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Biomedical Sciences
Andrew Yen, Ph.D.
Professor of Biomedical Sciences

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Phone: 607 253 3354
E-mail: ay13@cornell.edu

Yen Lab Website:
http://blogs.cornell.edu/yenden/

Dr. Andrew Yen, a professor in the Department of Biomedical Sciences, is a member of several graduate fields. His undergraduate and graduate training at Haverford College (BA, physics/mathematics 1969), University of Washington (MS, physics 1970) and Cornell University (PhD, biophysics 1976) led to postdoctoral work at Harvard with A.B. Pardee and subsequent faculty appointments at the Sloan-Kettering Institute for Cancer Research, the University of Iowa, and now Cornell University. Dr. Yen's research has focused on the cellular/molecular control mechanisms regulating cell growth and differentiation which may be pathologically aberrant in cancer. His work has been supported by the National Institutes of Health, The American Institute for Cancer Research, The Council for Tobacco Research, The Children's Leukemia Research Foundation, The United States Department of Agriculture, and the March of Dimes Foundation. Dr. Yen is Director of Graduate Studies in Environmental Toxicology, Director of the Biomedical Sciences Flow Cytometry Core Laboratory, and Associate Director of the Institute for Comparative Environmental Toxicology.

Research Interests

Research in Dr. Yen's laboratory is in the area of cell cycle regulation and cell differentiation. They study in particular a myeloblastic hematological tumor cell line, HL-60, which retains the capability to undergo GO arrest and differentiation along either the myeloid or the monocytic lineages. For example, retinoic acid causes GO arrest and myeloid differentiation, whereas 1,25-dihydroxy vitamin D3, a ligand for another member of the same steriod thyroid hormone receptor superfamily, causes arrest and monocytic differentiation. This established cell line has been one of the archtypical models for studies of myelo-monopoiesis and hematopoietic differentiation. Because it is derived from a patient with acute promyelocytic leukemia, a disease where retinoic acid has now been found to induce temporary remissions while conventional chemotherapy has not been effective, there is significant motivation for understanding its mechanism of action. The current work focuses on what retinoid receptors are implicated in initiating the metabolic cascade culminating in GO arrest and cell differentiation, how that process is modulated by cell surface receptors such as c-FMS (the CSF-1 receptor) that use MAPK signaling, and how the RB (retinoblastoma tumor suppressor) protein may function as a downstream effector of these signals to regulate cell cycle and cell differentiation. One of the central scientific questions addressed in the laboratory is the cellular molecular mechanisms of myeloid and monocytic cell differentiation.

The application of basic principles elucidated in these in vitro studies is directed toward understanding the mechanism of teratogenic agents and also toward the rational design of differentiation induction therapy of cancer. Whereas conventional chemotherapy seeks to expunge the tumor stem cell population, this alternative seeks to nullify the proliferative activity and differetiatively immature hallmarks of the tumor by inducing terminal differentiation. The host can thus be relieved of the tumor burden. The hope is that this potential form of therapy will spare the host of the severely toxicity inherent in conventional chemotherapy. Significantly certain dietary factors and environmental pollutants can induce terminal differentiation of neoplastic cells. The molecular mechanism by which they act is being studied by the above.

Select Publications

1. Reiterer, G. and Yen, A.: Inhibition of the Janus Kinase Family Increases ERK1/2 Phosphorylation and Causes Endoreduplication. Cancer Res. 66:9083-9084, 2006.
2. Yen, A.: Retinoic Acid Therapy Served by Ligands Cross Linking and Masking CD38. Leukemia Res. 31:423-425, 2007.

3. Reiterer, G. and Yen, A.: Platelet Derived Growth Factor Receptor Regulates Myeloid and Monocytic Differentiation of HL-60 Cells. Cancer Res. 67:7765-7772, 2007.
4. Wang, J.R. and Yen, A.: A MAPK positive feedback mechanism for BLR1 signaling propels retinoic acid triggered differentiation and cell cycle arrest. J Biol Chem. 283:4375-4386, 2008.
5. Reiterer, G., Bunaciu, P. B., Smith, J. L. and Yen, A.: Inhibiting the Platelet Derived Growth Factor Receptor Increases Signs of Retinoic Acid syndrome in Myeloid Differentiated HL-60 Cells. FEBS Letters 582:2508-2514, 2008.
6. Kauss, M.A., Reiterer, G., Bunaciu, P. B. and Yen, A.: Human myeloblastic leukemia cells (HL-60) express a membrane receptor for estrogen that signals and modulates retinoic acid-induced cell differentiation. Exp. Cell Res. 314:2999-3006, 2008.
7. Shen, M. and Yen, A.: c-Cbl Interacts with CD38 and Promotes RA-induced Differentiation and G0 Arrest of Human Myeloblastic Leukemia Cells. Cancer Res. 68: 8761-8769, 2008.
8. Shen, M. and Yen, A. Nicotinamide cooperates with RA and D3 to regulated cell differentiation and cell cycle arrest of human myeloblastic leukemia cells. Oncology 76:91-100, 2009.
9. Tallini, Y. N., Greene, K. S., Craven, M., Spealman, A., Breitbach, M., Smith, J., Fisher, P. J., Steffey, M., Hesse, M., Doran, R. M., Woods, A., Singh, B., Yen, A., Fleischmann, B. K. and Kotlikoff, M. I.: c-kit expression identifies cardiovascular precursors in the neonatal heart. Proc. Nat. Acad. Sci., US 106: 1808-1813, 2009
10. Jiang, H., Congleton, J., Liu, Q., Merchant, P., Malavasi, F., Lee, H., Hao, Q., Yen, A., Lin, H. Mechanism-based small molecule probes for labeling CD38 on live cells. J. Amer. Chem. Soc. In Press, 2009
11. Smith, J. Buncaciu, R. P., Reiterer, G., Coder, D., George, T., Asaly, M., and Yen, A.: Retinoic acid induces nuclear accumulation of Raf1 during differentiation of HL-60 cells. Exp. Cell Res. In Press, 2009

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