Positions

Chairman
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
Professor
Program in Integrative Molecular and Biomedical Sciences
Baylor College of Medicine
Professor
Program in Developmental Biology
Baylor College of Medicine
Professor
Program in Translational Biology & Molecular Medicine
Baylor College of Medicine
Director
Center for Skeletal Medicine and Biology
Baylor College of Medicine
Director
Skeletal Dysplasia Clinic
Texas Children's Hospital
Director
Medical Students Research Track
Baylor College of Medicine
Co-Director
Rolanette and Berdon Lawrence Bone Disease Program of Texas
Baylor College of Medicine

Education

BS from City University Of New York, Brooklyn College
PhD from State University Of New York Downstate Medical Center
MD from State University Of New York Downstate Medical Center
Residency at Baylor College Of Medicine
Pediatrics
Clinical Fellowship at Baylor College Of Medicine
Clinical Genetics
Clinical Fellowship at Baylor College of Medicine
Clinical Biochemical Genetics
Post-Doctoral Fellowship at Mount Sinai School of Medicine

Certifications

Clinical Biochemical Genetics
American Board of Medical Genetics
Clinical Genetics
American Board of Medical Genetics
General Pediatrics
American Board of Pediatrics

Honors & Awards

Fellow AAAS
2014
Institute of Medicine
2013
Investigator
Association of American Physicians
2010
American Society for Clinical Investigation
2010
E. Mead Johnson Award for “Outstanding Scientific Achievement in Pediatrics”
2009
Edith and Peter O'Donnell Award in Medicine
2009
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. My long standing interest has been the study of human inborn errors of metabolism and structural birth defects of the skeleton. In the study of metabolism, 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 study of structural birth defects, we have discovered paracrine and endocrine signaling pathways that regulate skeletal development including morphogens (TGFb, Wnt and Notch), post-transcriptional regulation by microRNAs, and extracellular matrix protein modifications (e.q., collagen prolyl-hydroxylation). These developmental pathways have led us to ask how their dysregulation in postnatal life leads to common diseases such as osteoporosis, osteoarthritis, and cancer.

An emerging area of focus is how these mechanisms may also broadly translate into the pathogenesis of other heritable disorders of connective tissue. Ultimately, I have attempted to translate these findings by developing cell and gene therapies for these conditions. Our approach has been to identify the diverse genetic basis of skeletal dysplasias (over 15) for informing 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 rare disease clinical research consortia.

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 bioavailability of different sources of nitrogen (enteral vs. parenteral) to the urea cycle. These human studies have evolved to 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 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; phenylbutyrate in maple syrup urine disease; and zoledronic acid, teriparatide, and anti-TGFb treatment in pediatric and adult osteogenesis imperfecta.

Selected Publications

Memberships

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