Prof. Pramod C. Rath
Molecular Biology Laboratory
Office/Lab : Room No. 402/433
School of Life Sciences, J.N.U., New Delhi
Phone: 011-26704525
Email: pcrath@mail.jnu.ac.in;
pramod.rath@gmail.com
ORCID | Research Gate | Google Scholar |
http://www.jnu.ac.in/Faculty/pcrath
Genomic Biology of Repetitive DNA and Noncoding RNA
Cytokines, Transcription Factors, Cell Signaling and Disease
Bone Marrow Stem Cells and Regenerative Medicine
Molecular Biology of Aging
RESEARCH SUMMARY
We have isolated and characterized many mammalian cDNAs with simple repeat sequences and shown that genomic repetitive DNA and retrotransposable sequences are widely expressed into long noncoding RNAs (lncRNAs) in rat tissues. These RNAs are processed into small noncoding RNAs (e.g., piRNAs& miRNAs) in immunological tissues and others. Expression of two such lncRNAs (LINC-RBE & LINC-RSAS) is regulated by retinoic acid (Vitamin A-metabolite) in neurons from hippocampus of rat brain at transcriptional & post-transcriptional levels, respectively. The lncRNAs show distinct age-related expression patterns in brain & testis of immature-young, adult and near-old rats. We also isolated cDNAs of variant mRNAs with repeat sequences (e.g., TPIP-C2, 4.1-DIPP & H3-SRY) and demonstrated their possible biological functions. TPIP-C2 induced apoptosis in cancer cells, 4.1-DIPP is expressed in rat brain, kidney, spleen and H3-SRY stimulated DNA-binding activity of SRY. This shows biological consequences of molecular diversity RNAs in the context of genomic repetitive DNA, transposable sequences, noncoding RNA and mRNA.
We have studied expression & structure-function relationship of transcription factors: Interferon Regulatory Factors (IRF-1& IRF-2) in relation to virus-responsive promoter elements, expression of interferon-inducible inflammatory genes (IFN-b, iNOS, Cox-2) in mammalian cells and endotoxin (LPS)-induced mouse liver. Expression of IRF-1, IRF-2 and IRF-inducible genes was also studied in the context of a high fat-diet induced aortic atherosclerosis mouse model. We showed that IRF-1 interacts with REDD-2, a radiation-induced factor, in mouse bone marrow cells. We also studied an interferon-inducible antiviral endoribonuclease: RNase L tumor suppressor gene and reported it as a stress-inducible factor and its protein-protein interactions. We reported constitutive activation of tumor necrosis factor-alpha (TNF-a)-induced transcription factor: Nuclear Factor-kappa B (NF-kB) in proliferating Burkitt Lymphoma Daudi cells and that this can be suppressed by Interferon-alpha (IFN-a). We reported that activation of NF-kB in lung cancer cells is related to cellular backgrounds of p53-mutations. All these show how cytokine-inducible transcription factors are involved in cellular signaling, disease-biology and pathology.
We isolated mesenchymal stem cells (MSCs) from mouse bone marrow cells and differentiated them into adipocytes, chondrocytes, osteocytes and neuron-like cells in order to study biology of stem cells, their differentiation potential and possible application in regenerative medicine. In a radiation-induced bone marrow-damage mouse-model, we transplanted bone marrow stem cells and MSCs in order to restore bone marrow and its function. We showed IRF-1 & IRF-2 transcription factors are radiation-sensitive and -responsive, which may be involved in bone marrow-damage by radiation & its restoration by stem cells.
Regarding molecular biology of aging, we are studying role of long noncoding RNAs in aging of brain & testis in rat and age-related diseases. LINC-RBE & LINC-RSAS may be good candidates for developing biomarker for aging and Vitamin A-metabolite (retinoic acid or RA)-inducible function in hippocampus of mammalian brain. We are also studying effect(s) of lncRNA & RA on expression of genes for learning & memory and adult neurogenesis in human neuronal cells.
AWARDS/ FELLOWSHIPS/ RECOGNITIONS
Swiss National Fund Post-Doctoral Research Fellowship, Institute for Molecular Biology, University of Zurich-E.T.H., Switzerland, 1989-90
N.I.H.-Workshop-Fellowship,Advanced Genome Sequencing & Analysis, Cold Spring Harbor Laboratory, New York, U.S.A., March, 1998
Visiting-Scientist, University of Texas-M.D. Anderson Cancer Centre, U.S.A., 1998-1999
N.I.H.-Workshop-Fellowship-Stem Cell Institute, Medical School, University of Minnesota, Minneapolis, U.S.A., Nov.-Dec., 2005
Expert, Selection/Promotion Committees, Faculty/Scientists, Central/State Univ./Institute(s)
Expert Member & Co-Chair, Department of Biotechnology Research Associate Fellowship (D.B.T.-RA) Committee (I.I.Sc. & R.C.B.)
Expert Member, Institutional Committee for Stem Cell Research, N.I.I., A.I.I.M.S., I.L.B.S.
Vice-President, Association of Gerontology India, 2014-2016
Expert Member (J.N.U.), Academic Committees for Ph.D. of N.I.I., C.D.R.I., I.U.A.C.
Expert Member, Centre for Excellence Committee-U.G.C., Guru Nanak Dev University, Amritsar
Expert Member, National Agricultural Innovation Project Committee-I.C.A.R., N.D.R.I., Karnal
F.I.M.S.A.-I.U.I.S.-Workshop Poster 2nd-Award, Beijing Medical University, China, 1996
Department of Science and Technology (D.S.T.) Young Scientist Research Project Award (1993-1995)
Tilak Award, Association of Gerontology India, 1988
U.G.C./C.S.I.R.-NET-JRF/SRF, (1982-88), C.S.I.R.-R.A. & Poolship (not availed)
A.B. Mishra Award for First Position in M.Sc. (Zoology), B.H.U., 1981
First-Class First-Position and Gold-Medal in M.Sc. (Zoology), B.H.U., 1981
M.Sc. Courses:
LS 431A Life Sciences Practicals II
LS 501A Molecular Genetics & Genetic Engineering
Ph.D. Courses:
M. Phil., Ph. D. Students supervised at J.N.U.: 24
Ph. D. (20)
Indranil Dey (2000) A study of chromatin structure and transcription using LINE DNA and simple repeat DNA probes.
Sanjiv Kumar (2000) Organization and expression of murine interferon regulatory factor-1 (IRF-1) gene.
S. Dhanalakshmi (2000) Chemomodulatory action of different spices on the drug metabolizing enzymes, antioxidant mechanisms and chemical carcinogenesis. (Joint supervision with Prof. A.R. Rao).
Mitali Pandey (2001) Organization and function of the interferon-inducible 2’,5’-oligoadenylate-dependent ribonuclease L (RNase L) gene of mouse.
B. Padmavathi (2001) Cancer chemopreventive potential of certain plants and their possible mechanisms. (Joint supervision with Prof. A.R. Rao).
Gagan Deep Bajaj (2002) Molecular cloning and characterization of human cDNAs by a simple repeat DNA probe: identification of novel candidate genes.
Meenakshi Upreti (2003) Interferon regulatory factor-1 (IRF-1) of mouse: analysis of the transactivation domain.
Ritakshi Arora (2003) Study of T-cell response to hepatitis-E virus antigen in patients with acute hepatitis-genotyped for cytokines. (Joint supervision with Prof. R.N.K. Bamezai).
Krishna Prakash (2007) Functional characterization of recombinant Interferon Regulatory Factor-2 (IRF-2) of mouse.
Rasmi Rekha Mishra (2009) Expression and functional characterization of repeat sequence-containing cDNAs.
Ankush Gupta (2009) Functional characterization of RNase L.
Jyothi Ramanathan (2010) Functional analysis of Interferon Regulatory Factor-1 (IRF-1) in Atherosclerosis.
Deepak Kumar Singh (2012) A study of the long interspersed nuclear element (LINE) from the rat genome: sequence and expression analysis.
Manish Kumar Gupta (2012) A study of interferon regulatory factor (IRF)-1 in mouse bone marrow cells.
Kumar Sandeep (2013) Expression of RNase L in prostate cancer.
Jitendra Kumar Chaudhary (2013) Molecular analysis of self-renewal and differentiation of mammalian bone marrow-derived multipotent mesenchymal stem cells.
Sukhleen Kour (2015) Functional characterization of the noncoding RNAs from the repetitive DNA of mammalian genome.
Naseem Ahamad (2017) Bone marrow regeneration in the mouse by using bone marrow derived stem cells.
Ajay Kumar Danga (2023) Expression and function of long noncoding RNAs in the testis of the rat during maturation and aging.
Anita Kumari (2024) Expression of long noncoding RNAs: LINC-RBE and LINC-RSAS in response to retinoic acid.
M. Phil. (04)
Indranil Dey (1995) Molecular cloning of “DNase I-resistant chromatin-DNA” from the rat skeletal muscle.
Krishna Prakash (2003) Expression of recombinant Interferon Regulatory Factor-2 (IRF-2) of mouse.
Kumar Sandeep (2008) Computational and expression analysis of RNase L.
Pankaj Keshari (2016) A study of the rat long noncoding RNA in heterologous system.
Molecular Biology of Aging:
Danga A.K., Kour S., Kumari A., Rath P.C. (2024) The long noncoding RNA (LINC-RBE) expression in testicular cells is associated with aging. Biogerontology http://doi:10.1007/s10522-024-10119-5
Danga A.K., Kour S., Kumari A, Rath P.C. (2024) Cell-type specific and differential expression of LINC-RSAS long noncoding RNA declines in the testes during ageing of the rat. Biogerontology http://doi.org/10.1007/s10522-023-10088-1
Rath P.C. Models, Molecules and Mechanisms in Biogerontology: Cellular Processes, Metabolism and Diseases (ed. P.C. Rath) Springer Nature, Singapore, 21 chapters, 497 pages,77 illustrations, ISBN 978-981-32-9005-1, June 2020
Mittal A., Rath P.C. Protein structure and function in aging and age-related diseases. In: Models, Molecules and Mechanisms in Biogerontology: Cellular Processes, Metabolism and Diseases, Springer Nature, chapter 1, pp3-26, 2020
Saint M., Rath P.C. Transcription and aging. In: Models, Molecules and Mechanisms in Biogerontology: Cellular Processes, Metabolism and Diseases. Springer Nature, chapter 3, pp 43-66, 2020
Manhas R., Rath P.C. Ribosome, protein synthesis and aging. In: Models, Molecules and Mechanisms in Biogerontology: Cellular Processes, Metabolism and Diseases. Springer Nature, chapter 4, pp 67-87, 2020
Banerjee R., Rath P.C. Mitochondria as a key player in aging. In: Models, Molecules and Mechanisms in Biogerontology: Cellular Processes, Metabolism and Diseases, Springer Nature, chapter 10, pp 181-198, 2020
Chaudhary J.K., Rath P.C. Stem cells and aging. In: Models, Molecules and Mechanisms in Biogerontology: Cellular Processes, Metabolism and Diseases, Springer Nature, chapter 12, pp 213-234, 2020
Pal A., Rath P.C. Metabolic diseases and aging. In: Models, Molecules and Mechanisms in Biogerontology: Cellular Processes, Metabolism and Diseases, Springer Nature, chapter 17, pp 347-391, 2020
Rath P.C. Models, Molecules and Mechanisms in Biogerontology: Physiological Abnormalities, Diseases and Interventions, (ed. P.C. Rath) Springer Nature, Singapore, 20 chapters, 436 pages, 86 illustrations. ISBN 978-981-13-3585-3,July 2019
Ahamad N., Rath P.C. Bone marrow stem cells, aging and age-related diseases. In: Models, Molecules and Mechanisms in Biogerontology: Physiological Abnormalities, Diseases and Interventions, Springer Nature,chapter 15 pp 321-352, 2019
Anand B. G., Prajapati K. P., Dubey K., Ahamad N., Shekhawat D. S., Rath P.C., Joseph G. K., Kar K. Self-assembly of artificial sweetener aspartame yields amyloid-like cytotoxic nanostructures.ACS Nano, 13(5): 6033-6049, 2019
Rath P.C. Cytokines and Aging. In: Hormones in Ageing and Longevity. Healthy Aging and Longevity 6, DOI 10.1007/978-3-319-63001-4, eds. S Rattan, R Sharma, Springer International Publishing AG, ISBN978-3-319-63000-7, chapter 13, pp 291-310, 2017
Rath P.C. Topics in Biomedical Gerontology, Springer Nature, Singapore (eds. P.C. Rath, R. Sharma, S. Prasad), 355 pages, 77 illustrations,ISBN 978-981-10-2154-1, 2017
Bone Marrow Stem Cells & Regenerative Medicine:
Chaudhary J.K., Ahamad N., Rath P.C. (2023) Mesenchymal stem cells (MSCs) from the mouse bone marrow show differential expression of interferon regulatory factors IRF-1 and IRF-2. Mol. Biol. Rep. (2024) 51: 97 http://doi.org/10.1007/s11033-023-09025-9
Ahamad N., Rath P.C. Expression of interferon regulatory factors (IRF-1 and IRF-2) during radiation-induced damage and regeneration of bone marrow by transplantation in mouse.Mol. Biol. Rep. 46(1): 551-567, 2019
Chaudhary J.K., Rath P.C. Microgrooved-surface topography enhances cellular division and proliferation of mouse bone marrow-derived mesenchymal stem cells. PLoS One 12(8): e0182.doi: 10.1371/journal.pone.0182128, 2017
Chaudhary J.K., Rath P.C. A simple method for isolation, propagation, characterization and differentiation of adult mouse bone marrow-derived multipotent mesenchymal stem cells. J. Cell Sci. Therapy 8: 261. DOI: 10.4172/2157-7013.1000261, 2017
Chaudhary J.K., Rath P.C. Stem cells, aging, challenges and the way forward. Ann. Pharmacol. Pharm. 2(2): 1017, 2017
Rath P.C., Chaudhary J.K. Geriatrics and Stem Cell Research. In: Textbook of Geriatric Medicine. ed. P. Sanchetee, Chapter 155, pp 778-785, Paras Medical Publisher, Hyderabad, New Delhi, ISBN 978-81-8191-418-7) 2017
Genomic Biology of Repetitive DNA & Noncoding RNA:
Danga A.K., Rath P.C. (2024) Molecular cloning, expression and cellular localization of two long noncoding RNAs (mLINC-RBE and mLINC-RSAS) in the mouse testis. Int. J. Biol. Macromol. 255 (2024) 128106
Kour S, Rath P.C. Expression of long noncoding RNA in rat brain during aging. In: Topics in Biomedical Gerontology, eds. P.C. Rath, R. Sharma, S. Prasad, Springer Nature, pp161-203, 2017
Kour S., Rath P. C. Age-Related Expression of a Repeat-Rich Intergenic Long Noncoding RNA in the Rat Brain. Mol. Neurobiol. 54(1): 639-660, 2017
Kour S., Rath P. C. Long noncoding RNAs in aging and age-related diseases. Ageing Res. Rev. 26:1-21 (review) 2016
Kour S., Rath P. C. All-Trans Retinoic Acid Induces Expression of a Novel Intergenic Long Noncoding RNA in Adult rat Primary Hippocampal Neurons. J. Mol. Neurosci. 58(2): 266-276, 2016
Kour S., Rath P. C. Age-dependent differential expression profile of a novel intergenic long noncoding RNA in rat brain. Int. J. Dev. Neurosci. 46: 55-66, 2015
Singh D.K. and Rath P.C. Long interspersed nuclear elements (LINEs) show tissue-specific, mosaic genome and methylation-unrestricted, widespread expression of noncoding RNAs in somatic tissues of the rat. RNA Biol. 9(11): 1380-1396, 2012
Mishra R.R., Chaudhary J.K. and Rath P.C. Cell cycle arrest and apoptosis by expression of a novel TPIP (TPIP-C2) cDNA encoding a C2-domain in HEK-293 cells. Mol. Biol. Rep. 39 (7): 7389-7402, 2012
Mishra R.R., Chaudhary J.K., Bajaj G.D. and Rath P.C. A novel human TPIP splice-variant (TPIP-C2) mRNA, expressed in human and mouse tissues, strongly inhibits cell growth in HeLa cells. PLoS One 6(12): e28433. Doi:10.1371/journal.pone.0028433, 2011
Dey I. and Rath P.C. A novel rat genomic simple repeat DNA with RNA-homology shows triplex (H-DNA)-like structure and tissue-specific RNA expression. Biochem. Biophys. Res. Commun. 327: 276-286, 2005
Dey I. and Rath P.C. Correlation between alterations in nucleosomal organization of LINEs in the promoter of Cytochrome P450 2B1/2 gene and induction of CYP2B1/2B2 mRNA expression by phenobarbitone in rat liver. DNA Cell Biol. 24: 359-370, 2005
Cytokines, Transcription Factors, Cell Signaling & Disease:
Gupta A. and Rath P.C. Curcumin, a natural antioxidant, acts as a noncompetitive inhibitor of human RNase L in presence of its cofactor 2-5A in vitro. Biomed. Res. Int. doi: 10.1155/2014/817024, 2014
Gupta A. and Rath P.C. Expression of mRNA and protein-protein interaction of the antiviral endoribonuclease RNase L in mouse spleen. Int. J. Biol. Macromol. 69: 307-318, 2014
Gupta M. and Rath P.C. Interferon regulatory factor-1 (IRF-1) interacts with regulated in development and DNA damage response 2 (REDD2) in the cytoplasm of mouse bone marrow cells. Int. J. Biol. Macromol. 65: 41-50, 2014
Gupta A. and Rath P.C. Expression, purification and characterization of the interferon-inducible, antiviral and tumour-suppressor protein, human RNase L. J. Biosci. 37(1): 103-113, 2012
Prakash K. and Rath P.C. Mouse interferon regulatory factor-2: expression, purification and DNA binding activity. Mol. Biol. Rep. 39 (1): 599-606, 2012
Prakash K. and Rath P.C. Replacement of the C-terminal tetrapeptide (314PAPV317 to 314SSSM317) in Interferon Regulatory Factor-2 alters its N-terminal DNA binding activity, J. Biosci. 35(4): 547-556, 2010
Rath P.C. and Mukhopadhyaya T. p53 gene expression and 2-methoxyestradiol treatment differentially induce NF-kB activation in human lung cancer cells with different p53 phenotypes, DNA Cell Biol. 28 (12):615-623, 2009
Pandey M. and Rath P.C. Organization of the interferon-inducible 2’,5’-oligoadenylate-dependent ribonuclease L (RNase L) gene of mouse. Mol. Biol. Rep. 34 (2): 97-104, 2007
Rath P.C. Relationship between constitutive Nuclear Factor-kappaB (NF-kB) and Inhibitor kappaB-alpha (IkB-a) in an Interferon-a-sensitive human Burkitt lymphoma cell line. Biochim. Biophys. Acta.: Molecular Basis of Disease. 1741: 253-263, 2005
Upreti M. and Rath P.C. Expression and DNA binding activity of the recombinant Interferon Regulatory Factor-1 (IRF-1) of mouse. Mol. Biol. Rep. 32:103-116, 2005
Pandey M. and Rath P.C. Expression of interferon-inducible recombinant human RNase L causes RNA degradation and inhibition of cell growth in Escherichia coli.Biochem. Biophys. Res. Commun. 317: 586-597, 2004
Pandey M., Bajaj G.D. and Rath P.C. Induction of the interferon-inducible RNA-degrading enzyme, RNase L by stress-inducing agents in the human cervical carcinoma cells. RNA Biology.1:21-27, 2004
Upreti M, Kumar S and Rath P.C. Replacement of 198MQMDII203 of mouse IRF-1 by 197IPVEVV202 of human IRF-1 abrogates induction of IFN-b, iNOS, and Cox-2 gene expression by IRF-1. Biochem. Biophys. Res. Commun. 314: 737-744, 2004