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

Chair

(713) 798-5443

Email

blee@bcm.edu

Positions

Chair: Molecular and Human Genetics
Baylor College of Medicine

Robert and Janice McNair Endowed Chair and Professor: Molecular and Human Genetics
Baylor College of Medicine
Houston, TX, US

Member: Development, Disease Models & Therapeutics Graduate Program
Baylor College of Medicine

Member: Genetics and Genomics Graduate Program
Baylor College of Medicine

Director: Center for Skeletal Medicine and Biology
Baylor College of Medicine

Director: Skeletal Dysplasia Clinic
Texas Children's Hospital

Associate Director: Medical Research Pathway
Baylor College of Medicine

Co-Director: Rolanette and Berdon Lawrence Bone Disease Program of Texas
Baylor College of Medicine

Member: Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine
Houston, Texas, United States

Professor: Molecular and Human Genetics
Baylor College of Medicine

Addresses

Skeletal Dysplasia Center (Clinic): Texas Children's Clinical Care Center
6701 Fannin St., 16th Floor
Houston, TX, 77030
United States
Phone: (832) 822-4298
Skeletal Dysplasia Center

Education

BS from City University Of New York, Brooklyn College: 06/1986 - Brooklyn, NY, United States

PhD from State University Of New York Downstate Medical Center: 06/1990 - Brooklyn, NY, United States

MD from State University Of New York Downstate Medical Center: 06/1993 - Brooklyn, NY, United States

Residency at Baylor College Of Medicine: 06/1995 - Houston, TX, United States; Pediatrics

Clinical Fellowship at Baylor College Of Medicine: 06/1997 - Houston, TX, United States; Clinical Genetics

Clinical Fellowship at Baylor College of Medicine: 06/1998 - Houston, Texas, United States; Clinical Biochemical Genetics

Post-Doctoral Fellowship at Mount Sinai School of Medicine: 01/1991 - New York, New York, United States

Certifications

Clinical Biochemical Genetics: American Board of Medical Genetics

Clinical Genetics: American Board of Medical Genetics

General Pediatrics: American Board of Pediatrics

Honors & Awards

William F. Neuman Award for Outstanding Scientific, Training, Research, and Administrative Contributions: 2022; American Society for Bone and Mineral Research

Curt Stern Award for Outstanding Scientific Achievement: 2016; American Society for Human Genetics

Fellow AAAS: 2014; American Association for the Advancement of Science

National Academy of Medicine: 2013

Investigator: Howard Hughes Medical Institute (10/2002 - 10/2014)

Association of American Physicians: 2010

E. Mead Johnson Award for “Outstanding Scientific Achievement in Pediatrics”: 2009

American Society for Clinical Investigation: 2008

Edith and Peter O'Donnell Award in Medicine: 2009; Texas Academy of Medicine, Science and Engineering

Michael E. DeBakey Excellence in Research Award: 2007

American Philosophical Society’s Judson Darland Prize for Achievement in Patient-Oriented Clinical Research: 2005

Society for Pediatric Research Young Investigator Award: 2000

Professional Interests

Developmental, translational and clinical studies of skeletal dysplasias and inborn errors of metabolism

Professional Statement

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. In the area of metabolism, we have applied genetic approaches to the study of biochemical genetic disorders (specifically urea cycle disorders) as models of complex diseases (those involving nitric oxide dysregulation). This has led us to study the consequences of metabolic derangements broadly in the endocrine, cardiovascular, skeletal, renal and neurological systems. In the area of structural birth defects, we have studied paracrine and endocrine signaling pathways that regulate skeletal development including morphogens (TGF, Wnt and Notch), and extracellular matrix proteins and their modifications (e.g., collagen prolyl-hydroxylation and lysyl-hydroxylation) that contribute to human skeletal dysplasias including brittle bone diseases and connective tissue diseases like Ehlers-Danlos syndrome. These developmental pathways have led us to ask how their dysregulation contributes to common diseases such as osteoporosis, osteoarthritis and bone cancer.

Our mechanistic discoveries are translated via clinical research that is performed as part of the Skeletal Dysplasia Clinic and the Metabolic Disorders Clinic at Texas Children’s Hospital, respectively, and as part of the NIH Rare Diseases Clinical Research Network (RDCRN) Brittle Bone Disorders Consortium. My clinical research program began with stable isotopic measurements in urea cycle disorder patients to better assess new treatments. I have led investigator-initiated studies testing combined phenylbutyrate/arginine treatment and nitric oxide supplementation in patients with argininosuccinic aciduria and phenylbutyrate in maple syrup urine disease and industry-sponsored Phase II and III studies of the now FDA-approved ammonia scavenger glyceryl-triphenylbutyrate in urea cycle patients. In the area of skeletal dysplasias, I have studied the utility of zoledronic acid, teriparatide and anti-TGF treatments in pediatric and adult osteogenesis imperfecta. Our preclinical gene therapy studies have led to a clinical trial of high-capacity adenoviral gene therapy in osteoarthritis. As an extension of these studies, I lead the RE-JOIN consortium of the NIH HEAL initiative mapping the neuronal pain mediators into the osteoarthritis joint. As part of my genomic medicine studies, I have focused on advancing the diagnosis of genetic diseases via gene discovery, multi-omic approaches to phenotyping and mechanistic studies in the NIH Undiagnosed Diseases Network. Finally, I am committed to developing a scientific workforce as part of the All of Us Evenings with Genetics Scholars Program.

Websites

VIICTR Publications List

Department of Molecular and Human Genetics

Center for Skeletal Medicine and Biology & Rolanette and Berdon Lawrence Bone Disease Program of Texas

Clinics

Research Laboratory

Lawrence Family Bone Disese Program of Texas

Selected Publications

Ketkar S, Dai H, Burrage LC, Murdock D, Dawson B, Acosta-Herrera M, Kerick M, Martin J, Wilhelm K, Asmussen JK, Lichtarge O, Center RG, Assassi S, Mayes MD, Lee BH. " Integrative exome sequencing and machine learning identify MICB and interferon pathway genes as contributors to SSc risk " Ann Rheum Dis. 2025 Aug ; 84 : 1363-1374.
Pubmed PMID: 40514331.
Chen YT, Jiang MM, Leynes C, Adeyeye M, Majano CF, Ibrahim B, Polak U, Hung G, Jin Z, Lanza DG, Liao L, Dawson B, Chen-Everson Y, Ruiz OE, Gibbons RJ, Heaney JD, Bae Y, Lee BH. " ATRX silences Cartpt expression in osteoblastic cells during skeletal development " J Clin Invest. 2025 Jan ; 135 : e163587.
Pubmed PMID: 40839202.
Marom R, Song IW, Busse EC, Washington ME, Berrier AS, (...), Lee BH. " The IFITM5 mutation in osteogenesis imperfecta type V is associated with an ERK/SOX9-dependent osteoprogenitor differentiation defect " J Clin Invest. 2024 Jun ; 134 : e170369.
Pubmed PMID: 38885336.
Song, I. W., Nagamani, S. C., Nguyen, D., Grafe, I., et al., Lee, B.. " Targeting TGF-β for treatment of osteogenesis imperfecta " J Clin Invest.. 2022 Apr ; 132 (7) : e152571.
Pubmed PMID: 35113812.
Marom R, Burrage LC, Venditti R, Clément A, Blanco-Sánchez B, (…), Undiagnosed Diseases Network, Westerfield M, De Matteis MA, Lee B. " COPB2 loss of function causes a coatopathy with osteoporosis and developmental delay " Am J Hum Genet.. 2021 ; 108 : 1710-1724.
Pubmed PMID: 34450031.
Lim J, Lietman C, Grol MW, Castellon A, Dawson B, (…), Lee BH. " Localized chondro-ossification underlies joint dysfunction and motor deficits in the Fkbp10 mouse model of osteogenesis imperfecta " Proc Natl Acad Sci U S A. 2021 ; 118 : e2100690118.
Pubmed PMID: 34161280.
Jin Z, Kho J, Dawson B, Jiang MM, Chen Y, Ali S, Burrage LC, Grover M, Palmer DJ, Turner DL, Ng P, Nagamani SC, Lee B. " Nitric oxide modulates bone anabolism through regulation of osteoblast glycolysis and differentiation " J Clin Invest. 2021 Mar 1; 131 (5) : e138935.
Pubmed PMID: 33373331.
Murdock DR, Dai H, Burrage LC, Rosenfeld JA, Ketkar S, Müller MF, Yépez VA, Gagneur J, Liu P, Chen S, Jain M, Zapata G, Bacino CA, Chao HT, Moretti P, Craigen WJ, Hanchard NA; Undiagnosed Diseases Network, Lee B. " Transcriptome-directed analysis for Mendelian disease diagnosis overcomes limitations of conventional genomic testing " J Clin Invest. 2021 Jan 4; 131 (1) : e141500.
Pubmed PMID: 33001864.
Burrage LC, Reynolds JJ, et al, Undiagnosed Diseases Network, Bertola D, Yamamoto GL, Baratela WAR, Butler MG, Ali A, Adeli M, Cohn DH, Krakow D, Jackson AP, Lees M, Offiah AC, Carlston CM, Carey JC, Stewart GS, Bacino CA, Campeau PM, Lee B.. " Bi-allelic Variants in TONSL Cause SPONASTRIME Dysplasia and a Spectrum of Skeletal Dysplasia Phenotypes " Am J Hum Genet.. 2019 ; 104 (3) : 422-438.
Pubmed PMID: 30773277.
Kho J, Tian X, Wong WT, Bertin T, Jiang MM, Chen S, Jin Z, Shchelochkov OA, Burrage LC, Reddy AK, Jiang H, Abo-Zahrah R, Ma S, Zhang P, Bissig KD, Kim JJ, Devaraj S, Rodney GG, Erez A, Bryan NS, Nagamani SCS, Lee BH.. " Argininosuccinate Lyase Deficiency Causes an Endothelial-Dependent Form of Hypertension. " Am J Hum Genet. 2018 ; 103 (2) : 276-287.
Pubmed PMID: 30075114.
Nixon AJ, Grol MW, Lang HM, Ruan MZC, Stone A, Begum L, Chen Y, Dawson B, Gannon F, Plutizki S, Lee BHL, Guse K. " Disease-Modifying Osteoarthritis Treatment With Interleukin-1 Receptor Antagonist Gene Therapy in Small and Large Animal Models. " Arthritis Rheumatol.. 2018 ; 70 (11) : 1757-1768.
Pubmed PMID: 30044894.
Joeng KS, Lee YC, Lim J, Chen Y, Jiang MM, Munivez E, Ambrose C, Lee BH. " Osteocyte-specific WNT1 regulates osteoblast function during bone homeostasis " J Clin Invest.. 2017 May ; 127 (7) : 2678-2688.
Pubmed PMID: 28628032.
Zeng HC, Bae Y, Dawson BC, Chen Y, Bertin T, Munivez E, Campeau PM, Tao J, Chen R, Lee BH. " MicroRNA miR-23a cluster promotes osteocyte differentiation by regulating TGF-β signalling in osteoblasts " Nat Commun. 2017 Apr 11; 8 : 15000.
Pubmed PMID: 28397831.
Egunsola AT, Bae Y, Jiang MM, Liu DS, Chen-Evenson Y, Bertin T, Chen S, Lu JT, Nevarez L, Magal N, Raas-Rothschild A, Swindell EC, Cohn DH, Gibbs RA, Campeau PM, Shohat M, Lee BH. " Loss of DDRGK1 modulates SOX9 ubiquitination in spondyloepimetaphyseal dysplasia " J Clin Invest. 2017 Mar 6; 127 (4) : 1475-1484.
Pubmed PMID: 28263186.
Tao J, Jiang MM, Jiang L, Salvo JS, Zeng HC, Dawson B, Bertin TK, Rao PH, R. Chen R, Donehower LA, Gannon F, Lee B (2014). " Notch activation as a driver of osteogenic sarcoma. " Cancer Cell. 2014 ; 26 (3)
Pubmed PMID: 25203324.
Grafe I, Yang T, Alexander S, Homan EP, Lietman C, Jiang MM, Bertin T, Munivez E, Chen Y, Dawson B, Ishikawa Y, Weis MA, Sampath TK, Ambrose C, Eyre D, Bächinger HP, Lee B. " Excessive transforming growth factor-β signaling is a common mechanism in osteogenesis imperfecta. " Nat Med.. 2014 Jun ; 20 (6) : 670-5.
Pubmed PMID: 24793237.
Orwoll ES, Shapiro J, Veith S, Wang Y, Lapidus J, Vanek C, Reeder JL, Keaveny TM, Lee DC, Mullins MA, Nagamani SC, Lee B. " Evaluation of teriparatide treatment in adults with osteogenesis imperfecta. " J Clin Invest.. 2014 Feb 3; 124 (2) : 491-8.
Pubmed PMID: 24463451.
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. " WNT1 mutations in early-onset osteoporosis and osteogenesis imperfecta. " N. Engl. J. Med.. 2013 May 9; 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. " Proteoglycan 4 expression protects against the development of osteoarthritis. " Sci Transl Med. 2013 Mar 13; 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. " Requirement of argininosuccinate lyase for systemic nitric oxide production. " Nat. Med.. 2011 Nov ; 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. " E-selectin ligand-1 regulates growth plate homeostasis in mice by inhibiting the intracellular processing and secretion of mature TGF-beta. " J. Clin. Invest.. 2010 Jul 1; 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 RE, Boyce BF, Lee B. " Dimorphic effects of Notch signaling in bone homeostasis. " Nat. Med.. 2008 Mar ; 14 (3) : 299-305.
Pubmed PMID: 18297084.
Zhou G, Zheng Q, Engin F, Munivez E, Chen Y, Sebald E, Krakow D, Lee B. " Dominance of SOX9 function over RUNX2 during skeletogenesis. " Proc. Natl. Acad. Sci. U.S.A.. 2006 Dec 12; 103 (50) : 19004-9.
Pubmed PMID: 17142326.
Morello R, Bertin TK, Chen Y, Hicks J, Tonachini L, Monticone M, Castagnola P, Rauch F, Glorieux FH, Vranka J, Bächinger HP, Pace JM, Schwarze U, Byers PH, Weis M, Fernandes RJ, Eyre DR, Yao Z, Boyce BF, Lee B. " CRTAP is required for prolyl 3- hydroxylation and mutations cause recessive osteogenesis imperfecta. " Cell. 2006 Oct 20; 127 (2) : 291-304.
Pubmed PMID: 17055431.
Toietta G, Mane VP, Norona WS, Finegold MJ, Ng P, McDonagh AF, Beaudet AL, Lee B. " Lifelong elimination of hyperbilirubinemia in the Gunn rat with a single injection of helper-dependent adenoviral vector. " Proc. Natl. Acad. Sci. U.S.A.. 2005 Mar 15; 102 (11) : 3930-5.
Pubmed PMID: 15753292.
Lee B, Yu H, Jahoor F, O'Brien W, Beaudet AL, Reeds P. " In vivo urea cycle flux distinguishes and correlates with phenotypic severity in disorders of the urea cycle. " Proc. Natl. Acad. Sci. U S A. 2000 Jul 5; 97 (14) : 8021-6.
Pubmed PMID: 10869432.
Morello R, Zhou G, Dreyer SD, Harvey SJ, Ninomiya Y, Thorner PS, Miner JH, Cole W, Winterpacht A, Zabel B, Oberg KC, Lee B. " Regulation of glomerular basement membrane collagen expression by LMX1B contributes to renal disease in nail patella syndrome. " Nat Genet.. 2001 Feb ; 27 (2) : 205-8.
Pubmed PMID: 11175791.

Memberships

American Society of Human Genetics: Member

Society for Pediatric Research: Member

American College of Medical Genetics: Member

American Society for Clinical Investigation: Member

Society for Inherited Metabolic Disease: Member

National Academy of Medicine

Association of American Physicians