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) that contribute to the 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.The mechanistic discoveries of my laboratory research program are translated into the clinical arena 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 two NIH rare diseases clinical research consortia (the Brittle Bone Disorders Consortium and the Urea Cycle Disorders Consortium). My clinical research program began with stable isotopic measurements in humans and urea cycle disorder patients to better diagnose and assess new treatments. These human studies evolved into the assessment of nitric oxide flux in patients with UCDs and specifically in those with argininosuccinic aciduria. I have participated in and led both investigator-initiated and industry-sponsored interventional studies including the design and implementation of Phase II and III studies of a novel ammonia scavenger glyceryl-triphenylbutyrate in urea cycle patients; combinatorial phenylbutyrate/arginine treatment and nitric oxide supplementation in patients with argininosuccinic aciduria; and phenylbutyrate in maple syrup urine disease. 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 helper-dependent adenoviral gene therapy in osteoarthritis. Finally, 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.
Websites
Selected Publications
- 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;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. 2678-2688. 2017;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;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
Log In to edit your profile