Manoj Mishra, PhD

At present my research is focused on the functional analysis of single nucleotide polymorphisms (SNPs) associated with complex human traits, including blood pressure (BP), located in noncoding regions of DNA. In this study, I am developing several approaches and methods to test the hypothesis that BP-associated noncoding SNPs regulate the expression of genes that are physiologically important to BP regulation, examining the underlying mechanisms, and investigating their influence on BP.

In another study my research is focused on the differentiation of human iPSCs into functional mature cardiomyocytes and disease modeling of diabetic cardiomyopathy (DCM). DCM is a common and important health concern in the rapidly growing population of diabetic patients. At present, no specific drug treatment exists to prevent diabetes-induced cardiac dysfunction, a complex multifactorial condition that is distinguished by a unique set of metabolic, structural, and molecular changes within the DCM. The advances in disease modeling using human induced pluripotent stem cells (iPSCs) have opened novel paths to study human physiology and disease at the cellular level. We characterized an in vitro cell based model for DCM developed by exposing human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to a diabetic-like environment. MicroRNAs (miRNAs) are key factors in controlling complex regulatory networks in cellular functions and disease processes. We performed a small RNA deep sequencing analysis to identify miRNAs associated with this in vitro DCM model. The study will examine functional roles for these miRNAs and identify the mechanisms by which these miRNAs might contribute to the development of DCM.

Publications

Pan X, Geng X, Liu Y, Yu M, Mishra MK, Xu X, Ding X, Liu P, Liang M. Transfer RNA Fragments in the Kidney in Hypertension. Hypertension. 2021;77(5):1627-1637. doi: 10.1161/HYPERTENSIONAHA.121.16994. PMID: 33775129.

Sengupta K, Mishra MK, Loro E, Spencer MJ, Pyle AD, Khurana TS. Genome editing-mediated Utrophin upregulation in Duchenne Muscular Dystrophy stem cells. Mol Ther Nucleic Acids. 2020; 22(3):500-509. doi.org/10.1016/j.omtn.2020.08.031. PMID: 33230452.

Mishra MK, Liang EY, Geurts AM, Auer PWL, Liu P, Rao S, Greene AS, Liang M, Liu Y. Comparative and Functional Genomic Resource for Mechanistic Studies of Human Blood Pressure-Associated Single Nucleotide Polymorphisms. Hypertension. 2020; 75(3):859-868. doi: 10.1161/HYPERTENSIONAHA.119.14109. PMID: 31902252.

Parashar D, Geethadevi A, Aure MR, Mishra J, George J, Chen C, Mishra MK, Tahiri A, Zhao W, Nair B, Lu Y, Mangala LS, Rodriguez-Aguayo C, Lopez-Berestein G, Camara AKS, Liang M, Rader JS, Ramchandran R, You M, Sood AK, Kristensen VN, Mills GB, Pradeep S, Chaluvally-Raghavan P. miRNA551b-3p Activates an Oncostatin Signaling Module for the Progression of Triple-Negative Breast Cancer. Cell Rep. 2019; 29(13):4389-4406.e10. doi: 10.1016/j.celrep.2019.11.085. PMID: 31875548.

Pant T, Mishra MK, Bai X, Ge ZD, Bosnjak ZJ, Dhanasekaran A. Microarray analysis of long non-coding RNA and mRNA expression profiles in diabetic cardiomyopathy using human induced pluripotent stem cell-derived cardiomyocytes. Diab Vasc Dis Res. 2019; 16(1):57-68. DOI: 10.1177/1479164118813888. PMID: 30482051.

Liu P, Liu Y, Liu H, Pan X, Li Y, Usa K, Mishra MK, Nie J, Liang M. Role of DNA De Novo (De)Methylation in the Kidney in Salt-Induced Hypertension. Hypertension 2018; 72(5):1160-1171. DOI: 10.1161/HYPERTENSIONAHA.118.11650 PMID: 30354815.

Loro E, Ramaswamy G, Chandra A, Tseng W, Mishra MK, Shore EM, Khurana TS. IL15RA is required for osteoblast function and bone mineralization. Bone 2017; 103:20-30. DOI: 10.1016/j.bone.2017.06.003. PMID: 28602725.

Mishra MK, Loro E, Wilton SD, Khurana TS. Functional improvement of dystrophic muscle by repression of utrophin: let-7c interaction. PloS One 2017; 12 (10), e0182676. DOI: 10.1371/journal.pone.0182676. PMID: 29045431.

Simonson B, Subramanya V, Franchino H, Ottaviano P, Chan MC, Mishra MK, Hunt D, Khurana TS, Kontaridis M, Seidman J, Seidman C, Rosenzweig A, Das S. DDiT4L promotes autophagy and inhibits pathological cardiac hypertrophy in response to stress. Sci Signal 2017; 10(468): eaaf5967. DOI: 10.1126/scisignal.aaf5967. PMID: 28246202.

Tao JQ, Sorokina EM, Vazquez Medina JP, Mishra MK, Yamada Y, Satalin J, Nieman GF, Nellen JR, Beduhn B, Cantu E, Habashi NM, Jungraithmayr W, Christie JD, Chatterjee S. Onset of Inflammation with Ischemia: Implications for Donor Lung Preservation and Transplant Survival. Am J Transplant 2016; 16(9):2598-611. DOI: 10.1111/ajt.13794. PMID: 26998598.

Loro E, Seifert EL, Moffat C, Romero F, Mishra MK, Sun Z, Krajacic P, Anokye-Danso F, Summer RS, Ahima RS, Khurana TS. IL-15Rα is a determinant of muscle fuel utilization, and its loss protects against obesity. Am J Physiol Regul Integr Comp Physiol 2015; 309(8):R835-44. DOI: 10.1152/ajpregu.00505.2014. PMID: 26269523.

Karar J, Dolt KS, Mishra MK, Arif E, Javed S, Pasha MA. Expression and functional activity of pro-oxidants and antioxidants in murine heart exposed to acute hypobaric hypoxia. FEBS Lett 2007; 581(24):4577-82. DOI: 10.1016/j.febslet.2007.08.044. PMID: 17825300.

Dolt KS, Karar J, Mishra MK, Salim J, Kumar R, Grover SK, Qadar Pasha MA. Transcriptional downregulation of sterol metabolism genes in murine liver exposed to acute hypobaric hypoxia. Biochem Biophys Res Commun 2007; 354(1):148-53. DOI: 10.1016/j.bbrc.2006.12.159. PMID: 17207770.

Dolt KS, Mishra MK, Karar J, Baig MA, Ahmed Z, Pasha MA. cDNA cloning, gene organization and variant specific expression of HIF-1α in high altitude yak (Bos grunniens). Gene 2007; 386(1-2):73-80. DOI: 10.1016/j.gene.2006.08.004. PMID: 17045424.