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The Center for Craniofacial Research (CCR) was established in 2013 as a collaborative endeavor between UTHealth’s School of Dentistry and McGovern Medical School.  Craniofacial anomalies are common affecting 1/30 or 3% of newborns with more than 4.5 million affected annually worldwide.  The CCR’s mission is to lead cutting-edge research to identify, understand, prevent and treat craniofacial abnormalities and disorders. 

“Craniofacial abnormalities are common, costly and crushing for families. Finding the causes of these birth defects is of critical importance and achievable in the near future. This will lead to prevention programs and better treatments.”
– Jacqueline T. Hecht, PhD, Director, Center for Craniofacial Research, UTHealth School of Dentistry

Distinctions of the CCR

  • 14 full-time faculty members conducting clinically relevant studies to improve the lives of individuals with craniofacial disorders.
  • Funded by private and federal granting agencies including the National Institute of Dental and Craniofacial Research.
  • Collections that include tissues, cells, DNA and RNA collected from thousands of patients and families with cleft lip and palate, other dental anomalies and oral/dental conditions.
  • Outstanding facilities with state-of-the-art equipment in world-class laboratories.
  • Full-time genetic counselor providing clinical and genetic assessment of patients with craniofacial anomalies to help families understand why craniofacial anomalies occur.

The CCR is under the direction of nationally recognized geneticist Jacqueline T. Hecht, PhD, MS, professor and director of the Pediatric Research Center at the UTHealth McGovern Medical School. CCR investigators include award winning faculty including recipients of the Krane Award from the American Society for Bone and Mineral Research, two AAAS Fellows, and other honorable mentions in recognition of research achievement.

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Dr. Jacqueline Hecht is a board-certified PhD Medical Geneticist with extensive clinical expertise in skeletal dysplasias (dwarfing conditions), orthopedic syndromes and common birth defects. The Hecht Lab currently focus on gene discovery in nonsyndromic cleft lip and palate (NSCLP) and modeling identified genetic variation in the zebrafish craniofacies and delineating the molecular mechanism underlying pseudoachondroplasia (PSACH), a severe dwarfing condition, and developing therapeutic interventions.

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Dr. Leticia Chaves de Souza’s research interests are focused on understanding the molecular mechanisms underlying apical periodontitis (AP) development, susceptibility and healing. She is also interested in the clinical outcome of endodontic procedures, such as disinfection protocols, obturation techniques, and physico-chemical and biological properties of endodontic instruments and materials.

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Dr. Brett Chiquet’s primary research interests lie in patient care for those with cleft lip with or without cleft palate.  His research focuses on factors that influence patient care by collaborating with the multidisciplinary team that provides comprehensive care to these patients, including (1) pediatric plastic surgeons and orthodontists to study the effect of early appliance intervention, (2) microbiologists to study the effect of the oral microbiome during infancy, appliance therapy, and childhood, (3) orthodontists to study the feasibility of 3D printing on presurgical infant orthopedics, and (4) genetics professionals to study the etiology of cleft lip and palate and normal craniofacial development.  His secondary research interests lie in patient safety, specifically surrounding pharmacologic behavior guidance techniques (pBGTs) utilized in pediatric dentistry, focusing on patient-factors, parental concerns, and provider attitudes towards patient safety during pBGT utilization.

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Dr. Walid Fakhouri’s research focuses on understanding the genetic and epigenetic regulation of cell fate determination during neural tube and craniofacial development. The Fakhouri Laboratory investigates the function of two developmental genes and their protein activities in regulating cell shape changes and cytoskeletal organization, and how the loss of function can lead to birth defects, including cleft lip and palate, craniosynostosis, and facial dysostosis. His lab uses mouse models, organ cultures, and biochemical assays to delineate further the underlying cellular mechanism and regulatory pathway that drive the proper formation of the neural tube and craniofacial bone development. His research aims to uncover druggable genes and signaling pathways that can be used to prevent and treat congenital birth defects. His lab also investigates the role of the cleft lip and palate gene, IRF6, in salivary gland development and maturation. His research also aims to accelerate the identification of pathological non-coding DNA variations to improve cancer screening and prevention.

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Dr. Farach-Carson’s studies in her laboratory aim to integrate extracellular matrix biology with three fields: a) salivary gland tissue engineering b) cancer biology and metastasis to bone, and (c) bone and cartilage structure-function relations. Three-dimensional engineered microtissue models are used to study the behavior of both normal and aberrant cells and to study their behavior in a physiologically relevant context. Their translational partnerships support the development of new technologies needed to study cell behavior including for regenerative medicine and cancer biology applications.

Key words: Salivary gland tissue engineering, extracellular matrix, complex 3D systems for culture of both normal and cancerous tissues.

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The Harrington Laboratory develops a range of polymeric and supramolecular biomaterials for use in tissue regeneration and in vitro 3D cell culture. Lab members apply functionalized hyaluronan-based hydrogel matrices for salivary cell culture, including multiple biomanufacturing methods such as bioprinting. These same materials also enable our complex in vitro co-cultures of cancer xenografts with associated stromal fibroblasts on a microfluidic platform for drug screening. In our collaborations, Dr. Daniel Harrington uses self-assembling peptide amphiphile hydrogel platforms for growth factor delivery to promote nerve viability.

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Dr. Syed Hashmi’s research focuses on the epidemiological and population-level aspects of birth defects that involve craniofacial structures. He has been involved in various epidemiological and genetic studies on various congenital defects, including research on maternal risk factors during pregnancy (e.g. maternal hyperthermia or folic acid use) that may influence the risk of giving birth to a child with oral clefts. He has expertise working with Big Data and has collaborated with and worked on large datasets from the Texas Birth Defects Epidemiology and Surveillance (BDES) Branch of the Texas Department of State Health Services and the Centers for Disease Control and Prevention (CDC).

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Dr. Junichi Iwata’s research is focused on cellular and molecular mechanisms underlying craniofacial birth defects (e.g. cleft lip with/without cleft palate, tooth and musculoskeletal defects) and diseases (e.g. Sjögren’s syndrome). The Iwata Laboratory has been characterizing cellular metabolic processes, membrane trafficking, and non-coding RNAs—which are crucial for craniofacial development and homeostasis—using multidisciplinary approaches including genetics, genomics, proteomics, biochemistry, and molecular biology.

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The Komatsu Laboratory’s research has focused on understanding the molecular mechanisms responsible for human congenital diseases, with an emphasis on craniofacial abnormalities. Dr. Yoshihiro Komatsu’s ultimate long-term goal is to acquire the molecular knowledge for understanding craniofacial skeletal defects and to develop strategies for craniofacial skeletal tissue regeneration.

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The Ono & Ono Laboratory seeks to understand the fundamental characteristics of stem cells of bones and cartilages – termed “skeletal stem cells” – and how these cells orchestrate bone development, regeneration and diseases, primarily by means of mouse genetics approaches. Their laboratory has substantial expertise on in vivo cell lineage analyses, and application of this technique to interrogate the essential functionality of skeletal stem cells in vivo, in combination of single-cell genomics approaches. Noriaki Ono, DDS, PhD and Wanida Ono, DDS, DMSc, PhD study skeletal stem cells across many bone compartments through the body, including those residing in the growth plate, the bone marrow and the craniofacial structure.

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The Wang Laboratory’s research is focused in studying the molecular and genetic regulation of craniofacial and cardiac development, diseases, and regeneration. Our goal is to develop novel diagnostic and therapeutic tools for cardiovascular and craniofacial diseases. Dr. Jun Wang uses a combination of state-of-the-art approaches including mouse genetics, physiology studies, and next generation sequencing techniques.

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Dr. Danielle Wu's main areas of expertise include mechanobiology and tissue engineering. Her research interests include developing and testing tissue engineering prototypes in preclinical models for the restoration of tissue function. She investigates mechanotransduction mechanisms in skeletal, salivary, and lung tissue using bioequivalent and scalable ‘tissue-avatars’ to interrogate therapeutic interactions in health and disease.

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Simon Young, DDS, MD, PhD is a board-certified oral & maxillofacial surgeon and scientist whose research efforts include the synthesis and characterization of implantable biomaterials designed to elicit in situ cell recruitment and programming. His work includes the use of materials able to simultaneously deliver multiple bioactive factors with distinct release profiles. These constructs have been used in a diverse set of applications such as the promotion of craniofacial bone regeneration and cancer immunotherapy. Current work in the Young Laboratory seeks to develop novel material-based immunotherapies for the treatment of head and neck cancer and explore mechanisms of how this approach may synergize with chemo/radiation therapy.  The paradigm of in situ cell programming using biomaterials is also being utilized in separate collaborative tissue engineering research projects exploring the use of semiconductor-based materials to enhance craniofacial bone regeneration and multidomain peptide hydrogels for nerve regeneration.

1. Yu, Y., Alvarado, R., Petty, L.E., Bohlender, R.J., Shaw, D.M., Below, J.E., Bejar, N., Ruiz, O.E., Tandon, B., Eisenhofer, G.T., Kiss, D.L., Huff, C.D., Letra, A., Hecht, J.T.: Hum Mol Genet. 2022 Feb 11:ddac037. doi: 10.1093/hmg/ddac037. Online ahead of print. PMID: 35147171.

2. Mukhopadhyay, N., Feingold, E., Moreno-Uribe, L., Wehby, G., Valencia-Ramirez, L.C., Restrepo Muneton, C.P., Padilla, C., Deleyiannis, F., Christensen, K., Poletta, F.A., Orioli, L.M., Hecht, J.T., Buxo, C.J., Butali, A., Adeyemo, W.L., Veira, A.R. Shaffer, J.R., Murray, J.C., Weinberg, S.M., Leslie, E.J.:  Genome-wide association study of multiethnic non-syndromic orofacial cleft families identifies novel loci specific to family and phenotypic subtypes. medRxiv. doi: https://doi.org/10.1101/2021.09.20.21263645

3. Young, J., Lifer, S.S., Blanton, S., Hecht, J.T.: DNA methylation variation is identified in monozygotic twins discordant for nonsyndromic cleft lip and palate. Frontiers Cell Dev Biol 2021 May 12 doi: 10.3389/fcell.2021.656865 PMCID:PMC8149607.

4. Wehr, C, A. Lignieres, C. Obinero, A. Cepeda, A. Cardenas, F. Kasper, B. Acharya, E. Bonfante-Mejia, R. Riascos-Castaneda, R. Patel, B. T. Chiquet, and M. Greives. “MRI Modeling for 3D Printed Fabrication of Nasoalveolar Molding Appliance in Patients with Cleft Lip and Palate.” Cleft Palate Craniofacial Journal (Submitted December 12, 2022)

5. Younan, M., K. Westerman, B. Acharya, J. Wu, R. Ekeoduru, and B. T. Chiquet. “Prolonged exposure to general anesthesia in very young pediatric dentistry patients – A Root Cause Analysis.” Pediatric Dentistry 44(4):269-277. 2022. PMID: 35999676.

6. Wu, D., Chapela, P., Barrows, C.M.L., Harrington, D.A., Carson, D.D., Witt, R. L., Mohyuddin, N.G., Pradhan-Bhatt, S., Farach-Carson, M.C. “MUC1 and polarity markers INADL and SCRIB identify salivary ductal cells.” J. Dent. Res. (online ahead of print), 2022. PMID: 35259994.

7. Tellman, T.V., Dede, M., Aggarwal, V.A., Naba, A., Farach-Carson, M.C. “Systematic analysis of actively transcribed core Matrisome genes across tissues and cell phenotypes” Matrix Biology 111:95-107, 2022 PMID: 35714875.

8. Sablatura LK, Bircsak KM, Shepherd P, Bathina M, Queiroz K, Farach-Carson MC, Kittles RA, Constantinou PE, Saleh A, Navone NM, Harrington DA. A 3D Perfusable Platform for In Vitro Culture of Patient Derived Xenografts. Adv Healthc Mater. 2022 Dec 2:e2201434. doi: 10.1002/adhm.202201434. Epub ahead of print. PMID: 36461624.

9. Trubelja A, Kasper FK, Farach-Carson MC, Harrington DA. Bringing hydrogel-based craniofacial therapies to the clinic. Acta Biomater. 2022 Jan 15;138:1-20. doi: 10.1016/j.actbio.2021.10.056. Epub 2021 Nov 4. PMID: 34743044; PMCID: PMC9234983.

10. Martin S, Harrington DA, Ohlander S, Stupp SI, McVary KT, Podlasek CA. Peptide amphiphile nanofiber hydrogel delivery of Sonic hedgehog protein to the penis and cavernous nerve suppresses intrinsic and extrinsic apoptotic signaling mechanisms, which are an underlying cause of erectile dysfunction. Nanomedicine. 2021 Oct;37:102444. doi: 10.1016/j.nano.2021.102444. Epub 2021 Jul 24. PMID: 34314869; PMCID: PMC8464506.

11. Wu D, Lombaert IMA, DeLeon M, Pradhan-Bhatt S, Witt RL, Harrington DA, Trombetta MG, Passineau MJ, Farach-Carson MC. Immunosuppressed Miniswine as a Model for Testing Cell Therapy Success: Experience With Implants of Human Salivary Stem/Progenitor Cell Constructs. Front Mol Biosci. 2021 Sep 30;8:711602. doi: 10.3389/fmolb.2021.711602. PMID: 34660692; PMCID: PMC8516353.

12. Souza, L.C.; Neves, G.S.T.; Kirkpatrick, T.; Letra, A.; Silva, R. Physicochemical and biological properties of AH Plus Bioceramic. J. Endod. 49:69-76. 2023.

13. Shen, Z.; Tsao, H.; LaRue, S.; Liu, R.; Kirkpatrick, T.C.; Souza, L.C.; Letra, A.; Silva, R.M. Vascular endothelial growth factor and/or nerve growth factor treatment induces expression of dentinogenic, neuronal, and healing markers in stem cells of the apical papilla. J. Endod. 47: 924-931. 2021.

14. Souza, L.C.; Cavalla, F.; Maili, L.; Garlet, G.P.; Vieira, A.R.; Silva, R.M.; Letra, A. WNT gene polymorphisms and predisposition to apical periodontitis. Sci Rep. 9:18980. 2019.

15. Souza, L.C.; Crozeta, B.M.; Guajardo, L.; Brasil, F.; Sousa-Neto, M.D.; Letra, A.; Silva, R.: Potential role of TP63 in apical periodontitis development. Int. Endod. J. 52: 1344-1353. 2019.

16. Souza, L.C.; Brito, P.R.; Oliveira, J.C.M.; Alves, F.R.F.; Moreira, E.J.L.; Sampaio Filho, H.R.; Roças, I.N.; Siqueira Jr, J.F.: Photodynamic Therapy with two different photosensitizers as a supplement to instumentation / irrigation procedures in promoting intracanal reduction of Enterococcus faecalis. J. Endod. 36: 292-296. 2010.

17. Reyes Fernandez, P.C., Wright, C.S., Masterson, A.N., Yi, X., Tellman, T.V., Bonteanu, A., Rust, K., Noonan, M.L., White, K.E., Lewis, K.J., Sankar, U., Hum, J.M., Bix, G., Wu, D., Robling, A.G., Sardar, R., Farach-Carson, M.C., and Thompson, W.R. Gabapentin Disrupts Binding of Perlecan to the α2δ1 Voltage Sensitive Calcium Channel Subunit and Impairs Skeletal Mechanosensation. Biomolecules 12, 1857. 2022. doi: 10.3390/biom12121857

18.  Wu, D., Witt, R. L., Harrington, D. A. & Farach-Carson, M. C. Dynamic Assembly of Human Salivary Stem/Progenitor Microstructures Requires Coordinated α1β1 Integrin-Mediated Motility. Frontiers in Cell and Developmental Biology 7, 224 2019. PMID: 31750298. doi: 10.3389/fcell.2019.00224

19. Wu, D., Ganatos, P., Spray, D.C., and Weinbaum, S. On the electrophysiological response of bone cells using a Stokesian fluid stimulus probe for delivery of quantifiable localized picoNewton level forces. J Biomech. 44 (3): 1702-08. 2011. PMID: 21511259

20. Wu, D., Schaffler, M.B., Weinbaum, S. and Spray, D.C. Matrix-dependent adhesion mediates network responses to physiological stimulation of the osteocyte cell process. PNAS. 110 (29): 12096-12101. 2013. PMID: 23818616.

2023 - Brett T. Chiquet, DDS, PhD, Course Co-Director, “Cleft Lip and Palate Symposium: Primary Lip Closure and Nasoalveolar Molding Techniques”, El Paso

2022 – Danielle Wu, PhD, Daniel Harrington, PhD, Mary C. Farach-Carson, PhD, JDR Cover Article, Journal of Dental Research, “MUC1 and Polarity Markers INADL and SCRIB Identify Salivary Ductal Cells”

2022 – Daniel Harrington, PhD, Regenerative Medicine Scholar, Gulf Coast Consortium Regenerative Medicine Cluster

2021 - Brett T. Chiquet, DDS, PhD, Course Co-Director, “Cleft Lip and Palate Symposium: Primary Lip Closure and Nasoalveolar Molding Techniques”, El Paso

2021 - Brett T. Chiquet, DDS, PhD, Recipient UTHealth SOD-SON Joint Seed Award Program with Deniz Dishman, PhD, CRNA for project “Identifying the incidence of post-sedation adverse events in pediatric dentistry”

2020 - Brett T. Chiquet, DDS, PhD, Induction into Omicron Kappa Upsilon Mu Mu Chapter

2019 - Leticia Chaves de Souza, DDS, MS, PhD, Journal of Endodontists Awards, Clinical research category, “Investigating potential correlations between endodontic pathology and cardiovascular diseases using epidemiological and genetic approaches”