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Toxicology

General

Education

Research

Hsin-Sheng Yang

Assistant Professor
Graduate Center for Toxicology

Mailing Address:

Graduate Center for Toxicology
1095 V.A. Drive
306 Health Sciences Research Building
Lexington, KY  40536-0305
Office: 348 HSRB
Phone: (859) 323-6684
Fax: (859) 323-1059
E-mail: hyang3@uky.edu

Research Interests

The interest of my laboratory is to study gene regulation events that occur during multistage carcinogenesis and to target these events for cancer prevention and therapeutics. Specifically, we focus on studying the molecular action of a novel tumor suppressor Programmed cell death 4 (Pdcd4) in inhibiting tumor promotion and progression.

The current project in my laboratory is to investigate the molecular mechanism of how Pdcd4 suppresses colon tumor invasion. Pdcd4 is a highly conserved protein in mammalian cells and expressed in most tissues. Over-expressing pdcd4 cDNA in invasive colon carcinoma RKO cells significantly and negatively impacted invasion, as evinced by decreased ability to penetrate a Matrigel barrier, reduced cell migration, and diminished extracellular matrix (ECM) proteinase activity when compared to RKO control cells with empty vector. In addition, over-expression of sense pdcd4 reduces the activation of JNK, c-Jun, and AP-1 in RKO cells. These findings lead us to hypothesize that Pdcd4 suppressing invasion of colon cancer cells is through inhibition of JNK signaling pathway and AP-1 activation.

The other research focus in my laboratory is to understand how Pdcd4 is down-regulated during lung tumor progression. Immunohistochemical analyses of primary lung tumor tissues indicate that the higher stage or grade of lung tumors express lower Pdcd4 protein level when compared to normal lung tissues. Northern blot and RT-PCR analyses of cultured lung carcinoma cells also showed that Pdcd4 expression is down-regulated in both non-small cell lung carcinomas (NSCLCs) and small cell lung carcinomas (SCLCs). Likewise, protein expression patterns from the NCI 60 human cancer cell lines show that the more progressed cancer cells have the less Pdcd4 protein. Most importantly, a higher Pdcd4 protein level correlates with a good prognosis in lung cancer patients. These findings suggest that elevating the expression of Pdcd4 has the potential to suppress lung tumor progression and prolong survival for the lung cancer patient. It would be of high interest to determine the molecular basis for down regulation of Pdcd4 at gene, mRNA, and protein levels in lung cancer cells.

For a list of Dr. Yang's publications, please visit the PubMed web site.

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Page last updated Thursday, August 16, 2012