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.
The family of signal transducer and activator of transcription (STAT) was first identified as the key intracellular signaling molecule in response to many cytokines and growth factors. Our earlier studies first demonstrated its possible involvement in cellular transformation and in human cancer (Science 269:81,1995). These findings identified the STAT pathway as a novel molecular target for cancer therapy that is being actively pursued in both academic institutions and pharmaceutical companies.
Our research currently focuses on a) the role of suppressor of cytokine signaling (SOCS) as tumor suppressor; and b) the role of STAT5 in cancer metabolism. SOCS proteins are critical in the negative feedback control of the STAT pathway. We reported earlier that, through different mechanisms, the expression of multiple SOCS family members is lost in tumor cells. We hypothesize that disrupted SOCS gene expression may contribute to constitutive STAT activation in cancer cells. The tumor-suppressing activity of SOCS is now thoroughly investigated in various tumor models both in cell culture and in mice. The other new project initiated in the lab is based on the novel interaction between the E2 subunit of pyruvate dehydrogenase complex (PDC-E2), a metabolic enzyme, and STAT5 in tumor cells. STAT5 and PDC-E2 association in the nucleus and the mitochondrion suggests an important crosstalk between the two compartments in regulating cell metabolism. Our current effort is focusing on elucidating the role of STAT5 in Warburg effect, a well-known metabolic shift in cancer.
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, immunological, and metabolic
Chueh, F.-Y., Cronk, R.J., Alsuwaidan, A.N., Mallers, T.M., Jaiswal, M.K., Beaman, K.D., and Yu, C.-L. 2014. Mouse LSTRA leukemia as a model of human natural killer T cell and highly aggressive lymphoid malignancies. Leuk. Lymphoma. 55:706-708.
Chueh, F.-Y. and Yu, C.-L. 2012. Engagement of TCR and CD4/CD8 co-receptors induces prolonged STAT activation through autocrine/paracrine stimulation in human primary T cells. Biochem. Biophys. Res. Commun. 426:242-246.
Venkitachalam, S., Chueh, F.-Y., and Yu, C.-L. 2012. Nuclear localization of lymphocyte-specific protein tyrosine kinase (Lck) and its role in regulating LIM domain only 2 (Lmo2) gene.Biochem. Biophys. Res. Commun. 417:1058-62.
Chueh, F.-Y.*, Leong, K.-F.*, Cronk, R.J., Venkitachalam, S., Pabich, S., and Yu, C.-L. 2011. Nuclear localization of PDC-E2 (pyruvate dehydrogenase complex-E2), a mitochondrial enzyme, and its role in signal transducer and activator of transcription 5 (STAT5)-dependent gene transcription. Cell. Signal. 23:1170-1178. (*equal contribution)
Venkitachalam, S., Chueh, F.-Y., Leong, K.-F., Pabich, S., and Yu, C.-L. 2011. Suppressor of cytokine signaling 1 interacts with lymphocyte-specific protein tyrosine kinase. Oncol. Rep. 25:677-683.
Chueh, F.-Y., Leong, K.-F., and Yu, C.-L. 2010. Mitochondrial translocation of signal transducer and activator of transcription 5 (STAT5) in leukemic T cells and cytokine-stimulated cells. Biochem. Biophys. Res. Commun. 402:778-783.
Cooper, J.C.*, Shi, M.*, Venkitachalam, S., Chueh, F.-Y., and Yu, C.-L. 2010. Enforced SOCS1 and SOCS3 expression attenuates Lck-mediated cellular transformation. Int. J. Oncol. 36:1201-1208. (*equal contribution)
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.