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Faculty Detail Faculty Entry   
Name YI-PING LI  
Campus Address SHEL 810 Zip 0007
Phone 205-975-2606
E-mail ypli@uab.edu" id="FacultyDetail1EmailAddress"><a href="mailto:ypli@uab.edu">ypli@uab.edu</a>
URL http://bioinformatics.forsyth.org/ypli/index.html
 
 

Department Affiliations(s)
Appointment Type Department Division Rank
Center  Arthritis & Musculoskeletal Diseases Center  Arthritis & Musculoskeletal Diseases Center Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor
Primary  Pathology   Joint Pathology Professor

Biographical Sketch 
Dr. Yi-Ping Li is the endowed Jay McDonald Professor and senior Vice Director of the UAB Center for Metabolic Bone Disease. He is also an adjunct professor at The Forsyth Institute, which is affiliated with Harvard School of Dental Medicine. Before joining UAB, Dr. Li was a tenured senior member of the staff (Professor) in the Department of Cytokine Biology, at the Forsyth Institute, Harvard School of Dental Medicine. Dr. Li received his BS degree from Zhejiang University and his Ph.D. in Molecular Genetics from Shanghai Institute of Biochemistry, the Academy of Sciences of China. Dr. Li then pursued his postdoctoral research training in the laboratory of Dr. Philip Stashenko in the Department of Immunology at the Forsyth Institute.

Society Memberships
Organization Name Position Held Org Link
American Association for Dental Research  Member  http://www.iadr.com 
American Association for the Advancement of Science  Member  http://www.aaas.org 
American Society for Bone and Mineral Research  Member  http://www.asbmr.org 
American Society for Cell Biology   Member  http://www.ascb.org 
 

Research/Clinical Interest
Title
Investigating the mechanisms of skeletal and craniofacial development, tumorigenesis and cancer metastasis; as well as developing effective new therapies for the treatment and prevention of related diseases.
Description
Dr. Li’s research covers a large scope of topics, including bone biology, osteoimmunology, skeleto-muscular development, brain and craniofacial development, tumorigenesis and cancer metastasis, and anti-cancer drug discovery. These varied research interests have proven to be synergistic as there are overlapping themes and techniques. 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. The lab has a long history of experience with animal models, including mouse, chicken, and fly (drosophila) models. This is pivotal as we seek to understand basic biological processes and translate that knowledge into new diagnostics, preventions, treatments, and products. Some of the ongoing research projects in Dr. Li’s laboratory are summarized below:

1) Overactivity of osteoclasts and related diseases, such as osteoporosis. In past years, our lab discovered attractive targets in osteoclasts, such as cathepsin K (an enzyme specific to osteoclast function), ATP6i (an osteoclast-specific subunit of proton pump), and RGS10 (an essential regulator of osteoclast differentiation). Our goal is to further investigate these novel therapeutic targets to develop a means to cure or alleviate bone diseases such as osteoporosis, periodontal disease, and Paget's disease without the risk of osteonecrosis of the jaw. Specifically, we seek to reveal the mechanisms underlying the transcription factors that regulate osteoclast lineage commitment, differentiation, and function; and to discover the role of subunits of the osteoclast proton pump in osteoclast functions. As a complementary approach to curing or alleviating bone abnormalities, we seek to elucidate the molecular mechanisms of bone formation and osteoblast lineage commitment and differentiation.

2) Osteoimmunology in autoimmunity. Rheumatoid arthritis is an autoimmune disease of the synovium of the joints that causes intense pain and leads to swelling and the eventual deformation of the joints. We are working to determine the role of cathepsin K in autoimmunity and the immune system in general with the hopes that we can target this gene to treat a number of osteoimmunologically related diseases, including oral inflammation and periodontitis as well as rheumatoid arthritis. We are developing a novel RNAi that will simultaneously prevent tissue damage & bone loss by reducing the inflammation & bone resorption caused by oral diseases, rheumatoid arthritis, or osteoarthritis through AAV (Adeno-associated virus) mediated silencing of ATP6i. The dual function of Atp6i gene products makes it an ideal target for knockdown in order to diminish inflammation-induced bone loss associated with periodontitis, endodontic disease, and rheumatoid arthritis.

3) Gene therapy, cell therapy, and tissue regeneration. Using adeno-associated virus (AAV) mediated gene knockdown and overexpression, our lab aims to develop a novel therapeutic tool for gene therapy for multiple diseases and multi-tissue injuries. AAV-mediated forced expression of Cnbp in muscle cells may be therapeutic since the reduction of Cnbp levels in Cnbp+/- mice is sufficient to produce symptoms that mimic human DM2. We are also using AAV technology to reprogram the genetic profile of human mesenchymal stem cells so that they can be induced to regenerate a variety of tissues and improve wound repair. AAVs have been successfully used clinically, making this research directly applicable to future clinical trials.

4) Embryonic development and birth defects. Craniofacial malformations are involved in three fourths of all congenital birth defects in humans, affecting the development of head, face, or neck. We have found that null mutation of CNBP is embryonically lethal and results in defects in anterior patterning, that CNBP may control forebrain induction through Myc, and that CNBP knockdown during early organogenesis resulted in forebrain truncation. Overall, this research promises to provide deeper insight into the mechanisms of embryonic development, a prerequisite for the eventual diagnosis and treatment of human craniofacial developmental defects.

5) Cancer bone metastases. In the later stages of the disease, both breast and prostate cancer tend to metastasize to bone, causing excruciating pain and leading to broken bones through bone degeneration. In fact, 70% of late stage breast cancer patients have bone metastases. Thus far, our studies have shown that wild-type mice injected with 4T1 (allogenic) cells intraosseous showed persistent latent carrying of the cells in the bone, while injections on RGS10 knockout mice didn’t. We have also found that knockdown of osteoimmune genes reduces tumor bone metastasis & protects mice from death following melanoma xenograft The goal of this project is to discover the fundamental features of cancer bone metastasis and to develop a therapeutic means to eliminate bone metastases.

6) Breast cancer and prostate cancer stem cells. Certain cancer cells are known as cancer "stem cells" for their ability to regenerate and self-propagate indefinitely. These cancer cells are more likely than other cancer cells to develop new tumors if transplanted into a new, compatible host. Our lab is interested in determining their identifying characteristics, especially in prostate and breast cancers, where they share a special relationship with the body's own stem cells. This relationship may be related to their ability and propensity for metastasizing to the bone, from which our blood cells derive, and may be targeted not only to block metastasis to the bone but inhibit overall cancer growth, recurrence, and metastasis.

7) The role of epigenetic regulators in tumorigenesis and tumor metastasis. We are working on uncovering the role of epigenetic factors in tumorigenesis and tumor metastasis. We have developed an AAV-mediated gene knockdown system that may serve as a therapeutic alternative for human breast cancer bone metastasis. This would provide us with the ability not only to eliminate tumors, but also to correct other hyperplastic disorders as well.

8) Drug discovery of a novel anti-tumor drug targeting breast cancer blood vessels with low toxicity. The overall goal of this research is to radically reduce the burdens of breast cancer by developing a novel vascular disrupting agent (VDA) that selectively and potently targets tumor vessels with minimal toxic side-effects. We are currently developing this drug and investigating the molecular mechanism of its antitumor effects. This study is likely to result in the debut of a revolutionary drug and the beginning of a new class of VDAs that incorporate new found characteristics that enable high anti-cancer potency and low cytotoxicity like never before.

Postdoc Positions Available
Date Posted Position Title
10/01/2010  Postdoc 
Please send a CV, three reference names and a brief statement of your research interests to Dr. Yi-Ping Li at ypli@uab.edu   
 

Selected Publications 
Publication PUBMEDID
*In these papers, Li Y-P is correspondence author.  0123456789 
*Chen W, Zhu G, Hao L, Wu M, Ci HL, and Li YP. C/EBPa is the Key Regulator of Osteoclast Lineage Commitment. Proc Natl Acad Sci U S A. PNAS 2013 ; published ahead of print  23580622 
*Jiang HB, Chen W, Zhu G, Zhang L, Tucker B, Hao L, Feng S, Ci H, Ma J, Wang L, Stashenko P, and Li YP. RNAi-Mediated Silencing of Atp6i and Atp6i Haploinsufficiency Prevents Both Bone Loss and Inflammation in a Mouse Model of Periodontal Disease. PLOS ONE. 2013;8(4):e58599.  23577057 
*Bo Gao, Wei Chen, Liang Hao, Guochun Zhu, Shengmei Feng, Hongliang Ci, Xuedong Zhou, Philip Stashenko and Li Y-P. Inhibiting periapical lesions through AAV-RNAi silencing of Cathepsin K. J Dent Res 2013; 92 (2): 180 - 186.   23166044 
Yang S, Li YP, Liu T, He X, Yuan X, Li C, Cao J, Kim Y. Mx1-Cre mediated Rgs12 conditional knockout mice exhibit increased bone mass phenotype. Genesis. 2013 Mar;51(3):201-9.  23349096 
*Ma, J, Chen W, Zhang L, Tucker B, Zhu G, Sasaki H, Hao L, Wang L, Ci H, Jiang H, Stashenko P, and Li YP. RNAi mediated silencing of Atp6i prevents both periapical bone erosion and periapical inflammation in the mouse model of endodontic disease. Infection and Immunity. 2013; 81 (4): 1021–1030.  23166162 
*Wu M, Wang Y, Deng LF, Chen W, Li Y-P. TRAF Family Member-Associated NF-kB Activator (TANK) Induced By RANKL Negatively Regulates Osteoclasts Survival and Function. Int J Biol Sci 2012; 8(10):1398-1407.   23139637 
*Yang DQ, Feng S, Chen W, Zhao H, Paulson C, Li YP. V-ATPase subunit ATP6AP1 (Ac45) regulates osteoclast differentiation, extracellular acidification, lysosomal trafficking, and protease exocytosis in osteoclast-mediated bone resorption. J Bone Miner Res. 2012 Aug;27(8):1695-707.   22467241 
*Chen G, Deng C, Li YP. TGF-beta; and BMP Signaling in Osteoblast Differentiation and Bone Formation. Int J Biol Sci. 2012;8(2):272-88. Epub 2012 Jan 21.   22298955 
Zuo C, Huang Y, Bajis R, Sahih M, Li YP, Dai K, Zhang X. Osteoblastogenesis regulation signals in bone remodeling. Osteoporos Int. 2012 Jan 31. [Epub ahead of print]   22290242 
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Keywords
Osteoclasts, Osteoblasts, Bone formation and bone resorption, Skeletal development, Tumorigenesis, Cancer bone metastasis, Muscular development, Brain and craniofacial development, Skeleto-muscular disease, and Anti-cancer drug discovery

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