Peter Choi, PhD
Assistant Professor of Pathology and Laboratory MedicinePerelman School of Medicine at the University of Pennsylvania
Contact InformationChildren's Hospital of Philadelphia
Department of Pathology and Laboratory Medicine
Colket Translational Research Building, Rm. 4064
3501 Civic Center Blvd
Philadelphia, PA 19104
Tel: 267-425-5490
Fax: 267-425-0025
Email: choip@chop.edu
Research Expertise
Research Interests
Our laboratory is interested in the genetics of cancer and in particular, how genetic alterations affecting processes such as RNA splicing drive cancer and expose potential therapeutic vulnerabilities.
Keywords
Cancer biology; Lung cancer; Genome editing; RNA splicing; Next-generation sequencing; Synthetic lethality
Research Details
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. Recent large-scale genomic surveys of multiple cancer types have identified somatic alterations in splicing factors and other RNA-binding proteins, demonstrating that global changes in RNA processing can play a significant role in tumorigenesis. Despite our 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.
Our group aims to decipher how patterns of alternative splicing control cellular processes, and when perturbed, can lead to pathogenic states such as cancer. We are 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. We are also interested in understanding how the expression of specific isoforms may regulate fundamental pathways involved in cell division and cell death. To tackle these questions, we make extensive use of genome editing to engineer faithful models of cancer-associated mutations and more rapidly characterize the function of alternatively spliced isoforms. We are also applying genome-wide CRISPR/Cas9 screens to identify genotype-specific dependencies in a systematic and unbiased fashion.
Rotation Projects
Potential rotation projects include (but are not limited to):
-Characterization of cancer-specific alternative splicing
-Role of RNA-binding proteins in tumor suppression
Please contact Peter Choi (choip@email.chop.edu) for further details.
Lab Personnel
Amanda Lee - PhD Graduate Student (CAMB CB Program)
Amanda Weiss - PhD Graduate Student (CAMB G&E Program)
Josue Medor - PhD Graduate Student (CAMB CB Program)
Anna Tangiyan - Research Technician
Benjamin Wales-McGrath - PhD Graduate Student (CAMB G&E Program)
Isha Singh - Undergraduate
Education
BS (Biology), Cornell University, 2002
PhD (Immunology), Stanford University, 2012
Specialty Certification
Postgraduate Training
Postdoctoral Scholar, Department of Medicine, Stanford University, 2012
Research Fellow, Department of Medical Oncology, Dana Farber Cancer Institute, 2012-16
Postdoctoral Scholar, Cancer Program, Broad Institute, 2012-18
Awards and Honors
International Association for the Study of Lung Cancer, Fellowship Award, 2013-15
Ruth L. Kirschstein NRSA Individual Postdoctoral Fellowship Award, 2015-16
Pathway to Independence Award, 2016-18
Memberships and Professional Organizations
Cell and Molecular Biology Graduate Group (CAMB), University of Pennsylvania, 2019-present
-------- CAMB Cancer Biology Graduate Admissions Committee, 2021-present
Tumor Biology Program, Abramson Cancer Center, Penn Medicine, 2020-present
RNA Society, 2022-present
Web Links
Selected Publications
BEERS2: RNA-Seq simulation through high fidelity in silico modeling
Brooks TG, Lahens NF, Mrčela A, Sarantopoulou D, Nayak S, Naik A, Sengupta S, Choi PS, Grant GR. bioRxiv [Preprint]. 2023 Apr 24:2023.04.21.537847. doi: 10.1101/2023.04.21.537847. PMID: 37162982; PMCID: PMC10168222.
A genome-scale CRISPR screen reveals PRMT1 as a critical regulator of androgen receptor signaling in prostate cancer
Tang S, Sethunath V, Metaferia NY, Nogueira MF, Gallant DS, Garner ER, Lairson LA, Penney CM, Li J, Gelbard MK, Alaiwi SA, Seo JH, Hwang JH, Strathdee CA, Baca SC, AbuHammad S, Zhang X, Doench JG, Hahn WC, Takeda DY, Freedman ML, Choi PS, Viswanathan SR. Cell Rep 38(8):110417, Feb 2022. doi: 10.1016/j.celrep.2022.110417. PMID: 35196489; PMCID: PMC9036938.
A predominant enhancer co-amplified with the SOX2 oncogene is necessary and sufficient for its expression in squamous cancer
Liu Y, Wu Z, Zhou J, Ramadurai DKA, Mortenson KL, Aguilera-Jimenez E, Yan Y, Yang X, Taylor AM, Varley KE, Gertz J, Choi PS, Cherniack AD, Chen X, Bass AJ, Bailey SD, Zhang X. Nat Commun 12(1):7139, Dec 2021. doi: 10.1038/s41467-021-27055-4. PMID: 34880227; PMCID: PMC8654995.
RNA-binding proteins of COSMIC importance in cancer
Choi PS, Thomas-Tikhonenko A. J Clin Invest 131(18):e151627, Sep 2021. doi: 10.1172/JCI151627. PMID: 34523614; PMCID: PMC8439603.
Chromatin Looping Shapes KLF5-Dependent Transcriptional Programs in Human Epithelial Cancers
Liu Y, Guo B, Aguilera-Jimenez E, Chu VS, Zhou J, Wu Z, Francis JM, Yang X, Choi PS, Bailey SD, Zhang X. Cancer Res 80(24):5464-5477, Dec 2020. doi: 10.1158/0008-5472.CAN-20-1287. Epub 2020 Oct 28. PMID: 33115806; PMCID: PMC7787512.
Multi-Omics Analysis Identifies MGA as a Negative Regulator of the MYC Pathway in Lung Adenocarcinoma
Llabata P, Mitsuishi Y, Choi PS, Cai D, Francis JM, Torres-Diz M, Udeshi ND, Golomb L, Wu Z, Zhou J, Svinkina T, Aguilera-Jimenez E, Liu Y, Carr SA, Sanchez-Cespedes M, Meyerson M, Zhang X. Mol Cancer Res 18(4):574-584, Apr 2020. doi: 10.1158/1541-7786.MCR-19-0657. Epub 2019 Dec 20. PMID: 31862696; PMCID: PMC7219472.
Identification and Characterization of Oncogenic SOS1 Mutations in Lung Adenocarcinoma
Cai D, Choi PS, Gelbard M, Meyerson M. Mol Cancer Res 17(4):1002-1012, Apr 2019. doi: 10.1158/1541-7786.MCR-18-0316. Epub 2019 Jan 11. PMID: 30635434; PMCID: PMC6445719.
Identification of ADAR1 adenosine deaminase dependency in a subset of cancer cells
Gannon HS, Zou T, Kiessling MK, Gao GF, Cai D, Choi PS, Ivan AP, Buchumenski I, Berger AC, Goldstein JT, Cherniack AD, Vazquez F, Tsherniak A, Levanon EY, Hahn WC, Meyerson M. Nat Commun 9(1):5450, Dec 2018. doi: 10.1038/s41467-018-07824-4. Erratum in: Nat Commun. 2022 Apr 1;13(1):1894. PMID: 30575730; PMCID: PMC6303303.
An alternative splicing switch in FLNB promotes the mesenchymal cell state in human breast cancer
Li J, Choi PS, Chaffer CL, Labella K, Hwang JH, Giacomelli AO, Kim JW, Ilic N, Doench JG, Ly SH, Dai C, Hagel K, Hong AL, Gjoerup O, Goel S, Ge JY, Root DE, Zhao JJ, Brooks AN, Weinberg RA, Hahn WC. Elife 7:e37184, Jul 2018. doi: 10.7554/eLife.37184. PMID: 30059005; PMCID: PMC6103745.
Genome-scale analysis identifies paralog lethality as a vulnerability of chromosome 1p loss in cancer
Viswanathan SR, Nogueira MF, Buss CG, Krill-Burger JM, Wawer MJ, Malolepsza E, Berger AC, Choi PS, Shih J, Taylor AM, Tanenbaum B, Pedamallu CS, Cherniack AD, Tamayo P, Strathdee CA, Lage K, Carr SA, Schenone M, Bhatia SN, Vazquez F, Tsherniak A, Hahn WC, Meyerson M. Nat Genet 50(7):937-943, Jul 2018. doi: 10.1038/s41588-018-0155-3. Epub 2018 Jun 28. PMID: 29955178; PMCID: PMC6143899.