Peter S. Choi, PhD
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Alternative splicing is an essential mode of gene regulation that greatly diversifies the coding potential of the transcriptome. However, this process is often dysregulated in human cancer. For example, mutations in splicing regulatory sequences can affect specific RNA transcripts and result in the expression of oncogenic protein products. In addition, recent large-scale genomic surveys of multiple cancer types have identified somatic alterations in splicing factors and other RNA-binding proteins, demonstrating that more global changes in RNA processing can also play a significant role in tumorigenesis. Despite the ability to comprehensively detect the landscape of alternatively spliced transcripts through next-generation sequencing, it has remained difficult to predict much of the functional impact of aberrant splicing.
Dr. Choi's group aims to decipher how patterns of alternative splicing control cellular processes and, when perturbed, can lead to pathogenic states such as cancer. He is particularly interested in characterizing RNA-binding proteins known to be mutated in cancer and their functional role in alternative splicing and other steps in RNA processing.
Dr. Choi and his team are also interested in understanding how the expression of specific isoforms may regulate fundamental pathways involved in cell division and cell death. To elucidate these questions, they make extensive use of genome editing to engineer faithful models of cancer-associated mutations, and custom high-throughput screening approaches to more rapidly characterize the function of alternatively spliced isoforms. Dr. Choi hopes to translate the wealth of genomic data and ever-evolving experimental tools into meaningful biological insights and more effective treatments for cancer.
Dr. Choi's notable career achievements include:
Cancer Biology - Dana-Farber Cancer Institute, Boston, MA
Cancer Biology - Stanford University, Stanford, CA
PhD in Immunology - Stanford University, Stanford, CA
Assistant Professor of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania
Li Ji*, Choi Peter S*, Chaffer Christine L, Labella Katherine, Hwang Justin H, Giacomelli Andrew O, Kim Jong Wook, Ilic Nina, Doench John G, Ly Seav Huong, Dai Chao, Hagel Kimberly, Hong Andrew L, Gjoerup Ole, Goel Shom, Ge Jennifer Y, Root David E, Zhao Jean J, Brooks Angela N, Weinberg Robert A, Hahn William C: An alternative splicing switch in FLNB promotes the mesenchymal cell state in human breast cancer. eLife 7, Jul 2018.
Zhang Xiaoyang*, Choi Peter S*, Francis Joshua M, Imielinski Marcin, Watanabe Hideo, Cherniack Andrew D, Meyerson Matthew: Identification of focally amplified lineage-specific super-enhancers in human epithelial cancers. Nature Genetics 48(2): 176-82, Feb 2016.
Choi Peter S, Meyerson Matthew: Targeted genomic rearrangements using CRISPR/Cas technology. Nature Communications 5: 3728, Apr 2014.
Brooks Angela N, Choi Peter S, de Waal Luc, Sharifnia Tanaz, Imielinski Marcin, Saksena Gordon, Pedamallu Chandra Sekhar, Sivachenko Andrey, Rosenberg Mara, Chmielecki Juliann, Lawrence Michael S, DeLuca David S, Getz Gad, Meyerson Matthew: A pan-cancer analysis of transcriptome changes associated with somatic mutations in U2AF1 reveals commonly altered splicing events. PloS One 9(1): e87361, Jan 2014.
Choi Peter S, Li Yulin, Felsher Dean W: Addiction to multiple oncogenes can be exploited to prevent the emergence of therapeutic resistance. Proceedings of the National Academy of Sciences of the United States of America 111(32): E3316-24, Aug 2014.
Li Yulin, Choi Peter S, Casey Stephanie C, Dill David L, Felsher Dean W: MYC through miR-17-92 suppresses specific target genes to maintain survival, autonomous proliferation, and a neoplastic state. Cancer Cell 26(2): 262-72, Aug 2014.
Choi Peter S*, van Riggelen Jan*, Gentles Andrew J, Bachireddy Pavan, Rakhra Kavya, Adam Stacey J, Plevritis Sylvia K, Felsher Dean W: Lymphomas that recur after MYC suppression continue to exhibit oncogene addiction. Proceedings of the National Academy of Sciences of the United States of America 108(42): 17432-7, Oct 2011.
2016-2018, Pathway to Independence Award
2015-2016, Ruth L. Kirschstein NRSA Individual Postdoctoral Fellowship Award
2013-2015, International Association for the Study of Lung Cancer Fellowship Award
2007-present, American Association for Cancer Research
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