Professor, Baylor College of Medicine
Investigator, Howard Hughes Medical Institute
B.S., City University of New York, Brooklyn College, 1986
M.D./Ph.D., State University of New York Health Science Center at Brooklyn, 1993
Postdoc, Mount Sinai School of Medicine, NY, 1990-91
Resident and Fellow, Baylor College of Medicine, Houston, TX, 1993-97
Translational studies of skeletal and kidney development, 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 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 skeletal and kidney development. 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 two transcription factors Runx2 and Lmx1b important in these processes, and how they contribute to environment-gene interactions that cause craniofacial/limb malformations and to Wnt-signaling pathways during skeletogenesis. These basic and translational studies are linked intimately with clinical research performed in 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 osteopenia associated with skeletal dysplasias.
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. With this already in hand, we have attempted to translate the basic information into stable isotope based metabolic protocols in urea cycle patients to develop new tools for diagnosis and clinical management. 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 other biochemical pathways that constitute key gene-nutrient interactions during postnatal growth and development. The ultimate goal is to translate information from these well studied pathways into treatment. This is the focus of our gene replacement studies using helper-dependent adenoviral vectors in urea cycle disorders. An integral 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.
Morello R, Bertin TK, Chen Y, Hicks J, Tonachini L, Monticone M, Castagnola P, Rauch F, Glorieux FH, Vranka J, Bachinger HP, Pace JM, Schwarze U, Byers PH, Weis M, Fernandes RJ, Eyre DR, Yao Z, Boyce BF, Lee B (2006) CRTAP is required for prolyl 3- hydroxylation and mutations cause recessive osteogenesis imperfecta. Cell 127:291-304.
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. Proceedings of the National Academy of Sciences USA 103:19004-19009.
Cerullo V, McCormack W, Seiler M, Mane V, Cela R, Clarke C, Rodgers JR, Lee B (2007) Antigen-specific tolerance of human alpha1-antitrypsin induced by helper-dependent adenovirus. Human Gene Therapy 18:1215-1224.
Cerullo V, Seiler MP, Mane V, Brunetti-Pierri N, Clarke C, Bertin TK, Rodgers JR, Lee B (2007) Toll-like receptor 9 triggers an innate immune response to helper-dependent adenoviral vectors. Molecular Therapy 15:378-385.
Cerullo V, Seiler MP, Mane V, Cela R, Clarke C, Kaufman RJ, Pipe SW, Lee B (2007) Correction of murine hemophilia A and immunological differences of factor VIII variants delivered by helper-dependent adenoviral vectors. Molecular Therapy 15:2080-2087.
Scott DA, Klaassens M, Holder AM, Lally KP, Fernandes CJ, Galjaard RJ, Tibboel D, de Klein A, Lee B (2007) Genome-wide oligonucleotide-based array comparative genome hybridization analysis of non-isolated congenital diaphragmatic hernia. Human Molecular Genetics 16:424-430.
Seiler MP, Gottschalk S, Cerullo V, Ratnayake M, Mane VP, Clarke C, Palmer DJ, Ng P, Rooney CM, Lee B (2007) Dendritic cell function after gene transfer with adenovirus-calcium phosphate co-precipitates. Molecular Therapy 15:386-392.
Engin F, Yao Z, Yang T, Zhou G, Bertin T, Jiang MM, Chen Y, Wang L, Zheng H, Sutton RE, Boyce BF, Lee B (2008) Dimorphic effects of Notch signaling in bone homeostasis. Nature Medicine 14:299-305.
Engin F, Bertin T, Ma O, Jiang MM, Wang L, Sutton RE, Donehower LA, Lee B (2009) Notch signaling contributes to the pathogenesis of human osteosarcomas. Human Molecular Genetics 18:1464-1470.
Guse K, Suzuki M, Sule G, Bertin TK, Tyynismaa H, Ahola-Erkkila S, Palmer D, Suomalainen A, Ng P, Cerullo V, Hemminki A, Lee B (2012) Capsid-modified adenoviral vectors for improved muscle-directed gene therapy. Human Gene Therapy 23:1065-1070.
Sule G, Suzuki M, Guse K, Cela R, Rodgers JR, Lee B (2012) Cytokine-conditioned dendritic cells induce humoral tolerance to protein therapy in mice. Human Gene Therapy 23:769-780.
Brendan Lee, M.D., Ph.D.
Department of Molecular and Human Genetics
Baylor College of Medicine
One Baylor Plaza 630E
Houston, Texas 77030, U.S.A.
Tel: (713) 798-8835
Fax: (713) 798-5073