Nitish R Mahapatra
|Lab:||BT 514 and BT 515 (Lab Website)|
Molecular Genetics of Cardiovascular Diseases.
Cardiovascular diseases (coronary heart disease, heart failure, stroke etc.) affect a large section of the adult population and are the leading causes of morbidity and mortality in many countries including India. Recent studies have documented that although the mortality associated with cardiovascular diseases are declining in the developed countries including Western Europe and North America, the burden of cardiovascular diseases continues to rise in the developing countries including India. Notably, South Asians have a greater prevalence of cardiovascular risk factors than the rest of the World, and India itself is estimated to have more than half of the World’s heart disease patients at present. These diseases not only cause enormous loss of human lives, but also lead to huge health care cost, tremendous economic and social burden, declining national productivity and quality of life.
The determinants of cardiovascular diseases are multi-factorial, complex and often interrelated. We are interested to understand the molecular and genetic bases of hypertension (elevated arterial blood pressure) because it is the chief risk factor for cardiovascular diseases. Despite extensive research over the past couple of decades, the pathogenesis of hypertension is only partially understood. Besides environmental factors (such as stress, inadequate physical activity, smoking/tobacco use and unhealthy diet that includes higher dietary fats/higher sodium/lower fruits and vegetables), strong influences of genes have been reported. Moreover, hypertension may be associated with and complicated by dyslipidemia (elevated levels of LDL-cholesterol and triglycerides and reduced level of HDL-cholesterol in the circulation), a major risk factor for cardiovascular diseases. In addition, diabetes mellitus is another major risk factor for cardiovascular diseases. Indeed, more than 65% of people with diabetes mellitus die of some form of heart disease/stroke and heart disease death rates in adults with diabetes are at least two times higher as compared to those without diabetes. Therefore, we are also interested to unravel the genetic and molecular mechanisms that govern the pathogenesis of lipid disorder and type 2 diabetes.
Our experimental approach involves identification, transcriptional and post-transcriptional regulation of the candidate/susceptibility genes for hypertension and related cardiovascular disease states. We also study the roles of translated protein products of the candidate genes in disease pathogenesis. Additionally, we work on discovering naturally-occurring functional genetic variants (single nucleotide polymorphisms and haplotypes) that may act as risk factors for development of cardiovascular diseases. We investigate at the cellular level (employing cultured cell lines), utilize animal models (genetically modified rodents) and human subjects (cases versus controls) for our various studies. Results from these studies are likely to shed light on the molecular mechanisms and ultimately help to develop diagnostic and therapeutic strategies for management of the cardiovascular diseases.
I. Selected Journal Articles.
18. Khan AA, Sundar P, Natarajan B, Gupta V, Arige V, Reddy SS, Barthwal MK, Mahapatra NR. 2021. An evolutionarily-conserved promoter allele governs HMG-CoA reductase expression in spontaneously hypertensive rat. J Mol Cell Cardiol (in press; doi: 10.1016/j.yjmcc.2021.05.017).
17. Natarajan B, Arige V, Khan AA, Reddy SS, Barthwal MK, Mahapatra NR. 2021. Hypoxia-mediated regulation of mitochondrial transcription factors in renal epithelial cells: implications for hypertensive renal physiology. Hypertens Res 44:154-167.
16. Khan AA, Agarwal H, Reddy SS, Arige V, Natarajan B, Gupta V, Kalyani A, Barthwal MK, Mahapatra NR. 2020. MicroRNA-27a is a key modulator of cholesterol biosynthesis. Mol Cell Biol 40:e00470-19.
15. Subramanian L, Maghajothi S, Singh M, Kesh K, Ananthamohan K, Sharma S, Khullar M, Victor SM, Swarnakar S, Asthana S, Mullasari AS, Mahapatra NR. 2019. A common tag nucleotide variant in MMP7 promoter increases risk for hypertension via enhanced interactions with CREB (Cyclic AMP Response Element-Binding Protein) Transcription Factor. Hypertension 74:1448-1459. (Featured in multiple news media including: https://timesofindia.indiatimes.com/city/chennai/study-finds-gene-that-triggers-hypertension/articleshow/72960922.cms; https://www.thehindubusinessline.com/news/science/iit-madras-researchers-find-link-between-a-tissue-remodelling-enzyme-and-hypertension-risk/article30388648.ece; https://educationtimes.com/article/campus-beat-college-events/72955058/IIT-Madras-collaborates-to-find-link-between-a-tissue-remodelling-enzyme-and-risk-of-Hypertension; https://www.outlookindia.com/newsscroll/iitm-finds-link-between-tissueremodelling-enzyme-hypertension/1693108; https://www.indiatoday.in/education-today/news/story/iit-madras-researchers-find-link-between-a-tissue-remodelling-enzyme-and-risk-of-hypertension-1631131-2019-12-24).
14. Arige V, Agarwal A, Khan AA, Kalyani A, Natarajan B, Gupta V, Reddy SS, Barthwal MK, Mahapatra NR. 2019. Regulation of Monoamine Oxidase B Gene Expression: Key Roles for Transcription Factors Sp1, Egr1 and CREB, and microRNAs miR-300 and miR-1224. J Mol Biol 431:1127-1147.
13. Mahata SK, Kiranmayi M, Mahapatra NR. 2018. Catestatin: A master regulator of cardiovascular functions. Curr Med Chem 25:1352-1374.
12. Subramanian L, Khan AA, Allu PKR, Kiranmayi M, Sahu BS, Sharma S, Khullar M, Mullasari AS, Mahapatra NR. 2017. A haplotype variant of the human chromogranin A gene (CHGA) promoter increases CHGA expression and the risk for cardiometabolic disorders. J Biol Chem 292:13970-13985. (Featured in the following news media: http://www.thehindu.com/sci-tech/health/blame-it-on-the-genes/article19778751.ece; http://vigyanprasar.gov.in/isw/heartdisease.html; https://scroll.in/pulse/852266/lab-notes-scientists-identify-a-gene-that-puts-indians-at-higher-risk-of-heart-disease; https://biotechtimes.org/2017/09/28/scientists-discover-genetic-link/; http://www.apnlive.com/science/study-identifies-genetic-link-to-heart-disease-in-indian-population-28428;http://www.downtoearth.org.in/news/carrying-set-of-genes-puts-you-on-higher-risk-of-cardiovascular-diseases-study-58765; http://www.biovoicenews.com/study-identifies-genetic-link-heart-disease-indian-population/;http://netindian.in/news/2017/09/29/00043430/study-identifies-genetic-link-heart-disease-indian-population).
11. Gupta V, Kapopara PR, Khan AA, Arige V, Subramanian L, Sonawane PJ, Sasi BK, Mahapatra NR. 2017. Functional promoter polymorphisms direct the expression of cystathionine gamma-lyase gene in mouse models of essential hypertension. J Mol Cell Cardiol 102: 61-73. (Cover page article).
10. Kiranmayi M, Chirasani VR, Allu PK, Subramanian L, Martelli EE, Sahu BS, Vishnuprabu D, Kumaragurubaran R, Sharma S, Bodhini D, Dixit M, Munirajan AK, Khullar M, Radha V, Mohan V, Mullasari AS, Naga Prasad SV, Senapati S, Mahapatra NR. 2016. Catestatin Gly364Ser variant alters systemic blood pressure and the risk for hypertension in human populations via endothelial nitric oxide pathway. Hypertension 68:334-347.
9. Kalyani A, Sonawane PJ, Khan AA, Subramanian L, Ehret GB, Mullasari AS, Mahapatra NR. 2015. Post-transcriptional Regulation of Renalase Gene by miR-29 and miR-146 MicroRNAs: Implications for Cardio-metabolic Disorders. J Mol Biol 427: 2629–2646.
8. Gupta V, Khan AA, Sasi BK, Mahapatra NR. 2015. Molecular mechanism of monoamine oxidase A gene regulation under inflammation and ischemia-like conditions: key roles for the transcription factors GATA2, Sp1 and TBP. J Neurochem 134:21-38.
7. Sonawane PJ, Gupta V, Sasi BK, Kalyani A, Natarajan B, Khan AA, Sahu BS, Mahapatra NR. 2014. Transcriptional Regulation of the Novel Monoamine Oxidase Renalase: Crucial Roles of Transcription Factors Sp1, STAT3 and ZBP89. Biochemistry 53: 6878-6892.
6. Allu PK, Chirasani VR, Ghosh D, Mani A, Bera AK, Maji SK, Senapati S, Mullasari AS, Mahapatra NR. 2014. Naturally occurring variants of the dysglycemic peptide pancreastatin: differential potencies for multiple cellular functions and structure-function correlation. J Biol Chem 289: 4455–4469.
5. Sasi BK, Sonawane PJ, Gupta V, Sahu BS, Mahapatra NR. 2014.Coordinated transcriptional regulation of Hspa1a gene by multiple transcription factors: crucial roles for HSF-1, NF-Y, NF-κB and CREB. J Mol Biol 426:116-35.
4. Sahu BS, Mohan J, Sahu G, Allu PKR, Subramanian L, Sonawane PJ, Singh PK, Sasi BK, Senapati S, Maji SK, Bera AK, Gomathi BS, Mullasari AS, Mahapatra NR. 2012. Functional genetic variants of the catecholamine-release-inhibitory peptide catestatin in an Indian population: allele-specific effects on metabolic traits. J Biol Chem 287: 43840-43852 (Featured in Nature India: https://www.natureasia.com/en/nindia/article/10.1038/nindia.2012.177).
3. Sahu BS, Mohan J, Sahu G, Singh PK, Sonawane PJ, Sasi BK, Allu PKR, Maji SK, Bera AK, Senapati S, Mahapatra NR. 2012. Molecular interactions of the physiological anti-hypertensive peptide catestatin with the neuronal nicotinic acetylcholine receptor. J Cell Sci 125: 2323–2337.
2. Sahu BS, Sonawane PJ, Mahapatra NR. 2010. Chromogranin A: a novel susceptibility gene for essential hypertension. Cell Mol Life Sci 67:861-874.
1. Mahapatra NR. 2008. Catestatin is a novel endogenous peptide that regulates cardiac function and blood pressure. Cardiovasc Res 80:330-338.
II. Selected Book Chapters.
1. Gupta V, Arige V, Mahapatra NR. 2019. Role of monoamine oxidases in heart diseases. In: Modulation of Oxidative Stress in Heart Disease (S. Chakraborti et al.; Eds). pp. 129-150. Springer Nature Singapore Private Limited, Singapore.
2. Mahapatra NR, Ghosh S, Mahata M, Bandyopadhyay GK, Mahata SK. 2017. Naturally Occurring Single Nucleotide Polymorphisms in Human Chromogranin A (CHGA) Gene: Association with Hypertension and Associated Diseases. In:Chromogranins: from Cell Biology to Physiology and Biomedicine (Angelone T, Cerra M & Tota B; Eds). pp. 195-211. Springer International Publishing AG, Cham, Switzerland.
3. Sonawane PJ, Sahu BS, Mahapatra NR. 2011. Pharmacogenomics of cardiovascular drugs. In: Drug Design-Basics and Applications (Doble M, Ed.). pp. 280-310. Tata-McGraw-Hill Publishers, New Delhi, India.