All Cancers

Current Projects
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
Ge Zheng, PhD

Dr. Zheng is taking an interdisciplinary approach to understand how transcription factors that regulate the transcription of DNA to RNA malfunction in human cancers. The B cell lymphoma/leukemia 11A (BCL11A) gene encodes a zinc-finger transcription factor, which plays a critical role in silencing fetal globin expression in the fetal-to-adult switch in red blood cells and is implicated in cancer. Dr. Zheng aims to develop novel approaches to interfere with BCL11A function, which will provide a general strategy to manipulate transcription factors as molecular targets for therapeutic benefit.

Project title: "Novel approaches to targeting zinc-finger domain of the transcription repressor BCL11A"
Institution: Boston Children's Hospital
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Stuart Orkin, MD
Cancer Type: All Cancers
Research Area: Cell Biology
Xin Zhou, PhD

Dr. Zhou is using creative protein engineering approaches to interrogate two post-translational modifications (PTMs), phosphotyrosine (pY) and citrullination. A large percentage of proteins in the human proteome undergo PTMs. Characterization of these specific protein variants is critical for understanding their biological role in diseases. The function of the vast majority of pY events identified in proteomics experiments has not been understood because it is difficult to generate high-quality sequence-specific pY antibodies. Dr. Zhou proposes a novel method named pY Targeting by Recombinant Antibody Pairs (pY-TRAP) for generating tight and highly selective protein-specific pY binders. Protein citrullination is the conversion of an arginine to a citrullin catalyzed by Protein Arginine Deiminases (PADs). The substrate specificities and the function of this modification have been largely unexplored due to lack of methods and molecular tools. Dr. Zhou proposes to develop a new phage display approach to characterize substrates preference of PAD enzymes.

Project title: "Understanding and perturbing protein post-translational modifications in cancer and autoimmune diseases"
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
John C. Zinder, PhD

Dr. Zinder studies telomeres that cap the ends of chromosomes and the role they play in cancer development. Telomeres normally shorten every time a cell divides until they become so short that cell division stops. Dr. Zinder is focusing on shelterin, a multiprotein complex that binds to telomeres to protect them from being mistaken as damaged DNA. Mutations in the shelterin components are found in both cancer and premature aging diseases. By purifying this complex and visualizing it in atomic detail, he aims to gain fundamental insights into how telomeres are protected and how their length is controlled in normal cells and in cancer.

Project title: "Structure and biochemistry of human shelterin and associated factors"
Institution: The Rockefeller University
Named Award: Lorraine W. Egan Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Titia de Lange, PhD
Cancer Type: All Cancers
Research Area: Chromosome and Telomere 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
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