Zefeng Wang

PhD, Pharmacology, UNC-Chapel Hill, Molecular Therapeutics

Zefeng Wang

UNC-Chapel Hill
Molecular Therapeutics

4097 Genetic Medicine Building

Area of interest

Human cancers are closely related to the alternative splicing of pre-mRNA. Specific splicing variants of many genes (such as CD44, WT1 and NF1) are associated with a variety of cancers and could be used as cancer markers. Many tumor suppressors like p53 and its paralogues, p63 and p73, have multiple splicing variants which have different activity. A splicing factor SF2/ASF that can mediate alternative splicing was found to be up-regulated in various human tumors. Over expression of this splicing factor SF2/ASF is sufficient to transform immortal rodent fibroblasts, which form sarcomas in nude mice. Other splicing factors probably have similar roles, suggesting the choice of different splicing variants could play important roles in tumorigenesis. Therefore to understand how alternative splicing is regulated is an indispensable branch in cancer research.

The long-term goal of our lab is to understand how splicing is regulated in a systematic level. Our main approach is to collect a part list of splicing regulation, and to further determine how they functionally interact to each other so that to assemble a set of general rules of splicing (i.e. the splicing code). Our research is also motivated by a major surprise from the sequencing of the human genome, which is the total number of protein coding genes is much lower than previously estimated. This finding indicated that additional genomic complexity might be added at the level of RNA processing. More than 60% of human genes undergo alternative splicing, which is tightly regulated in different tissues and developmental stages, the disruption of such regulation can cause various diseases including cancer. Like the transcriptional regulation, the splicing is regulated by trans-factors that either enhance or silence splicing. These trans-factors are recruited to pre-mRNA through binding to specific RNA sequences known as splicing regulatory cis-elements. Depending on the locations and effects on splicing, these cis-elements are defined as exonic splicing enhancer (ESE), exonic splicing silencer (ESS), intronic splicing enhancer (ISE) and intronic splicing silencer (ISS).

Awards and Honors

1990-1993 Scholarship for Academic Excellence, Tsinghua University, Beijing
1993-1994 Guang Hua scholarship, Tsinghua University, Beijing
1994 Graduate with highest honor from Tsinghua University, Beijing
1996-1997 DiAo scholarship, Chinese Academy of Science, Beijing
1999 Burroughs Wellcome Fellowship, Marine Biological Lab, Woods Hole, MA
2002 Paul Ehrlich Research Award, Johns Hopkins School of Medicine, Baltimore, MD
2003-2006 Damon Runyon Postdoctoral Fellowship, Damon Runyon Cancer Research Foundation
2006 NRMCB poster award for interdisciplinary science, 11th annual meeting of RNA Society
2007 RNA Society/Scaringe Young Scientist Award
2008-2010 Sloan Research Fellow, Alfred P. Sloan Foundation
2008-2011 Beckman Young Investigator, Arnold and Mabel Beckman Foundation
2009-2011 Sidney Kimmel Scholar Award, Sidney Kimmel foundation for cancer research

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