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Faculty Detail    
Name YI-PING LI
 
Campus Address SHEL 810 Zip 0007
Phone 205-975-2606
E-mail ypli@uab.edu
Other websites http://bioinformatics.forsyth.org/ypli/index.html
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Pathology   Molecular & Cellular Pathology Professor
Secondary  Periodontology  Periodontology Professor
Center  Arthritis & Musculoskeletal Diseases Center  Arthritis & Musculoskeletal Diseases Center Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor

Graduate Biomedical Sciences Affiliations
Cancer Biology 
Cell, Molecular, & Developmental Biology 
Integrative Genetics Graduate Program 
Molecular and Cellular Pathology Program 
Pathobiology and Molecular Medicine 

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. Liís 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. Liís 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 didnít. 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.

Selected Publications 
Publication PUBMEDID
Mengrui Wu, Chenguan Li, Guochun Zhu, Yiping Wang, Joel Jules, Yun Lu, Matthew McConnell, Yong-Jun Wang, Jian-Zhong Shao, Li Y-P, and Wei Chen. Chondrocyte-specific knockout of Cbfb reveals the indispensable function of Cbfb in chondrocyte maturation, growth plate development and trabecular bone formation in mice. Int J Biol Sci. 2014 (In Press).   
Mengrui Wu, Li Y-P, Guochun Zhu, Yun Lu, Yiping Wang, Joel Jules, Matthew McConnell, Rosa Serra, Jian-Zhong Shao, Wei Chen. Deletion of Core-binding factor b (Cbfb) in mesenchymal progenitor cells provides new insights into Cbfb/Runxs complex function in cartilage and bone development. Bone. 2014 May 4;65C:49-59. doi: 10.1016/j.bone.2014.04.031. [Epub ahead of print]  24798493 
Chen W, Ma J, Zhu G, Jules J, Wu M, McConnell M, Zhou X, Tain F, Paulson C, Wang L, and Li YP. Cbfb Deletion in Mice Recapitulates Cleidocranial Dysplasia and Reveals Multiple Functions of Cbfb; Required for Skeletal Development. Proc Natl Acad Sci U S A. PNAS. 2014 May 21. pii: 201310617. [Epub ahead of print]  24850862 
Keinan D, Yang S, Cohen RE, Yuan X, Liu T, Li YP. Role of regulator of G protein signaling proteins in bone. Front Biosci (Landmark Ed). 2014 Jan 1;19:634-48.  24389209 
Fei Tian, Mengrui Wu, Deng L, Zhu G, Ma J, Gao B, Wang L, Li YP, Chen W. Core binding factor beta (Cbfb) controls the balance of chondrocyte proliferation and differentiation by up-regulating Indian hedgehog (Ihh) expression and inhibiting parathyroid hormone-related protein Receptor (PPR) expression in postnatal cartilage and bone formation .J Bone Miner Res. 2014 May 12. doi: 10.1002/jbmr.2275. [Epub ahead of print]  24821091 
Wang Y, Li Y-P, Christie Paulson, Jian-Zhong Shao, Xiaoling Zhang, Mengrui Wu, and Wei Chen. Wnt and the Wnt Signaling Pathway in Bone Development and Disease. Frontiers Biosci 2014 Jan 1;19:379-407.  24389191 
Chen GQ, Zhuang QY, Wang KC, Liu S, Shao JZ, Jiang WM, Hou GY, Li JP, Yu JM, Li Y-P, Chen JM. Identification and survey of a novel avian coronavirus in ducks. PLoS One. 2013 Aug 30; 8(8):e72918.  24023656 
Feng S, Guochun Zhu, Matthew McConnell, Lianfu Deng, Qiang Zhao, Mengrui Wu, Qi Zhou, Jinshen Wang, Jin Qi, Li Y-P,and Wei Chen. Silencing of Atp6v1c1 Prevents Breast Cancer Growth and Bone Metastasis. International Journal of Biological Sciences 2013; 9(8): 853-862.  24155661 
Yang S, Liang Hao, McConnell Matthew, Xuedong Zhou, Min Wang, Xiaoyi Wang2 Li Y-P,Wei Chen. AAV RGS10 RNAi inhibits immune cells infiltration in periodontal disease lesion and prevents bone erosion by osteoclasts. Bone Research (2013) 3: 267-281.  24761229 
Chen W, Zhu G, Hao L, Wu M, Ci HL, and Li Y-P. C/EBPa is the Key Regulator of Osteoclast Lineage Commitment. Proc Natl Acad Sci U S A. PNAS. 2013; 110(18):7294-9.  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 
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 
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 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 
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 
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 
Qin B, Wang Y, Liu S, Li Y-P. Osteoarthritis: genetic factors, animal models, mechanisms, and therapies. Frontiers Biosci. Front Biosci (Elite Ed). 2012 Jan 1;4:74-100   22201856 
Haoa X, Wangb Y, Renb F, Zhub S, Renb Y, Jiac B, Li Y-P, Shie Y, Changa Z. SNX25 regulates TGF-beta signaling by enhancing the receptor degradation. Cell Signal. 2011; 23(5):935-46.   21266196 
Raheem O, Olufemi S-E, Bachinski L, Vihola A, Sirito M, Holmlund-Hampf J, Haapasalo H, Li Y-P, Udd B, Krahe R. Mutant (CCTG)n Expansion Causes Abnormal Expression of Zinc Finger Protein 9 in Myotonic Dystrophy Type 2. Am J Pathol. 2010;177:3025-36.   20971734 
Horst D, Gu X, Bhasin M, Yang Q, Verzi M, Lin D, Joseph M, Zhang X, Chen W, Li Y-P, Shivdasani1 RA, Libermann TA. Requirement of the Epithelial-Specific Ets Transcription Factor Spdef for Mucous Gland Cell Function in the Gastric Antrum. J Biol Chem. 2010; 285:35047-35055   20801882 
Li C, Li Y-P, Fu X-Y, Deng C-X. Anterior Visceral Endoderm SMAD4 Signaling Specifies Anterior Embryonic Patterning and Head Induction in Mice. Int J Biol Sci 2010;6:569-583.   20941375 
Wu M, Deng L, Zhu G, Li Y-P. G Protein and Its Signaling Pathway in Bone Development and Disease. Frontiers Biosci. Frontiers Biosci. 2010;15:957-85   20515736 
Soltanoff CS, Chen W, Yang S, Li Y-P. The signaling networks that control the lineage commitment and differentiation of bone cells. Crit. Rev. Eukaryot. Gene Exp. 2009 19: (1)1-46.   19191755 
Wu, H; Xu, G; Li Y-P. Atp6v0d2 is an essential component of the osteoclast-specific proton pump and has a function in extracellular acidification. J Bone Miner Res 2009. 24:1–15.   19113919  
Feng M, Deng , Chen W, Shao J, Xu G, Li Y-P. Atp6v1c1 is an essential component of the osteoclast proton pump and in F-actin ring formation in osteoclast. Biochem J 2009; 417 (1) 195-205.   18657050 
Tu Q, Zhang J, Fix A, Brewer E, Li YP, Zhang ZY, Chen J. Targeted overexpression of BSP in osteoclasts promotes bone metastasis of breast cancer cells. J Cell Physiol 2008; 218(1):135-45.   18756497 
Yang S, Chen W, Stashenko P, Li Y-P. Specificity of RGS10A as a key component in the RANKL signaling mechanism for osteoclast differentiation. J Cell Sci 2007;120:3362-71.   17881498 
Yang S, Li Y-P. RGS10 null mutation impairs osteoclast differentiation resulting from the loss of [Ca2+]i oscillation regulation. Genes Dev 2007;21(14):1803-16.   17626792 
Chen W, Wang Y, Abe Y, Cheney L, Udd B, Li Y-P. Haploinsuffciency for Znf9 in Znf9+/- mice is associated with multiorgan abnormalities resembling myotonic dystrophy. J Mol Biol 2007;368(1):8-17.   17335846 
Huang W, Shao J, Li Y-P. Osteoblast differentiation and gene regulation. Frontiers Biosci 2007;12:3068-92.   
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 
Chen W, Yang S, Abe Y, Li M, Wang Y, Shao J, Li E, Li Y-P. Novel pycnodysostosis mouse model uncovers cathepsin K function as a potential regulator of osteoclast apoptosis and senescence. Hum Mol Genet 2007;16:410-23.   17210673 
Yang S, Li Y-P. RGS12 is essential for RANKL-evoked signaling for terminal differentiation of osteoclasts. J Bone Miner Res 2007;22(1):45-54.   17042716 
Kawai T, Matsuyama T, Hosokawa Y, Makihira S, Seki M, Karimbux NY, Goncalves RG, Valverde P, Dibart S, Li Y-P, Miranda LA, Ernst CWO, Izumi Y, Taubman MA. B and T lymphocytes are the primary sources of RANKL in the bone resorptive lesion of periodontal disease. Am J Pathol 2006;169(3):987-98.   16936272 
Abe Y, Chen W, Huang W, Li Y-P. CNBP regulates forebrain formation at organogenesis stage in chick embryos. Dev Biol 2006;295(1):116-27.   16626683 
Ogbureke KUE, Zhao Q, Li Y-P. Human osteopetrosis and the osteoclast V-H+ ATPase system. Frontiers Biosci 2005;10:2940-54.  15970548 
Kamolmatyakul S, Chen W, Yang S, Abe Y, Moroi R, Ashique AM, Li Y-P. IL-1alpha stimulates cathepsin K expression in osteoclasts via the tyrosine kinase-NF-kappaB pathway. J Dent Res 2004;83(10):791-6.   15381721 
Shimizu K, Chen W, Ashique AM, Moroi R, Li Y-P. Molecular cloning, developmental expression, promoter analysis and functional characterization of the mouse CNBP gene. Gene 2003;307:51-62.   12706888 
Kamolmatyakul S, Chen W, Li Y-P. Interferon-gamma down-regulates gene expression of cathepsin K in osteoclasts and inhibits osteoclast formation. J Dent Res 2001;80(1):351-5.   11269728 
Chen W, Liang Y, Deng W, Shimizu K, Ashique AM, Li E, Li Y-P. The zinc-finger protein, CNBP, is required for forebrain formation in the mouse. Development 2003;130(7):1367-79.   12588852 
Deng W, Stashenko P, Chen W, Liang Y, Shimizu K, Li Y-P. Characterization of mouse Atp6i gene, the gene promoter, and the gene expression. J Bone Miner Res 2001;16(6):1136-46.   11393791 
Li Y-P, Chen W, Liang Y, Li E, Stashenko P. Atp6i-deficient mice exhibit severe osteopetrosis due to loss of osteoclast-mediated extracellular acidification. Nature Genetic. 1999;23(4):447-51.   10581033 
Li Y-P, Chen W. Characterization of mouse cathepsin K gene, the gene promoter, and the gene expression. J Bone Miner Res 1999;14(4): 487-99.   10234569 
Chen W, Li Y-P. Generation of mouse osteoclastogenic cell lines immortalized with SV-40 large T antigen. J Bone Miner Res 1998;13(7):1112-23.   9661075 
Li Y-P, Chen W, Stashenko P. Molecular cloning and characterization of a putative novel human osteoclast-specific 116-kDa vacuolar proton pump subunit. Biochem Biophys Res Commun 1996;218(3):813-21.   8579597 
Li Y-P, Chen W, Stashenko P. Characterization of a silencer element in the first exon of the human osteocalcin gene. Nucleic Acids Res 1995;23:5064-72.  8559666 
Li Y-P, Alexander M, Wucherpfennig AL, Yelick P, Chen W, Stashenko P. Cloning and complete coding sequence of a novel human cathepsin expressed in giant cells of osteoclastomas. J Bone Miner Res 1995;10:1197-1202.  8585423 
Wucherpfennig AL, Li Y-P, Stetler-Stevenson WG, Rosenberg AE, Stashenko P. Expression of 92-kDa type IV collagenase/gelatinase B in human osteoclasts. J Bone Miner Res 1994;9:549-56.  8030443 
Stashenko P, Nguyen L, Li Y-P. Mechanisms of regulation of bone formation by proinflammatory cytokines. In: Genco R et al, editors. Molecular Pathogenesis of Periodontal Disease. American Society for Microbiology; 1994. p. 171-181.   

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