genetic approaches to disentangle the cellular diversity of the AP organ while identifying potential molecular detectors for nausea stimuli. She plans to focus on a particular group of neurons in AP that are potentially involved in nausea responses and use techniques to map and manipulate this circuit to reveal the neuronal substrates for nausea sensation in the brain. This project will advance our basic understanding of how nausea-inducing stimuli are detected and processed, and may lay the foundation for developing new treatment strategies.

Project title: "Molecular dissection of the Area Postrema and its role in nausea"
Institution: Harvard Medical School
Award Program: Fellow
Sponsor(s) / Mentor(s): Stephen D. Liberles, PhD
Cancer Type: All Cancers
Research Area: Neuroscience
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