Background
Early Education
Parameswaran Ramakrishnan obtained his BSc in 1993 and MSc in Biotechnology in 1996 from Mahatma Gandhi University, India. Later, he worked in an Indo-Swiss collaborative project studying the genome diversity in Mycobacterium leprae in the Department of Biotechnology, Madurai Kamaraj University, India, until the end of 1999.
PhD and Postdoc in Weizmann Institute of Science, Israel
In December 1999, he joined Weizmann Institute of Science, Israel, for his research toward
PhD under the guidance of Prof. David Wallach. He studied signal transduction in the immune system with a focus on mechanisms involved in the regulation and function of the protein NF-κB inducing kinase and obtained PhD in 2006. He continued in the same lab as a postdoctoral fellow and studied ubiquitination and proteasomal degradation of molecules in the NF-κB signaling pathway till the end of 2007. He also obtained 9 international patents on various inventions that emerged from his graduate and postdoctoral work at Weizmann
Institute of Science.
Postdoc in California Institute of Technology, United States
In January 2008, Dr. Ramakrishnan joined the lab of Nobel Laureate Prof. David Baltimore in the Department of Biology at California Institute of Technology. While in Baltimore lab, Dr. Ramakrishnan studied the regulation of NF-κB activation and T cell survival by glucose and identified the role of unique intracellular glycosylation called O-GlcNAcylation in NF-kB activation in T cells. He also discovered the role of the RNA-binding protein, Sam68, as an adaptor in proinflammatory signaling by TNF. Both of these findings are patented and are
active areas of current investigation. Dr. Ramakrishnan joined ÐÇ¿Õ´«Ã½'s Department of Pathology as an Assistant Professor in Immunology in July 2013.
I research the regulation of signal transduction in health and disease: autoimmune diabetes, inflammatory diseases and cancer.
Research Information
Research Projects
Dr. Ramakrishnan's lab focuses on signal transduction in autoimmunity and inflammation as well as immunometabolism. Studies involve cellular and molecular approaches, animal models and patient samples as well as collaborations with chemists aimed at drug discovery. Diseases of research interest are:
- Type 1 diabetes
- Inflammatory bowel diseases and Inflammation-induced colon cancer
- Leukemia
- Skin inflammation
NF-κB is known to be a family of dimeric transcription factor that act as a key regulator of the immune and inflammatory responses. Because inflammation has been linked to so many diseases in recent times, there is much interest in the role of NF-κB in chronic inflammatory diseases, cancer and autoimmune conditions like diabetes.
Regulation of NF-κB activity by O-GlcNAc glycosylation and its role in diabetes and cancer Significance: NF-κB is a preformed protein and its activation is dependent on posttranslational regulations. O-GlcNAcylation is a reversible intracellular protein modification whose levels are affected by glucose and other signals. Both O-GlcNAcylation and NF-κB activation has been associated in several physiological and pathological conditions including experimental and clinical diabetes, and multiple types of cancer, yet a direct link between NF-κB and O-GlcNAcylation remains poorly defined. Cancer cells consume high glucose and exhibit constitutively elevated O-GlcNAcylation.
This project will identify O-GlcNAcylated NF-κB proteins, the site(s) of modification and study this
process both structurally and functionally, under physiological and pathological conditions. Studies will also include generation of transgenic and knockout mouse models to determine the in vivo role of OGlcNAcylation of NF-κB in type 1 diabetes and acute myeloid leukemia
Role of Sam68 in chronic inflammatory diseases and inflammation-induced cancer Significance: We discovered that Sam68 plays crucial role in innate immune and apoptotic signaling by TNF and TLR. These findings link Sam68 function in inflammatory and autoimmune diseases as well as inflammation-induced cancer. We also found that Sam68 is a critical mediator of ulcerative colitis.
This project aims to understand the molecular determinants of Sam68 function and its role in inflammatory signaling and cancer. The study will also delineate the physiological role of Sam68 in vivo in the immune system and elucidate its RNA binding independent functions.
External Appointments
Publications
Liu AR, Sarkar N, Cress JD, de Jesus TJ, Vadlakonda A, Centore JT, Griffith AD, Rohr B, McCormick TS, Cooper KD, Ramakrishnan P. NF-κB c-Rel is a critical regulator of TLR7-induced inflammation in psoriasis. EBioMedicine. 2024 Dec;110:105452. doi: 10.1016/j.ebiom.2024.105452. Epub 2024 Nov 24. PMID: 39586195; PMCID: PMC11625363.
Hart GW, Ramakrishnan P. Editorial: O-GlcNAcylation and the immune system. Front Immunol. 2024 Aug 20;15:1474042. doi: 10.3389/fimmu.2024.1474042. PMID: 39229269; PMCID: PMC11369405.
Ramakrishnan P. Editorial: Deregulated signaling pathways in inflammation and cancer. Front Cell Dev Biol. 2024 Jul 19;12:1459926. doi: 10.3389/fcell.2024.1459926. PMID: 39100093; PMCID: PMC11294245.
Ramakrishnan P, (2024)- O-GlcNAcylation and immune cell signaling: A review of known and a preview of unknown. Invited review, J Biol Chem. 2024 May 6:107349. doi: 10.1016/j.jbc.2024.107349. PMID: 38718861
Schauner R*, Cress J*, Hong C, Wald DN#, Ramakrishnan P# (2024). Deciphering the role of the hexosamine biosynthetic pathway in acute myeloid leukemia using single cell RNA sequencing, Frontiers in Immunology, Mar 27;15:1327405. 2024 | doi: 10.3389/fimmu.2024.1327405. PMID:38601153, #Co-corresponding Author
Gowd V, Kass JD, Sarkar N, Ramakrishnan P. Role of Sam68 as an adaptor protein in inflammatory signaling. Cellular and Molecular Life Sciences. 2024 Feb 14;81(1):89. doi: 10.1007/s00018-023-05108-9. PMID: 38351330; PMCID: PMC10864426.
Liu AR, Basavarajappa SC, Sarkar N, Bruchez A, Ramakrishnan P. Inhibition of SARS-CoV-2 infection in cellular systems using engineered trimeric receptor-binding domain of spike protein. STAR Protocols. 2023 Mar 17;4(1):102127. doi: 10.1016/j.xpro.2023.102127. Epub 2023 Feb 10. PMID: 36853707; PMCID: PMC9915046.
Basavarajappa S, Liu A, Bruchez A, Li Z, Suzart VG, Liu Z, Chen Y, Xiao TS, Buck B, Ramakrishnan P (2022). Trimeric receptor-binding domain of SARS-CoV-2 acts as a potent inhibitor of ACE2 receptor-mediated viral entry. iScience, Volume 25, Issue 8, 19 August 2022, 104716, https://doi.org/10.1016/j.isci.2022.104716. PMID: 35813876, PMCID: PMC9251894.
Feinberg D, Ramakrishnan P, Wong DP, Asthana A, Parameswaran R. Inhibition of O-GlcNAcylation Decreases the Cytotoxic Function of Natural Killer Cells. Frontiers in Immunology. 2022 Apr 11;13:841299. doi: 10.3389/fimmu.2022.841299. PMID: 35479087; PMCID: PMC9036377.
Centore J, Church D, Prossnitz A, Hutnick M, de Jesus TJ, Pokorski J, Ramakrishnan P (2021). Selective inhibition of O-GlcNAcylated NFkappaB c-Rel-dependent transcription by a structure-based de novo designed peptoid. In revision.
Goodman WA, Basavarajappa SC, Liu AR, Staback FD, Mathes T, Ramakrishnan P (2021). . Cellular and Molecular Life Sciences, 2021, Oct 9. PMID: 34693458
Liu AR and Ramakrishnan P (2021) . Invited Review. Frontiers in Cell and Developmental Biology, 2021 Sep 23, DOI: 10.3389/fcell.2021.751761
Vicioso Y, Zhang K, Ramakrishnan P, Parameswaran R (2021). . Frontiers in Immunology. 29 April, doi: 10.3389/fimmu.2021.652786. PMID 33995369.
Zhang L, Ghosh SK, Basavarajappa SC, Muller-Greven J, Penfield J, Brewer A, Ramakrishnan P, Buck M and Weinberg A. . bioRxiv. (2021) Jan 7:2021.01.07.425621. doi: 10.1101/2021.01.07.425621. PMID: 33442698. PMCID: PMC7805467. Submitted. Co-corresponding author, in revision, iScience.
Chukwurah E, Farabaugh KT, Guan BJ, Ramakrishnan P*, Hatzoglou M*. FEBS J (2021). Jan 2. Doi:10.1111/febs.15691. PMID: 33387379. *Cocorresponding author.
de Jesus TJ*, Tomalka JA*, Centore TJ*, Staback Rodriguez F, Agarwal R, Liu AR, Kern TS, and Ramakrishnan P (2021). Glycobiology. 2021 Jan 12: cwab001. doi: 10.1093/glycob/cwab001. PMID: 33442719
Farabaugh KT, Krokowski D, Guan BJ, Gao Z, Gao XH, Wu J, Jobava R, Ray G, de Jesùs TJ, Bianchi MG, Chukwurah E, Bussolati O, Kilberg M, Buchner DA, Sen GC, Cotton C, McDonald C, Longworth M, Ramakrishnan P*, Hatzoglou M (2020). . Elife. 2020 Mar 16;9. pii: e52241. doi: 10.7554/eLife.52241. PMID: 32175843; PMCID: PMC7145421. *Co-corresponding author
Basavarajappa SC, Ramakrishnan P (2020). . Cell Mol Life Sci. 2020 Mar 4. doi: 10.1007/s00018-020-03488-w. [Epub ahead of print] Review. PMID: 32130429
de Jesùs TJ, Ramakrishnan P (2020). . iScience. 2020 Mar 27;23(3):100876. doi: 10.1016/j.isci.2020.100876. Epub 2020 Feb 1. PMID: 32062419; PMCID: PMC7031323
de Jesùs TJ , Centore JT, Ramakrishnan P (2019). . Cell Mol Immunol. 2019 Aug;16(8):720-723. doi: 10.1038/s41423-019-0242-0. Epub 2019 May 29. PMID:31142799; PMCID: PMC6804592
Asthana A, Ramakrishnan P, Vicioso Y, Zhang K, Parameswaran R (2018). . Mol Cancer Ther. 2018 Oct;17(10):2226-2237. doi: 10.1158/1535-7163.MCT-18-0426. Epub 2018 Aug 6. PMID: 30082471; PMCID: PMC6168390
de Jesùs T, Shukla S, Ramakrishnan P (2018). . Cell Immunol. 2018 Nov;333:85-92. doi: 10.1016/j.cellimm.2018.05.010. Epub 2018 Jun 2. Review. PMID: 29887419; PMCID: PMC6275141.
Farabaugh KT, Majumder M, Guan BJ, Jobava R, Wu J, Krokowski D, Gao XH, Schuster A, Longworth M, Chan ED, Bianchi M, Dey M, Koromilas AE, Ramakrishnan P*, Hatzoglou M (2017). . Mol Cell Biol. 2017 Feb 1;37(4). pii: e00521-16. doi: 10.1128/MCB.00521-16. Print 2017 Feb 15. PMID: 27920257; PMCID: PMC5288580. *Co-corresponding author
Tomalka J, de Jesùs TJ, Ramakrishnan P*. (2016). . Cell Mol Immunol. Cell Mol Immunol. 2017 Jan;14(1):107-117. doi: 10.1038/cmi.2016.32. Epub 2016 Jul 4. PMID: 27374795.
Ramakrishnan P*, Yui M, Tomalka J, Majumdar D, Parameswara R, Baltimore D (2016). . Diabetes. 2016 Aug;65(8):2367-79. doi: 10.2337/db15-1607. Epub 2016 May 23. PMID: 27217485. *Co-corresponding author.
Parameswaran R, Ramakrishnan P, De Lima M, Lee DA, Moreton S and Wald DN. . Nat Commun. 2016 Apr 4;7:11154. doi: 10.1038/ncomms11154, PMID: 27040177; PMCID: PMC4822012
de Jesùs TJ and Ramakrishnan P* (2015). . Austin Journal of Clinical Pathology. 2015 Nov; 2(3): 1035.
So AY, Chaudhuri A, Sookram R, Minisandram A, Cheng D, Xie C, Lim L, Garcia Flores Y, Jiang S, Keown C, Ramakrishnan P, Baltimore D (2014). . Blood. 2014 Aug 28;124(9):1502-12. doi: 10.1182/blood-2014-02-553842. Epub 2014 Jul 8. PMID: 25006123; PMCID: PMC4148772
Ramakrishnan P, Clark PM, Mason DE, Peters ED, Hsieh-Wilson LC and Baltimore D (2013). . Science Signaling, August 27. Vol 6 Issue 290 ra75.
Yang L, Boldi MP, Yu Y, Liu CS, Ea CK, Ramakrishnan P, Taganov KD, Zhao JL and Baltimore D (2012). . J Exp Med. Aug 27;209(9):1655-70.
Raskatov JA, Meier JL, Puckett JW, Yang F, Ramakrishnan P, and Dervan PB (2012). . Proc Natl Acad Sci U S A. Jan 24;109(4):1023-8.
Ramakrishnan P, Baltimore D (2011). . Molecular Cell, Jul 22;43(2):167-79.
Ramakrishnan P, Kahn D, Baltimore D (2011). . Cell Death and Differentiation, April;18(4):690-9.
Citri A, Harari D, Shohat G, Ramakrishnan P, Gan J, Lavi S, Eisenstein M, Kimchi A, Wallach D, Pietrokovski S, Yarden Y (2006). . J Biol Chem. May 19;281(20):14361-9.
Sanchez-Valdepenas C, Martin AG, Ramakrishnan P, Wallach D, Fresno M (2006). . J Immunol. Apr 15;176(8):4666-74.
Hauer J, Puschner S, Ramakrishnan P, Simon U, Bongers M, Federle C, Engelmann H (2005). . Proc Natl Acad Sci U S A 102, 2874-2879.
Ramakrishnan P, Wang W, Wallach D (2004). . Immunity 21, 477-489.
Kang TB, Ben-Moshe T, Varfolomeev EE, Pewzner-Jung Y, Yogev N, Jurewicz A, Waisman A, Brenner O, Haffner R, Gustafsson E, Ramakrishnan P, Lapidot T, Wallach D (2004). . J Immunol 173, 2976-2984.