|Last Name: ||Zheng|
|First Name: ||Qiping|
|M. I.: |
|Degree & Certifications: ||PhD|
|Endowed Professorship: |
|Rank & Title: ||Assistant Professor |
|Department: ||Anatomy and Cell Biology|
|College: ||Graduate College, Rush Medical College|
|Office Location: ||1750 W. Harrison Street|
Suite 1303 Jelke
Chicago IL, 60612
|Laboratory Location: ||1750 W. Harrison Street|
Suite 1306 Jelke
Chicago IL, 60612
|Phone: ||(312) 942-5514|
|Fax: ||(312) 942-5744|
|Education: ||PostD Skeletal Dev. Genetics, Baylor College of Medicine, Houston, 1999-2004|
PhD Human Molecular Genetics, Fudan University, Shanghai, China, 1998
MS, Suzhou Medical College, China, 1990
MD, Anhui Medical University, China, 1987
|Research Areas: ||Biological Sciences, Genetic Phenomena, Genetic Processes, Musculoskeletal Diseases|
|Laboratory Techniques: ||Animal surgery/Modeling, Bioinformatics, Gene Transfection, Imaging Techonology, Immunohisto-/immunocytochemistry, In Situ Hybridization, Microscopy (Electron Transmission Fluorescence Confocal), PCR, Proteomics, Real-time PCR, si RNA, Spectrophotometry, Transgenic Animal Technology/Microinjection, Western Northern Southern Blotting|
|Faculty/Staff Description: ||
My lab has a long-standing research interest in understanding the molecular mechanisms that regulate tissue-specific type X collagen gene (Col10a1) expression and chondrocyte maturation (hypertrophy) during skeletal development. The type X collagen gene is specifically expressed when chondrocytes undergo hypertrophy, a critical stage of endochondral bone formation linking both bone and cartilage development. Abnormal Col10a1 expression and chondrocyte maturation have been observed in multiple skeletal diseases, such as Cleidocranial Dysplasia (CCD), Schmid Metaphyseal Chondrodysplasia (SMCD), osteoarthritis, and possibly, bone cancer (osteosarcoma) formation. My goals are to characterize the specific regulators for Col10a1 expression and chondrocyte maturation during skeletal development and diesease progression. Specifically,
1), Characterize the molecular network regulating cell-specific Col10a1 expression.
We have previously shown that a 4-kb Col10a1 proximal promoter containing conserved Runx2 binding sites can only direct week reporter expression in hypertrophic chondroyctes (Zheng et al., JCB, 2003). Our recent results demonstrated that a 150-bp Col10a1 distal promoter/cis-enhancer containing a tandem-repeat Runx2 bindings sites is able to direct high-level cell-specific Col10a1/reporter expression in vivo (Zheng et al., JBMR, 2009; Li et al., JBMR, 2011). We have also shown that these Runx2 sites are required but not sufficient to confer cell-specific Col10a1 promoter activity suggesting requirement of additional transactivators or repressors for Col10a1 tissue-specificity (Li et al., JBMR, 2011). Characterization of the putative molecular network, centered by Runx2, that regulates hypertrophic chondrocyte-specific Col10a1 expression are expected to identify potential therapeutic targets for multiple skeletal diseases showing altered Col10a1 expression and chondrocyte maturation.
2), Delineate the correlation of chondrocyte maturation with osteoarthritis progression.
Both Runx2 and Col10a1 genes have been associated with osteoarthritis (OA). We and others have shown that Runx2 regulates cell-specific Col10a1 expression in different species (Li et al., JBMR, 2011). We have also shown that targeting Runx2 expression in hypertrophic chondrocytes results in delayed chondrocyte maturation in transgenic mice (Ding et al., JCP, 2012). Interestingly, these transgenic mice are chondro-protective when subjected to TGfb1 injection and treadmill overrunning to induce OA. Regulated Col10a1 expression by Runx2 may play a role in chondrocyte maturation and have an impact on initiation and progression of OA. Further delineation of the correlation of chondrocyte maturation with OA progression will help to identify novel regulators as potential therapeutic targets for OA.
3), Osteosarcoma translational research.
Osteosarcoma (OS) is the most common bone cancer in children and young adults. It is also the leading cause of cancer death in this age group. The characteristic feature of OS is the abnormal bone formation in its tumor tissue. We surmise that chondrocyte maturation, a critical stage of cartilage development during endochondral bone formation, may be involved in OS tumorigenesis. We have generated unique Col10a1-Runx2 (Ding et al., JCP, 2012) and Col10a1-P63 (Li et al., Gene, under review) mouse models that show either delayed or accelerated chondrocyte maturation and apoptosis. These mouse models allow us to genetically determine how chondrocyte maturation affects OS progression in a p53 and pRb deficient OS mouse model (Walkley et al., 2008). We will also analyze candidate genes relating to both OS pathogenesis and chondrocyte maturation in human OS tissues. Such translational studies will advance our understanding of OS etiology and help the prevention and treatment of OS.