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Molecular and Human Genetics

Houston, Texas

Department of Molecular and Human Genetics
Department of Molecular and Human Genetics
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Brendan Lee, M.D., Ph.D.

Brendan Lee, M.D., Ph.D.

Professor, Department of Molecular and Human Genetics

Other Positions

Professor, Programs in Cell & Molecular Biology, Developmental Biology, and Translational Biology & Molecular Medicine
Investigator, Howard Hughes Medical Institute
Director, Skeletal Dysplasia Clinic
Director, Medical Students Research Track
Director, The Rolanette and Berdon Lawrence Bone Disease Program of Texas

Education

B.S., City University of New York, Brooklyn College, 1986
Ph.D., State University of New York Health Science Center at Brooklyn, 1990
M.D., State University of New York Health Science Center at Brooklyn, 1993
Postdoctoral Fellow, Mount Sinai School of Medicine, 1991
Resident, Pediatrics, Baylor College of Medicine, 1995
Fellow, Medical Genetics, Baylor College of Medicine, 1997

Board Certifications

American Board of Pediatrics
American Board of Medical Genetics: Biochemical Genetics and Clinical Genetics

Professional Organizations

Member, American Society of Human Genetics
Member, American Society for Clinical Investigation
Member, American College of Medical Genetics
Member, Society for Inherited Metabolic Disease
Member, Society for Pediatric Research

Clinical Interests

Skeletal Dysplasias, Inborn Errors of Metabolism, Urea Cycle Disorders

Research Interests

Genetic pathways that specify development and homeostasis: Translational studies of skeletal development and urea cycle disorders, and therapy for metabolic diseases

The overall mission of my research program is to elucidate basic developmental and biochemical pathways that regulate mammalian organogenesis and homeostasis, and to apply this to the development of new diagnostic and therapeutic tools for disorders resulting from the dysregulation of these pathways. A common theme is an approach involving the flow of information from the study of human genetic disease phenotypes, to the generation and testing of hypotheses in cell and animal models, to the evaluation of the consequences of these dysregulated processes back in humans, and finally, to the development of treatment protocols. We have focused on elucidating the transcriptional networks governing development and the signaling pathways that regulate them. We correlate human genetic disease phenotypes with mouse models to ask what genes are regulated by and targets of key transcription factors during chondrogenesis, osteoblastogenesis, and limb and kidney formation. Current studies are focused on the transcription factors Runx2, Trps1, Sox9, and Lmx1b, to Tgfβ and Notch signaling pathways during skeletogenesis, and novel post-translational modifications of matrix proteins. These basic and translational studies are linked intimately with clinical research performed at the Texas Children’s Hospital Skeletal Dysplasia Clinic. Here, the multidisciplinary care of pediatric patients with skeletal malformations is closely linked with studies aimed at understanding the consequences of genetic mutations, and at quantitation and treatment of osteoporosis associated with skeletal dysplasias.

Collagen Type X

Pericellular localization of collagen type X in hypertrophic chondrocytes.

In contrast to developmental pathways, much basic information is already available in well studied biochemical pathways that are critical for homeostasis, such as the urea cycle. Here, we have translated this basic information into stable isotope based metabolic protocols to develop new tools for diagnosis and clinical management of urea cycle patients. By using this unique human disease model and physiologic tools that measure the in vivo activity of this pathway, we are asking questions about the interaction of the urea cycle and the nitric oxide pathways that contribute to key gene-nutrient interactions during postnatal growth and development. The ultimate goal is to develop new treatments and this is the focus of our gene replacement studies using helper-dependent adenoviral vectors. An important component of this is work focused on understanding and preventing the host innate immune response and acute toxicity associated with adenovirus treatment. The spectrum of my research program extends from gene identification in human disease, to correlating mechanisms of disease with normal biological processes, to measuring and manipulating these pathways for diagnosis and treatment in humans and in animal models.

Selected Publications

  1. Engin F, Yao Z, Yang T, Zhou G, Bertin T, Jiang MM, Chen Y, Wang L, Zheng H, Sutton R, Boyce BF, Lee B (2008). Dimorphic effects of Notch signaling in bone homeostasis. Nat. Med. 14(3): 299-305. [Pub Med]
  2. Zhou G, Zheng Q, Engin F, Munivez E, Chen Y, Sebald E, Krakow D, Lee B (2006). Dominance of SOX9 function over RUNX2 during skeletogenesis. Proc. Natl. Acad. Sci. USA 103(50): 19004-9. [Pub Med]
  3. Morello R, Bertin T, Chen Y, Hicks J, Tonachini L, Monticone M, Castagnola P, Rauch F, Glorieux FH, Vranka J, Bächinger HP, Schwarze U, Byers PH, Weis MA, Fernandes RJ, Eyre DR, Yao Z, Boyce BF, Lee B (2006). CRTAP is required for 3-prolyl-hydroxylation and loss of its function causes recessive Osteogenesis Imperfecta. Cell 127(2): 291-304. [Pub Med]
  4. Toietta G, Mane V, Norona WS, Finegold MJ, Ng P, McDonagh AF, Beaudet AL, Lee B (2005). Complete, long-term correction of hyperbilirubinemia in the Gunn rat. Proc. Natl. Acad. Sci. USA 102(11): 3930-5. [Pub Med]
  5. Zheng Q, Zhou G, Morello R, Chen Y, Garcia-Rojas X, Lee B (2003). Type X collagen gene regulation by Runx2 contributes to its hypertrophic chondrocyte-specific expression in vivo. J. Cell Biol. 162(5): 833-42. [Pub Med]
  6. Miner JH, Morello R, Li C, Andrews KL, Antignac C, Shaw AS, Lee B (2002). A role for Lmx1b in podocyte development and function as a transcriptional regulator of Cd2ap and Nphs2 (podocin). J. Clin. Invest. 109(8): 1065-1072. [Pub Med]
  7. Morello R, Zhou G, Dreyer SD, Harvey SJ, Ninomiya Y, Thorner PS, Cole W, Winterpacht A, Zabel B, Oberg KC, Lee B (2001). Regulation of glomerular basement membrane collagen expression by Lmx1b contributes to renal disease in nail patella syndrome. Nat. Genet. 27(2): 205-8. [Pub Med]
  8. Lee B, Yu H, Jahoor F, O'Brien W, Beaudet AL, Reeds P (2000). In vivo urea cycle flux distinguishes and correlates with phenotypic severity in disorders of the urea cycle. Proc. Natl. Acad. Sci. USA 97(14): 8021-8026. [Pub Med]
  9. Lee B, Dennis JA, Healy PJ, Mull B, Pastore L, Yu H, Aguilar-Cordova E, O'Brien W, Reeds P, Beaudet AL (1999). Hepatocyte gene therapy in a large animal: A neonatal bovine model of citrullinemia. Proc. Natl. Acad. Sci. USA 96(7): 3981-3986. [Pub Med]
  10. Dreyer SD, Zhou G, Baldini A, Winterpacht A, Zabel B, Cole W, Johnson RL, Lee B (1998). Mutations in LMX1B cause abnormal skeletal patterning and renal dysplasia in nail patella syndrome. Nat. Genet. 19(1): 47-50. [Pub Med]
  11. Lee B, Thirunavukkarasu K, Zhou L, Pastore L, Baldini A, Hecht J, Geoffrey V, Ducy P, Karsenty G (1997). Missense mutations abolishing DNA binding domain of the Osteoblast-Specific Transcription Factor CBFA1/OSF2 in cleidocranial dysplasia. Nat. Genet. 16(3): 307-10. [Pub Med]

More Publications (PubMed)

Awards and Honors

2009: E. Mead Johnson Award for “Outstanding Scientific Achievement in Pediatrics”
2009: Edith and Peter O'Donnell Award
2007: Michael E. Debakey Excellence in Research Award
2005: American Philosophical Society’s Judson Darland Prize for Achievement in Patient-Oriented Clinical Research
2000: Society for Pediatric Research Young Investigator Award

Contact Information

Brendan Lee, M.D., Ph.D.
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza, MS BCM225
Houston, TX, 77030, U.S.A.

Phone: 713-798-8835
Fax: 713-798-5168
E-mail:

Community of Science Expertise Record: 407477

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