Brendan Lee, M.D., Ph.D.
Robert and Janice McNair Endowed Chair in Molecular and Human Genetics
Professor of Molecular and Human Genetics
Professor, Programs in Integrative Molecular and Biomedical Sciences; Developmental Biology; and Translational Biology & Molecular Medicine
Investigator, Howard Hughes Medical Institute
Director, Center for Skeletal Medicine and Biology
Director, Skeletal Dysplasia Clinic
Director, Medical Students Research Track
Co-Director, The Rolanette and Berdon Lawrence Bone Disease Program of Texas
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
American Board of Pediatrics
American Board of Medical Genetics: Clinical Biochemical Genetics and Clinical Genetics
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
Skeletal Dysplasias, Inborn Errors of Metabolism, Urea Cycle Disorders
Developmental, translational and clinical studies for skeletal disorders and inborn errors of metabolism
As a pediatrician and geneticist, the overall mission of my research program is to translate the study of structural birth defects and inborn errors of metabolism into a basic understanding of development, disease and novel therapeutic approaches. My long standing focus has been the study of human inborn errors of metabolism and structural birth defects of the skeleton. We have applied genetic approaches to the study of biochemical genetic disorders (specifically urea cycle disorders) as models of complex disease (those involving nitric oxide dysregulation). Because of this focus, we have studied metabolic derangements broadly in the endocrine, cardiovascular, skeletal, renal systems.
In the area of structural birth defects, we have studied paracrine and endocrine signaling pathways that regulate skeletal development including morphogens (TGFb, Wnt and Notch), post-transcriptional regulation by microRNAs, and extracellular matrix modifications (collagen prolyl-hydroxylation). These developmental pathways have led me to ask how their dysregulation in postnatal life lead to common diseases such as osteoporosis, osteoarthritis, and cancer.
An emerging area is how these mechanism may also broadly translate into the pathogenesis of heritable disorders of connective tissue. Ultimately, I have attempted to translate these findings by developing cell and helper-dependent adenoviral gene transfer for these conditions. A unifying approach is to identify new genetic basis of skeletal dysplasias (over 15) to inform mechanistic and therapeutic studies. My laboratory research program is linked with clinical research that is performed as part of the Skeletal Dysplasia Clinic and the Metabolic Disorders Clinic at Texas Children’s Hospital, respectively, and two clinical research networks.
My clinical research program began with stable isotopic measurements in humans and urea cycle disorder patients to better diagnose patients with disorders of urea cycle flux and to evaluate the differential bioavailability of different sources of nitrogen (enteral vs. parenteral) to the urea cycle. These human studies have evolved to assessment of nitric oxide flux in patients with UCDs and specifically with argininosuccinic aciduria. I have participated in and led both investigator initiated and industry sponsored interventional studies including the design of Phase II and III studies of a novel ammonia scavenger glyceryl-triphenylbutyrate in urea cycle patients, combinatorial phenylbutyrate/arginine treatment in patients with argininosuccinic aciduria, and zoledronic acid and teriparatide treatment in pediatric and adult osteogenesis imperfecta, respectively.
- Laine CM, Joeng KS, Campeau PM, Kiviranta R, Tarkkonen K, Grover M, Lu JT, Pekkinen M, Wessman M, Heino TJ, Nieminen-Pihala V, Aronen M, Laine T, Kröger H, Cole WG, Lehesjoki AE, Nevarez L, Krakow D, Curry CJ, Cohn DH, Gibbs RA, Lee BH, Mäkitie O (2013). WNT1 mutations in early-onset osteoporosis and osteogenesis imperfecta. N. Engl. J. Med. 368(19): 1809-16. PubMed PMID: 23656646
- Ruan MZ, Erez A, Guse K, Dawson B, Bertin T, Chen Y, Jiang MM, Yustein J, Gannon F, Lee BH (2013). Proteoglycan 4 expression protects against the development of osteoarthritis. Sci. Transl. Med. 5(176): 176ra34. PubMed PMID: 23486780
- Erez A, Nagamani SC, Shchelochkov OA, Premkumar MH, Campeau PM, Chen Y, Garg HK, Li L, Mian A, Bertin TK, Black JO, Zeng H, Tang Y, Reddy AK, Summar M, O'Brien WE, Harrison DG, Mitch WE, Marini JC, Aschner JL, Bryan NS, Lee B (2011). Requirement of argininosuccinate lyase for systemic nitric oxide production. Nat. Med. 17(12): 1619-26. PubMed PMID: 22081021
- Yang T, Mendoza-Londono R, Lu H, Tao J, Li K, Keller B, Jiang MM, Shah R, Chen Y, Bertin TK, Engin F, Dabovic B, Rifkin DB, Hicks J, Jamrich M, Beaudet AL, Lee B (2010). E-selectin ligand-1 regulates growth plate homeostasis in mice by inhibiting the intracellular processing and secretion of mature TGF-beta. J. Clin. Invest. 120(7): 2474-85. PubMed PMID: 20530870
- 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. PubMed PMID: 18297084
- 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. U S A 103(50): 19004-9. PubMed PMID: 17142326
- 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. PubMed PMID: 17055431
- Toietta G, Mane V, Norona WS, Finegold MJ, Ng P, McDonagh AF, Beaudet AL, Lee B (2005). Lifelong elimination of hyperbilirubinemia in the Gunn rat with a single injection of helper-dependent adenoviral vector. Proc. Natl. Acad. Sci. U S A 102(11): 3930-5. PubMed PMID: 15753292
- 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. PubMed PMID: 11175791
- 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. U S A 97(14): 8021-8026. PubMed PMID: 10869432
Awards and Honors
2013: Elected to the Institute of Medicine
2010: Association of American Physicians
2010: American Society for Clinical Investigation
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
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.
Community of Science Expertise Record: 407477