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Faculty Detail    
Name XU FENG
 
Campus Address VH G019 Zip 0019
Phone
E-mail  xfeng@uabmc.edu
Other websites
     

Education
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
Primary  Pathology   Molecular & Cellular Pathology Professor
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

Graduate Biomedical Sciences Affiliations
Cancer Biology 
Immunology 
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)    http://www.asbmb.org/ 
American Society for Bone and Mineral Research (ASBMR)    http://www.asbmr.org/Default.aspx 



Research/Clinical Interest
Title
The RANKL/RANK/OPG System in Health and Disease
Description
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
McHugh KP, Hodivala-Dilke K, Zheng MH, Namba N, Lam J, Novack D, Feng X, Ross FP, Hynes RO, Teitelbaum SL (2000) Mice lacking beta3 integrins are osteosclerotic because of dysfunctional osteoclasts. J Clin Invest. 105(4):433-40.   10683372 
Feng X, Teitelbaum SL, Quiroz ME, Cheng SL, Lai CF, Avioli LV, Ross FP (2000) Sp1/Sp3 and PU.1 differentially regulate beta(5) integrin gene expression in macrophages and osteoblasts. J Biol Chem. 275(12):8331-40.  10722663 
Cheng SL, Lai CF, Fausto A, Chellaiah M, Feng X, McHugh KP, Teitelbaum SL, Civitelli R, Hruska KA, Ross FP, Avioli LV (2000) Regulation of alphaVbeta3 and alphaVbeta5 integrins by dexamethasone in normal human osteoblastic cells. J Cell Biochem. 77(2):265-76.   10723092 
Lai CF, Feng X, Nishimura R, Teitelbaum SL, Avioli LV, Ross FP, Cheng SL (2000) Transforming growth factor-beta up-regulates the beta 5 integrin subunit expression via Sp1 and Smad signaling. J Biol Chem. 275(46):36400-6.   10964912 
Wan M, Shi X, Feng X, Cao X (2001) Transcriptional mechanisms of bone morphogenetic protein-induced osteoprotegrin gene expression. J Biol Chem. 276(13):10119-25. Epub 2001 Jan 3.   11139569 
Feng X, Novack DV, Faccio R, Ory DS, Aya K, Boyer MI, McHugh KP, Ross FP, Teitelbaum SL (2001) A Glanzmann's mutation in beta 3 integrin specifically impairs osteoclast function. J Clin Invest. 107(9):1137-44.  11342577 
Gupta A, Tenenhouse HS, Hoag HM, Wang D, Khadeer MA, Namba N, Feng X, Hruska KA (2001) Identification of the type II Na(+)-Pi cotransporter (Npt2) in the osteoclast and the skeletal phenotype of Npt2-/- mice. Bone. 29(5):467-76.   11704500 
Feng X, Takeshita S, Namba N, Wei S, Teitelbaum SL, Ross FP (2002) Tyrosines 559 and 807 in the cytoplasmic tail of the macrophage colony-stimulating factor receptor play distinct roles in osteoclast differentiation and function. Endocrinology. 143(12):4868-74.   12446614 
Kintscher U, Lyon C, Wakino S, Bruemmer D, Feng X, Goetze S, Graf K, Moustakas A, Staels B, Fleck E, Hsueh WA, Law RE (2002) PPARalpha inhibits TGF-beta-induced beta5 integrin transcription in vascular smooth muscle cells by interacting with Smad4. Circ Res. 91(11):e35-44.   12456495 
Wang Q, Xie Y, Du QS, Wu XJ, Feng X, Mei L, McDonald JM, Xiong WC (2003) Regulation of the formation of osteoclastic actin rings by proline-rich tyrosine kinase 2 interacting with gelsolin. J Cell Biol. 160(4):565-75.   12578912 
Liu Y, Shi Z, Silveira A, Liu J, Sawadogo M, Yang H, Feng X (2003) Involvement of upstream stimulatory factors 1 and 2 in RANKL-induced transcription of tartrate-resistant acid phosphatase gene during osteoclast differentiation. J Biol Chem. 278(23):20603-11.   12663664 
Xiong WC, Feng X (2003) PYK2 and FAK in osteoclasts. Front Biosci. 8:d1219-26.   12957821 
Zhang L, Feng X, McDonald JM (2003) The role of calmodulin in the regulation of osteoclastogenesis. Endocrinology. 144(10):4536-43.   12960067 
Wu X, McKenna MA, Feng X, Nagy TR, McDonald JM (2003) Osteoclast apoptosis: the role of Fas in vivo and in vitro. Endocrinology. 144(12):5545-55.   12960091 
Wang S, Skorczewski J, Feng X, Mei L, Murphy-Ullrich JE (2004) Glucose up-regulates thrombospondin 1 gene transcription and transforming growth factor-beta activity through antagonism of cGMP-dependent protein kinase repression via upstream stimulatory factor 2. J Biol Chem. 279(33):34311-22.   15184388 
Pan G, Wu X, McKenna MA, Feng X, Nagy TR, McDonald JM (2004) AZT enhances osteoclastogenesis and bone loss. AIDS Res Hum Retroviruses. 20(6):608-20.   15242537 
Xu D, Shi Z, McDonald J, Pan G, Cao X, Yu X, Feng X (2004) Development of a chimaeric receptor approach to study signalling by tumour necrosis factor receptor family members. Biochem J. 383(Pt 2):219-25.   15250821 
Liu W, Xu D, Yang H, Xu H, Shi Z, Cao X, Takeshita S, Liu J, Teale M, Feng X (2004) Functional identification of three receptor activator of NF-kappa B cytoplasmic motifs mediating osteoclast differentiation and function. J Biol Chem. 279(52):54759-69.   15485878 
Shi Z, Silveira A, Patel P, Feng X (2004) YY1 is involved in RANKL-induced transcription of the tartrate-resistant acid phosphatase gene in osteoclast differentiation. Gene. 343(1):117-26.   15563837 
Shi Z, Silveira A, Patel P, Feng X (2004) YY1 is involved in RANKL-induced transcription of the tartrate-resistant acid phosphatase gene in osteoclast differentiation. Gene. 343(1):117-26.   15563837 
Feng X (2005) Regulatory roles and molecular signaling of TNF family members in osteoclasts. Gene. 350(1):1-13. Review.   15777737 
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 
Feng X (2005) RANKing intracellular signaling in osteoclasts. IUBMB Life. 57(6):389-95. Review.   16012047 
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 
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 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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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 
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  
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 
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 X (2009) Chemical and Biochemical Basis of Cell-Bone Matrix Interaction in Health and Disease. Curr Chem Biol. 3(2):189-196.   20161446 
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 
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, 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 
Feng X, McDonald JM (2011) Disorders of bone remodeling. Annu Rev Pathol. 6:121-45. Review.   20936937 
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 
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 
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 
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 
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  
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 

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