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Faculty

S Mahalingam

S Mahalingam

Ph.D., Madurai Kamaraj University

M.Sc., Madurai Kamaraj University

Professor

mahalingam@iitm.ac.in

Office : Block:2 BT 05

+91-44-2257-4130

Lab : Block:2 BT 101 Lab website ➔

Research Interests

1. Molecular pathogenesis of HIV/AIDS
  • Virus-host interaction, mechanism of HIV mediated cell cycle arrest, and role of integrase during very early steps in viral infection.
2. Regulation of nucleo-cytoplasmic transport proteins
  • Identification and characterization of protein nuclear and nucleolar transport using both cellular and viral proteins.
3. Cancer biology
  • a.Understanding the cross talk between tumor suppressors and activators of cell proliferation, mechanism of Ras associated tumor suppressor mediated cell growth control

  • b.Nucleolus on cell proliferation and cancer: Nucleolus play a very important role in rRNA production, processing, and ribosome biogenesis. Understanding the role nucleolar proteins in cell proliferation and tumor development is critical.

  • c.Cancer Genomics: Cancer specific biomarkers for early detection and drug target identification, Development of cancer Genome database specific to Indian population

  • d.Genomics of pancreatic cancer and childhood leukemia.

Career Profile

  • Professor, Department of Biotechnology, Indian Institute of Technology Madras, Chennai (May 2010- present)

  • Associate Professor, Department of Biotechnology, Indian Institute of Technology Madras, Chennai (May 2007- May 2010).

  • Staff Scientist-V, Centre DNA Fingerprinting and Diagnostics, Hyderabad (May 2005 - May 2007).

  • Visiting Scientist, Institute of Molecular and Cellular Biology, Singapore (Aug-Dec. 2003).

  • Visiting Scientist, University of Pittsburgh, Pittsburgh, USA (March-May 2002).

  • Staff Scientist-IV, Centre DNA Fingerprinting and Diagnostics, Hyderabad (Oct 2000-April 2005).

  • Research Associate, University of Alabama, Birmingham, USA (1997-00).

  • Research Associate, University of Pennsylvania, Philadelphia, USA (1996-97).

  • Postdoctoral Fellow, Thomas Jefferson Univ, Philadelphia, USA (1994-95).

Publications

A. Cancer Biology:

1.Krishnan R, Murugiah M, Padma Lakshmi N, Mahalingam S. (2020) Guanine Nucleotide Binding Protein Like - 1 (GNL1) promotes cancer cell proliferation and survival through AKT/p21CIP1 signalling cascade. Molecular Biology of the cell. 31(26): 2904-2919.

  1. Krishnan R, Boddapati N, Mahalingam S. (2018) Interplay between human nucleolar GNL1 and RPS20 is critical to modulate cell proliferation. Scientific Reports 8(1):11421.

  2. Kumaraswamy A, Mamidi A, Desai P, Sivagnanam A, Perumalsamy LR, Ramakrishnan C, Gromiha M, Rajalingam K, Mahalingam(2018) The non-enzymatic RAS effector RASSF7 inhibits oncogenic c-Myc function. Journal of Biological Chemistry. 5;293(40):15691-15705.

4.Karthik IP, Desai P, Sukumar S, Dimitrijevic A, Rajalingam K, Mahalingam S. (2018) E4BP4/NFIL3 modulates the epigenetically repressed RAS effector RASSF8 function through histone methyltransferases. Journal of Biological Chemistry 293 (15): 5624-5635.

5.Krishnan R, Boddapati N, Mahalingam S. (2018) Interplay between human nucleolar GNL1 and RPS20 is critical to modulate cell proliferation. Scientific Reports; 8(1):11421.

6.Thoompumkal I.J., Rehna K., Anbarasu K., Mahalingam S. (2016) Leucine Zipper Down-regulated in Cancer-1 (LDOC1) interacts with Guanine nucleotide binding protein-like 3-like (GNL3L) to modulate Nuclear Factor-kappa B (NF-?B) signaling during cell proliferation. Cell Cycle 15 (23): 3251-3267.

  1. Datta D., Anbarasu K., Rajabather S., Priya R.S., Desai P., Mahalingam S. (2015) Nucleolar GTP-binding protein-1 (NGP-1) promotes G1 to S phase transition by activating cyclin-dependent kinase inhibitor p21Cip1/Waf1. Journal of Biological Chemistry 290 (35): 21536-21552

  2. Thoompumkal I.J., Rao M.R.K.S., Kumaraswamy A., Krishnan R., Mahalingam S. (2015) GNL3L is a nucleo-cytoplasmic shuttling protein: Role in cell cycle regulation. PLoS ONE 10 (8): e0135845

  3. Suryaraja R., Anitha M., Anbarasu K., Kumari G., Mahalingam S. (2013) The E3 ubiquitin ligase itch regulates tumor suppressor protein RASSF5/NORE1 stability in an acetylation-dependent manner. Cell Death and Disease (4): 3

  4. Boddapati N., Anbarasu K., Suryaraja R., Tendulkar A.V., Mahalingam S. (2012) Subcellular distribution of the human putative nucleolar GTPase GNL1 is regulated by a novel arginine/lysine-rich domain and a GTP binding domain in a cell cycle-dependent manner. Journal of Molecular Biology 416 (3): 346-366.

  5. Chennupati V., Datta D., Rao M.R.S., Boddapati N., Kayasani M., Sankaranarayanan R., Mishra M., Seth P., Mani C., Mahalingam S. (2011) Signals and pathways regulating nucleolar retention of novel putative nucleolar GTPase NGP-1(GNL-2). Biochemistry 50 (21): 4521-4536

  6. Kumari G., Singhal P.K., Suryaraja R., Mahalingam S. (2010) Functional Interaction of the Ras Effector RASSF5 with the Tyrosine Kinase Lck: Critical Role in Nucleocytoplasmic Transport and Cell Cycle Regulation. Journal of Molecular Biology 397 (1): 89-109

  7. Kumari G., Mahalingam S. (2009) Extracellular signal-regulated kinase 2 (ERK-2) mediated phosphorylation regulates nucleo-cytoplasmic shuttling and cell growth control of Ras-associated tumor suppressor protein, RASSF2. Experimental Cell Research 315 1 (6): 2775-2790

  8. Kumari G., Singhal P.K., Rao M.R.K.S., Mahalingam S. (2007) Nuclear Transport of Ras-associated Tumor Suppressor Proteins: Different Transport Receptor Binding Specificities for Arginine-rich Nuclear Targeting Signals. Journal of Molecular Biology 367 (5): 1294-1311

  9. Rao M.R.K.S., Kumari G., Balasundaram D., Sankaranarayanan R., Mahalingam S (2006) A Novel Lysine-rich Domain and GTP Binding Motifs Regulate the Nucleolar Retention of Human Guanine Nucleotide Binding Protein, GNL3L. Journal of Molecular Biology 364 (4): 637-654

16 Du X., Subba Rao M.R.K., Chen X.Q., Wu W., Mahalingam S., Balasundaram D. (2006) The homologous putative GTPases Grn1p from fission yeast and the human GNL3L are required for growth and play a role in processing of nucleolar pre-rRNA. Molecular Biology of the Cell (1): 460-474

B. Molecular pathogenesis of HIV/AIDS:

  1. Prakash Singh S, Raja S, Mahalingam S. (2020) Viral protein X unlocks the nuclear pore complex through a human Nup153-dependent pathway to promote nuclear translocation of the lentiviral genome. Molecular Biology of the Cell 31(4): 304-317. (Cover article)

  2. Prakash Singh S, Raja S, Mahalingam S. (2019) Lentiviral Vpx induces alteration of mammalian cell nuclear envelope integrity. Biochem. Biophys. Res. Commun. 511(1):192-198.

  3. Rangasamy S.P., Menon V., Dhopeshwarkar P., Pal R., Vaniambadi K.S., Mahalingam S. (2016) Membrane bound Indian clade C HIV-1 envelope antigen induces antibodies to diverse and conserved epitopes upon DNA prime/protein boost in rabbits. Vaccine 34 (21): 2444-2452

  4. Sneha Priya R., Veena M., Kalisz I., Whitney S., Priyanka D., LaBranche C.C., Sri Teja M., Montefiori D.C., Pal R., Mahalingam S., Kalyanaraman V.S. (2015) Antigenicity and immunogenicity of a trimeric envelope protein from an Indian clade C HIV-1 isolate. Journal of Biological Chemistry 290 (14): 9195-9208

  5. Menon V., Sneha Priya R., Labranche C., Montefiori D., Mahalingam S., Kalyanaraman V.S., Pal R. (2015) Characterization of protective immune response elicited by a trimeric envelope protein from an Indian clade C HIV-1 isolate in rhesus macaques. Journal of Medical Primatology 44 (5): 275-285

  6. Gupta P., Singhal P.K., Rajendrakumar P., Padwad Y., Tendulkar A.V., Kalyanaraman V.S., Schmidt R.E., Srinivasan A., Mahalingam S. (2011) Mechanism of host cell MAPK/ERK-2 incorporation into lentivirus particles: Characterization of the interaction between MAPK/ERK-2 and proline-rich-domain containing capsid region of structural protein Gag. Journal of Molecular Biology 410 (4): 681-697

  7. Pandey R.C., Datta D., Mukerjee R., Srinivasan A., Mahalingam S., Sawaya B.E. (2009) HIV-1 Vpr: A closer look at the multifunctional protein from the structural perspective. Current HIV Research 7 (2): 114-128

  8. Srinivasan A., Ayyavoo V., Mahalingam S., Kannan A., Boyd A., Datta D., Kalyanaraman V.S., Cristillo A., Collman R.G., Morellet N., Sawaya B.E., Murali R. (2008) A comprehensive analysis of the naturally occurring polymorphisms in HIV-1 Vpr: Potential impact on CTL epitopes. Virology Journal (5): 99

  9. Singhal P.K., Kumar P.R., Subba Rao M.R.K., Kyasani M., Mahalingam S. (2006) Simian immunodeficiency virus Vpx is imported into the nucleus via importin alpha-dependent and -independent pathways. Journal of Virology 80 (1): 526-536

  10. Singhal P.K., Kumar P.R., Subba Rao M.R.K., Mahalingam S. (2006) Nuclear export of simian immunodeficiency virus Vpx protein. Journal of Virology 80 (24): 12271-12282

  11. Kumar P.R., Singhal P.K., Subba Rao M.R.K., Mahalingam S (2005) Phosphorylation by MAPK regulates simian immunodeficiency virus Vpx protein nuclear import and virus infectivity. Journal of Biological Chemistry 280 (9): 8553-8563

  12. Varadarajan P., Mahalingam S., Liu P., Ng S.B.H., Gandotra S., Dorairajoo D.S.K., Balasundaram D. (2005) The functionally conserved nucleoporins Nup124p from fission yeast and the human Nup153 mediate nuclear import and activity of the Tf1 retrotransposon and HIV-1 Vpr. Molecular Biology of the Cell 16 (4): 1823-1838

  13. Kumar P.R., Singhal P.K., Vinod S.S., Mahalingam S. (2003) A non-canonical transferable signal mediates nuclear import of simian immunodeficiency virus Vpx protein. Journal of Molecular Biology 331: 1141-1156

  14. Majumder B., Gray B., McBurney S., Schaefer T.M., Dentchev T., Mahalingam S., Reinhart T.A., Ayyavoo V. (2003) Attenuated nef DNA vaccine construct induces cellular immune response: Role in HIV-1 multiprotein vaccine. Immunology Letters 89 (3): 207-214

  15. Mahalingam S., Van Tine B., Santiago M.L., Gao F., Shaw G.M., Hahn B.H. (2001) Functional analysis of the simian immunodeficiency virus Vpx protein: Identification of packaging determinants and a novel nuclear targeting domain. Journal of Virology 75 (1): 362-374

  16. Vanitharani R., Mahalingam S., Rafaeli Y., Singh S.P., Srinivasan A., Weiner D.B., Ayyavoo V. (2001) HIV-1 Vpr transactivates LTR-directed expression through sequences present within -278 to -176 and increases virus replication in vitro. Virology 289 (2): 334-342

  17. Singh S.P., Tomkowicz B., Lai D., Cartas M., Mahalingam S., Kalyanaraman V.S., Murali R., Srinivasan A. (2000) Functional role of residues corresponding to helical domain II (amino acids 35 to 46) of human immunodeficiency virus type 1 Vpr. Journal of Virology 74 (22): 10650-10657

  18. Kim J.J., Trivedi N.N., Nottingham L.K., Morrison L., Tsai A., Hu Y., Mahalingam S., Dang K., Ahn L., Doyle N.K., Wilson D.M., Chattergoon M.A., Chalian A.A., Boyer J.D., Agadjanyan M.G., Weiner D.B. (1998) Modulation of amplitude and direction of in vivo immune responses by co-administration of cytokine gene expression cassettes with DNA immunogens. European Journal of Immunology 28 (3): 1089-1103

  19. Mahalingam S., Ayyavoo V., Patel M., Kieber-Emmons T., Kao G.D., Muschel R.J., Weiner D.B. (1998) HIV-1 Vpr interacts with a human 34-kDa mov34 homologue, a cellular factor linked to the G2/M phase transition of the mammalian cell cycle. Proceedings of the National Academy of Sciences of the United States of America 95 (7): 3419-3424

  20. Kim J.J., Trivedi N.N., Wilson D.M., Mahalingam S., Morrison L., Tsai A., Chattergoon M.A., Dang K., Patel M., Ahn L., Boyer J.D., Chalian A.A., Shoemaker H., Kieber-Emmons T., Agadjanyan M.A., Weiner D.B. (1998) Molecular and immunological analysis of genetic prostate specific antigen (PSA) vaccine. Oncogene 17 (24): 3125-3135

  21. Kirn J.J., Bagarazzi M.L., Trivedi N., Hu Y., Kazahaya K., Wilson D.M., Ciccarelli R., Chattergoon M.A., Dang K., Mahalingam S., Chalian A.A., Agadjanyan M.G., Boyer J.D., Wang B., Weiner D.B. (1997) Engineering of in vivo immune responses to DNA immunization via codelivery of costimulatory molecule genes. Nature Biotechnology 15 (7): 641-646

  22. Mahalingam S., MacDonald B., Ugen K.E., Ayyavoo V., Agadjanyan M.G., Williams W.V., Weiner D.B. (1997) In vitro and in vivo tumor growth suppression by HIV-1 Vpr. DNA and Cell Biology 16 (2): 137-143

  23. Ayyavoo V., Mahalingam S., Rafaeli Y., Kudchodkar S., Chang D., Nagashunmugam T., Williams W.V., Weiner D.B. (1997) Hiv-1 viral proytein R (Vpr) regulates viral replication and cellular proliferation in T cells and monocytoid cells in vitro. Journal of Leukocyte Biology 62 (1): 93-99

  24. Mahalingam S., Ayyavoo V., Patel M., Kieber-Emmons T., Weiner D.B. (1997) Nuclear import, virion incorporation, and cell cycle arrest/differentiation are mediated by distinct functional domains of human immunodeficiency virus type 1 Vpr. Journal of Virology 71 (9): 6339-6347

  25. Ayyavoo V., Mahboubi A., Mahalingam S., Ramalingam R., Kudchodkar S., Williams W.V., Green D.R., Weiner D.B. (1997) HIV-1 Vpr suppresses immune activation and apoptosis through regulation of nuclear factor ?B. Nature Medicine 3 (10): 1117-1123

  26. Ayyavoo V., Nagashunmugam T., Boyer J., Mahalingam S., Fernandas L.S., Le P., Lin J., Nguyen C., Chattargoon M., Goedert J.J., Friedman H., Weiner D.B. (1997) Development of genetic vaccines for pathogenic genes: Construction of attenuated vif DNA immunization cassettes. AIDS 11 (12): 1433-1444

27.Mahalingam S., Khan S.A., Murali R., Jabbar M.A., Monken C.E., Collman R.G., Srinivasan A. (1995) Mutagenesis of the putative a-helical domain of the Vpr protein of human immunodeficiency virus type 1: Effect on stability and virion incorporation. Proceedings of the National Academy of Sciences of the United States of America 92 (9): 3794-3798

  1. Mahalingam S., Khan S.A., Jabbar M.A., Monken C.E., Collman R.G., Srinivasan A. (1995) Identification of residues in the N-terminal acidic domain of HIV-1 Vpr essential for virion incorporation. Virology 207 (1): 71081 297-302

  2. Mahalingam S., Collman R.G., Patel M., Monken C.E., Srinivasan A. (1995) Role of the conserved dipeptide Gly75 and Cys76 on HIV-1 Vpr function. Virology 210 (2): 71368 495-500

  3. Mahalingam S., Collman R.G., Patel M., Monken C.E., Srinivasan A. (1995) Functional analysis of HIV-1 Vpr: Identification of determinants essential for subcellular localization. Virology 212 (2): 71490 331-339

  4. Mahalingam S., Patel M., Collman R.G., Srinivasan A. (1995) The carboxy-terminal domain is essential for stability and not for virion incorporation of HIV-1 Vpr into virus particles. Virology 214 (2): 70079 647-652

C. Cancer Biomarker Identification:

  1. Ramachandran P, Balamurali D, Peter JJ, Kumar MM, Safwan M, Vij M, Rela M, Mahalingam (2019) RNA-seq reveals outcome-specific gene expression of MMP7 and PCK1 in biliary atresia. Mol Biol Rep. doi: 10.1007/s11033-019-04969-3

  2. Ananthi S, Lakshmi CNP, Atmika P, Anbarasu K, Mahalingam S. (2018) Global Quantitative Proteomics reveal Deregulation of Cytoskeletal and Apoptotic Signalling Proteins in Oral Tongue Squamous Cell Carcinoma. Nature Scientific Reports; 8 (1):1567

D. Publications from Collaborations:

  1. Ghosh D., Bodiuzzaman., Som A., Raja S., Baksi A., Ghosh A., Ghosh J., Ganesh A, Samji P., Mahalingam S., Karunagaran D, and Pradeep T. (2019) Internalization of a preformed atomically precise silver cluster in 2 proteins by multistep events and emergence of luminescent counterparts retaining bioactivity. Phy. Chem. 123 (48): 29408-29417.

  2. Kowshik J., Mishra R., Sophia J., Rautray S., Anbarasu K., Reddy G.D., Dixit M., Mahalingam S., Nagini S. (2017) Nimbolide upregulates RECK by targeting miR-21 and HIF-1a in cell lines and in a hamster oral carcinogenesis model. Nature Scientific Reports 7 (1): 2045

  3. Sethupathy S., Ananthi S., Selvaraj A., Shanmuganathan B., Vigneshwari L., Balamurugan K., Mahalingam S., Pandian S.K. (2017) Vanillic acid from Actinidia deliciosa impedes virulence in Serratia marcescens by affecting S-layer, flagellin and fatty acid biosynthesis proteins. Nature Scientific Reports 7 (1): 16328

  4. Dev R.R., Ganji R., Singh S.P., Mahalingam S., Banerjee S., Khosla S. (2017) Cytosine methylation by DNMT2 facilitates stability and survival of HIV-1 RNA in the host cell during infection. Biochemical Journal 474 (12): 2009-2026

  5. Sethupathy S., Prasath K.G., Ananthi S., Mahalingam S., Balan S.Y., Pandian S.K. (2016) Proteomic analysis reveals modulation of iron homeostasis and oxidative stress response in Pseudomonas aeruginosa PAO1 by curcumin inhibiting quorum sensing regulated virulence factors and biofilm production. Journal of Proteomics 145: 112-126

  6. Nakajima-Kambe T., Edwinoliver N.G., Maeda H., Thirunavukarasu K., Gowthaman M.K., Masaki K., Mahalingam S., Kamini N.R. (2012) Purification, cloning and expression of an Aspergillus niger lipase for degradation of poly (lactic acid) and poly(e-caprolactone) Polymer Degradation and Stability 97 (2): 139-144.

Book Chapter

  1. Mahalingam.S, M.R.K. Subba Rao, Neelima B, Indu T and D. Datta (2013) Nucleolar Transport of putative GTPase GNL1 and related proteins. 197-208. Proteins of the Nucleolus: Regulation, Translocation and Biomedical Functions. Eds. D. H. O-Day and A. Catalano. Springer, New York.

  2. Rajendra Kumar. P., Singhal, P. K, and Mahalingam. S. (2004) A transferable signal mediates nuclear import of simian immunodeficiency virus Vpx protein. 173- 178.Deep Roots, Open Skies: New Biology in India. Eds. S.K. Basu., Batra J.K and D.M. Salunke. Narosa Publishing House, New Delhi, India.

  3. Srilakshmi. P., Rajendra Kumar. P, and Mahalingam. S. (2007) HIV-1 Pathogenesis: Role of viral protein R. 186-200. Research Issues in HIV/AIDS. Eds. D. Raghunath and C. Durga Rao. Tata McGraw-Hill Publishing Company Ltd. New Delhi, India.

Other Recognitions

  1. Editorial member, Nature Scientific Reports, Nature Publications, London (2019)

  2. Editorial member, International Journal of Virology- Academic Journals, New York (2005-2009)

  3. Ad-hoc reviewer for (a) for Virology, Academic Press (b) Journal of Virology, American Society for Microbiology

  4. Organized the 5th Transcriptional Assembly meeting, August 2002, CDFD, Hyderabad (as an organizer).

  5. Organized the -International conference on HIV pathogenesis- December 2006, Hyderabad. (as an organizer).

  6. Organized the 77th Society of Biological Chemists of India meeting at IIT-Madras Chennai, Dec 2008 (as an co-organizer).

  7. Organizing the International conference on cancer Biology: Molecular mechanism and Novel Therapeutics at IIT-Madras, Chennai 2010 (as an organizer).

  8. Organizing the International Cancercon2014: Molecular mechanism and Novel Therapeutics at IIT-Madras, Chennai 2014 (as an organizer).