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    Usha Rajagopalan Jairaj Acharya PhD

    TitleAssistant Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentProgram in Molecular Medicine
    AddressUniversity of Massachusetts Medical School
    364 Plantation Street, LRB-515
    Worcester MA 01605
    Phone508-856-1194
      Other Positions
      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentProgram in Gene Function and Expression

        Overview 
        Narrative

        Academic Background

        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

        Photo: Usha Acharya, Ph.D. 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.



        Rotation Projects

        Rotation Projects

        1. Phenotypic analyses of Drosophila ceramidase mutants.
        2. Characterization of Drosophila ceramide kinase and functional analyses.



        Post Docs

        A postdoctoral position is available to study in this laboratory. Contact Dr. Acharya for additional details.



        Bibliographic 
        selected publications
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        1. Rahman M, Nirala NK, Singh A, Zhu LJ, Taguchi K, Bamba T, Fukusaki E, Shaw LM, Lambright DG, Acharya JK, Acharya UR. Drosophila Sirt2/mammalian SIRT3 deacetylates ATP synthase ß and regulates complex V activity. J Cell Biol. 2014 Jul 21; 206(2):289-305.
          View in: PubMed
        2. Kunduri G, Yuan C, Parthibane V, Nyswaner KM, Kanwar R, Nagashima K, Britt SG, Mehta N, Kotu V, Porterfield M, Tiemeyer M, Dolph PJ, Acharya U, Acharya JK. Phosphatidic acid phospholipase A1 mediates ER-Golgi transit of a family of G protein-coupled receptors. J Cell Biol. 2014 Jul 7; 206(1):79-95.
          View in: PubMed
        3. Rao RP, Scheffer L, Srideshikan SM, Parthibane V, Kosakowska-Cholody T, Masood MA, Nagashima K, Gudla P, Lockett S, Acharya U, Acharya JK. Ceramide transfer protein deficiency compromises organelle function and leads to senescence in primary cells. PLoS One. 2014; 9(3):e92142.
          View in: PubMed
        4. Nirala NK, Rahman M, Walls SM, Singh A, Zhu LJ, Bamba T, Fukusaki E, Srideshikan SM, Harris GL, Ip YT, Bodmer R, Acharya UR. Survival response to increased ceramide involves metabolic adaptation through novel regulators of glycolysis and lipolysis. PLoS Genet. 2013 Jun; 9(6):e1003556.
          View in: PubMed
        5. Yonamine I, Bamba T, Nirala NK, Jesmin N, Kosakowska-Cholody T, Nagashima K, Fukusaki E, Acharya JK, Acharya U. Sphingosine kinases and their metabolites modulate endolysosomal trafficking in photoreceptors. J Cell Biol. 2011 Feb 21; 192(4):557-67.
          View in: PubMed
        6. Yuan C, Rao RP, Jesmin N, Bamba T, Nagashima K, Pascual A, Preat T, Fukusaki E, Acharya U, Acharya JK. CDase is a pan-ceramidase in Drosophila. Mol Biol Cell. 2011 Jan 1; 22(1):33-43.
          View in: PubMed
        7. Dasgupta U, Bamba T, Chiantia S, Karim P, Tayoun AN, Yonamine I, Rawat SS, Rao RP, Nagashima K, Fukusaki E, Puri V, Dolph PJ, Schwille P, Acharya JK, Acharya U. Ceramide kinase regulates phospholipase C and phosphatidylinositol 4, 5, bisphosphate in phototransduction. Proc Natl Acad Sci U S A. 2009 Nov 24; 106(47):20063-8.
          View in: PubMed
        8. Wang X, Rao RP, Kosakowska-Cholody T, Masood MA, Southon E, Zhang H, Berthet C, Nagashim K, Veenstra TK, Tessarollo L, Acharya U, Acharya JK. Mitochondrial degeneration and not apoptosis is the primary cause of embryonic lethality in ceramide transfer protein mutant mice. J Cell Biol. 2009 Jan 12; 184(1):143-58.
          View in: PubMed
        9. Acharya JK, Dasgupta U, Rawat SS, Yuan C, Sanxaridis PD, Yonamine I, Karim P, Nagashima K, Brodsky MH, Tsunoda S, Acharya U. Cell-nonautonomous function of ceramidase in photoreceptor homeostasis. Neuron. 2008 Jan 10; 57(1):69-79.
          View in: PubMed
        10. Sanxaridis PD, Cronin MA, Rawat SS, Waro G, Acharya U, Tsunoda S. Light-induced recruitment of INAD-signaling complexes to detergent-resistant lipid rafts in Drosophila photoreceptors. Mol Cell Neurosci. 2007 Sep; 36(1):36-46.
          View in: PubMed
        11. Rao RP, Yuan C, Allegood JC, Rawat SS, Edwards MB, Wang X, Merrill AH, Acharya U, Acharya JK. Ceramide transfer protein function is essential for normal oxidative stress response and lifespan. Proc Natl Acad Sci U S A. 2007 Jul 3; 104(27):11364-9.
          View in: PubMed
        12. Acharya U, Edwards MB, Jorquera RA, Silva H, Nagashima K, Labarca P, Acharya JK. Drosophila melanogaster Scramblases modulate synaptic transmission. J Cell Biol. 2006 Apr 10; 173(1):69-82.
          View in: PubMed
        13. Acharya U, Mowen MB, Nagashima K, Acharya JK. Ceramidase expression facilitates membrane turnover and endocytosis of rhodopsin in photoreceptors. Proc Natl Acad Sci U S A. 2004 Feb 17; 101(7):1922-6.
          View in: PubMed
        14. Acharya U, Patel S, Koundakjian E, Nagashima K, Han X, Acharya JK. Modulating sphingolipid biosynthetic pathway rescues photoreceptor degeneration. Science. 2003 Mar 14; 299(5613):1740-3.
          View in: PubMed
        15. Acharya U, Mallabiabarrena A, Acharya JK, Malhotra V. Signaling via mitogen-activated protein kinase kinase (MEK1) is required for Golgi fragmentation during mitosis. Cell. 1998 Jan 23; 92(2):183-92.
          View in: PubMed
        16. Acharya U, Jacobs R, Peters JM, Watson N, Farquhar MG, Malhotra V. The formation of Golgi stacks from vesiculated Golgi membranes requires two distinct fusion events. Cell. 1995 Sep 22; 82(6):895-904.
          View in: PubMed
        17. Acharya U, McCaffery JM, Jacobs R, Malhotra V. Reconstitution of vesiculated Golgi membranes into stacks of cisternae: requirement of NSF in stack formation. J Cell Biol. 1995 May; 129(3):577-89.
          View in: PubMed
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