Jian Q. (Jerry) Feng
Department of Biomedical Sciences
Member of the GSBS Faculty
3302 Gaston Ave.
Dallas, Texas 75246
Education and Post-Graduate Training
Postdoctoral Fellowship, Medicine, University of Texas Health Science Center, San Antonio (1991-1995)
Postdoctoral Fellowship, Physiology, Medicine, University of Michigan, Ann Arbor, MI (1985-1987)
Ph.D., Physiology, University of Connecticut, Storrs, CT (1991)
M.S., Physiology, University of Qindao, Medical College, Qindao, China (1982)
B.S., Medicine, University of Qindao, Medical College, Qindao, China (1976)
Professor with tenure, Department of Biomedical Sciences, Texas A&M Health Science Center Baylor College of Dentistry (2007-present)
Professor with tenure, Department of Oral Biology, University of Missouri-Kansas City (2006-2007)
Associate Professor with tenure, Department of Oral Biology, University of Missouri-Kansas City (1998-2006)
Research Assistant Professor, Department of Pediatric Dentistry, University of Texas Health Science Center, School of Dentistry, San Antonio (1996-1998)
Research Assistant Professor, Department of Medicine (Endocrinology), University of Texas Health Science Center, School of Dentistry, San Antonio (1997-1998)
Assistant Professor, Department of Pediatric Dentistry, University of Texas Health Science Center, School of Dentistry, San Antonio (1996-1997)
Teaching responsibilities include:
Physiology (Dental students) and Hard Tissue Physiology (Graduate)
Dr. Feng performs research in craniofacial, tooth and bone developmantal biology, with a particular interest in understanding the roles of Dentin matrix protein-1, Bmp receptor 1A, beta-catenin, periostin and mechanical loading during development. In addition, Dr. Feng is interested in understanding tooth root formation using a naturally occurring osteoporosis mouse model. Lastly, Dr. Feng is interested in understanding the mechanism by which Pax-9 in mutation in exon 3 leads to tooth agenesis.
Roles of Dentin matrix protein-1 (DMP1) in mineralized tissues. Dentinogenesis, skeletal morphogenesis, and mineralization require precise spatial and temporal coordination of programs for cell growth and differentiation. If one of these programs is interrupted or perturbed, dental or skeletal disorders will likely occur. In a search for genes required for normal calcified tissue development potentially linked to human diseases, we have studied Dentin matrix protein-1 (DMP1) using in vivo loss of function and gain of function approaches. Dr. Feng's research interests in this project include:
1) Roles of DMP1 in craniofacial and tooth development. In this project, Dr. Feng plans to 1) determine the role of DMP1 in bone, cartilage and tooth morphogenesis and mineralization in the craniofacial tissues by characterizing the bone, cartilage, cement, and dentin phenotypes of DMP1 null mice; 2) identify the control elements in the DMP1 gene specific to bone, cartilage, cement, and dentin by generation and analyses of transgenic mice; and 3) determine if the dentin and bone phenotype in DMP1-deficient mice can be rescued by targeting DMP1 (full or C-terminal or N-terminal domain) expression to either odontoblast or osteoblasts in vivo. Successful completion of this proposal will provide unique insights into normal craniofacial morphogenesis, dentinogenesis, osteogenesis and mineralization.
2) Roles of DMP1 in osteocyte morphology and function. The central hypothesis for the proposed studies is that DMP1 is a critical regulator of osteocyte function through its dual roles in the regulation of mineralization and osteocyte responses to mechanical strain. Successful completion of this research will integrate a largely unknown extracellular matrix molecule, DMP1, with the essential biological function of controlling osteocyte function and bone mineralization. The data generated will have major implications for our understanding of skeletal and osteocyte biology and may highlight novel pathways for mechanical stimulation in osteocytes that could be targeted in the treatment of metabolic bone diseases.
3) Roles of DMP1 in phosphate homeostatis. The most unexpected phenotype in DMP1 null mice is hypophosphatemia. This finding leads to a new concept that a non-collagenous matrix protein regulates Pi homeostasis and to the discovery of DMP1 mutations in autosomal recessive hypophosphatemia rickets (ARHA). The hypothesis is that cells known as osteocytes, which account for over 90% of bone cells but whose function is largely unknown, control Pi homeostasis through the DMP1-FGF23 pathway. In turn, Pi regulates the maturation of the osteoblasts into osteocytes and the DMP1 expression in osteocytes. Dr. Feng's objectives are: 1) to determine the molecular genetics and pathophysiology of ARHR through the generation and analysis of mice harboring natural human DMPα mutations; 2) to elucidate the mechanism by which DMP1 controls FGF23 through the MAP kinase pathway and osterix; and 3) to define the role of Pi in the regulation of the maturation of osteoblasts into osteocytes and DMP1 expression.
Roles and control mechanisms of bone morphogenetic protein 4 (BMP4). Epithelial-mesenchymal interactions are required for tooth formation. Bone morphogenetic protein 4 (Bmp4) is a crucial signaling molecule during this process. To better understand the role of the Bmp4 gene during tooth development, we studied the mechanisms that control its temporal and spatial expression during development. Using a transgenic approach, we determined that the domains controlling Bmp4 expression in epithelium-derived ameloblasts are located in the region between 0.26 kb to 1.1 kb of the murine Bmp4 promoter. By contrast, the domains controlling Bmp4 expression in mesenchyme-derived odontoblasts and pulp cells exist in other regions of the Bmp4 gene. Dr. Feng's lab has also developed transgenic mice overexpressing Bmp4 for gain function study in later amelogenesis. This research includes: 1) searching for domains that control Bmp4 expression in chondrocytes, osteoblasts, and odontoblasts by generating transgenic mouse lines containing different promoter regions; 2) understanding the roles of Bmp4 in later amelogenesis by characterizing transgenic mice harboring a human Bmp4 cDNA driven by a 1.1 kb mouse Bmp4 promoter; and 3) studying the roles of Bmp4 in odontogenesis during postnatal development by deleting the mouse Bmp4 gene at an early mesenchymal tooth bud (using MX1-Cre mice and 3.6 kb Col 1-Cre mice) and later odontogenesis (using Dspp-Cre mice) through crossing Bmp4 loxP mice.
Other studies performed in Dr. Feng's lab include: 1) roles of bone morphologic protein recepton 1A (BMPR1a); 2) roles of beta-catenin in tooth development; 3) studies of periostin function in vivo and characterization of early onset periodontitis in mice lacking periostin; 4) tooth root formation in an osteopetrotic mouse model; and 5) mechanisms of the PAX9 mutation in non-syndromic tooth agenesis.
- DMP1 Mutations: Defects in Odontogenesis. NIH/NIDCR R01 DE15209; 2008-2013. (PI)
- Studies of the Roles of DMP1 and DSPP in Osteogenesis and Dentinogenesis. NIH/NIDCR R01 DE005092; 2009-2013. (Co-PI)
- Effects of Mechanical Strain on Osteocyte Function. NIH/NIAM P01 AR046798-06; 2006-2012. (Co-PI, Project 3)
- Disturbance of Phosphate Homeostasis Changes in Osteocyte Morphology and Function, Genzyme Renal Innovations Program 2008-2011. (PI)
- A Preclinical Study Proposal: Effects of Sci-Ab on Rodent Periodontal Disease Model - DMP1 null mice. Amgen Inc., #427411; 2009-2011. (PI)
- Evaluation of the Mandible Bond Phenotype of Gene-altered Animals and/or the Effects of Novel Bone Active Compounds in Animals. Amgen Inc., #427301; 2009-2011. (PI)
- Zhang J., C. Niu, H. Huang, L. Ye, X. He, W. Tong, J. Ross, J. Haug, T. Johnson, J.Q. Feng, S. Harris, L. Wiedemann, Y. Mishina, and L. Li. Identification of the hematopoietic stem cell niche and control of the niche size. Nature 425:836-841, 2003.
- Feng J.Q., H. Huang, Y. Lu, L. Ye, Y. Xie, T. W. Tsutsui, T. Kunieda, T. Castranio, G. Scott, L.B. Bonewald and Y. Mishina. Dmp1 is specifically expressed in mineralized tissues. Journal of Dental Research 82:776-780, 2003.
- Feng J.Q., L. Xing, J. Zhang, M. Zhao, D. Horn, J. Chan, B.F. Boyce, S.E. Harris, G.R. Mundy, and D. Chen. NF-kB specifically activates BMP-2 gene expression in growth plate chondrocytes in vivo and in a chondrocyte cell line in vitro. J Biol Chem 278:29130-29135, 2003.
- Gluhak-Heinrich J., L. Ye, L.F. Bonewald, J.Q. Feng, M. MacDougall, S.E. Harris, and D. Pavlin. Mechanical loading stimulates dentin matrix protein 1 (Dmp1) expression osteocytes in vivo. Journal of Bone and Mineral Research 18:807-817, 2003.
- Ye L., M. MacDougall, S. Zhang, Y. Xie, J. Zhang, Z. Li, Y. Lu, Y. Mishina and J.Q. Feng. Deletion of dentin matrix protein-1 leads to a partial failure of maturation of predentin into dentin, hypomineralization and expanded cavities of pulp and root canal during postnatal tooth development. J Biol Chem 279:19141-8, 2004.
- Yang W., I. Kalajzic, Y. Lu, D. Guo, M.A. Harris, J. Gluhak-Heinrich, L.F. Bonewald, J.Q. Feng, D.W. Rowe, S.E. Harris. In vitro and in vivo study on osteocyte-specific mechanical signaling pathways. J Musculoskelet Neuronal Interact 4:386-7, 2004.
- Wei Z., Y. Xie, G. Li, J. Kong, J.Q. Feng, and Y.C. Li. Critical role of calbindin-D28k in calcium homeostasis revealed by mice lacking both vitamin D receptor and calbindin-D28k. J Biol Chem 279:52406-52413, 2004.
- Yongbo L., S. Zhang, Y. Pi, Y. Xie, and J.Q. Feng. Differential regulation of DMP1 expression during odontogenesis. Cells Tissues Organs 181:241-247, 2005.
- Rios H.F., L. Ye, V. Dusevich, D. Eick, L.F. Bonewald, J.Q. Feng. DMP1 is essential for osteocyte formation and function. J Musculoskelet Neuronal Interact 5:325-327, 2005.
- Ling Y., H.F. Rios, E.R. Myers, Y. Lu, J.Q. Feng, and A. Boskey. DMP1 depletion decreases bone mineralization in vivo. J Bone Miner Res 20:2169-77, 2005.
- Rios H., V. Shrinagesh Koushik, H. Wang, J. Wang, H.-M. Zhou, A. Lindsley, R. Rogers, Z. Chen, M. Maeda, A. Kruzynska-Freitag, J.Q. Feng, and S.J. Conway. Periostin null mice exhibit dwarfism, incisor enamel defects, and an early-onset periodontal disease-like phenotype. Mol Cell Biol 25:11131-44, 2005.
- Yang W., Y. Lu, I. Kalajzic, D. Guo, M.A. Harris, J. Gluhak-Heinrich, S. Kotha, L.F. Bonewald, J.Q. Feng, D.W. Rowe, C.H. Turner, A.G. Robling, S.E. Harris. Dentin matrix protein 1 gene cis-regulation: Use in osteocytes to characterize local responses to mechanical loading in vitro and in vivo. J Biol Chem 280:20680-90, 2005.
- Ye L., Y. Mishina, D. Chen, H. Huang, S. Dallas, M. Dallas, T. Kunieda, T. Tsutsui, L.F. Bonewald, and J.Q. Feng. Dentin matrix protein 1 (Dmp1) deficient mice display severe defects in cartilage formation responsible for a chondrodysplasia-like phenotype. J Biol Chem 280:6197-203, 2005.
- Zhang J., X.C. He, W.G. Tong, T. Johnson, L.M. Wiedemann, Y. Mishina, J.Q. Feng and L. Li. BMP signaling inhibits hair follicle anagen induction by restricting epithelial stem/progenitor cell activation and expansion. Stem Cells 0:2005-0544v1, 2006.
- Feng J.Q., L.M. Ward, S. Liu, Y. Lu, B. Yuan, X. Yu, F. Rauch, Y. Xie, S.I. Davis, D. Zhang, H. Rios, M.K. Drezner, L.F. Bonewald, L.D. Quarles and K.E. White. Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism. Nature Genetics 38:1310-1315, 2006.
- Zhang K., C. Barragan-Adjemian, L. Ye, S. Kotha, M. Dallas, Y. Lu, S. Zhao, M. Harris, S.E. Harris, J.Q. Feng, L.F. Bonewald. E11/gp38 selective expression in osteocytes: Regulation by mechanical strain and role in dendrite elongation. Mol Cell Biol 26:4539-52, 2006.
- Lu Y., Y. Xie, S. Zhang, D. Vladimir, L.F. Bonewald, and J.Q. Feng. DMP1 targeted Cre expression in odontoglasts and osteocytes. J Dent Res 86:320-325, 2007.
- Lu Y., L. Ye, Y. Xie, S. Zhang, S. Yu, M.D. McKee, Y. Li, D. Eick, S.L. Dallas and J.Q. Feng. Rescue of odontogenesis in DMP1-deficient mice by targeted reexpression of DMP1 reveals roles for DMP1 in early odontogenesis and dentin apposition in vivo. Developmental Biology 303:191-201, 2007.
- Qin C., R. D'Souza, and J.Q. Feng. Dentin matrix protein 1 (DMP1): New and important roles for biomineralization and phosphate homeostasis. J Dent Res 86 (12):1134-1141, 2007.
- Xu K., Y. Zhang, K. Ilalov, C.S. Carlson, J.Q. Feng, P.E.D. Cesare, and C-J. Liu. Cartilage oligomeric matrix protein associates with granulin-epithelin precursor (GEP) and potentiates GEP-stimulated chondrocyte proliferation. J Biol Chem 282:11347-11355, 2007.
- Feng J.Q., G. Scott, D. Guo, B. Jiang, M. Harris, T. Ward, R. Ray. L.F. Bonewald, S.E. Harris, and Y. Mishina. Generation of a conditional null allele for DMP1 in mouse. Genesis 46:87-91, 2008.
- Baozhi Y., M. Takaiwa, T.L. Clemens, J.Q. Feng, R. Kumar, P.S. Rowe, Y. Xie, and M.K. Drezner. Bone is the physiologically relevant site of the PHEX/Phex mutation in X-linked hypophosphatemia. J Clin Invest 118:722-734, 2008.
- Kamiya N., L. Ye, T. Kobayashi, D.J. Lucas, Y. Mochida, M. Yamauchi, H.M. Kronenberg, J.Q. Feng, Y. Mishina. Disruption of BMP signaling in osteoblasts through Type IA receptor (BMPRIA) increases bone mass. J Bone Miner Res 23:2007-17, 2008.
- Hu J.C.C., Y. Hu, C.E. Smith, M.D. McKee, J.T. Wright, Y. Yamakoshi, P. Papagerakis, G.K. Hunter, J.Q. Feng, F. Yamakoshi, J.P. Simmer. Enamel defects and ameloblast-specific expression in Enam knock-out/lacZ knock-in mice. J. Biol. Chem. 283:10858-10871, 2008.
- Ye L., S. Zhang, H.Z. Ke, L. Bonewald, and J.Q. Feng. Periodontal breakdown in the Dmp1 null mouse model of hypophosphatemic rickets. J Dent Res, 87:624-629, 2008.
- Rios H.F., D. Ma, Y. Xie, W.V. Giannobile, L.F. Bonewald, S.J. Conway, and J.Q Feng. Periostin is essential for the integrity and periodontal ligament function during occlusal loading. J. Periodontology 79:1480-90, 2008.
- Maciejewska I., D. Qin, B. Huang, Y. Sun, G. Mues, K. Svoboda , L.F. Bonewald, W.T. Butler, J.Q. Feng, C. Qin. Distinct compartmentalization of dentin matrix protein 1 fragments in mineralized tissues and cells. Cells Tissues Organs 189:186-191, 2009.
- Lu Y., C. Qin, Y. Xie, L.F. Bonewald, and J.Q. Feng. Studies of the DMP1 57-kDa functional domain both in vivo and in vitro. Cells Tissues Organs 189:175-185, 2009.
- Peng T., B. Huang, Y. Lu, Y. Sun, L.F. Bonewald, W.T. Butler, J.Q. Feng, S. Chen, R. D'Souza, C. Qin. Blocking of proteolytic processing and deletion of glycosaminoglycan side chain of mouse DMP1 by substituting critical amino acid residues. Cells Tissues Organs 189:192-197, 2009.
- Feng J.Q., L. Ye, S. Schiavi. Do osteocytes contribute to phosphate (Pi) homeostasis? Current Opinion in Nephrology and Hypertension 18:285-291, 2009.
- Lu X., H.F. Rios, B. Jiang, L. Xing, R. Kadlcek, E.M. Greenfield, G. Luo, J.Q. Feng. A new osteopetrosis mutant mouse strain (ntl) with odontoma-like proliferations and lack of tooth roots. Eur J Oral Sci 117:625-35, 2009.
- Sun Y., V. Gandhi, M. Prasad, W. Yu, X. Wang, Q. Zhu, J.Q. Feng, R.J. Hinton, C. Qin. Distribution of small integrin-binding ligand, N-linked glycoprotains (SIBLING) in the condylar cartilage of rat mandible. Int J Oral Maxillofac Surg 39:272-281, 2010.
- Feng J.Q., F.J. Guo, B.C. Jiang, Y. Zhang, S. Frenkel, D.W. Wang, W. Tang, Y. Xie, C.J. Liu. Granulin epithelin precursor: A bone morphogenic protein 2-inducible growth factor that activates Erk1/2 signaling and JunB transcription factor in chondrogenesis. FASEB J 24:1879-92, 2010.
- Gluhak-Heinrich J., D. Guo, W. Yang, M.A. Harris, A. Lichtler, B. Kream, J. Zhang, J.Q. Feng, L.C. Smith, P. Dechow, S.E. Harris. New roles and mechanism of action of BMP4 in postnatal tooth cytodifferentiation. Bone 46:1533-45, 2010.
- Kramer I., C. Halleux, H. Keller, M. Pegurri, J.H. Gooi, P.B. Weber, J.Q. Feng, L.F. Bonewald, M. Kneissel. Osteocyte Wnt/beta-catenin signaling is required for normal bone homeostasis. Mol Cell Biol 30:3071-85, 2010.
- Jiang B., Z. Cao, Y. Lu, C.V. Janik, S. Lauziere, Y. Xie, A. Poliard, C. Qin, L.M. Ward, J.Q. Feng. DMP1 C-terminal mutant mice recapture the human ARHR tooth phenotype. J Bone Miner Res 25:2155-64, 2010.
- Cao Z., B. Jiang, Y. Xie, C. Liu, J.Q. Feng. GEP, a local growth factor, is critical for odontogenesis and amelogenesis. Int J Biol Sci 6:719-729, 2010.
- Sun Y., M. Prasad, T. Gao, X. Wang, Q. Zhu, R. D'Souza, J.Q. Feng, C. Qin. Failure to process dentin matrix protein 1 (DMP1) into fragments leads to its loss of function in osteogenesis. J Biol Chem 285:31713-22, 2010.
- Zhou X., Z. Zhang, J.Q. Feng, V.M Dusevich, K. Sinha, H. Zhang, B.G. Darnay, B. de Crombrugghe. Multiple functions of Osterix are required for bone growth and homeostasis in postnatal mice. Proc Natl Acad Sci USA 107:12919-24, 2010.
- Zhu Q., Y. Sun, M. Prasad, X. Wang, A.K. Yamoah, Y. Li, J. Feng, C. Qin. Glycosaminoglycan chain of dentin sialoprotein proteoglycan. J Dent Res 89:808-812, 2010.
- Wang X., J. Hao, Y. Xie, Y. Sun, B. Hernandez, A.K. Yamoah, M. Prasad, Q. Zhu, J.Q. Feng, C. Qin. Expression of FAM20C in the osteogenesis and odontogenesis of mouse. J Histochem Cytochem 58:957-967, 2010.
- Sun Y., S. Ma, J. Zhou, A. Yamoah, J.Q. Feng, R.J. Hinton, C. Qin. Distribution of small integrin-binding ligand, n-linked glycoproteins (SIBLING) in the articular cartilage of the rat femoral head. J Histochem Cytochem 58, 1033-43, 2010.
- Schiavi S.C., J.Q. Feng. Osteocytes and mineral metabolism. In: K. Olgaard, I. Slausky and J. Silver, eds. The Spectrum of Renal Osteodystrophy and Vascular Calcifications in Uremia, Oxford University Press, 2010.
- Lv K., H. Huang, Y. Lu, C. Qin, Z. Li, J. Feng. Circling behavior developed in Dmp1 null mice is due to bone defects in the vestibular apparatus. Int J Biol Sci 6:537-545, 2010.
- Zhang, R., Y. Lu, L. Ye, B. Yuan, S. Yu, C. Qin, Y. Xie, T. Gao, M.K. Drezner, L.F. Bonewald, J.Q. Feng. Unique roles of phosphorus in endochondral bone formation and osteocyte maturation. J Bone Mener Res 26:1047-56, 2011.
- Lu Y., J.Q. Feng. FGF23 in skeletal modeling and remodeling. Curr Osteoporos Rep 9:103-108, 2011.
- Sun Y., Y. Lu, L. Chen, T. Gao, R. D'Souza, J.Q. Feng, C. Qin. DMP1 processing is essential to dentin and jaw formation. J Dent Res 90:619-624, 2011.
- Lu, Y., B. Yuan, C. Qin, Y. Xie, S. Dallas, M. McKee, M. Drezner, L. Bonewald, J. Feng. The biological function of DMP1 in osteocyte maturation is mediated by its 57 kDa C-terminal fragment. J Bone Mineral Res 26:331-340, 2011.
- Ma, D., R. Zhang, H. Rios, N. Haruyama, Y. Sun, Y, Xie, A. Kulkarni, C. Qin, J. Feng. Novel role of Periostin in postnatal tooth formation and mineralization. J Biol Chem 286:4302-09, 2011.
- Sun Y., L. Chen, S. Ma, J. Zhou, H. Zhang, J. Feng, C. Qin. Roles of DMP1 processing in osteogenesis, dentinogenesis and chondrogenesis. Cells Tissues Organs 194:199-204, 2011.
- Prasad M, Q. Zhu, Y. Sun, X. Wang, A. Kulkarni, A. Boskey, J. Feng, C. Qin. Expression of dentin sialophosphoprotein in non-mineralized tissue. J Histochem Cytochem 59:1009-21, 2011.
- Tang W., et al. The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science 332:478-84, 2011.
- Nakashima T., M. Hayashi, T. Fukunaga, K. Kurata, M. Oh-hora, J. Feng, L. Bonewald, T. Kodama, A. Wutz, E. Wagner, J. Penninger, H. Takayanagi. Evidence for osteocyte regulation of bone homeostasis through RANKL expression. Nature Medicine 17:1231-34, 2011.
- Han X., M. Liu, A. Voisey, Y. Ren, P. Kurimoto, T. Gao, L. Tefera, P. Dechow, H. Ke, J. Feng. Postnatal effect of overexpressed DKK1 on mandibular molar formation. J Dent Res 90:1312-17, 2011.
- Martin A., S. Liu, V. David, H. Li, A. Karydis, J. Feng, L. Quarles. Bone proteins PHEX and DMP1 regulate fibroblastic growth factor Fgf23 expression in osteocytes through a common pathway involving FGF receptor (FGFR) signaling. FASEB J 25: 2551-62, 2011.
- Wang X., S. Wang, C. Li, T. Gao, Y. Liu, A. Rangiani, Y. Sun, J. Hao, A. George, Y. Lu, J. Groppe, B. Yuan, J. Feng, C. Qin. Inactivation of a novel FGF23 regulator, FAM20C, leads to hypophosphatemic rickets in mice. PloS Genetics 8 (5): e1002708, 2012.
- Jaiprakash A, I. Prasadam, J. Feng, Y. Liu, R. Crawford, Y. Xiao. Phenotypic characterization of osteoarthritic osteocytes from the sclerotic zones: A possible pathological role in subchondral bone sclerosis. Int J Biol Sci 8:406-417, 2012.