Andrew Yen - Professor of Biomedical Sciences at Cornell University

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Andrew Yen, Ph.D.
Professor of Biomedical Sciences

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

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

Battle, T.E., Roberson, M.S., Zhang, T., Varvayanis, S., and Yen, A.: Retinoic Acid-induced BLR1 Expression Requires RAR±, RXR, and MAPK Activation and Uses ERK2 But Not JNK/SAPK to Accelerate Cell Differentiation. Eur. J. Cell Biol. 80:59-67, 2001.
Yen, A., Norman A.W., and Varvayanis, S.: Non-genomic Vitamin D3 Analogs Activating ERK2 in HL-60 Cells Show That Retinoic Acid Induced Differentiation and Cell Cycle Arrest Require Early Concurrent MAPK and RAR and RXR Activation. In Vitro Cell. Dev. Biol. 37: 93-99, 2001.
Yen, A.., Placanica, L., Bloom, S., and Varvayanis, S.: Polyoma Small T Antigen Prevents Retinoic Acid-Induced RB Hypophosphorylation and Redirects Retinoic Acid-induced G0 Arrest and Differentiation to Apotosis. J. Virology. 25:5302-5314, 2001.
Hong, H.-Y., Varvayanis, S., and Yen, A.: Retinoic Acid Causes MEK-Dependent RAF Phosphorylation Through RARa Plus RXR Activation in HL-60 Cells. Differentiation 68:55-66, 2001.
Wightman, J., Roberson, M. S., Lamkin, T. J., Varvayanis, S. and Yen, A.: Retinoic Acid-Induced Growth Arrest and Differentiation: Retinoic Acid Up-regulates CD32 (FcgRII) Expression Whose Ectopic Expression Retards the Cell Cycle. Mol. Cancer Therapeutics. 1:493-506, 2002.
Battle, T.E. and Yen, A.: Ectopic Expression of CXCR5/BLR1 Accelerates Retinoic acid- and Vitamin D3-Induced Monocytic Differentiation of U937 Cells. Exp. Biol. Med. 227:753-762, 2002.
Wang, J. and Yen, A.: A Novel Retinoic Acid-Responsive Element Regulates Retinoic Acid-Induced BLR1 Expression. Mol. Cell. Biology. 24:2423-2443, 2004.
Yen, A., Lin, D.M., Lamkin, T.J., and Varvayanis, S.: Retinoic Acid, Bromodeoxyuridine, and the D205 Mutant Polyoma Virus Middle T Antigen Regulate Expression Levels of a Common Ensemble of Proteins Associated with Early Stages of Inducing HL-60 Leukemic Cell Differentiation. In Vitro Cell Dev. Biol. 40:216241, 2004.
Flaminio, M.J.B.F., Yen, A., and Antczak, D.: The Proliferation Inhibitory Proteins p27Kipl and Retinoblastoma are Involved in the Control of Equine Lymphocyte Proliferation. Vet. Immunol. and Immunopath. 102:363-377, 2004.
Yen, A., Fenning, R., Chandraratna, R., Walker, P., and Varvayanis, S.: A Retinoic Acid Receptor b/g-Selective Prodrug (tazarotene) Plus a Retinoid X Receptor Ligand Induces Extracellular Signal-Regulated Kinase Activation, Retinoblastoma Hypophosphorylation, G0 Arrest, and Cell Differentiation. Mol. Pharmacol. 66:1727-1737, 2004.
Lamkin, T.J., Chin, V., Varvayanis, S., Smith, J.L., Sramkoski, R.M., Jacobberger, J.W., and Yen, A.: Retinoic Acid-induced CD38 Expression in HL-60 Myeloblastic Leukemia Cells Regulates Cell Differentiation or Viability Depending on Expression Levels. J. Cell. Biochem. 97:1328-1338, 2006.
Yen, A., Varvayanis, S., Smith. J.L., and Lamkin, T.J.: Retinoic Acid Induces Expression of SLP-76: Expression with c-FMS Enhances ERK Activation and Retinoic-Induced Differentiation/G0 Arrest of HL-60 Cells. Eur. J. Cell Biol. 85:117-132, 2006.
Lamkin, T.J., Chin, V., and Yen, A.: All-trans Retinoic Acid Induces p62^DOK1 and p56^DOK2 Expression wich Enhances Induced Differentiation and G0 Arrest of HL-60 Leukemia Cell. Amer. J. Hematol. 81:603-615, 2006.
Chikamori, K., Hill, J.E., Grabowski, D.R., Zarkhin, E., Grozav, A.G., Vaziri, S.A.J., Wang., J., Gudkov, A.V., Rybicki, L.R., Bukowski, R.M., Yen, A., Tanimoto, M., Ganapathi, M.K., and Ganapathi, R.: Down Regulation of Topoisomerase β In Myeloid Leukemia Cell Lines Leads To Activation of Apoptosis Following All-Trans Retinoic Acid-Induced Differentiation/Growth Arrest. Leukemia 20:1809-1818, 2006.
Yen, A.: Retinoic Acid Therapy Served by Ligands Cross Linking and Masking CD38. Leukemia Res. , On line, doi:10.1016/j.leukres.2006.07.003
Reiterer, G. and Yen, A.: Inhibition of the Janus Kinase Family Increases ERK1/2 Phosphorylation and Causes Endoreduplication. Cancer Res. 66:9083-9084, 2006.