Name: Sreedhar Chinnaswamy
Position: Assistant Professor
Highest Educational Qualification: Ph.D. (Biochemistry); Texas A&M University, College Station.
Past Appointments: Research Assistant, Dept. Of Biochemistry & Biophysics, Texas A&M University, College Station, TX, USA and Dept. of Chemistry & Biochemistry, New Mexico State University at Las Cruces, NM, USA.
Fellowships: Junior Research Fellowship 2000-2002, Indian Council of Agricultural Research, New Delhi, India.
Research Interests: Positive-strand RNA viruses like hepatitis C virus (HCV) and and dengue virus (DENV) cause important human diseases. They generally exist as genetically variant forms (quasispecies) in the population and hence 'virus- targeted' therapies are often not useful to treat such viral diseases. Pathogenesis is a phenomenon that is a result of virus-host-environment interactions and involves significant contributions from both the host and the virus in deciding the outcome of the virus infection. A stronger and sustained immune response often successfully clears the infection, while a weaker and insufficient response allows the virus to gain an upper hand and cause disease. It is noteworthy that some individuals in the population are more resistant to pathogen infections than others, underlying the importance of host genetic variation in virus pathogenesis. Many a times identifying these genetic variants in the host can lead us to a better understanding of viral pathogenesis. For example: 1) HCV is a flavivirus that causes chronic liver diseases, including liver cancer. However, about 20% of the individuals infected with the genotype 1 HCV are able to clear the infection at the acute stage. Furthermore, when the chronically infected patients are treated for HCV infections with the standard therapy of interferon-α (IFN-α ) and ribavirin (RBV, a nucleoside analog), only ~50% people infected with the genotype 1 HCV respond while the remaining cannot clear the virus; 2) DENV is another flavivirus that causes acute febrile diseases in humans. While some individuals are asymptomatic, others show a mild and self-limiting fever (dengue fever, DF). A small proportion of DF cases progress to a fatal condition called dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). These and many other similar examples show that host genetic variation is critical in deciding the outcome of a viral infection. Identifying the factors that play decisive roles in overcoming the viral infections in the resistant population can help identify novel proteins which can be developed in to drugs to treat the susceptible population.
HCV project: Genetic variation in the form of single nucleotide polymorphisms (SNPs) in the interferon-λ (IFN-λ) gene cluster has been recently identified to be associated with viral clearance and treatment response in chronic HCV (cHCV) infections. IFN-λ has the potential to be an alternative to IFN-α to treat HCV infections, since it has much lesser side effects than the latter. However, the mechanism of IFN-λ mediated suppression of HCV infections is not known. It is also not known what epigenetic changes are involved in immunomodulatory gene loci in cHCV infections. This project has a broader goal of understanding the molecular role of IFN-λ in HCV pathogenesis and how HCV epigenetically regulates cytokine expression and establishes a chronic infection.
DENV Project: Innate immunity is the first line of host defense that tries to eliminate or control virus multiplication and is also important to prime the adaptive immunity, which ultimately eliminates the virus infection. RIG-I, MDA5, TLR3, TLR7 and TLR8 are innate immunity receptors involved in suppressing RNA virus replication in humans by mediating the expression of antiviral chemokines. The project aims to do an analysis of genetic variation involving these innate immunity receptor genes and their association with DF versus DHF/DSS.
Current Projects: "The role of IFN-λ in HCV pathogenesis: a study on the genetic and epigenetic factors regulating the expression of IFN-λ in chronic HCV infections"
Past Major Projects: "Mechanism of de novo initiation RNA synthesis by the HCV RNA-dependent RNA polymerase"
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NATIONAL INSTITUTE OF BIOMEDICAL GENOMICS, Netaji Subhas Sanatorium (T.B. Hospital), 2nd Floor P.O.: N.S.S., Kalyani 741251, West-Bengal, INDIA