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Faculty Detail    
Campus Address VH G019 Zip 0019
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Undergraduate  Fudan University, Shanghai, China    1987  Bachelor of Science  
Graduate  University of Vermont, Burlington, VT    1994  Ph.D. in Zoology/Molecular Biology 
Fellowship  Washington University School of Medicine, St. Louis, MO    1999  Bone Biology 

Faculty Appointment(s)
Appointment Type Department Division Rank
Center  Biomedical Engineering  Biomatrix Eng Regen Med (BERM) Ctr Professor
Center  Pathology   Cell Adhesion & Matrix Research Center Professor
Center  Center for Biophysical Sciences/Engineering  Center for Biophysical Sciences/Engineering Professor
Center  Comp Arthritis, MSK, Bone & Autoimmunity Ctr  Comp Arthritis, MSK, Bone & Autoimmunity Ctr Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor
Center  Integrative Center for Aging Research  Integrative Center for Aging Research Professor
Primary  Pathology   Molecular & Cellular Pathology Professor

Graduate Biomedical Sciences Affiliations
Cancer Biology 
Medical Scientist Training Program 
Molecular and Cellular Pathology Program 
Pathobiology and Molecular Medicine 

Biographical Sketch 
Dr. Feng received his B.S. degree in 1987 from Fudan University in China and his Ph.D. in Zoology/Molecular Biology from the University of Vermont in 1994 (Advisor, Dr. George Happ). He then pursued his postdoctoral research training in the laboratory of Dr Steven Teitelbaum in Department of Pathology at Washington University School of Medicine in St. Louis. In 2000, Dr. Feng joined Department of Pathology at the University of Alabama at Birmingham. He received National Research Service Award from National Institutes of Health (1997-1999) and was also a recipient of John Haddad Young Investigator Award from Advances in Mineral Metabolism (AIMM) and the American Society for Bone and Mineral Research (ASBMR) in 2000.

Society Memberships
Organization Name Position Held Org Link
American Society for Biochemistry and Molecular Biology (ASBMB) 
American Society for Bone and Mineral Research (ASBMR) 

Research/Clinical Interest
The RANKL/RANK/OPG System in Health and Disease
Our laboratory uses molecular and cell biology techniques as well as mouse models (knockout and knockin) to delineate the signaling mechanisms by which the RANKL/RANK/OPG system regulates cell differentiation and function. Currently, we have the following research focuses: (1) RANK signaling mechanism in osteoclast differentiation and function. RANKL is a key factor regulating the formation and function of osteoclasts, our body’s sole bone-resorbing cells, which play a pivotal role in skeletal development and adult skeletal maintenance (bone remodeling). Moreover, the RANKL/RANK/OPG system is also implicated in the pathogenesis of various diseases including postmenopausal osteoporosis, bone erosion in rheumatoid arthritis, periodontal bone loss, and tumor (breast and prostate) skeletal metastasis. Our long-term goals are a) to elucidate the signaling mechanism by which the RANKL/RANK/OPG system regulates osteoclast formation and function and b) to delineate the molecular and cellular mechanisms underlying the role of the RANKL/RANK/OPG system in the various bone diseases. (2) The molecular mechanism by which the RANKL/RANK/OPG system regulates mammary gland development and promotes breast cancer development and metastasis. While the crucial role of the RANKL/RANK/OPG system in mammary gland development has been well established, the signaling mechanism controlling RANKL-mediated mammary gland development has not been fully understood. The objectives of this research focus are a) to delineate novel RANK signaling pathways involved in mammary gland development and b) to better understand the molecular mechanism by which the RANKL/RANK/OPG system promotes breast cancer initiation and progression. (3) Drug discovery/translational research. Our work on RANK signaling mechanism in osteoclast biology has led to identification of several RANK cytoplasmic motifs/signaling pathways that play important functional roles in osteoclast formation and function. The potency and selectivity of these RANK motif-mediated signaling pathways in osteoclast biology have convinced us to expand our research program into the translational research. We have developed cell-based assay systems for identifying compounds targeting these RANK motif-mediated signaling pathways through high throughput screening (HTS). The goal of this translational research is to develop new antiresorptive drugs targeting the RANKL/RANK/OPG system.

Selected Publications 
Publication PUBMEDID
Zhao Y, Li Z, Su L, Ballesteros-Tato A, Katz J, Michalek S, Feng X, Zhang P (2020) Characterization and regulation of osteoclast precursors following chronic Porphyromonas gingivalis infection Journal of Leukocyte Biology, 108(4):1037-1050  33463750 
Cai X, Li Z, Zhao Y, Katz J, Michalek SM, Feng X, Li Y, Zhang P (2020) Enhanced dual function of osteoclast precursors following calvarial Porphyromonas gingivalis infection. J Periodontal Res 55(3):410-425  31944305 
Li Y, Shi Z, Jules J, Chen S, Kesterson RA, Zhao D, Zhang P, Feng X (2019) Specific RANK cytoplasmic motifs drive osteoclastogenesis. J Bone Miner Res. 34:1938-1951  31173390 
Jules J, Chen W, Feng X, Li YP (2018) C/EBPα is regulated by the RANK cytoplasmic IVVY535-538 motif and stimulates osteoclastogenesis more strongly than c-Fos. J Biol Chem. 293(4):1480-1492.   29122885  
Jules J, Chen W, Feng X, Li YP. (2016) CCAAT/enhancer binding protein α (C/EBPα) is important for osteoclast differentiation and activity J Biol Chem. 291(31):16390-403  27129246 
Chen Z, Su L, Xu Q, Katz J, Michalek SM, Fan M, Feng X, Zhang P (2015) IL-1R/TLR2 through MyD88 divergently modulates osteoclastogenesis through regulation of nuclear factor of activated T cells c1 (NFATc1) and B lymphocyte-induced maturation protein-1 (Blimp1). J Biol Chem. 290(50):30163-74.  26483549 
Jules J, Wang S, Shi Z, Liu J, Wei S, Feng X (2015) The IVVY Motif and Tumor Necrosis Factor Receptor-associated Factor (TRAF) Sites in the Cytoplasmic Domain of the Receptor Activator of Nuclear Factor κB (RANK) Cooperate to Induce Osteoclastogenesis. J Biol Chem. 290(39):23738-50.  26276390 
Zhao D, Shi Z, Warriner AH, Qiao P, Hong H, Wang Y, Feng X. Molecular mechanism of thiazolidinedione-mediated inhibitory effects on osteoclastogenesis. PLoS One. 2014 Jul 17;9(7):e102706.  25032991 
Jules J and Feng X (2014) In vitro investigation of the roles of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1 in murine osteoclastogenesis. Methods Mol Biol. 1155:109-23.  24788177 
Chu GC, Zhau HE, Wang R, Rogatko A, Feng X, Zayzafoon M, Liu Y, Farach-Carson MC, You S, Kim J, Freeman MR, Chung L (2014) RANK- and c-Met-mediated signal network promotes prostate cancer metastatic colonization. Endocr Relat Cancer. 21: 311-26  24478054 
Feng X and Teitelbaum SL (2013) Osteoclasts: New Insights. Bone Research. 1 (1) 11-26  26273491 
Hong H, Shi Z, Qiao P, Li H, McCoy EM, Mao P, Xu H, Feng X, Wang S (2013) Interleukin-3 plays dual roles in osteoclastogenesis by promoting the development of osteoclast progenitors but inhibiting the osteoclastogenic process. Biochem Biophys Res Commun. 440(4):545-50.  24103757 
Xia WF, Tang FL, Xiong L, Xiong S, Jung JU, Lee DH, Li XS, Feng X, Mei L, Xiong WC (2013) Vps35 loss promotes hyperresorptive osteoclastogenesis and osteoporosis via sustained RANKL signaling. J Cell Biol. 200(6):821-37.   23509071 
Cody JJ, Rivera AA, Lyons GR, Yang SW, Wang M, Ashley JW, Meleth S, Feng X, Siegal GP, Douglas JT (2013) Expression of osteoprotegerin from a replicating adenovirus inhibits the progression of prostate cancer bone metastases in a murine model. Lab Invest. 93(3):268-78.   23358109 
McCoy EM, Hong H, Pruitt HC, Feng X (2013) IL-11 produced by breast cancer cells augments osteoclastogenesis by sustaining the pool of osteoclast progenitor cells. BMC Cancer. 13:16.   23311882 
Sawant A, Deshane J, Jules J, Lee CM, Harris BA, Feng X, Ponnazhagan S (2013) Myeloid-derived suppressor cells function as novel osteoclast progenitors enhancing bone loss in breast cancer. Cancer Res. 73(2):672-82.   23243021  
Izawa T, Zou W, Chappel JC, Ashley JW, Feng X, Teitelbaum SL (2012) c-Src links a RANK/αvβ3 integrin complex to the osteoclast cytoskeleton. Mol Cell Biol. 32(14):2943-53.  22615494  
MohanKumar K, Kaza N, Jagadeeswaran R, Garzon SA, Bansal A, Kurundkar AR, Namachivayam K, Remon JI, Bandepalli CR, Feng X, Weitkamp JH, Maheshwari A (2012) Gut mucosal injury in neonates is marked by macrophage infiltration in contrast to pleomorphic infiltrates in adult: evidence from an animal model. Am J Physiol Gastrointest Liver Physiol. 303(1):G93-102.   22538401  
Jules J, Zhang P, Ashley JW, Wei S, Shi Z, Liu J, Michalek SM, Feng X (2012) Molecular basis of requirement of receptor activator of nuclear factor κB signaling for interleukin 1-mediated osteoclastogenesis. J Biol Chem. 287(19):15728-38.   22416138  
Cheng J, Liu J, Shi Z, Jules J, Xu D, Luo S, Wei S, Feng X (2012) Molecular mechanisms of the biphasic effects of interferon-γ on osteoclastogenesis. J Interferon Cytokine Res. 32(1):34-45.   22142221 
Ashley JW, Shi Z, Zhao H, Li X, Kesterson RA, Feng X (2011) Genetic ablation of CD68 results in mice with increased bone and dysfunctional osteoclasts. PLoS One. 6(10):e25838.   21991369  
Cody JJ, Rivera AA, Liu J, Liu JM, Douglas JT, Feng X (2011) A simplified method for the generation of human osteoclasts in vitro. Int J Biochem Mol Biol. 2(2):183-189.   21968748 
Cheng J, Liu J, Shi Z, Xu D, Luo S, Siegal GP, Feng X, Wei S (2011) Interleukin-4 inhibits RANKL-induced NFATc1 expression via STAT6: a novel mechanism mediating its blockade of osteoclastogenesis. J Cell Biochem. 112(11):3385-92.   21751242  
Zhang P, Liu J, Xu Q, Harber G, Feng X, Michalek SM, Katz J (2011) TLR2-dependent modulation of osteoclastogenesis by Porphyromonas gingivalis through differential induction of NFATc1 and NF-kappaB. J Biol Chem. 286 (27): 24159-69.   21566133 
Cui S, Xiong F, Hong Y, Jung JU, Li XS, Liu JZ, Yan R, Mei L, Feng X, Xiong WC (2011) APPswe/Aβ regulation of osteoclast activation and RAGE expression in an age-dependent manner. J Bone Miner Res. 26(5):1084-98.   21542009 
Pan G, Zheng R, Yang P, Li Y, Clancy JP, Liu J, Feng X, Garber DA, Spearman P, McDonald JM (2011) Nucleosides accelerate inflammatory osteolysis, acting as distinct innate immune activators. J Bone Miner Res. 26(8):1913-25.   21472777 
Ashley JW, McCoy EM, Clements DA, Shi Z, Chen T, Feng X (2011) Development of cell-based high-throughput assays for the identification of inhibitors of receptor activator of nuclear factor-kappa B signaling. Assay Drug Dev Technol. 9(1):40-9.   21050071 
Feng X, McDonald JM (2011) Disorders of bone remodeling. Annu Rev Pathol. 6:121-45. Review.   20936937 
Jules J, Shi Z, Liu J, Xu D, Wang S, Feng X (2010) Receptor activator of NF-{kappa}B (RANK) cytoplasmic IVVY535-538 motif plays an essential role in tumor necrosis factor-{alpha} (TNF)-mediated osteoclastogenesis. J Biol Chem. 285(48):37427-35. Epub 2010 Sep 24.   20870724 
Cody JJ, Rivera AA, Lyons GR, Yang SW, Wang M, Sarver DB, Wang D, Selander KS, Kuo HC, Meleth S, Feng X, Siegal GP, Douglas JT (2010) Arming a replicating adenovirus with osteoprotegerin reduces the tumor burden in a murine model of osteolytic bone metastases of breast cancer. Cancer Gene Ther. 17(12):893-905.   20798695 
Jules J, Ashley JW, Feng X (2010) Selective targeting of RANK signaling pathways as new therapeutic strategies for osteoporosis. Expert Opin Ther Targets. 14(9):923-34. Review.   20678025 
Feng X (2009) Chemical and Biochemical Basis of Cell-Bone Matrix Interaction in Health and Disease. Curr Chem Biol. 3(2):189-196.   20161446 
Tang Y, Wu X, Lei W, Pang L, Wan C, Shi Z, Zhao L, Nagy TR, Peng X, Hu J, Feng X, Van Hul W, Wan M, Cao X (2009) TGF-beta1-induced migration of bone mesenchymal stem cells couples bone resorption with formation. Nat Med. 15(7):757-65.   19584867 
Feng H, Cheng T, Steer JH, Joyce DA, Pavlos NJ, Leong C, Kular J, Liu J, Feng X, Zheng MH, Xu J (2009) Myocyte enhancer factor 2 and microphthalmia-associated transcription factor cooperate with NFATc1 to transactivate the V-ATPase d2 promoter during RANKL-induced osteoclastogenesis. J Biol Chem. 284(21):14667-76.   19321441 
Liu J, Wang S, Zhang P, Said-Al-Naief N, Michalek SM, Feng X (2009) Molecular mechanism of the bifunctional role of lipopolysaccharide in osteoclastogenesis. J Biol Chem. 284(18):12512-23.   19258321  
Chen Y, Wang X, Di L, Fu G, Chen Y, Bai L, Liu J, Feng X, McDonald JM, Michalek S, He Y, Yu M, Fu YX, Wen R, Wu H, Wang D (2008) Phospholipase Cgamma2 mediates RANKL-stimulated lymph node organogenesis and osteoclastogenesis. J Biol Chem. 283(43):29593-601.  18728019 
Zhou Z, Han JY, Xi CX, Xie JX, Feng X, Wang CY, Mei L, Xiong WC (2008) HMGB1 regulates RANKL-induced osteoclastogenesis in a manner dependent on RAGE. J Bone Miner Res. 23(7):1084-96.   18302500 
Lu W, Kim KA, Liu J, Abo A, Feng X, Cao X, Li Y (2008) R-spondin1 synergizes with Wnt3A in inducing osteoblast differentiation and osteoprotegerin expression. FEBS Lett. 582(5):643-50.   18242177 
Takeshita S, Faccio R, Chappel J, Zheng L, Feng X, Weber JD, Teitelbaum SL, Ross FP (2007) c-Fms tyrosine 559 is a major mediator of M-CSF-induced proliferation of primary macrophages. J Biol Chem. 282(26):18980-90.   17420255 
Wang S, Shi Z, Liu W, Jules J, Feng X (2006) Development and validation of vectors containing multiple siRNA expression cassettes for maximizing the efficiency of gene silencing. BMC Biotechnol. 6:50.  17187675 
Chen T, Feng X (2006) Cell-based assay strategy for identification of motif-specific RANK signaling pathway inhibitors. Assay Drug Dev Technol. 4(4):473-82. Review.   16945019 
Cui T, Schopfer FJ, Zhang J, Chen K, Ichikawa T, Baker PR, Batthyany C, Chacko BK, Feng X, Patel RP, Agarwal A, Freeman BA, Chen YE (2006) Nitrated fatty acids: Endogenous anti-inflammatory signaling mediators. J Biol Chem. 281(47):35686-98.   16887803 
Zhou Z, Immel D, Xi CX, Bierhaus A, Feng X, Mei L, Nawroth P, Stern DM, Xiong WC (2006) Regulation of osteoclast function and bone mass by RAGE. J Exp Med. 203(4):1067-80.   16606672 
Kim HK, Guan H, Zu G, Li H, Wu L, Feng X, Elmets C, Fu Y, Xu H (2006) High-level expression of B7-H1 molecules by dendritic cells suppresses the function of activated T cells and desensitizes allergen-primed animals. J Leukoc Biol. 79(4):686-95.   16461745 
Xu D, Wang S, Liu W, Liu J, Feng X (2006) A novel receptor activator of NF-kappaB (RANK) cytoplasmic motif plays an essential role in osteoclastogenesis by committing macrophages to the osteoclast lineage. J Biol Chem. 281(8):4678-90.  16373338 
Liu W, Wang S, Wei S, Sun L, Feng X (2005) Receptor activator of NF-kappaB (RANK) cytoplasmic motif, 369PFQEP373, plays a predominant role in osteoclast survival in part by activating Akt/PKB and its downstream effector AFX/FOXO4. J Biol Chem. 280(52):43064-72.   16260781 
Wu Y, Liu J, Feng X, Yang P, Xu X, Hsu HC, Mountz JD (2005) Synovial fibroblasts promote osteoclast formation by RANKL in a novel model of spontaneous erosive arthritis. Arthritis Rheum. 52(10):3257-68.   16200600 
Liu J, Yang H, Liu W, Cao X, Feng X (2005) Sp1 and Sp3 regulate the basal transcription of receptor activator of nuclear factor kappa B ligand gene in osteoblasts and bone marrow stromal cells. J Cell Biochem. 96(4):716-27.   16052479 
Feng X (2005) RANKing intracellular signaling in osteoclasts. IUBMB Life. 57(6):389-95. Review.   16012047 
Zhang L, McKenna MA, Said-Al-Naief N, Wu X, Feng X, McDonald JM (2005) Osteoclastogenesis: the role of calcium and calmodulin. Crit Rev Eukaryot Gene Expr. 15(1):1-13.   15831075 

RANKL, RANK, OPG, Cell Differentiation, Cell Signaling, Osteoclast, Mammary Gland, Breast Cancer