Positions

Henry and Emma Meyer Chair and Professor
Molecular and Human Genetics
Baylor College of Medicine
Houston, TX, US
Professor
Molecular & Cellular Biology
Baylor College of Medicine
Houston, Texas, United States
Professor
Pediatrics
Baylor College of Medicine
Houston, Texas, United States
Faculty Member
Program in Integrative Molecular and Biomedical Sciences
Baylor College of Medicine
Houston, Texas, United States

Education

BS from College Of The Holy Cross
MD from Yale University School Of Medicine
Residency at Johns Hopkins Hospital
Post-Doctoral Fellowship at National Institutes of Health

Certifications

Clinical Molecular Genetics
American Board of Medical Genetics
Diplomate
National Board of Medical Examiners
General Pediatrics
American Board of Pediatrics
Clinical Biochemical Genetics
American Board of Medical Genetics
Clinical Genetics
American Board of Medical Genetics

Honors & Awards

Victor A. McKusick Leadership Award
Recipient, October 2017
National Academy of Sciences
Elected, 2011
NIH Gene Therapy Resource Program Scientific Review Board
Appointed, 2007
The American Society of Human Genetics Allen Award
Recipient, October 2007
Colonel Harland Sanders Award for Lifetime Achievement in Genetic Research and Education
2002, March of Dimes
The Dr. Claudia Benton Award for Scientific Research
2001, Angelman Syndrome Foundation
Baylor Medical Alumni Association Distinguished Faculty Award
2001
Michael E. DeBakey Excellence in Research Award
1999
Texas Genetics Society Barbara H. Bowman Award
1999
Henry and Emma Meyer Chair in Molecular Genetics
1996-present

Professional Interests

  • Neuronal carnitine deficiency as a risk factor for autism
  • Prader-Willi and Angelman syndrome
  • Genotype-phenotype correlations for CHRNA7
  • Molecular diagnosis in the CLIA lab

Professional Statement

In 2012, we described a novel inborn error of carnitine biosynthesis caused by deficiency of the X-linked TMLHE gene. This deficiency is present in 1 in 350 control males and is a risk factor for autism. This has led us to hypothesize that brain carnitine deficiency can cause autism in a subset of patients. We suggest that abnormalities of carnitine metabolism including low dietary intake, renal loss, impaired transport, or defective synthesis may be important in up to 10-20% of autism cases, especially in males with a normal physical examination and normal MRI of the brain. Thus some cases of autism may be preventable or treatable through dietary supplementation with carnitine. We suggest that a strong male predominance is explained by lack of X-inactivation of SLC6A14, an X-linked carnitine transporter that transports carnitine across the blood-brain barrier (BBB). Wild-type female mice transport radioactive carnitine across the BBB better than males and mice null for Slc6a14 have impaired transport. This hypothesis has now been described in depth in BioEssays.

Our lab has studies the role of genomic imprinting and its effect in Prader-Willi syndrome (PWS), Angelman syndrome (AS), and autism. They are caused by deficiency of paternally (PWS) or maternally (AS) expressed genes within chromosome 15q11-q13. We have contributed to identification of molecular defects causing PWS and AS, identified the Ube3a locus encoding E6-AP ubiquitin-protein ligase as the AS gene, and made numerous mouse models related to PWS and AS. We have recently demonstrated the use of oligonucleotides in mice to knockdown the antisense transcript for Ube3a to unsilence expression of the sense transcript from the paternal chromosome as a treatment for Angelman syndrome. We are collaborating with Ionis Pharmaceuticals to develop a phase 1 trial of oligonucleotide treatment for AS. We are preparing a “humanized” mouse expressing the human UBE3A antisense for use in preclinical studies.

We are developing a new form of genetic prenatal diagnosis isolating fetal cells from the maternal blood that we believe would be a major improvement over existing tests. We have published evidence for the feasibility of fetal trophoblastic cell-based noninvasive prenatal testing as listed.

Together with Mary Dickinson, we lead the Baylor component of an international collaboration to analyze the function of all mouse genes called the KnockOut Mouse Project (KOMP). A large NIH grant received a renewal with five years of funding. A recent KOMP publication is listed.

Selected Publications

Memberships

American Society of Human Genetics