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Rena N. D'Souza

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Rena N. D'Souza, DDS, PhD

Professor
Department of Biomedical Sciences
Member of the GSBS Faculty

3302 Gaston Ave.
Dallas, Texas 75246
Phone: 214-828-8375
Fax: 214-874-4538
Email: rdsouza@bcd.tamhsc.edu

Education and Post-Graduate Training

Ph.D., Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston (1987)

M.S., Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston (1985)

D.D.S., University of Texas Health Science Center, Houston (1985)

General Practice Residency, Departments of Oral Surgery, Operative Dentistry and Periodontics, Government Dental College and St. George's Hospital, University of Bombay, India (1977-78)

B.D.S. (Bachelor of Dental Surgery), University of Bombay, India (1977)

Career History

Professor with tenure, Department of Biomedical Sciences, Texas A&M Health Science Center Baylor College of Dentistry (2006-present)

Professor with tenure, Department of Orthodontics, University of Texas Health Science Center, Houston (2001-2006)

Associate Professor with tenure, Department of Orthodontics (1999-2001); Department of Basic Sciences (1995-1999), University of Texas Health Science Center, Houston

Assistant Professor (Full-time), Departments of Basic Sciences and Anatomical Sciences, University of Texas Health Science Center, Houston (1989-1995)

Assistant Professor (part-time), Department of Anatomical Sciences, University of Texas Health Science Center, Houston (1985-1988)

Research Interests

Briefly, specific research interests include the role of signaling molecules involved in epithelial-mesenchymal interactions in tooth and bone development; Genetic etiology of tooth agenesis; Molecular control of odontoblast differentiation and the use of tooth-derived stem cells for regeneration of the dentin-pulp complex and periodontium.  A detailed description of our current projects follows:

The roles of Runx2 and Twist-1 in tooth morphogenesis

Mammals, including humans and rodents, develop a specific number of tooth in a single row along the long axis of each jaw quadrant.  This tooth morphogenesis and patterning is tightly controlled by several signaling molecules, as well as many transcription factors.  The known signaling molecules include members of transforming growth factor β (TGFβ), fibroblast growth factor (FGF), sonic hedgehog (Shh), Wnt and tumor necrosis factor (TNF).  The transcription factors involved include Msx1, Pax 9, Osr2, Runx2 and Twist-1, etc.  These signaling molecules and transcription factors mediate the sequential interactions between and within epithelial and mesenchymal tissues by regulating the expression of signaling receptors, new signaling molecules and other transcription factors. Any disturbance in the signaling pathway or mutations in transcription factors will result in either supernumerary teeth or tooth agenesis.

In this project, we mainly focus on two transcription factors to study their roles in tooth morphogenesis: Runx2 and Twist-1, which have been shown to have antagonistic functions in osteoblast differentiation.  Runx2 is a transcription factor with homology to the Drosophila pair-rule gene runt.  Runx2 mutations in humans result in autosomal-dominant cleido-cranial dysplasia (CCD), characterized by dysplastic clavicles, patent sutures and fontanelles and supernumerary teeth.  Runx2 mutant mice develop molars arrested at the late bud stage.  Twist-1 is a basic-helix-loop-helix (bHLH) containing transcription factor.  Twist-1 mutations in humans cause Saethre-Chotzen Syndrome (SCS), which shows an overlapping phenotype with mutations in the FGFR3 or FGFR2 genes.  The hallmark features of the disorder are craniosynostoses, syndactyly of the fingers, duplicated halluces, and facial asymmetry.   Dental anomalies reported in SCS include multiple hypoplastic, peg-shaped incisors and tooth agenesis, as well as pulp stone seen in teeth with broad, bulbous crowns and narrow, tapering roots.

Our goal is to understand the molecular mechanisms underlying the supernumerary teeth produced in CCD patients and tooth agenesis in Runx2 mutant mice. Specifically, we study the antagonistic role of Twist-1 on Runx2 in tooth morphogenesis, using both molecular and genetic approaches described as follows: 1) To determine whether Twist-1 also exerts the same antagonistic function on Runx2 in odontoblst differentiation, using lentivirus-mediated overexpression or silencing of Runx2 and Twist-1 in dental pulp stem cells (DPSC); 2) To perform a genetic rescue study by generating compound mutants that completely lack Runx2 and are also heterozygous for Twist-1 genes, and to determine whether lower Twist-1 activity will rescue the tooth defects in Runx2 mutants; and 3) To study how Runx2 and Twist-1 are integrated into the known signaling pathways to regulate tooth morphogenesis using both in vitro and in vivo approaches.

Signaling mechanisms in early tooth development

Our research in this area focuses on the elaboration of the interaction between transcription factors Pax9 and Msx1 and signaling protein Bmp4 in the mesenchymal layer of the tooth bud.  The paired domain transcription factor Pax9 and the homeodomain transcription factor Msx1 are of special interest because mutations in either gene cause severe tooth agenesis in humans.  The products of both genes are also necessary for the induction of the TGFβ superfamily member bone morphogenetic protein Bmp4.  Bmp4 is the critical signaling factor for progression of the bud stage to the cap stage of odontogenesis.  Specifically our goals are:

1)  To define the molecular relationship between Pax9, Msx1 and Bmp4 and other partner genes that leads to the progression of tooth bud development.  This research involves mapping the protein-protein interaction domains of Pax9 and Msx1, delineating regulatory sequences within the Msx1 and Bmp4 promoters, performing a functional analysis of naturally occurring PAX9 mutant proteins, identification of other Pax9-interacting proteins and of Pax9-dependent genes.  We also intend to clarify mechanism(s) of Bmp4 induction by Msx1.

2) To identify new tooth agenesis and Pax9/Msx1 partner genes through genetic studies of patients with familial tooth agenesis.  Here we will continue to pursue a high throughput candidate sequencing approach.  We will also add association studies for the evaluation of common sequence variants in hypodontia.  Gene detection through linkage analysis will be attempted in large enough families.

Recent Grants

  • Self-assembling Peptide Nanofiber Hydrogels for Delivery of Proteins and Cells.  NIH/NIDCR R01 DE021798, 2011-2016
  • Nanostructured Peptide Hydrogels and Stem Cells for Dentin-Pulp Complex Regeneration. IADR/GlaxoSmithKline Innovation in Oral Care Awards, 2009-2011
  • Signaling Mechanisms in Early Tooth Development.  NIH 5 R01 DE019471, 2008-2012

          - ARRA Administrative Collaborative Supplement, 2009-2001
          - ARRA Administrative Supplement for Summer Research Experiences for Dental Students, 2009

  • Regulation of Runx2 Function by Twist-1 in Tooth Development. NIH R01 DE13368, 2006-2010
          - ARRA Administrative Supplement for Summer Research Experiences for Science Educators, 2009
  • Baylor's Program for Bioengineering Sciences and Translational Research: B-BEST.  NIH 1 P30 DE020742-01, 2009-2011
  • Baylor's Scientific Training Program for Dental Academic Researchers: B-STARS. NIH 5 T32 DE018380, 2008-2012
  • Self-assembling Peptide-amphiphile Nanofibers as a Scaffold for Dental Stem Cells. Alliance for Nano Health Seed Grant; 2006-2009

Selected Publications

  1. Prasad M, Zhu Q, Liu Q, D'Souza RN, Feng JQ, Qin C.  Loss of dentin sialophosphoprotein leads to periodontal disease in mice.  Journal of Periodontal Research.  In press, 2012.
  2. Napierala D, Sun Y, Maciejewska I, Bertin TK, Dawson B, D'Souza R, Qin C, Lee B. Transcriptional repression of the Dspp gene leads to dentinogenesis imperfecta phenotype in Collal-Trps1 transgenic mice.  Journal of Bone and Mineral Research 27:1735-45, 2012.
  3. Jones DL, Hinton RJ, Dechow PC, Abdellatif H, McCann AL, Schneiderman ED, D'Souza R.  The evidence-based dentistry initiative at Baylor College of Dentistry.  Tex Dent J  128:177-180, 2011.
  4. Galler KM, Cavender AC, Koeklue U, Suggs LJ, Schmalz G, D'Souza RN.  Bioengineering of dental stem cells in a PEGylated fibrin gel.  Regenerative  Medicine 6:191-200, 2011.
  5. Kong H, Wang Y, Patel M, Mues G, D'Souza RN.  Regulation of Bmp4 expression in odontogenic mesenchyme: From simple to complex.  Cells Tissues Organs 194:156-160, 2011.
  6. Sun Y, Lu Y, Chen L, Gao L, D'Souza R, Feng J, Qin C.  DMP1 processing is essential to dentin and jaw formation.  J Dent Res 90:619-624, 2011.
  7. Hinton RJ, Dechow PC, Abdellatif H, Jones DL, Schneiderman ED, McCann AL, D'Souza RN.  The winds of change: Creating an EBD culture at Baylor College of Dentistry.  J Dent Educ 75:279-290, 2011.
  8. Wang Y, Kapadia H, Kong H, Mues G, D'Souza RN. MSX1 mutations: How do they cause tooth agenesis?  J Dent Res 90:311-316, 2011.
  9. Galler KM, D'Souza RN,  Tissue engineering approaches for regenerative dentistry.  Regenerative Medicine 6:111-124, 2011.
  10. Galler KM, Schweikl H, Hiller KA, Cavender AC, Bolay C, D'Souza RN, Schmalz G.  TEGDMA reduces mineralization in dental pulp cells.  J Dent Res 90:257-262, 2011.
  11. Galler KM, D'Souza RN, Hartgerink JD.  Biomaterials and their potential applications for dental tissue engineering.  J Mater Chem 20:8730-46, 2010.
  12. Sun Y, Prasad M, Gao T, Wang Y, Zhu Q, D'Souza RN, Feng JQ, Qin C.  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.
  13. Galler KM, Aulisa L, Regan KR, D'Souza RN, Hartgerink JD.  Self-assembling multidomain peptide hydrogels: Designed susceptibility to enzymatic cleavage allows enhanced cell migration and spreading.  J Am Chem Soc 132:3217-23, 2010.
  14. Mues G, Tardivel A, Willen L, Kapadia H, Seaman R, Frazier-Bowers S, Schneider P, D'Souza RN.  Functional analysis of Ectodysplasin-A mutations causing selective tooth agenesis.  Eur J Hum Genet 18:19-25, 2010.
  15. Mues G, Kapadia H, Wang Y, D'Souza RN.  Genetics and human malformations.  J Craniofac Surg 20 Suppl 2:165204, 2009.
  16. Wang Y, Groppe JC, Wu J, Ogawa T, Mues G, D'Souza RN, Kapadia H.  Pathogenic mechanisms of tooth agenesis linked to paired domain mutations in human PAX9.  Hum Mol Genet 18:2863-84, 2009.
  17. Wright JT, Morris C, Clements SE, D'Souza RN, Gaide O, Mikkola M, and Zonana J.  Classifying ectodermal dysplasias: Incorporating the molecular basis and pathways (Workshop II). Am J Med Genet A 149A:2062-67, 2009. 
  18. Mues GI, Griggs R, Hartung AJ, Whelan G, Best LG, Srivastava AK, D'Souza RN. From ectodermal dysplasia to selective tooth agenesis.  Am J Med Genet A 149A: 2037-41, 2009.
  19. Lin Y, Cheng YS, Qin C, Lin C, D'Souza R, Wang F.  FGFR2 in the dental epithelium is essential for development and maintenance of the maxillary cervical loop, a stem cell niche in mouse incisors.  Dev Dyn 238:324-330, 2009.
  20. Wang Y, Wu H, Wu J, Zhao H, Zhang X, Mues G, D'Souza RN, Feng J, and Kapadia H.  Identification and functional analysis of two novel PAX9 mutations.  Cells Tissues Organs 189:80-87, 2009.
  21. Komabayashi T, D'Souza RN, Dechow PC, Safavi KE, Spangberg LS.  Particle size and shape of calcium hydroxide.  J Endod 35:284-287, 2009.
  22. Venugopalan SR, Amen MA, Wang J, Wong L, Cavender AC, D'Souza RN, Akerlund M, Brody SL, Hjalt TA, Amendt BA.  Novel expression and transcriptional regulation of FoxJ1 during oro-facial morphogenesis.  Hum Mol Genet 17:3643-54, 2008.
  23. Peng T, Huang B, Sun Y, Lu Y, Bonewald L, Chen S, Butler WT, Feng J, D'Souza RN, Qin C.  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, 2008. 
  24. Galler KM, Cavender A, Yuwono V, Dong H, Shi S, Schmalz G, Hartgerink JD, D'Souza RN. Self-assembling poptide amphiphile nanofibers as a scaffold for dental stem cells.  Tissue Eng Part A 14:2051-8, 2008.
  25. Qin C, D'Souza RN, Feng JQ. Dentin matrix protein 1 (DMP1): New and important roles for biomineralization and phosphate homeostasis. J Dent Res 86:1134-1141, 2007.
  26. Galler KM, Yasue A, Cavender AC, Bialek P, Karsenty G and D'Souza RN. A novel role for Twist-1 in pulp homeostasis. J Dent Res 86:951-955, 2007.
  27. D'Souza RN and Klein OD. Unraveling the molecular mechanisms that lead to supernumerary teeth in mice and men: Current concepts and novel approaches. Cells Tissues Organs 186:60-69, 2007.
  28. Christgau M, Caffesse RG, Schmalz G and D'Souza RN. Extracellular matrix expression and periodontal wound-healing dynamics following guided tissue regeneration therapy in canine furcation defects. J Clin Periodontol, published online, June 21, 2007.
  29. Kapadia H, Mues R and D'Souza RN. Genes affecting tooth morphogenesis. Orthod Craniofacial Res 10:1-9, 2007.
  30. D'Souza RN and Klein OD. Unraveling the molecular mechanisms that lead to supernumerary teeth in mice and men: Current concepts and novel approaches. Cells Tissues Organs 186:60-69, 2007.
  31. Ogawa T, Kapadia H, Feng JQ, Raghow R, Peters H and D'Souza RN. Functional consequences of interactions between Pax9 and Msx1 genes in normal and abnormal tooth development. J Biol Chem 281 (27):18363-18369, 2006.
  32. Kapadia H, Frazier-Bowers S, Ogawa T, D'Souza RN. Molecular characterization of a novel PAX9 missense mutation causing posterior tooth agenesis. Eur J Hum Genet 14:403-409, 2006.
  33. Galler KM, Schweikl H, Thonemann B, D'Souza RN and Schmalz G. Human pulp-derived cells immortalized with SV40 T-Ag. Euro J Oral Sci 114(2):138-146, 2006.
  34. Bronckers ALJJ, Sasaguri K, Cavender AC, D'Souza RN and Englese MA. Expression of RUNX2/CBFA1/PEBP2αA during angiogenesis in postnatal rodent and fetal human orofacial tissues. J Bone Min Res 20 (3):428-437, 2005.
  35. Ogawa T, Kapadia H, Wang B and D'Souza RN. Studies on Pax9-Msx1 protein interactions. Arch Oral Biol 50 (2):141-145, 2005.
  36. Mensah JK, Ogawa T, Kapadia H, Cavender AC and D'Souza RN. Functional analysis of a mutation in PAX9 associated with familiar tooth agenesis in humans. J Biol Chem 279:5924-5933, 2004.
  37. Åberg T, Cavender A, Gaikwad JS, Bronckers ALJJ, Wang X, Waltimo-Sirén J, Thesleff I, and D'Souza RN. Phenotypic changes in dentition of Runx2 homozygote-null mutant mice. J Histochem Cytochem 52(1):131-140, 2004.
  38. Zou SJ, D'Souza RN, Åberg T and Bronckers ALJJ. Tooth eruption and cementum formation in the Runx2/Cbfa1 heterozygous mouse. Arch Oral Bio 48:673-677, 2003.
  39. Sreenath T, Thyagarajan T, Hall B, Longenecker G, D'Souza RN, Hong S, Wright JT, MacDougall M, Sauk J and Kulkarni AB. Dentin sialophosphoprotein knockout mouse teeth display widened predentin zone and develop defective dentin mineralization similar to human dentinogenesis imperfecta-III. J Biol Chem 278(27):24874-80, 2003.
  40. Frazier-Bowers SA, Pham KY, Le EV, Cavender AC, Kapadia JP, King TM, Milewicz DM and D'Souza RN. A unique form of hypodontia observed in Vietnamese patients: Clinical and molecular analysis. J Med Genet June; 40 (6):e79, 2003.
  41. Frazier-Bowers S, Scott M, Cavender A, and D'Souza RN. Mutational analysis of families affected with molar oligodontia. Conn Tiss Res 43:296-300, 2002.
  42. Das P, Stockton DW, Bauer C, Shaffer LG, D'Souza RN, Wright T, and Patel PI. Haploinsufficiency of PAX9 is associated with autosomal dominant hypodontia. Hum Genet 110(4):371-376, 2002.
  43. Frazier-Bowers SA, Guo DC, Cavender A, Xue L, Evans B, King T, Milewicz D, and D'Souza RN. A novel mutation in human PAX9 causes molar oligodontia. J Dent Res 81(2):129-133, 2002.