Meet Faculty and Staff

Ying Huang, M.D., Ph.D. Associate Professor, Pharmacology 4319 Weiskotten Hall Upstate Medical University 750 East Adams Street Syracuse, NY 13210 (315) 464-8009

Research Program and Department Affiliations

Research Interests

Research Abstract

Oncogenic signaling pathways in cellular transformation and apoptosis

Carcinogenesis is a multi-step process that involves activation of proto-oncogenes and inactivation of tumor suppressor genes. Gain-of-function mutations in oncogenes are frequently detected in human cancers. Activation of oncogenes plays an important role in cancer development and in altering cellular sensitivities to anti-cancer agents. Research in my laboratory focuses on a number of areas: (1) Cellular kinases signaling in cancer cell proliferation, survival and death; (2) Studying the function and regulation of tumor suppressor RASSF1A; (3) Investigating the role of a novel family of GTPases, RBEL1A, B, C and D in regulation of cell death and proliferation; (4) Investigating the role of a novel growth suppresive lipase in cell growth control and cancer development; (5) Identification and development of novel anticancer agents using traditional Chinese medicines.

SELECTED PUBLICATIONS:

Meltzer, S. J., Yin, J., Huang, Y., McDaniel, T. K., Newkirk, C., Iseri, O., Vogelstein, B. and Resau, J. Reduction to homozygosity involving p53 in esophageal cancers demonstrated by the polymerase chain reaction. Proc. Natl. Acad. Sci. USA, 1991, 88: 4976-4980.

Boynton, R. F., Huang, Y., Blount, P. L., Reid, B.J., Raskind, W. H., Haggitt, R. C., Newkirk, C., Resau, J. H., Yin, J., MeDaniel, T. and Meltzer, S. J. Frequent loss of heterozygosity at the retinoblastoma locus in human esophageal cancers. Cancer Res., 1991, 51: 5766-5769.

McDaniel, T.K., Huang, Y., Needleman, S.W. and Meltzer, S. J. Direct labeling of polymerase chain reaction products using Klenow fragment. BioTechniques, 1991, 11:164-166.

McDaniel, T.K., Carbone, D., Takahashi, T., Chumakov, P., Chang, E.H., Pirollo, K.F., Yin. J., Huang, Y., and Meltzer, S. J. Polymorphism in intron 6 of p53 detected by digesting PCR products with MSP I. Nucleic Acids Res., 1991, 19: 4796.

Boynton, R. F., Blount, P. L., Yin, J., Brown, V., Huang, Y., Tong, Y., McDaniel, T., Newkirk, C., Resau, J., Raskind, W. H., Haggitt, R. C., Reid, B. and Meltzer, S. J. Loss of heterozygosity involving the APC and MCC genetic loci occurs in majority of human esophageal cancers. Proc. Natl. Acad. Sci. USA, 1992, 89: 3385-3388.

Greenwald, B., Huang, Y., Baum. R., Meltzer, S. J. Barrett's carcinoma in a 25-year-old man with point mutation of the p53 tumor suppressor gene. Int. J. Oncology, 1992, 1:271-275.

Greenwald, B. D., Harpaz, N., Yin, J., Huang, Y., Tong, Y., Brown, V. L., McDaniel, T., Newkirk, C., Resau, J. H. and Meltzer, S. J. Loss of heterozygosity affecting the p53, Rb, and mcc/apc tumor suppressor gene loci in dysplastic and cancerous ulcerative colitis. Cancer Res., 1992, 52:741-745.

Huang, Y., Boynton, R. F., Blount, P. L., Silverstein, R., Yin, J., Tong, Y., Newkirk, C., Resau, J. H. Sridhara, R., Reid, B. J. and Meltzer, S. J. Loss of heterozygosity involves multiple tumor suppressor genes in human esophageal cancers. Cancer Res., 1992, 52:6525-6530.

Huang, Y., Meltzer, S. J., Yin, J., Tong, Y., Chang, E. H., Sirvastava, S., McDaniel, T., Boynton, R. F., Zou, Z-Q. Altered mRNA and unique mutational profiles of p53 and Rb in human esophageal carcinomas. Cancer Res., 1993, 53:1889-1894.

Yin, J., Harpaz, N., Tong, Y., Huang, Y., Laurin, J., Greenwald, B. D., Hontanosas, M., Newkrik, C., and Meltzer, S. J. p53 point mutations in dysplastic and cancerous ulcerative colitis lesions. Gastroenterology, 1993, 104:1633-1639.

Blount, P. L., Meltzer, S. J., Yin, J., Huang, Y., Krasna, M. J., and Reid, B. J. Clonal ordering of 17p and 5q allelic losses in Barrett's dysplasia and adenocarcinoma. Proc. Natl. Acad. Sci., USA, 1993, 90:3221-3225.

Huang, Y., Yin, J., Meltzer, S. J. A unique p53 intragenic deletion flanked by short direct repeats results in loss of mRNA expression in a human esophageal carcinoma. Carcinogenesis, 1994, 15:1653-1655.

Huang, Y., Saez, R., Chao, L., Santos, E., Aaronson, S. A and Chan, A. M-L. A novel insertion mutation in the TC21 gene activates its transforming activity in a human leiomyosarcoma cell line. Oncogene, 1995, 11:1255-1260.

Huang, Y., Chan, A. M-L., Liu, Y., Wang, X., Holbrook, N. J. Serum withdrawal and etoposide induce apoptosis in human lung carcinoma cell line A549 via distinct pathways. Apoptosis, 1997, 2:199-206.

Wang, X., Gorospe, M., Huang, Y., and Holbrook, N. J. p27/Kip1 over-expression causes apoptotic death of mammalian cells. Oncogene, 1997, 15:2991-2997.

Sheikh, M.S., Burns, T.F., Huang, Y., Wu, G. S., Amundson, S., Brooks, K. S., Fornace Jr., A. J. and El-Deiry, W.S. p53-dependent and -independent regulation of the death receptor KILLER/DR5 gene expression in response to genotoxic stress and tumor necrosis factor α. Cancer Res., 1998, 588:1593-1598.

Sheikh, M. S., Antinore, M. J., Huang, Y. and Fornace Jr., A. J. Ultraviolet-irradiation- induced apoptosis is mediated via ligand independent activation of tumor necrosis factor receptor 1. Oncogene, 1998, 17:2555-2563.

Huang, Y., Sheikh, M. S., Fornace, A. J., Holbrook, N. J. Serine protease inhibitor TPCK prevents Taxol-induced cell death and c-Raf-1 and bcl-2 phosphorylation in human breast carcinoma. Oncogene, 1999, 18:3431-3439.

Sheikh, M. S, Huang Y., Fernandez-Salas, E. A., El-Deiry, W. S., Amundson, S., Yin J., Meltzer, S. J., Holbrook N. J., Fornace, Jr. A. J. The antiapoptotic decoy receptor TRID/TRAIL-R3 is a p53 regulated DNA damage-inducible gene that is overexpressed in primary tumors of the gastrointestinal tract. Oncogene, 1999, 18, 4153-4159.

Zhang Y., Huang Y., Rishi A., Sheikh, M. S., Shroot, B., Reichert U., Dawson M., Poirer, G., and Fontana J. A. Activation of p38 and JNK/SAPK mitogen activated protein kinase pathways during apoptosis mediated by novel retinoid. Exp. Cell Res., 1999, 247: 233-40.

Sheikh, M.S., Fernandez-Sala, E., Yu, M., Hussain, A., Huang, Y., and Fornace Jr., A. J. Cloning and characterization of mammalian genotoxic stress-inducible cDNA that encodes a putative translation initiation factor. J. Biol. Chem., 1999, 274: 16487-16493.

Huang, Y., Hutter, D., Liu, Y., Wang, X., Liu, Y., Sheikh, M. S., Chan, A-M-L., Holbrook, N.J. TGFâ1 suppresses serum deprivation-induced death of A549 cells through different effects on c-Jun and JNK activities. J. Biol. Chem., 2000, 275:18234-18242.

Huang, Y., He, Q., Hillman, M.J., Rong, R., Sheikh, M.S. The sulindac sulfide-induced apoptosis involves death receptor 5 and caspase 8-dependent pathway in human colon and prostate cancer cells. Cancer Res., 2001, 61:6918-6924.

Rong, R., He, Q., Liu, Y., Sheikh, M.S. Huang, Y. TC21 mediates transformation and cell survival via activation of phosphatidylinositol 3-kinase/Akt and NF-kappa B signaling pathway. Oncogene, 2002, 21:1062-70.

He, Q., Lee, D.K., Rong, R., Yu, M., Luo, X., Klein, M., Huang, Y., Hussain, A., Sheikh, M.S., Endoplasmic reticulum calcium pool depletion-induced apoptosis is coupled with activation of death receptor 5 pathway. Oncogene, 2002, 21:2623-33.

He, Q., Rashid, A., Rong, R., Hillman, M.J., Huang, Y., Sheikh, M.S. Death receptor 5 regulation during selenium-mediated apoptosis in human prostate cancer cells. Cancer Biology & Therapy, 2002, 1:3, 287-290.

He, Q., Luo, X., Huang, Y. and Sheikh, M.S. Apo2L/TRAIL differentially modulate the apoptotic effects of sulindac and COX-2 selective non-steroidal anti-inflammatory agent in Bax deficient cells. Oncogene, 2002, 21:6032-6040.

He, Q., Montalbano J., Corcoran, C., Jin, W., Hunag, Y., and Sheikh, M.S. Effect of Bax deficiency on death receptor 5 and mitochondrial pathway during endoplsamic reticulum calcium pool depletion-induced apoptosis. Oncogene, 2003, 22:2674-2679.

Luo, X., Huang, Y., and Sheikh, M. S. Cloning and characterization of a novel gene PDRG that is differentially regulated by p53 and ultraviolet radiation. Oncogene, 2003, 22:7247-7257.

Sheikh, M.S., Huang, Y. Death receptor as targets of cancer therapeutics. Current Cancer Drug Target. 2004, 4: 97-104.

Fahana, L., Dawson, M.I., Huang, Y., Zhang, Y., Rishi A.K., Reichert, U., and Fontana, J.A. Inhibition of Phosphoinositol 3-Kinase activity and AKT kinase activity by novel retinoid CD437 in breast and prostate carcinoma cells. Oncogene, 2004, 23:1874-1884.

He, Q., Huang, Y., Sheikh, M.S. Bax deficiency affects caspase-2 activation during ultraviolet irradiation-induced apoptosis. Oncogene, 2004, 23: 1321-1325.

He, Q., Huang, Y., Sheikh, M.S. The proteasome inhibitor MG132 upregulates death receptor 5 and cooperates with Apo2L/TRAIL to induce apoptosis in Bax-proficient and deficient cells. Oncogene, 2004, 23:2554-2558.

Rong, R. Jin, W., Zhang, J., Sheikh, M.S., Huang, Y. Tumor suppressor RASSF1A is a microtubule-associated protein that stabilizes microtubule and induces G2/M cell cycle arrest. Oncogene, 2004, 23:8216-8230.

Corcoran, C.A., He, Q., Huang, Y., and M. S. Sheikh. Cyclooxygenase-2 (COX-2) interacts with p53 and interferes with p53-dependent transcription and apoptosis. Oncogene, 2005, 24:1634-40.

Rong, R., Montalbano J., Jin W., Zhang J., Garling M., Sheikh M.S., Huang Y. Oncogenic Ras-mediated downregulation of Gadd153/CHOP is required for Ras-induced cellular transformation. Oncogene, 2005, 24:4867-72.

Luo, X., He, Q., Huang, Y., Sheikh, M. S. Transcriptional upregulation of PUMA modulates endoplasmic reticulum calcium pool depletion-induced apoptosis via Bax activation. Cell death and differentiation, Cell Death and Differentiation, 2005, 12:1310-8.

Luo, X., He, Q., Huang, Y., Sheikh, M.S. Cloning and characterization of a p53 and DNA damage down-regulated gene PIQ that codes for a novel calmodulin-binding IQ motif and is upregulated in gastrointestinal cancers. Cancer Res. 2005, 65:10725-10733.

Corcoran, C.A., Luo, X., He, Q., Jiang, C., Huang, Y., Sheikh, M.S. Genotoxic and endoplasmic reticulum stresses differentially regulates TRB3 expression. Cancer Biology & Therapy, 2005, 4:1063-1067.

Rong, R., Jiang, LY., Sheikh, MS., and Huang, Y. Mitotic kinase Aurora-A phosphorylates RASSF1A and modulates RASSF1A-mediated microtubule interaction and M-phase cell cycle regulation.  Oncogene. 2007, 26: 7700-7708.

Montalbano, J., Jin, W., Sheikh, MS., Huang, Y. RBEL1 is a novel gene that encodes a nucleo-cytoplasmic Ras superfamily GTP-binding protein and is overexpressed in breast cancer. J. Biol Chem. 2007, 282:37640-37649.

He, Q., Luo, X., Jin, W., Huang, Y., Ramana Reddy, M.V., Reddy, E. P. and Sheikh, M.S. Celecoxib and a novel COX-2 inhibitor ON09310 upregulate Death Receptor 5 expression via GADD153/CHOP. Oncogene, 2008, 27, 2656–2660.

Corcoran, C.A., He, Q.,  Ponnusamy, S., Ogretmen, B., Huang, Y., and Sheikh, MS. Neutral Sphingomyelinase-3 Is a DNA Damage and Nongenotoxic Stress-Regulated Gene That Is Deregulated in Human Malignancies. Molecular Cancer Research, 2008, 6, 795-807. (Cover article)

He, Q., Shi, J., Jones, S., An, J., Liu, Y., Huang, Y., Sheikh, M.S. Smac deficiency affects endoplasmic reticulum stress-induced apoptosis in human colon cancer cells. Mol. Cell. Pharm. 2009, 1(1), 23-28.

Montalbano, J., Lui, K., Sheikh, MS., Huang, Y. Ientification and characterization of RBEL1 subfamily of GTPases in the Ras superfamily involved in cell growth regulation. J. Biol Chem., 2009, 284, 18129-18142.

Corcoran, C.A., Montalbano, J., Sun, H., He, Q., Huang, Y., Sheikh, M.S. Iendtification and chacracterization of two novel isoforms of Pirh2 Ubiquitin ligase that negatively regulate p53 indendendent of RING finger domains. J. Biol. Chem., 2009, 284, 21955-21970. 

Shi, J., He, Q., An, J., Sun, H., Huang, Y., Sheikh, M.S. Sulindac sulfide defferentially induces apoptosis in Smac-proficient and -deficient human caolon cancer cells. Mol. Cell. Pham. 2009 1(2), 92-97.

Sun, H., Luo, X., Montalbano, J., Jin, W., Shi, J., Sheikh, M.S., Huang, Y. DOC45, a novel DNA damage-regulated nucleocytoplasmic ATPase that is overexpressed in multiple human malignacies. Submitted. 

Jin,W., Sun, Q., Rong, R., He, Q., Sheikh, M.S., Huang, Y. EMOC, a novel stress-regulated gene, encodes an endoplasmic reticulum transmembrane protein and is overexpressed in multiple human malignancies. Submitted.

This profile was last updated on 10/30/2009

A short link is available for this profile:
http://www.upstate.edu/pharm/faculty.php?ID=huangy

Return to Faculty List