Research:

My laboratory is interested in studying the genetic and epigenetic causes of Non-alcoholic fatty liver disease (NAFLD) in Indian populations. NAFLD is emerging as an important cause of liver disease in India, with a prevalence of 9% in rural India to 32% in the general population. NAFLD is an umbrella term which describes a range of related and progressive disorders, characterized by insulin resistance. The earliest stage of NAFLD is hepatic steatosis, which is characterized by the deposition of TG as lipid droplets in hepatocytes. Nonalcoholic steatohepatitis (NASH) is another stage of NAFLD characterized by hepatocyte injury, inflammation, and fibrosis. NASH, in turn, can progress to cirrhosis and hepatocellular carcinoma. NAFLD is a complex genomic disorder which is the hepatic manifestation of the metabolic syndrome.

In a recent, community-based epidemiological study of inhabitants of a rural area in West Bengal, the prevalence rates of NAFLD and cryptogenic cirrhosis were 8.7% and 0.2%, respectively. Surprisingly, these were low income lean individuals with mostly low or normal BMI. With continuous ongoing collection of epidemiological data in other parts of West Bengal, we are undertaking a genome-wide association analyses of NAFLD, which will complement our understanding of this novel Indian trait (perhaps a “Third world phenotype”), which is quite  distinct from the Western phenotype, which is associated with obesity.

Recent results based on environmental and in vitro studies hypothesize a role for DNA methylation in the transcriptional control of key genes in liver disease. Epidemiologic evidence indicates that NAFLD in lean individuals might be a consequence of the transitional nutritional features/ malnutrition in these individuals. This observation points to the role of factors such as environment and lifestyle in determining the risk of disease, in addition to the genetic component. We think that these factors might have a huge influence on the methylome of these individuals, since only a subset of individuals develop NAFLD. Also, it is unclear whether NASH is an advanced stage of simple steatosis or if they are distinct patho-physiologies. Therefore, a second objective of my laboratory is to examine the roles that epigenetic factors play in NAFLD susceptibility and whether there is any interaction with genetic factors.

Projects: (extramurally funded) Genomic and Epigenomic analyses of Non Alcoholic Fatty Liver Disease (NAFLD) in the Indian population (funded by Dept. of Biotechnology)

Selected Publications:

• BASU P, Lung T, Lemsaddek W, Giang Sargent T, Williams DC Jr, Basu M, Redmond LC, Lingrel JB, Haar JL, Lloyd JA. (2007) EKLF and KLF2 have compensatory roles in embryonic e-globin gene expression and primitive erythropoiesis, Blood. 110:3417-3425.

• BASU P, Morris PE, Haar J, Wani MA, Lingrel JB, Gaensler KML and Lloyd JA. (2005) KLF2 is essential for primitive erythropoiesis and regulates the human and murine embryonic β–like globin gene in vivo, Blood. 106:2566-71.

• BASU P, Sargent TG, Redmond LC, Aisenberg JC, Kransdorf EP, Wang SZ, Ginder GD and Lloyd JA. (2004) Evolutionary conservation of KLF transcription factors and functional conservation of human β-globin gene regulation in chicken, Genomics. 84, 311-319.

• BASU P, Majumder PP, Roychoudhury S and Bhattacharyya NP. (2001) Haplotype analysis of genomic polymorphisms in and around the myotonic dystrophy locus in diverse populations of India, Human Genetics. 108, 310-317.

• Bhattacharyya NP, BASU P, Das M, Pramanik S, Banerjee R, Roychoudhury S and Majumder PP. (1999) Negligible male gene flow across ethnic boundaries in India, revealed by analysis of Y-chromosomal DNA polymorphisms, Genome Research. 9, 711-719.