Jairaj K. Acharya, MBBS, Ph.D.

Jairaj K. Acharya, MBBS, Ph.D.
Senior Investigator
Head, Sphingolipid and Phospholipid Signaling Section

Contact Info

Jairaj K. Acharya, MBBS, Ph.D.
Center for Cancer Research
National Cancer Institute
Building 560, Room 22-6
Frederick, MD 21702-1201
Ph: 301-846-7051
acharyaj@mail.nih.gov

Phospholipid Signaling

Our long-term objective is to understand the complex interrelationship between phospholipid and sphingolipid metabolism and metabolic signaling in vivo. Intermediates of phospholipid (PL) and sphingolipid (SL) metabolism serve as second messengers for a number of signaling cascades including activation of G-protein-coupled receptors such as adrenaline and thrombin as well as receptor tyrosine kinases by growth factors. They mediate a number of processes ranging from protein secretion to activation of apoptosis. We have initiated studies to understand several aspects of lipid signaling in Drosophila.

Lipid Reservoirs and Signaling. Sphingomyelin (or phosphorylethanolamine ceramide, CPE, in flies) could serve as a reservoir for several lipid messengers such as ceramide, ceramide 1-phosphate, sphingosine, and sphingosine 1-phosphate. We have initiated studies to delineate the in vivo role of some of the enzymes of the putative "Sphingomyelin Cycle". We have begun by identifying homologous genes in Drosophila. We are using transgenic gain of function and mutagenic loss of function studies to analyze the importance of such a pathway in Drosophila. We have recently demonstrated that modulation of the sphingolipid biosynthetic pathway such as targeted expression of ceramidase, rescues degeneration in certain photoreceptor mutants. We have also demonstrated that ceramidase facilitates membrane turnover and rhodopsin endocytosis in Drosophila photoreceptors.

Sphingolipids are synthesized vectorially. While the steps that lead up to the generation of ceramide occurs in the endoplasmic reticulum (ER) the biosynthesis of sphingomyelin(or CPE) and most complex sphingolipids occurs outside of the ER, either in the Golgi Complex or in the plasma membrane. This necessitates the active transport of ceramide from ER to the Golgi Complex. The transport is largely mediated by a protein called ceramide transfer protein (CERT). We have now demonstrated that CERT-mediated transfer of ceramide is critical for the biosynthesis of sphingomyelin (or CPE in Drosophila) and complex sphingolipids. Lack of CERT in Drosophila leads to decreased CPE and they have plasma membranes with altered physical and physiological properties. The changes render them susceptible to normal loads of reactive oxygen species encountered in a cell. The ensuing oxidative damage of plasma membrane leads to production of lipid peroxides that will further oxidize membrane and cellular constituents leading to a rapid deterioration in the metabolic function of cell. The underlying pathoglogic changes manifest as accelerated aging in these mutant flies and consequently they have a short adult life span.

Lipid Distribution and Signaling. PL and SL at the plasma membrane play an important role in stimulus-response coupling, cell differentiation, movement, and exo- and endocytosis. They are asymmetrically distributed in biological membranes and different proteins catalyzing uni- and bidirectional movements of lipids perpetuate asymmetry. Our initial studies involving the generation and characterization of mutants of scramblases in Drosophila indicate a modulatory role for these proteins in regulated exocytosis and no determining role in scrambling of phospholipids. This has implications in a wide range of cellular processes. Further studies should enable us to dissect its role further.

Scientific Focus Areas:
Cancer Biology, Cell Biology, Genetics and Genomics, Neuroscience
View Dr. Acharya's PubMed Summary.

Selected Recent Publications

  1. Kunduri G, Turner-Evans D, Konya Y, Izumi Y, Nagashima K, Lockett S, Holthuis J, Bamba T, Acharya U, Acharya JK.
    Proc Natl Acad Sci U S A.. 2018. [ Journal Article ]
  2. Kosakowska-Cholody T, Lin J, Srideshikan SM, Scheffer L, Tarasova NI, Acharya JK.
    Cell Death Dis. 5: e1240, 2014. [ Journal Article ]
  3. Rao RP, Scheffer L, Srideshikan SM, Parthibane V, Kosakowska-Cholody T, Masood MA, Nagashima K, Gudla P, Lockett S, Acharya U, Acharya JK.
    PLoS ONE. 9: e92142, 2014. [ Journal Article ]
  4. Rahman M, Nirala NK, Singh A, Zhu LJ, Taguchi K, Bamba T, Fukusaki E, Shaw LM, Lambright DG, Acharya JK, Acharya UR.
    J. Cell Biol. 2014. [ Journal Article ]
  5. 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.
    J. Cell Biol. 206: 79-95, 2014. [ Journal Article ]

Dr. Jairaj Acharya obtained his M.B.B.S. from the University of Gulbarga (Government Medical College, Bellary), India, in 1985 and received his Ph.D. in biochemistry from the Indian Institute of Science, Bangalore, in 1993 under Prof. Appaji Rao. He joined Dr. Charles Zuker at the University of California, San Diego as an associate of the Howard Hughes Medical Institute for his postdoctoral training. He was recruited by the NCI in 1999.

Name Position
Parthibane Velayoudame Ph.D. Postdoctoral Fellow (Visiting)
Govind Kunduri Ph.D. Postdoctoral Fellow (Visiting)
Thiruvaimozhi Abimannan Ph.D. Postdoctoral Fellow (Visiting)
Kenneth Kim Postbaccalaureate Fellow (CRTA)
Prateek Paul
Prateek Paul Werner H. Kirsten Student Intern 2014

 

Hirsh Shah
Hirsh Shah Werner H. Kirsten Student Intern 2014

 

Abhishek Kapoor
Abhishek Kapoor Werner H. Kirsten Student Intern 2014

 

Jing-Jing Ma, Ph.D.
Jing-Jing Ma, Ph.D. Postdoctoral Fellow 2009 - 2013

Current Affiliation:

Associate Medical Affairs Manager
GeneScience Pharmaceuticals
Changchun, China


 

Anish Gonchigar, B.S.
Anish Gonchigar, B.S. Postbaccalaureate Fellow 2013

 

 

Razi Raziuddin, Ph.D.
Razi Raziuddin, Ph.D. Biologist 2012


 

Diwash Acharya, B.S.
Diwash Acharya, B.S. Postbaccalaureate Fellow (ORISE/NCI) 2009 - 2012

Current Affiliation:

Ph.D. Student
University of Massachusetts Medical School
Worcester, MA


 

Meena Sharma, B.S.
Meena Sharma, B.S. Postbaccalaureate Fellow 2011 - 2012

Current Affiliation:

Postbaccalaureate Fellow
Laboratory of Protein Dynamics and Signaling
Center for Cancer Research, NCI


 

Rohan Hangal
Rohan Hangal Summer Student 2012

 

Surabhi Rao
Surabhi Rao Summer Student 2012

 

Zachary Daar
Zachary Daar Werner H. Kirsten Student Intern 2012

Current Affiliation:

Undergraduate Student
University of Maryland, College Park

 

 

Yasmin Lachir
Yasmin Lachir Werner H. Kirsten Student Intern 2012

 

Shelby Payne
Shelby Payne Werner H. Kirsten Student Intern 2012

 

Odilia Sendze
Odilia Sendze Werner H. Kirsten Student Intern 2012

 

Rishabh Sharan
Rishabh Sharan Werner H. Kirsten Student Intern 2012

 

Pralhada Rao Raghavendra
Pralhada Rao Raghavendra, Ph.D. Research Fellow 2005 - 2011

Current Affiliation:

Lead Scientist
Drug Target Validation Group
Connexios Life Sciences
Bangalore, India



 

Luanna Scheffer, Ph.D.
Luana Scheffer, Ph.D. Postdoctoral Fellow 2010 - 2011

Current Affiliation:

Confocal Specialist
Center for Genetic Medicine Research
Children's National Medical Center
Washington, DC


 

Priyanka Maskikar
Priyanka Maskikar Special Volunteer 2011

 

Abid R. Mattoo, Ph.D.
Abid R. Mattoo, Ph.D. Postdoctoral Fellow 2009 - 2010

Current Affiliation:

Postdoctoral Fellow
Laboratory of Experimental Carcinogenesis
Center for Cancer Research, NCI