Chao-Lan Yu , Ph.D.
Associate Professor
Room 2.345, Telephone (847) 578-8333
E-mail: chao-lan.yu@rosalindfranklin.edu

Dr. Yu received his B.S. in 1985, from Taipei Medical University, Taiwan, and his Ph.D. in Microbiology and Immunology at the University of Michigan, Ann Arbor, in 1995. He did a postdoctoral fellowship in 1995, in the laboratory of Dr. Richard Jove in the Molecular Oncology Program of the H. Lee Moffitt Cancer Center and Research Institute of Tampa, FL, and from 1996-99, in the lab of Dr. Steven J. Burakoff in the Department of Pediatric Oncology at the Dana-Farber Cancer Institute of Boston, MA . From 1999-2001, he was an instructor of Pediatrics at Harvard Medical School of Boston, and from 2001-2007, Assistant Professor of Molecular Physiology and Biophysics at Vanderbilt University School of Medicine in Nashville, TN. Dr.Yu joined the Department of Microbiology and Immunology as Associate Professor at Rosalind Franklin University of Medicine and Science in April of 2007.

Research
The family of Janus protein tyrosine kinases (JAKs) and the downstream signal transducers and activators of transcription (STATs) were first identified as the critical intracellular signaling components in response to many cytokines and growth factors. Our earlier studies first demonstrated their possible involvement in cellular transformation and in human cancer (Science 269:81,1995). These findings identified the JAK-STAT pathway as a novel molecular target for cancer therapy that is being actively pursued in both academic institutions and pharmaceutical companies. The underlying mechanisms of constitutive JAK-STAT activation in tumor cells, however, are complex and not fully understood.

Our research currently focuses on the suppressors of cytokine signaling (SOCS) that are critical in the negative feedback control of the JAK-STAT pathway. We observed the loss of expression of multiple SOCS family members in cells transformed by oncogenic Lck, a key protein tyrosine kinase in T cell signal transduction. We further established a link between novel STAT5b serine phosphorylation and SOCS gene induction. We hypothesize that disrupted SOCS gene expression may contribute to constitutive STAT activation in cancer cells and enforced SOCS expression may have tumor-suppressing activity. We will explore the detailed mechanisms of how different SOCS genes are normally regulated and how this regulation breaks down in cancer cells. The role of SOCS as tumor suppressor will be thoroughly investigated in various tumor models both in cell culture and in mice.

JAK-STAT signaling pays an essential role in a wide spectrum of physiological functions. Therefore, results from our studies will reveal important insights into the molecular details of their regulations. This knowledge also has profound implications in designing novel therapeutic approaches for many human diseases, such as cancer and immunological disorders.

Selected Publications
Shi, M., Cooper, J.C., and Yu, C.-L. 2006. A constitutively active Lck kinase promotes cell proliferation and resistance to apoptosis through signal transducer and activator of transcription 5b activation. Mol. Cancer Res. 4:39-45.

Cooper, J.C., Boustead, J.N., and Yu, C.-L. 2006. Characterization of STAT5B phosphorylation correlating with expression of cytokine-inducible SH2-containing protein (CIS). Cell. Signal. 18:851-860.

Su, M.W.-C., Pyarajan, S., Chang, J.-H., Yu, C.-L., Jin, Y.-J., Stierhof, Y.-D., Walden, P., and Burakoff, S.J. 2004. Fratricide of CD8 + cytotoxic T lymphocytes is dependent on cellular activation and perforin-mediated killing. Eur. J. Immunol. 34:2459-2470.

Tkaczuk, J., Yu, C.-L., Baksh, S., Milford, E.L., Carpenter, C.B., Burakoff, S.J., and McKay, D.B. 2002. Effect of anti-IL-2Ralpha antibody on IL-2-induced Jak/STAT signaling. Am.J. Transplant. 2:31-40.

Su, M.W.-C., Yu, C.-L., Burakoff, S.J., and Jin, Y.-J. 2001. Targeting Src homology 2 domain-containing tyrosine phosphatase (SHP-1) into lipid rafts inhibits CD3-induced T cell activation. J. Immunol. 166:3975-3982.

Tkaczuk, J., Milford, E., Yu, C.-L., Baksh, S., Carpenter, C., Burakoff, S.J., and McKay, D.B. 2001. Intracellular signaling consequences of anti-IL-2R a blockade by Daclizumab. Transplant. Proc. 33:212-213.

Yu, C.-L. , Jin, Y.-J., and Burakoff, S.J. 2000. Cytosolic tyrosine dephosphorylation of STAT5: Potential role of SHP-2 in STAT5 regulation. J. Biol. Chem. 275:599-604.

Jin, Y.-J., Yu, C.-L., and Burakoff, S.J. 1999. Human 70-kDa SHP-1L differs from 68-kDa SHP-1 in its C-terminal structure and catalytic activity. J. Biol. Chem. 274:28301-28307.

McKay, D.B., Tao, L., Yu, C.-L., and Burakoff, S.J. 1999. Alloantigen-unresponsiveness results in defects in intracellular signaling and transcriptional activation of the IL-2 promoter. Transplant. 67:S406.

Yu, C.-L. , Jove, R., and Burakoff, S.J. 1997. Cutting edge: constitutive activation of the Janus kinase-STAT pathway in T lymphoma overexpressing the Lck protein tyrosine kinase. J. Immunol. 159:5206-5210.

Yu, C.-L. and Burakoff, S.J. 1997. Involvement of proteasomes in regulating Jak-STAT pathways upon interleukin-2 stimulation. J. Biol. Chem. 272:14017-14020.

Garcia, R., Yu, C.-L., Hundall, A., Nelson, K.L., Smithgall, T., Fujita, D.J., Ethier, S.P., and Jove, R. 1997. Constitutive activation of Stat3 in fibroblasts transformed by diverse oncoproteins and in breast carcinoma cells. Cell Growth Differ. 8:1267-1276.

Sartor, C.I., Dziubinski, M.L., Yu, C.-L., Jove, R., and Ethier, S.P. 1997. Role of epidermal growth factor receptor and STAT-3 activation in autonomous proliferation of SUM-102PT human breast cancer cells. Cancer Res. 57:978-987.

Campbell , G.S., Yu, C.-L., Jove, R., and Carter-Su, C. 1997. Constitutive activation of JAK1 in Src-transformed cells. J. Biol. Chem. 272:2591-2594.

Stofega, M.R., Yu, C.-L., Wu, J., and Jove, R. 1997. Activation of extracellular signal-regulated kinase (ERK) by mitogenic stimuli is repressed in v-Src-transformed cells. Cell Growth Differ. 8:113-119.

Yu, C.-L. , Prochownik, E.V., and Jove, R. 1995. Proximal promoter region of the junB gene mediates attenuation of serum inducibility in Src transformed cells. Cell Growth Differ. 6:1513-1521.

Yu, C.-L. , Meyer, D.J., Campbell, G.S., Larner, A.C., Carter-Su, C., Schwartz, J., and Jove, R. 1995. Enhanced DNA-binding activity of a Stat3-related protein in cells transformed by the Src oncoprotein. Science 269:81-83.

Yu, C.-L. , Prochownik, E.V., Imperiale, M.J., and Jove, R. 1993. Attenuation of serum inducibility of immediate early genes by oncoproteins in tyrosine kinase signaling pathways. Mol. Cell. Biol. 13:2011-2019.

Apel, I., Yu, C.-L., Wang, T., Dobry, C., Van Antwerp, M.E., Jove, R., and Prochownik, E.V. 1992. Regulation of the junB gene by v-src. Mol. Cell. Biol. 12:3356-3364.

This page was updated on 07/17/09.