Faculty Directory

Stephen T. Warren, PhD

Stephen T. Warren, PhD headshot

W. P. Timmie Professor & C. H. Candler Chair of Human Genetics
Department of Human Genetics
Emory University School of Medicine

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PHONE: 404-727-5979

PubMed

Biography

Research Interests:

Dr. Warren’s research over the past 25 years has focused upon the mechanistic understanding of fragile X syndrome, a leading cause of inherited intellectual disability and autism. Dr. Warren organized and led an international effort that isolated the FMR1 gene responsible for this syndrome in 1991. The cloning of this locus also uncovered, for the first time, a trinucleotide repeat expansion mutation. 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 recently shown 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’s group 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 of drugs of both classes to evaluate the therapeutic efficacy for fragile X syndrome.

More recently, Dr. Warren’s work has also has focused on psychiatric disease. He recently discovered of deletion on chromosome 3 that increases the risk of schizophrenia by 40-fold, one of the most significant genetic risk factors for this disorders identified to date. Currently his group is creating a mouse model of schizophrenia using the syntenic deletion in the mouse.

Collaborations:

Throughout his career, Dr. Warren has been fortunate to have enjoyed many collaborations. He maintains a 22 year collaboration with David Nelson at Baylor College of Medicine and has worked closely with Bob Darnell (Rockefeller), Mark Bear (MIT), Evan Eichler (U Washington), Ann Pulver (Hopkins) and Tom Glover (Michigan). Locally, he has collaborated closely with Stephanie Sherman (Human Genetics), Gary Bassell (Cell Biology), Yue Feng (Pharmacology), Danny Reines (Biochemistry), Keith Wilkinson (Biochemistry), Carlos Moreno (Pathology) and many others.
 

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