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Albert Tsai, PhD


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Project title: "Single-molecule imaging of transcription factors binding dynamics in Drosophila embryos"
Institution: HHMI Janelia Research Campus
Award Program: Fellow
Sponsor(s) / Mentor(s): Robert H. Singer, PhD
Cancer Type: All Cancers
Research Area: Biophysics
Neil T. Umbreit, PhD

Dr. Umbreit [HHMI Fellow] studies chromosome segregation, the process by which the genetic information on chromosomes is duplicated and the copies are segregated equally into two new cells. Cancer cell proliferation is marked by frequent errors in chromosome segregation, resulting in abnormal genetic content in the progeny. He is investigating one type of chromosome segregation error, called a “chromosome bridge,” a major mechanism through which genetic information can be amplified and/or rearranged to distort gene function in cancer cells. When these genetic rearrangements include oncogenes and growth factor genes, they can result in acquired drug resistance, unrestrained cell proliferation, and metastasis. Identifying and understanding the pathways that give rise to these alterations is critical, as they represent cancer-specific targets that can be exploited to develop effective therapeutics.

Project title: "Elucidating the mechanism of chromosome bridge resolution"
Institution: Dana-Farber Cancer Institute
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): David S. Pellman, MD
Cancer Type: All Cancers
Research Area: Chromosome and Telomere Biology
Eliezer M. Van Allen, MD

Many cancers are treated with chemotherapies that affect DNA repair, such as platinum chemotherapy, and some patients derive significant benefit from these agents. However, the underlying genomic features that drive selective response to these treatments is incompletely characterized. Dr. Van Allen aims to blend precision cancer medicine principles with DNA repair treatments and enhance cancer care. He will do so by studying the genomics of response to existing and emerging DNA repair therapies in preclinical models as well as patients across different tumor types.

Project title: "Dissecting response to conventional and emerging DNA damage and repair therapies"
Institution: Dana-Farber Cancer Institute
Award Program: Clinical Investigator
Sponsor(s) / Mentor(s): Geoffrey I. Shapiro, MD, PhD
Cancer Type: All Cancers
Research Area: Computational Biology
Thomas S. Vierbuchen, PhD

Dr. Vierbuchen [HHMI Fellow] aims to understand how neurons adapt to experience by modifying the complement of genes they express. He is using high-throughput sequencing-based approaches to identify and characterize the function of genomic regulatory elements that control neuronal activity-regulated gene transcription. 

Project title: "Understanding the developmental programming and function of the enhancers that control activity-regulated transcription in the mammalian cortex"
Institution: Harvard Medical School
Named Award: HHMI Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Michael E. Greenberg, PhD
Cancer Type: All Cancers
Research Area: Developmental Biology
Linda T. Vo, PhD

Dr. Vo focuses on T cell-based cancer immunotherapy, such as chimeric antigen receptor “CAR” T cells, as a transformative therapeutic approach. While recent studies have demonstrated the efficacy of CAR-T cell therapy in treating certain leukemias and lymphomas, further advancements are required to broaden its therapeutic utility. Pluripotent stem cells (PSCs) have the capacity to generate any cell type of the body and represent a potentially inexhaustible source of clinically useful cells. Using a novel strategy to promote the continuous generation of T cell progenitors from PSCs, she will engineer “off-the-shelf” T cells with improved tumor-recognition capability from stem cells. The successful generation of potent, dual-antigen specific T cells from PSCs in large quantities as an off-the-shelf product would be invaluable to the widespread application of T cell-based immunotherapies.

Project title: "Off-the-shelf T cells from human pluripotent stem cells with precise tumor recognition using combinatorial antigen-sensing circuits"
Institution: University of California, San Francisco
Award Program: Fellow
Sponsor(s) / Mentor(s): Jeff A. Bluestone, PhD
Cancer Type: All Cancers
Research Area: Immunotherapy
Jakob von Moltke, PhD

Immunotherapies that take the brakes off the immune response and direct cytotoxic T lymphocytes (CTLs) to hunt down tumors have revolutionized cancer treatment in the last decade. Stories of patients who are cured by immunotherapy even after exhausting all other treatment options are increasingly common – but unfortunately, only a minority of patients achieve such remarkable benefits. Now, two pressing challenges are to understand why immunotherapy fails in non-responders and to develop new or modified therapies that achieve durable remission for these patients as well. Successful immunotherapy is predicated on the infiltration of the tumor microenvironment by tumor-specific CTLs. The cells and signals that generate and sustain these cells are collectively known as type 1 immunity. Conversly, the immune cells and signals associated with the distinct processes of tissue remodeling and wound healing are known as type 2 immunity. At best, a tumor microenvironment dominated by a type 2 immune response precludes a robust type 1 response, but there is also evidence that the type 2 response may actually promote tumor growth and survival. The success of cancer immunotherapy may therefore rely in part on preventing type 2 responses. The goal of this work is to understand the regulation of type 2 immune responses, with a particular focus on the earliest events that lead to initiation of type 2 immunity. It is our hope that insights gained from these studies will inform that development of improved cancer immunotherapies that guide immune responses away from type 2 towards type 1.

Project title: "Initiation of type 2 immune response"
Institution: University of Washington
Award Program: Dale Frey Scientist
Cancer Type: All Cancers
Victoria E.H. Wang, MD, PhD

Dr. Wang seeks to understand the mechanisms by which tumor cells become resistant to drug therapy and spread to distant organs. She is utilizing functional genomics tools to identify novel pathways modulating these processes in the hope of developing new therapies to augment treatment response in cancer patients. 

Project title: "The role of the c-Met/Hepatocyte growth factor (HGF) pathway in drug resistance and tumor metastasis"
Institution: University of California, San Francisco
Award Program: Fellow
Sponsor(s) / Mentor(s): Frank McCormick, PhD
Cancer Type: Other Cancer, Lung, All Cancers
Research Area: Chemoresistance
Lan Wang, PhD

Dr. Wang studies tailed-anchored proteins, a class of membrane proteins that perform important physiological functions. Cells possess machinery that ensures the correct distribution of tail-anchored proteins to their specific organelle. Her research aims to understand how cells accurately distribute the tail-anchored proteins amongst their multiple organelles and what happens when such mechanisms fail.

Project title: "Conferring organelle-specificity to tail-anchored proteins"
Institution: University of California, San Francisco
Award Program: Fellow
Sponsor(s) / Mentor(s): Peter Walter, PhD
Cancer Type: All Cancers
Research Area: Cell Biology
Kurt J. Warnhoff, PhD

Dr. Warnhoff is studying how the timing of developmental events is regulated at the genetic level. Importantly, failures in normal developmental biology often give rise to cancer. microRNAs (miRNAs) are a class of key regulators of developmental timing. These small RNA molecules regulate gene expression, developmental transitions, metabolism, cell fate, and cell death. His research will examine new genes and pathways that modify miRNA biogenesis and activity to affect these critical developmental processes.

Project title: "Molybdenum cofactor biosynthetic enzymes modulate miRNA biology and development"
Institution: Massachusetts General Hospital
Award Program: Fellow
Sponsor(s) / Mentor(s): Gary B. Ruvkun, PhD
Cancer Type: All Cancers
Research Area: Developmental Biology
Emma Watson, PhD

Dr. Watson [Suzanne and Bob Wright Fellow] is taking advantage of high-throughput genetic screens to map gene networks involved in the response to metabolic stress. Cancer cells tap into growth-promoting metabolic programs, enabling them to robustly proliferate using limited resources from the tissue microenvironment and bloodstream. The metabolic plasticity observed in cancer cells can be at least partly attributed to metabolic stress response pathways that enable the cancer to mobilize resources for growth. Identifying the genes involved in sensing and enacting responses to metabolic stress will provide potentially novel therapeutic targets in the treatment of cancer.

Project title: "Metabolic stress response: Exploring transcript-level regulation of metabolic feedback"
Institution: Brigham and Women's Hospital
Named Award: Suzanne and Bob Wright Fellow
Award Program: Fellow
Sponsor(s) / Mentor(s): Stephen Elledge, PhD
Cancer Type: All Cancers
Research Area: Genomics
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