Usha Rajagopalan Jairaj Acharya PhD
|Institution||University of Massachusetts Medical School|
|Department||Molecular, Cell and Cancer Biology|
|Address||University of Massachusetts Medical School|
364 Plantation Street, LRB-515
Worcester MA 01605
|Institution||UMMS - School of Medicine|
|Department||Program in Molecular Medicine|
Usha Acharya received her Ph.D. in Biochemistry in 1993 from the Indian Institute of Science in Bangalore, India. From 1993 to 1999, she was a post-doctoral fellow in the Department of Biology at the University of California, San Diego, where she received support from the American Heart Association. Subsequently, she worked in the Regulation of Cell Growth Laboratory at the National Cancer Institute. Dr. Acharya joined the Program in Gene Function and Expression at the University of Massachusetts Medical School as an Assistant Professor in the spring of 2004.
Molecular Genetics of Lipid Metabolism and Signaling
Sphingolipids are essential components of eukaryotic cell membranes. In addition to being important structural constituents of membranes, many of them serve as second messengers in a variety of signaling events ranging from angiogenesis to apoptosis. One of the major goals of the laboratory is to understand how organisms integrate sphingolipid biosynthesis and trafficking with their dual function as structural components of membranes and as second messengers. It is our hope that understanding networks that control normal sphingolipid homeostasis and function will provide opportunities for therapeutic strategies to treat diseases associated with alterations in sphingolipid metabolism.
With this goal in mind, we have begun to characterize and examine functions of enzymes involved in sphingolipid metabolism in vivo in their normal cellular environment. To accomplish this, we use Drosophila as a model organism and a combination of genetic, molecular and cell biological approaches. We are currently using Drosophila phototransduction, a prototypic G-protein coupled receptor (GPCR) signaling cascade, as our model system. Recently, we have found that modulating the sphingolipid biosynthetic pathway rescues retinal degeneration in certain Drosophila phototransduction mutants. Specifically, targeted expression of Drosophila neutral ceramidase or absence of one copy of the gene encoding for serine palmitoyl transferase, the rate-limiting enzyme of the biosynthetic pathway, suppresses degeneration in arrestin and norp A mutants. Suppression of degeneration correlates with a decrease in ceramide levels in these photoreceptors. Moreover, targeted expression of ceramidase or the absence of one copy of serine palmitoyl transferase modulates the endocytic machinery because they suppress defects in a dynamin mutant. These findings link sphingolipid metabolism to membrane turnover during GPCR signaling. We are currently elucidating mechanisms downstream of ceramidase expression in suppression of degeneration. We have also initiated studies on enzymes downstream of ceramidase including ceramide kinase and sphingosine kinases. Comprehensive genetic screens have been carried out to isolate mutants deficient in these genes and functional analysis is in progress.
A number of recent developments in cell biology indicate that membrane trafficking plays an important role in modulating and regulating signaling pathways. The partnership between membrane biogenesis and signaling is an exciting area of research that will uncover novel roles for proteins and signaling cascades in physiological as well as pathological conditions.
- Phenotypic analyses of Drosophila ceramidase mutants.
- Characterization of Drosophila ceramide kinase and functional analyses.
A postdoctoral position is available to study in this laboratory. Contact Dr. Acharya for additional details.
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