Stephen T Warren, Ph.D., FACMG
William Patterson Timmie Professor of Human Genetics Charles Howard Candler Chair in Human Genetics Chairman of the Department of Human Genetics Chief, Section of Human Genetics, The Emory Clinic Professor of Biochemistry and Professor of Pediatrics Pubmed SearchPubMed Search for Stephen WarrenEmailswarren@emory.eduPhone404-727-5979 Office305-E Lab375 Lab Web SiteVisit the Warren LaboratoryMailing Address Whitehead Biomedical Research Building 615 Michael St. Atlanta, GA 30322
|
Biography
Steve Warren received his Ph.D.
in Human Genetics from Michigan State University in 1981 and completed his
postdoctoral training at the University of Illinois College of Medicine. While at the University of Illinois,
Dr. Warren also spent time as a visiting scientist at the European Molecular
Biology Laboratory in Heidelberg. In
1985 he was recruited to Emory as an Assistant Professor of Biochemistry with a
joint appointment in the Department of Pediatrics. Currently, Dr. Warren is William Patterson Timmie Professor
of Human Genetics, Charles Howard Candler Chair in Human Genetics, Associate
Director of the Baylor-Emory National Fragile X Research Center, the
Founding Chair of the Department of Human Genetics, and Chief of the Section of Human Genetics in the The Emory Clinic. He also continues to hold secondary appointments in the
Departments of Pediatrics and Biochemistry. He is a Founding Fellow of the American College of Medical
Genetics and a Diplomat of the American Board of Medical Genetics with
specialty certification in both clinical cytogenetics and clinical molecular
genetics.
Dr. Warren has held various
national and international service positions. He serves or has served on the Editorial Boards of eleven
other scientific journals, seven currently. From 1999 – 2005 he was Editor-in-Chief
for the American Journal of Human
Genetics, the first PhD to hold this position since the journals founding
in 1949. He has held several committee memberships in the American Society of
Human Genetics, including election to the Board of Directors in 1997 and
serving as President in 2006. Dr. Warren has been a member of the NIMH Council
and currently serves on the NIMH Board of Scientific Counselors.
Dr. Warren has received numerous
awards and accolades in recognition of his contributions to the scientific community. In 1991 Dr. Warren was named as
Associate Investigator of the Howard Hughes Medical Institute and was promoted
to Full Investigator in 1995. He
has also received the Albert E. Levy Faculty Award from Emory University, the
inaugural William Rosen Research Award from the National Fragile X Foundation,
and a MERIT award from the National Institutes of Health. In 1999, Dr. Warren was awarded the
William Allan Award from the American Society of Human Genetics for his research
on fragile X syndrome. He was an
inaugural inductee of the National Institute of Child Health and Human Development’s
Hall of Honor and was elected to the Institute of Medicine of the National
Academies in 2004. He won the
William Rosen Research Award an unprecedented second time from the National
Fragile X Foundation in 2006. He was also awarded the Michigan State University
Outstanding Alumni Award, the Brandwein Award in Genetic Research, the
“Champion for Babies” award from the March of Dimes, the Jacob’s Ladder
International Research Prize, the American Academy of Neurology “Frontiers in
Clinical Neuroscience” award, and the
March of Dimes/Colonel Harland Sanders Award for Lifetime Achievement in
Genetics. In 2011, Dr. Warren was
elected to membership in the National Academy of Sciences (NAS), one of the
highest honors given to a scientist in the United States.
Research Description
Dr. Warren is best known for his
genetics research on intellectual disability (ID). It had been appreciated since the 1930s that cognitive
impairment was more common in males than females, subsequently leading to the
hypothesis that there are likely genes on the X chromosome (of which males have
only one copy) that, when mutated, result in ID. In the 1960s it was discovered
that rather than many genes on the X chromosome that are involved in ID, a
single locus accounted for most X-linked ID and this disorder was later called
fragile X syndrome. Dr. Warren organized
and led an international group of collaborators that isolated the FMR1 gene
responsible for this syndrome in 1991. The cloning of this locus also discovered,
for the first time, a trinucleotide repeat expansion mutation, now known to be
responsible for dozens of diseases. Dr. Warren subsequently demonstrated that
the expanded FMRI repeat in patients
leads to transcriptional suppression and the absence of the encoded protein, FMRP. He has shown that this
protein is a selective RNA-binding protein and identified FMRP associated
mRNAs. He has demonstrated that FMRP is involved in the regulation of local
protein synthesis at the synapse and that in the absence of FMRP, the
FMRP-associated mRNAs are over translated, in an activity-dependent manner. He
has shown that this leads to enhanced AMPA receptor internalization and
directly to weakened synaptic strength, likely the direct cause of the
cognitive deficit in patients. This decades long investigation into this
disorder has led to a theory that posits therapeutic approaches using mGluR
antagonists and Dr. Warren recent completed a chemical library screen to rescue
FMRP-deficient phenotypes and identified GABA agonists as additional candidate
drugs. This work has now directly led to several ongoing clinical trials, here
at Emory and elsewhere, of drugs of both classes to evaluate the therapeutic
efficacy in fragile X syndrome.
Current work in the Warren
laboratory involve elucidating the regulation of FMRP at the synapse,
particularly involving phosphorylation; functional studies of conventional
mutations of FMR1 found in patients
with intellectual disability and/or autism spectrum disorder; mechanisms of the
transcriptional silencing of FMR1 in
full mutations induced pluripotent stem cells; and characterization of recently
identified nuclear functions of FMRP. In addition, we continue our work on the
genetics of schizophrenia, following up on our discovery of 3q29 deletions,
while extremely rare in patients, greatly elevate risk. We are in the process
of recapitulating the deletion in the mouse and ultimately identify the
responsible gene.
|