Tim J. Yen, PhD

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Professor

Facility Director, Biological Imaging Facility

Adjunct Associate Professor, University of Pennsylvania

Lab Overview

The Yen Lab

My research in fundamental mechanisms of cell division is directly relevant to understanding the biology of cancer, as well as its treatment. My focus over this time was on characterizing the kinetochore: a macromolecular structure assembled onto centromeric chromatin that specifies accurate chromosome segregation. We study the molecular functions of various proteins that reside at kinetochores as it pertains to chromosome segregation and spindle checkpoint signaling. Defects in this process lead to aneuploidy, and is, thus, of fundamental importance to problems, such as birth defects, cancer and other diseases.

We are also interested in developing new ways to enhance the efficacy of existing chemotherapies to improve treatment outcomes of cancers. In particular, we are focused on recalcitrant cancers, such as pancreatic, ovarian, brain and melanomas because the treatment outcomes are poor. Efforts to understand how these cancers survive toxic chemo and radiation therapies will reveal new targets for drug development. We, therefore, use genome-wide approches, such as RNAi and CRISPR cas9, to perform synthetic lethal screens to identify pathways that facilitate survival of cells to drugs.

Network of intersecting pathways that specify formation of a kinetochore module. Schematic depiction of the molecular organization the centromere and kinetochore complex (blue) of a chromosome (pink). The centromere complex is organized through self assembly of repetitive modules (blue spheres). The protein composition within each module is depicted below the image.

Educational Background

Postdoctoral Fellow, Molecular Cell Biology, John Hopkins University School of Medicine, Baltimore, MD, 1990
PhD, Molecular Biology, University of California, Santa Barbara, CA, 1985
MA, Biochemistry, University of California, Santa Barbara, CA, 1981
BS, Biochemistry, University of California, Santa Barbara, CA, 1978

Honors & Awards

Leukemia Society of America Scholar, 1995-2000
Lucille P. Markey Scholar, 1989-1995
Young Investigator's Award, Johns Hopkins University School of Medicine, 1988
Postdoctoral Fellowship Award, American Cancer Society, 1985-1988

People

James Hittle, BS

Technical Specialist

R310

215-728-4311

[email protected]
Corinne Stobbe, MSc.

Scientific Assistant

R310

215-728-4311

[email protected]

Research Facility

Biological Imaging Facility

Research Interests

Genome Stability in normal and disease states

Mechanisms that ensure accurate chromosome segregation
Mechanisms disrupted in cells with chromosome instability
Strategies to enhance response of cancer cells to conventional chemoradiation therapies

Selected Publications

Mancuso P., Tricarico R., Bhattacharjee V., Cosentino L., Kadariya Y., Jelinek J., Nicolas E., Einarson M., Beeharry N., Devarajan K., Katz R.A., Dorjsuren D.G., Sun H., Simeonov A., Giordano A., Testa J.R., Davidson G., Davidson I., Larue L., Sobol R.W., Yen T.J., Bellacosa A., Thymine DNA glycosylase as a novel target for melanoma. Oncogene. 38(19): 3710-3728, 2019.PMC6563616. 6.634

Sannai M., Doneddu V., Giri V., Seeholzer S., Nicolas E., Yip S.C., Bassi M.R., Mancuso P., Cortellino S., Cigliano A., Lurie R., Ding H., Chernoff J., Sobol R.W., Yen T.J., Bagella L., Bellacosa A., Modification of the base excision repair enzyme mbd4 by the small ubiquitin-like molecule sumo1. DNA Repair. 82: 102687, 2019.PMC6785017. 3.711

Bellacosa A., Yen T., Illuminating the route of precision medicine and inhibitor discovery: Real-time measurement of DNA repair capacity with molecular beacons. Oncotarget. 9(96): 36818-36819, 2018.PMC6305151. 5.168

Ghelli Luserna Di Rora A., Beeharry N., Imbrogno E., Ferrari A., Robustelli V., Righi S., Sabattini E., Verga Falzacappa M.V., Ronchini C., Testoni N., Baldazzi C., Papayannidis C., Abbenante M.C., Marconi G., Paolini S., Parisi S., Sartor C., Fontana M.C., De Matteis S., Iacobucci I., Pelicci P.G., Cavo M., Yen T.J., Martinelli G., Targeting wee1 to enhance conventional therapies for acute lymphoblastic leukemia. J Hematol Oncol. 11(1): 99, 2018.PMC6090987. 8.731

Eytan E, Wang K, Miniowitz-Shemtov S, Sitry-Shevah D, Kaisari S, et al. Disassembly of mitotic checkpoint complexes by the joint action of the AAA-ATPase TRIP13 and p31(comet). Proc Natl Acad Sci U S A. 2014 Aug 19;111(33):12019-24. PubMed PMID: 25092294; PubMed Central PMCID: PMC4142996. PubMed

Wang K, Sturt-Gillespie B, Hittle JC, Macdonald D, Chan GK, et al. Thyroid hormone receptor interacting protein 13 (TRIP13) AAA-ATPase is a novel mitotic checkpoint-silencing protein. J Biol Chem. 2014 Aug 22;289(34):23928-37. PubMed PMID: 25012665; PubMed Central PMCID: PMC4156041. PubMed

Bhattacharjee V, Zhou Y, Yen TJ. A synthetic lethal screen identifies the Vitamin D receptor as a novel gemcitabine sensitizer in pancreatic cancer cells. Cell Cycle. 2014;13(24):3839-56. PubMed PMID: 25558828. PubMed

Tipton AR, Wang K, Link L, Bellizzi JJ, Huang H, et al. BUBR1 and closed MAD2 (C-MAD2) interact directly to assemble a functional mitotic checkpoint complex. J Biol Chem. 2011 Jun 17;286(24):21173-9. PubMed PMID: 21525009; PubMed Central PMCID: PMC3122179. PubMed

Sudakin V, Chan GK, Yen TJ. Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2. J Cell Biol. 2001 Sep 3;154(5):925-36. PubMed PMID: 11535616; PubMed Central PMCID: PMC2196190. PubMed

Chan GK, Schaar BT, Yen TJ. Characterization of the kinetochore binding domain of CENP-E reveals interactions with the kinetochore proteins CENP-F and hBUBR1. J Cell Biol. 1998 Oct 5;143(1):49-63. PubMed PMID: 9763420; PubMed Central PMCID: a.a. PubMed

Schaar BT, Chan GK, Maddox P, Salmon ED, Yen TJ. CENP-E function at kinetochores is essential for chromosome alignment. J Cell Biol. 1997 Dec 15;139(6):1373-82. PubMed PMID: 9396744; PubMed Central PMCID: PMC2132614. PubMed

Liao H, Li G, Yen TJ. Mitotic regulation of microtubule cross-linking activity of CENP-E kinetochore protein. Science. 1994 Jul 15;265(5170):394-8. PubMed PMID: 8023161. PubMed

Yen TJ, Li G, Schaar BT, Szilak I, Cleveland DW. CENP-E is a putative kinetochore motor that accumulates just before mitosis. Nature. 1992 Oct 8;359(6395):536-9. PubMed PMID: 1406971. PubMed

Additional Publications

My NCBI

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