John Paul Y.C. Shen, M.D.
Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine
About Dr. John Paul Y.C. Shen
I am a physician-scientist with a scientific background in chemical biology and clinical training in Internal Medicine, Hematology, and Oncology. I am currently an Assistant Professor in the Department of Gastrointestinal Medical Oncology at the University of Texas MD Anderson Cancer Center with a clinical practice focused on colon and appendix cancers. My long-term research goal is to better understand the cancer genome, and to leverage that understanding to better the delivery of chemotherapy. My immediate research goals include the discover of new synthetic lethal genetic relationships as a means to both repurpose already FDA approved drugs and also identify new chemotherapeutic drug targets. I am also actively involved in several projects to identify genomic biomarkers to predict what specific patients will response to a given therapy. This research builds on my prior training in chemical biology and high-throughput screening, functional genomics and the creation of genetic interaction networks, as well as clinical oncology. My training in chemistry began as an undergraduate at MIT and continued at the Broad Institute as an HHMI fellow. Under the direction of Drs. James Bradner and Stuart Schreiber and I learned how small molecule probes could be used to study biological systems. At the Broad I also learned how to design, optimize and ultimately analyze the data from high-throughput and high-content chemo-genetic screens. This work led to publications in Chemistry & Biology and PNAS. After completing medical school at Washington University I matched into a combined Internal Medicine residency and Hematology-Oncology fellowship program at UCSD as part of the Physician-Scientist pathway. During the research portion of my fellowship I joined the laboratory of Dr. Trey Ideker, an internationally recognized leader in the field of network and systems biology. The Ideker lab specializes in utilizing knowledge of network relationships to draw biological conclusions from large datasets as well as performing high-throughput genetic interaction experiments in both human and model organism systems.
Present Title & Affiliation
Primary Appointment
Assistant Professor, Department of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
Research Interests
(1) Development and use of systems biology techniques to create comprehensive molecular ‘maps’ of the cancer cell;
(2) high-throughput functional genomic screening with CRISPR-Cas9 to map genetic interaction networks and identify novel synthetic lethal interactions in cancer model systems;
(3) translation of advances in cancer biology to bring about improved outcomes in clinical oncology, in particular use of tumor molecular data to guide precision oncology;
(4) analysis of existing tumor molecular data using systems and network techniques;
(5) development of small molecules for use as targeted chemotherapeutics.
Clinical Interests
Colorectal cancer
Appendix cancer
Education & Training
Degree-Granting Education
| 2008 | Washington University School of Medicine, Saint Louis, MO, USA, MD, Medicine |
| 2002 | Massachusetts Institute of Technology, Cambridge, MA, USA, BS, Chemistry |
Postgraduate Training
| 2013-2018 | Research Fellowship, Cancer Genomics, UC San Diego, San Diego, TX |
| 2010-2013 | Clinical Fellowship, Hematology-Oncology, UC San Diego, San Diego, CA |
| 2009-2010 | Clinical Residency, Internal Medicine, UC San Diego, San Diego, CA |
| 2008-2009 | Clinical Internship, Internal Medicine, UC San Diego, San Diego, CA |
Board Certifications
| 2014 | Medical Oncology |
| 2014 | Hematology |
| 2011 | Internal Medicine |
Honors & Awards
| 2016 | Next Generation Star, American Association of Cancer Research |
| 2013 | Young Investigator Award, American Society of Clinical Oncology |
Professional Memberships
Selected Publications
Peer-Reviewed Articles
- Wang S, Ma J, Zhang W, Shen JP, Huang J, Peng J, Ideker T. Typing tumors using pathways selected by somatic evolution. Nat Commun 9(1):4159, 2018. e-Pub 2018. PMID: 30297789.
- Bui N, Huang JK, Bojorquez-Gomez A, Licon K, Sanchez KS, Tang SN, Beckett AN, Wang T, Zhang W, Shen JP, Kreisberg JF, Ideker T. Disruption of NSD1 in Head and Neck Cancer Promotes Favorable Chemotherapeutic Responses Linked to Hypomethylation. Mol Cancer Ther 17(7):1585-1594, 2018. e-Pub 2018. PMID: 29636367.
- Zhang W, Bojorquez-Gomez A, Velez DO, Xu G, Sanchez KS, Shen JP, Chen K, Licon K, Melton C, Olson KM, Yu MK, Huang JK, Carter H, Farley EK, Snyder M, Fraley SI, Kreisberg JF, Ideker T. A global transcriptional network connecting noncoding mutations to changes in tumor gene expression. Nat Genet 50(4):613-620, 2018. e-Pub 2018. PMID: 29610481.
- Shen JP, Zhao D, Sasik R, Luebeck J, Birmingham A, Bojorquez-Gomez A, Licon K, Klepper K, Pekin D, Beckett AN, Sanchez KS, Thomas A, Kuo CC, Du D, Roguev A, Lewis NE, Chang AN, Kreisberg JF, Krogan N, Qi L, Ideker T, Mali P. Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions. Nat Methods 14(6):573-576, 2017. e-Pub 2017. PMID: 28319113.
- Du D, Roguev A, Gordon DE, Chen M, Chen SH, Shales M, Shen JP, Ideker T, Mali P, Qi LS, Krogan NJ. Genetic interaction mapping in mammalian cells using CRISPR interference. Nat Methods 14(6):577-580, 2017. e-Pub 2017. PMID: 28481362.
- Srivas R, Shen JP, Yang CC, Sun SM, Li J, Gross AM, Jensen J, Licon K, Bojorquez-Gomez A, Klepper K, Huang J, Pekin D, Xu JL, Yeerna H, Sivaganesh V, Kollenstart L, van Attikum H, Aza-Blanc P, Sobol RW, Ideker T. A Network of Conserved Synthetic Lethal Interactions for Exploration of Precision Cancer Therapy. Mol Cell 63(3):514-25, 2016. e-Pub 2016. PMID: 27453043.
- Johnson TC, Chin MR, Han T, Shen JP, Rana T, Siegel D. Synthesis of Eupalinilide E, a Promoter of Human Hematopoietic Stem and Progenitor Cell Expansion. J Am Chem Soc 138(18):6068-73, 2016. e-Pub 2016. PMID: 27096704.
- Shen JP, Srivas R, Gross A, Li J, Jaehnig EJ, Sun SM, Bojorquez-Gomez A, Licon K, Sivaganesh V, Xu JL, Klepper K, Yeerna H, Pekin D, Qiu CP, van Attikum H, Sobol RW, Ideker T. Chemogenetic profiling identifies RAD17 as synthetically lethal with checkpoint kinase inhibition. Oncotarget 6(34):35755-69, 2015. PMID: 26437225.
- Choueiri MB, Shen JP, Gross AM, Huang JK, Ideker T, Fanta P. ERCC1 and TS Expression as Prognostic and Predictive Biomarkers in Metastatic Colon Cancer. PLoS One 10(6):e0126898, 2015. e-Pub 2015. PMID: 26083491.
- Agrawal N, Akbani R, Aksoy BA, Ally A,Arachchi H,Asa SL, Auman JT, Balasundaram M, Balu S, Baylin SB, Behera M, Bernard B, Beroukhim R, Bishop JA, Black AD,Bodenheimer T, Boice L, Bootwalla MS, Bowen J, Bowlby R, Bristow CA, Brookens R, Brooks D, Bryant R, Buda E, Butterfield YS, Carling T, Carlsen R, Carter SL, Carty SE, Chan TA, Chen AY, Cherniack AD, Cheung D, Chin L, Cho J, Chu A, Chuah E, Cibulskis K, Ciriello G, Clarke A, Clayman GL, Cope L, Copland JA, Covington K, Danilova L, Davidsen T, Demchok JA, DiCara D, Dhalla N, Dhir R, Dookran SS, Dresdner G, Eldridge J, Eley G, El-Naggar AK, Eng S, Fagin JA, Fennell T, Ferris RL, Fisher S, Frazer S, Frick J, Gabriel SB, Ganly I, Gao J, Garraway LA, Gastier-Foster JM, Getz G, Gehlenborg N, Ghossein R, Gibbs RA, Giordano TJ, Gomez-Hernandez K, Grimsby J, Gross B, Guin R, Hadjipanayis A, Harper HA, Hayes DN, Heiman DI, Herman JG, Hoadley KA, Hofree M, Holt RA, Hoyle AP, Huang FW, Huang M, Hutter CM, Ideker T, Iype L, Jacobsen A, Jefferys SR, Jones CD, Jones SJ, Kasaian K, Kebebew E, Khuri FR, Kim J, Kramer R, Kreisberg R, Kucherlapati R, Kwiatkowski DJ, Ladanyi M, Lai PH, Laird PW, Lander E, Lawrence MS, Lee D, Lee E, Lee S, Lee W, Leraas KM, Lichtenberg TM, Lichtenstein L, Lin P, Ling S, Liu J, Liu W, Liu Y, LiVolsi VA, Lu Y, Ma Y, Mahadeshwar HS, Marra MA, Mayo M, McFadden DG, Meng S, Meyerson M, Mieczkowski PA, Miller M, Mills G, Moore RA, Mose LE, Mungall AJ, Murray BA, Nikiforov YE, Noble MS, Ojesina AI, Owonikoko TK, Ozenberger BA, Pantazi A, Parfenov M, Park PJ, Parker JS, Paull EO, Pedamallu CS, Perou CM, Prins JF, Protopopov A, Ramalingam SS, Ramirez NC, Ramirez R, Raphael BJ, Rathmell WK, Ren X, Reynolds SM, Rheinbay E, Ringel MD, Rivera M, Roach J, Robertson AG, Rosenberg MW, Rosenthal M, Sadeghi S, Saksena G, Sander C, Santoso N, Schein JE, Schultz N, Schumacher SE, Seethala RR, Seidman J, Senbabaoglu Y, Seth S, Sharpe S, Shaw KR, Shen JP, Shen R,Sherman S, Sheth M,Shi Y, Shmulevich I, Sica GL, Simons. Integrated genomic characterization of papillary thyroid carcinoma. Cell 159(3):676-90, 2014. PMID: 25417114.
- Gross AM, Orosco RK, Shen JP, Egloff AM, Carter H, Hofree M, Choueiri M, Coffey CS, Lippman SM, Hayes DN, Cohen EE, Grandis JR, Nguyen QT, Ideker T. Multi-tiered genomic analysis of head and neck cancer ties TP53 mutation to 3p loss. Nat Genet 46(9):939-43, 2014. e-Pub 2014. PMID: 25086664.
- Hofree M, Shen JP, Carter H, Gross A, Ideker T. Network-based stratification of tumor mutations. Nat Methods 10(11):1108-15, 2013. e-Pub 2013. PMID: 24037242.
- Ghashghaei R, Popa R, Shen JP. Evans syndrome. Am J Med 126(11):e7-8, 2013. PMID: 24157305.
- Bradner JE, Mak R, Tanguturi SK, Mazitschek R, Haggarty SJ, Ross K, Chang CY, Bosco J, West N, Morse E, Lin K, Shen JP, Kwiatkowski NP, Gheldof N, Dekker J, DeAngelo DJ, Carr SA, Schreiber SL, Golub TR, Ebert BL. Chemical genetic strategy identifies histone deacetylase 1 (HDAC1) and HDAC2 as therapeutic targets in sickle cell disease. Proc Natl Acad Sci U S A 107(28):12617-22, 2010. e-Pub 2010. PMID: 20616024.
- Bradner JE, McPherson OM, Mazitschek R, Barnes-Seeman D, Shen JP, Dhaliwal J, Stevenson KE, Duffner JL, Park SB, Neuberg DS, Nghiem P, Schreiber SL, Koehler AN. A robust small-molecule microarray platform for screening cell lysates. Chem Biol 13(5):493-504, 2006. PMID: 16720270.
Invited Articles
- Shen JP, Ideker T. Synthetic Lethal Networks for Precision Oncology: Promises and Pitfalls. J Mol Biol 430(18 Pt A):2900-2912, 2018. e-Pub 2018. PMID: 29932943.
- Shen JP, Ideker T. Correcting CRISPR for copy number. Nat Genet 49(12):1674-1675, 2017. PMID: 29186130.
Abstracts
- John Paul Shen, Dongxin Zhao, Brenton Munson, Amanda Birmingham, Roman Sasik, Ana Bojorquez-Gomez, Katherine Licon, Kristin Klepper, Alex Beckett, Kyle Salinas Sanchez, Prashant Mali, Trey Ideker. High-throughput combinatorial CRISPR-Cas9 gene knockout reveals most genetic interactions are context dependent. Cancer Research 78, 2018.
Grant & Contract Support
| Title: | High-Throughput Functional Genomics to Guide Precision Oncology in Gastrointestinal Tumors |
| Funding Source: | NIH/NCI |
| Role: | Principal Investigator |
| Title: | recruitment of Frist Time Tenure-Track Faculty Members |
| Funding Source: | Cancer Prevention & Research Institute of Texas (CPRIT) |
| Role: | Principal Investigator |