Ying Huang, MD, PhD
- Professor of Pharmacology
Research Programs and Affiliations
- Biomedical Sciences Program
- Cancer Research Institute
- Research Pillars
- Oncogenic signaling in cellular transformation and apoptosis; tumor suppressor genes.
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.
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. Identification 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. Idendtification and characterization of two novel isoforms of Pirh2 Ubiquitin ligase that negatively regulate p53 independent 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 differentially induces apoptosis in Smac-proficient and -deficient human colon 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 malignancies. Molecular Cancer Research, 2010, 8(1), 57-66.
He Q., Shi J., Shen X-L., An J., Sun H., Wang L., Hu Y-J., Sun Q., Fu L-C., Sheikh M.S., Huang Y. Dihydroartemisinin upregulates death receptor 5 expression and cooperates with TRAIL to induce apoptosis in human prostate cancer cells. Cancer Biology and Therapy, 2010, 9(10):819-24.
Jiang L., Luo X., Sun H., Sun Q., Sheikh M.S. Huang Y. PDRG1, a novel tumor marker for multiple malignancies that is selectively regulated by genotoxic stress. Cancer Biology and Therapy, 2011, 11 (6).
Jiang L., Rong R., Sheikh M.S., Huang Y. Cul4A-DDB1 E3 ligase complex targets tumor suppressor RASSF1A degradation during mitosis. J. Biol. Chem. 2011, 286(9), 6971-6978.
An J., Shi J., He Q., Lui K, Liu Y., Huang Y., Sheikh MS. CHCM1/CHCHD6, a novel mitochondrial protein linked to regulation of mitofilin and mitochondrial cristae morphology. J. Biol. Chem. J Biol Chem. 2012, 287(10):7411-26
Sun H., Jiang L., Luo X., Jin W., He Q., An J., Lui K., Shi J., Rong R., Su W., Lucchesi C., Liu Y., Sheikh M.S., Huang Y. Potential tumor suppressive role of Monoglyceride Lipase in human colorectal cancer. Oncogene, 2013, 3(2):234-41.
Jin, W., Sun, Q., Zou, J., Zhang, C., He, Q., Yang, Y.Y., Sheikh, M.S., Huang, Y. EMOC, a novel endoplasmic protein that regulates cell growth and Ca2+-operated channel. Submitted.
Lui, K., An, J., Montalbano, J., Shi, J., Corcoran, C., He, Q., Sun, H., Sheikh, M.S., Huang, Y. Negative regulation of p53 by Ras superfamily protein RBEL1A. Journal of Cell Science, 2013, in press.
Eric Wohlford received a 2012 travel award from the American Society of Tropical Medicine and Hygiene and spent two months in Kenya working in the lab of Rosemary Rochford, PhD, professor and chair of Upstate’s Department of Microbiology & Immunology. Eric studied the effects of malaria on B cells (producers of antibodies that fight infection) and Epstein-Barr Virus infection in the region. “Tropical medicine is unique, in that small, focused improvements in patient care make dramatic improvements in the well-being of patients,” he said.