All Cancers

Current Projects
Christopher Wilson, PhD

Dr. Wilson  is developing molecular tools to specifically modify RNA as a potential pathway to novel cancer therapeutics. RNA modification affects RNA fate and influences the way genes are expressed, including cell cycle control, cell differentiation, and transcript stability, which have been linked to a variety of diseases, including cancer. Dr. Wilson aims to use the CRISPR/Cas9 homologs to alter RNA translation, ultimately leading to an increased understanding of the role of the transcriptome— all of the messenger RNA molecules expressed from the genes of an organism.

Project title: Development of a programmable writer and eraser of m6A RNA methylation
Institution: Harvard University
Named Award: Marion Abbe Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): David R. Liu, PhD
Cancer Type: All Cancers
Research Area: RNA (RNA processing, miRNA and piRNA mechanisms, enzymatic RNAs, etc.)
Evan J. Worden, PhD

Dr. Worden examines how the decision to “turn on” or “turn off” genes is determined by a highly coordinated series of events that rely on the chemical modification of histone proteins. Misregulation of histone modification can cause a variety of human cancers. Dr. Worden is using structural biology and biophysical approaches to understand how the precise patterning of histone modifications - the “histone code” - is established. He plans to study the regulatory mechanisms that control histone methylation, which is important for the formation of leukemias.

Project title: "The mechanistic basis of crosstalk between histone H2B ubiquitylation and H3K79 methylation"
Institution: The Johns Hopkins University School of Medicine
Award Program: Fellow
Sponsor(s) / Mentor(s): Cynthia Wolberger, PhD
Cancer Type: Blood, All Cancers
Research Area: Biophysics
Jing Lin Xie, PhD

Dr. Xie focuses on uncovering mutation-independent mechanisms of drug resistance in cancer. The prevalence of drug resistance in tumors – and collateral damage to healthy tissues – have been major roadblocks to improving the efficacy of chemotherapy. While current research has been focused on identifying mutations that confer cancer drug resistance, an emerging paradigm is that mutation-independent changes in the chromatin or proteins could be a hidden force that promotes the development of drug resistance. Her goal is to identify and characterize the heritable “molecular memories” that can confer a fitness advantage during future exposure to chemotherapeutics and other stresses.

 

Project title: "Remembering the past: epigenetic mechanisms of cancer drug resistance"
Institution: Stanford University
Named Award: The Mark Foundation for Cancer Research Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Daniel F. Jarosz, PhD
Cancer Type: All Cancers
Research Area: Epigenetics
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
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
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
Yuxiang Zhang, PhD

Dr. Zhang is studying the mechanisms that promote recurrent DNA double strand break clusters (RDCs) in the brain and liver, and how these breaks in the DNA are repaired to maintain genomic stability and suppress tumors. Recently, RDCs were found in neural stem and progenitor cells. This work may reveal if DNA breaks in RDC genes predispose individuals to genomic variations that could contribute to cancers and other diseases.

Project title: Mechanisms that promote DNA double strand break clusters in brain and liver
Institution: Boston Children's Hospital
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Frederick W. Alt, PhD
Cancer Type: All Cancers
Research Area: Genomics
Xiaoyu Zhang, PhD

Dr. Zhang is developing small molecules that promote targeted protein degradation in human cancers. Although targeted cancer therapies have been successful in recent years, many oncogenic proteins are still considered “undruggable” because the conventional drug design strategy often fails to interfere with these proteins. One potential way to address “undruggable” oncogenic proteins may be to create a new type of bifunctional small molecule that delivers these proteins to the cellular degradation system, therefore promoting their destruction.

Project title: Discovery of chemical probes that support targeted protein degradation in human cancer
Institution: The Scripps Research Institute
Award Program: Fellow
Sponsor(s) / Mentor(s): Benjamin F. Cravatt, PhD
Cancer Type: All Cancers
Research Area: Chemical Biology
Xin Zhou, PhD

Dr. Zhou is using a creative protein engineering approach to break the “size barrier” of protein studies. Precise understanding of cancer protein structures can greatly facilitate the understanding of the molecular mechanisms of cancer biology and guide the design of new drugs. Recently, electron cryomicroscopy (cryo-EM) rapidly emerged as a powerful tool to deliver high-resolution protein structures. However, it remains extremely difficult to be used for proteins under a certain size (100 kDa), because most small proteins lack intrinsic structural features required for accurate structure determination. A vast number of proteins, including numerous cancer-related proteins, are smaller than 100 kDa. The successful completion of her project will result in experimental tools that are useful for the entire scientific community and will help cancer biologists to study the structures of any proteins of interest.

Project title: "Engineering 'Glue' domains to enable cryo-EM study of small cancer protein structures"
Institution: University of California, San Francisco
Named Award: Merck Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): James A. Wells, PhD
Cancer Type: All Cancers
Research Area: Chemical Biology
Boris Zinshteyn, PhD

Dr. Zinshteyn [HHMI Fellow] is using a combination of high-throughput genetic and biochemical techniques to identify the fundamental mechanisms underlying a process called nonsense-mediated decay (NMD). NMD enables cells to detect and destroy messages that are the result of potentially damaging genetic mutations. This process augments many genetic diseases and is important for cancer cells to adapt to the hostile tumor environment.

Project title: "Mechanisms of splicing-independent nonsense-mediated mRNA decay"
Institution: The Johns Hopkins University School of Medicine
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Rachel Green, PhD
Cancer Type: All Cancers
Research Area: Biochemistry
  • You can support our innovative researchers.