Yi-Ping Li, PhD
Jay McDonald-Endowed Professor of Pathology
Senior Vice Director, UAB Center for Metabolic Bone Disease
|Address:||1825 University Blvd
Shelby Building, 810
Birmingham, AL 35294
|Members of the Laboratory|
B.S., Zhejiang University, P.R. China, 1979
Ph.D. (Molecular Genetics), Shanghai Institute of Biochemistry, the Academy of Sciences of China, P.R. China, 1988
Post-doctoral Research Training (Medical Genetics), Department of Immunology at the Forsyth Institute, Harvard School of Dental Medicine, Boston, 1990-1993
Bone formation and bone resorption are physiologically controlled by the activities of osteoblasts and osteoclasts. Imbalances in these activities can arise from a variety of hormonal or inflammatory perturbations, resulting in skeletal abnormalities characterized by decreased bone mass, as in osteoporosis, or increased bone mass, in osteopetrosis. Increased osteoclast activity is seen in many osteopenic disorders, including postmenopausal osteoporosis, Paget's disease, bone metastases, periodontitis, and rheumatoid arthritis.
Dr. Yi-Ping Li was one of the first scientists to apply molecular biology approaches to the study of osteoclasts. His work resulted in the publication of a number of seminal papers on the cloning and characterization of genes critical to osteoclast function, including cathepsin K, ATP6i, and RGS10A. His work has also resulted in the awarding of 6 patents. Additional research interests include brain and craniofacial development and related diseases, skeleto-muscular development and related diseases, tumorigenesis and cancer bone metastasis, and anti-cancer drug discovery.
The objectives of research in the Li laboratory are: (1.) To reveal the mechanisms underlying the transcription factors that regulate osteoclast lineage commitment, differentiation, and function. We have determined the essential and dose-dependent role of a number of transcription factors in osteoclast lineage commitment, differentiation, activation, and function. (2.) To discover the role of subunits of the osteoclast proton pump (SOPP) in osteoclast functions (e.g., osteoclast-mediated extracellular acidification, membrane trafficking, exocytosis) and to elucidate their potential role in developing a means to cure or alleviate human osteolytic diseases. Previously, we have shown that inactivation of subunit a3 (also known as ATP6V0A3 or TCIRG1) leads to osteopetrosis in mice because of nonfunctional osteoclasts that are incapable of acidifying the extracellular resorption lacuna. Knockdown of subunits d2 (ATP6V0D2), C1 (ATP6V1C1), and Ac45 (ATP6AP1) resulted in defects in osteoclast function. We have characterized the unique isoform of the proton pump responsible for osteoclastic bone resorption. (3. ) To understand signal transduction and the ways in which it controls osteoclast differentiation and function. We characterized the response of osteoclast signaling pathways to RANKL and revealed the role of RGS10 as a critical regulator in the RANKL-evoked RGS10/calmodulin-PLCγ-[Ca2+]i oscillation-NFATc1 signaling pathway for osteoclast differentiation. (4. ) To elucidate the mechanism of bone formation and develop a means to cure or alleviate bone abnormalities such as osteoporosis. Attractive targets are osteoblast cells, which increase bone formation. Our previous work shows that cellular nucleic acid binding protein (CNBP) is expressed in all stages of osteoblast lineage. Furthermore, we have demonstrated that CNBP is located in both the nucleus and the cytoplasm, which indicates that it may be a dual regulator of transcription and translation. (5. ) To identify how cellular nucleic acid binding protein (CNBP) and other transcription factors regulate craniofacial development and disease and to expand our understanding of the biological and molecular basis of craniofacial morphogenesis. We have characterized the functions of CNBP in head formation in chicken and mouse models through gene knockout misexpression and tissue-specific targeted disruption approaches. (6. ) To develop novel means that will simultaneously prevent tissue damage and bone loss by reducing the inflammation and bone resorption caused by oral infectious and inflammatory diseases. We are developing a therapeutic tool for periodontal and endodontic diseases using AAV (Adeno-associated virus) mediated gene knockdown and overexpression. (7. ) To define the role of Znf9 in myotonic dystrophy type 2 (DM2) and muscle development. We characterized Znf9+/- mice and found that their phenotype reflects many of the features in myotonic dystrophy. Znf9 is highly expressed in skeletal and heart muscle. Our data demonstrated that Znf9 haploinsufficiency might contribute to the myotonic dystrophy phenotype in Znf9+/- mice. (8. ) To discover and develop a novel anti-cancer drug that acts as a vascular disrupting agent (VDA) to selectively target tumor vessels --a drug which harbors significant anti-vascular capabilities and minimal toxic side-effects. We have identified a remarkable new drug that powerfully acts against tumors, while circumventing the difficulties and adverse effects of conventional antitumor treatments. We are currently developing this drug and investigating the molecular mechanism of its antitumor effects. (9. ) To investigate stem cell reprogramming for tissue regeneration and organogenesis. We are currently investigating if gene profile reprogrammed human mesenchymal stem cells (hMSCs) seeded on scaffolding biomaterial will mimic natural tissue generation and enable improved tissue regeneration and maxillofacial wound repair. We have already identified some key transcription factors that will be used. This concept is of vital importance since hMSCs are the major stem cells that can be realistically obtained from adults and since only autologous (patient's own) stem cells can be used therapeutically. (10. ) To characterize the molecular mechanisms of tumorigenesis and cancer bone metastasis, and to development new diagnostic and therapeutic alternatives for human cancer metastasis. We have defined a new tumor suppressor gene and the role of its mutation in prostate metastasis. We have developed an AAV-mediated gene knockdown system that may serve as a therapeutic alternative for human breast cancer bone metastasis.
- Last Updated on June 25, 2013