Gene Silencing Studies

Gene silencing studies being conducted at the University of Massachusetts
By Robert H. Brown, Jr., M.D. PhD.

Dr. Brown reports that “Havisha Karnuam is an outstanding MD-PhD student” in his laboratory, who is being co-mentored by Dr. Brown and “an extremely capable, knowledgeable faculty member, Prof. Anastasia Khvorova, who has many years experience (including patenting relevant inventions) in gene silencing”. Havisha has generated modified oligonucleotides, which are short single stranded DNA or RNA molecules that can be used as tools to study gene function or as therapeutic agents. Oligonucleotides can inhibit expression and induce a blockade in the transfer of genetic information from DNA to protein, thereby “silencing” the gene. The oligonucleotides Havisha has generated silence the gene for the SPT (serine palmitoyltransferase) enzyme, a mutation of which is responsible for HSAN1, in the laboratory. Her research on the gene causing HSAN1 is Havisha’s doctoral work. She has completed one year on this project and will continue this work for about another 3 years. Dr. Brown states that “Dr. Khvorova has been terrific – and has had a pivotal role in Havisha Karnuam’s success.”

This approach, at the level of the disease causing gene, is an entirely different method to

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New Study Proposed

New Study Proposed for “Creating an in vitro model of HSAN1 in which to study disease mechanisms and potential treatments.” By John K. Fink, M.D. Professor, Department of Neurology, University of Michigan

Our objective is to grow nerve cells (neurons) from individuals with HSAN1 in the laboratory (“in vitro”). We want to examine these neurons for patterns of nerve degeneration, and importantly, use these cultures to screen chemicals to find potential treatments. Our approach is to obtain superficial skin biopsies (3 millimeter diameter) from individuals with HSAN1 (and from normal control subjects), grow skin fibroblasts, and transform these fibroblasts into adult stem cells. We then differentiate these stem cells into neurons and study molecular mechanisms of degeneration and treatment approaches. Once developed, stem cells from HSAN1 subjects will serve as an important resource that can be distributed to other investigators so that studies into mechanisms and treatments for HSAN1 can proceed simultaneously in many laboratories. Our studies are approved by the University of Michigan Institutional Review Board.


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