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Faculty Detail    
Name YI-PING LI
  
Campus Address SHEL 810 Zip 0007
Phone  (20-5) -606
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  Comp Arthritis, MSK, Bone & Autoimmunity Ctr  Comp Arthritis, MSK, Bone & Autoimmunity Ctr Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor

Graduate Biomedical Sciences Affiliations
Cancer 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. 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.

Selected Publications 
Publication PUBMEDID
Wang Y, Chen W, Hao L, McVicar A, Wu J, Gao N, Liu Y, Li YP. C1 Silencing Attenuates Inflammation and Alveolar Bone Resorption in Endodontic Disease. J Endod. 2019 Jul;45(7):898-906. doi: 10.1016/j.joen.2019.02.024. Epub 2019 May 16. PMID: 31104818
 		 31104818 
Li Z, Liu T, Gilmore A, Gómez NM, Fu C, Lim J, Yang S, Mitchell CH, Li YP, Oursler MJ, Yang S. Regulator of G Protein Signaling Protein 12 (Rgs12) Controls Mouse Osteoblast Differentiation via Calcium Channel/Oscillation and Gai-ERK Signaling. J Bone Miner Res. 2019 Apr;34(4):752-764. doi: 10.1002/jbmr.3645. Epub 2019 Jan 28. PubMed PMID: 30489658.  30489658 
Guo S, Zhang Y, Zhou T, Wang D, Weng Y, Chen Q, Ma J, Li YP, Wang L. GATA4 as a novel regulator involved in the development of the neural crest and craniofacial skeleton via Barx1. Cell Death Differ. 2018 Nov;25(11):1996-2009. doi: 10.1038/s41418-018-0083-x. Epub 2018 Mar 9. PubMed PMID: 29523871; PubMed Central PMCID: PMC6219484.  29523871 
Chen J, Deng L, Porter C, Alexander G, Patel D, Vines J, Zhang X, Chasteen-Boyd D, Sung HJ, Li YP, Javed A, Gilbert S, Cheon K, Jun HW. Angiogenic and Osteogenic Synergy of Human Mesenchymal Stem Cells and Human Umbilical Vein Endothelial Cells Cocultured on a Nanomatrix. Sci Rep. 2018 Oct 24;8(1):15749. doi: 10.1038/s41598-018-34033-2. PubMed PMID: 30356078; PubMed Central PMCID: PMC6200728.  30356078 
Huang H, Wang J, Zhang Y, Zhu G, Li YP, Ping J, Chen W. Bone resorption deficiency affects tooth root development in RANKL mutant mice due to attenuated IGF-1 signaling in radicular odontoblasts. Bone. 2018 Sep;114:161-171. doi: 10.1016/j.bone.2017.12.026.  29292230 
Chen W, Zhu G, Jules J, Nguyen D, Li YP. Monocyte-specific knockout of C/ebpa results in osteopetrosis phenotype, blocks bone loss in ovariectomized mice and reveals an important function of C/ebpa in osteoclast differentiation and function. J Bone Miner Res. 2018 Apr;33(4):691-703. doi: 10.1002/jbmr.3342.   29149533 
Chen W, Zhu G, Tang J, Zhou HD, Li YP. C/ebpa controls osteoclast terminal differentiation, activation, function, and postnatal bone homeostasis through direct regulation of Nfatc1. J Pathol. 2018 Mar;244(3):271-282. doi: 10.1002/path.5001.  29083488  
Jules J, Li YP, Chen W. C/EBPa and PU.1 exhibit different responses to RANK signaling for osteoclastogenesis. Bone. 2018 Feb;107:104-114. doi: 10.1016/j.bone.2017.05.009.
 		 29032174 
Jules J, Chen W, Feng X, Li YP. C/EBPa is Regulated by the RANK Cytoplasmic IVVY535-538 Motif and Stimulates Osteoclastogenesis more Strongly than c-Fos. J Biol Chem. 2018 Jan 26;293(4):1480-1492. doi: 10.1074/jbc.M116.736009.   29122885 
Wu M, Wang Y, Shao JZ, Wang J, Chen W, Li YP. Cbfb governs osteoblast-adipocyte lineage commitment through enhancing b-catenin signaling and suppressing adipogenesis gene expression. Proc Natl Acad Sci U S A. 2017 Sep 19;114(38):10119-10124.   28864530  
Wu M, Chen W, Lu Y, Zhu G, Hao L, Li YP. Ga13 negatively controls osteoclastogenesis through inhibition of the Akt-GSK3b;-NFATc1 signalling pathway. Nature Communication. 2017 Jan 19;8:13700.   28102206 
Pan J, Wang J, Hao L, Zhu G, Nguyen DN, Li Q, Liu Y, Zhao Z, Li YP, Chen W. The Triple Functions of D2 Silencing in Treatment of Periapical Disease. Journal of endodontics. 2017 Feb 28; 43(2):272-8.   28132712 
Matthew McConnell, Shengmei Feng, Wei Chen, Guochun Zhu, Dejun Shen, Selvarangan Ponnazhagan, Lianfu Deng,, and Yi-Ping Li. Osteoclast proton pump regulator Atp6v1c1 enhances breast cancer growth by activating the mTORC1 pathway and bone metastasis by increasing V-ATPase activity. Oncotarget. 2017 Jul 18;8(29):47675-47690.  28504970 
Ping Z, Siegal GP, Harada S, Eltoum IE, Youssef M., Shen T, He J, Huang Y, Chen D, Li Y, Bland KI, Chang HR, Shen D. ERBB2 mutation is associated with a worse prognosis in patients with CDH1 altered invasive lobular cancer of the breast. Oncotarget. 2016, 7(49).  27811364  
Mengrui Wu, Guiqian Chen; & Li YP TGF-b and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease. Bone research. April 26, 2016. 4, 16009.   27563484 
*Joel Jules, Wei Chen, Xu Feng, and Li YP; CCAAT/enhancer binding protein a; (C/EBPa) is important for osteoclast differentiation and activity. J Biol Chem 2016 Apr 20. pii: jbc.M115.674598. [Epub ahead of print]   27129246 
*Wei Chen#, Bo Gaoa#, Liang Hao, Guochun Zhu, Mary J. Macdougall, Xiaozhe Han, Xuedong Zhou, and Li YP. The silencing of cathepsin K used in gene therapy for periodontal disease reveals the role of cathepsin K in chronic infection and inflammation. Journal of Periodontal research 2016 Jan 11. doi: 10.1111/jre.12345. [Epub ahead of print]   26754272 
Yuan X, Cao J, Liu T, Li YP, Scannapieco F, He X, Oursler MJ, Zhang X, Vacher J, Li C, Olson D, Yang S. Regulators of G protein signaling 12 promotes osteoclastogenesis in bone remodeling and pathological bone loss. Cell Death Differ. 2015 Apr 24.   25909889 
Jules J, Yang S, Chen W, Li YP*. Role of Regulators of G Protein Signaling Proteins in Bone Physiology and Pathophysiology. RGS Protein Physiology and Pathophysiology. Volume 133, 2015, Pages 47–75.   26123302 
Sheng Li, Liang Hao, Lin Wang, Yun Lu, Qian Li, Zheng Zhu, Jian-Zhong Shao, Li YP*, Wei Chen. Targeting Atp6v1c1 Prevents Inflammation and Bone Erosion Caused by Periodontitis and Reveals Its Critical Function in Osteoimmunology. Plos One. 2015 Aug; 10(8): e0134903.   26274612 
Liang Hao, Guochun Zhu, Yun Lu, Min Wang, Joel Jules, Xuedong Zhou, Li YP, Wei Chen*. Deficiency of cathepsin K prevents inflammation and bone erosion in rheumatoid arthritis and periodontitis and reveals its shared osteoimmune role. FEBS Letters. 2015 May; 589 (12): 1331-1339.   25896020 
Zheng Zhu, Wei Chen, Liang Hao, Guochun Zhu, Yun Lu, Sheng Li, Lin Wang*, Yi-Ping Li*. Ac45 silencing mediated by AAV-sh-Ac45-RNAi prevents both bone loss and inflammation caused by periodontitis. Journal of Clinical Periodontology. J Clin Periodontol. 2015 May 7.   25952706 
Liang Hao, Wei Chen*, Matthew McConnell, Zheng Zhu, Sheng Li, Michael Reddy, Paul D. Eleazer, Min Wang* and Yi-Ping Li. A small molecule, Odanacatib, inhibits inflammation and bone loss caused by endodontic disease. Infection and immunity. 2015 Apr;83(4):1235-45.  25583522 
Hao L, Chen J, Zhu Z, Reddy MS, Mountz JD, Chen W, Li YP*. Odanacatib, Cathepsin K Specific Inhibitor, Inhibits Inflammation and Bone Loss Caused by Periodontal Diseases. J Periodontol. 2015 Apr 16:1-18.  25879791 
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 Jul 29;10(8):861-72.  25170300 
*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 beta; (Cbfb) in mesenchymal progenitor cells provides new insights into Cbfb/Runxs complex function in cartilage and bone development. Bone. 2014 Aug;65:49-59.   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 Jun 10;111(23):8482-7.  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 Jul;29(7):1564-74.  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 
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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