Venugopalan Nair, PhD
- ASSOCIATE PROFESSOR | Neurology
Research Topics:Apoptosis/Cell Death, Cell Biology, Epigenomics, Gene Expressions, Genomics, Molecular Biology, Oxidative Stress, Parkinson's Disease, Signal Transduction, Stem Cells
It is well-known that signaling components constituting a network of pathways control cellular processes. However, how these components are precisely regulated to achieve signaling specificity within individual cells and respond to internal and external stimuli is not well understood. Alterations in intrinsic signaling pathways in response to stimuli have been shown to play an important role in the dysregulated cell division and cell death found in many human diseases. Since the decisions of cell division and cell death are made at the cellular level, understanding the intrinsic signaling mechanisms at the single cell level will be important for developing therapeutic strategies for the treatment of diseases where abnormal cell growth and loss have been implicated. By combining cellular, molecular, genomic, and bioinformatics techniques, we have demonstrated that spatial and temporal regulation of signaling components play an important role in cell cycle progression, cell death, and survival. We reported for the first time a dopamine agonist-mediated transactivation of the Akt/PI3K signaling pathway; a differential single cell response to oxidative stress, that determines cell death or survival; temporal interaction of LSD1, a demethylating enzyme, with DNA during cell cycle progression; and the cell cycle-dependent expression of miR-137, a microRNA expressed only in mitotic cells. New technologies are also being developed in the lab to understand genomic diversity at the cellular level and ultimately improve the detection and treatment of diseases.
Ruf-Zamojski F, Ge Y, Nair V, Zamojski M, Pincas H, Toufaily C, Tome-Garcia J, Stoeckius M, Stephenson W, Smith GR, Bernard DJ, Tsankova NM, Hartmann BM, Fribourg M, Smibert P, Swerdlow H, Turgeon JL, Sealfon SC. Single-cell stabilization method identifies gonadotrope transcriptional dynamics and pituitary cell type heterogeneity. Nucleic acids research 2018 Oct;.
Ruf-Zamojski F, Fribourg M, Ge Y, Nair V, Pincas H, Zaslavsky E, Nudelman G, Tuminello SJ, Turgeon JL, Sealfon SC. Regulatory Architecture of the LβT2 Gonadotrope Cell Underlying the Response to Gonadotropin-Releasing Hormone. Front. Endocrinol. 2018; doi: 10.3389.
Hirschfield H, Bian CB, Higashi T, Nakagawa S, Zeleke TZ, Nair VD, Fuchs BC, Hoshida Y. In vitro modeling of hepatocellular carcinoma molecular subtypes for anti-cancer drug assessment. Experimental & molecular medicine 2018 Jan; 50(1).
Trépo E, Goossens N, Fujiwara N, Song WM, Colaprico A, Marot A, Spahr L, Demetter P, Sempoux C, Im GY, Saldarriaga J, Gustot T, Devière J, Thung SN, Minsart C, Sersté T, Bontempi G, Abdelrahman K, Henrion J, Degré D, Lucidi V, Rubbia-Brandt L, Nair VD, Moreno C, Deltenre P, Hoshida Y, Franchimont D. Combination of Gene Expression Signature and Model for End-stage Liver Disease Score Predicts Survival of Patients With Severe Alcoholic Hepatitis. Gastroenterology 2017 Nov;.
Nakagawa S, Wei L, Song W, Higashi T, Ghoshal S, Kim RS, Bian CB, Yamada S, Sun X, Venkatesh A, Goossens N, Bain G, Lauwers GY, Koh AP, El-Abtah M, Ahmad NB, Hoshida H, Erstad DJ, Gunasekaran G, Lee Y, Yu M, Chuang WL, Dai CY, Kobayashi M, Kumada H, Beppu T, Baba H, Mahajan M, Nair VD, Lanuti M, Villanueva A, Sangiovanni A, Iavarone M, Colombo M, Llovet JM, Subramanian A, Tager AM, Friedman SL, Baumert TF, Schwarz ME, Chung RT, Tanabe KK, Zhang B, Fuchs BC, Hoshida Y, Precision Liver Cancer Prevention Consortium.. . Molecular Liver Cancer Prevention in Cirrhosis by Organ Transcriptome Analysis and Lysophosphatidic Acid Pathway Inhibition.. Cancer Cell 2016; 30(6): 879-890.
Nair VD, Ge Y. Alterations of miRNAs reveal a dysregulated molecular regulatory network in Parkinson's disease striatum. Neuroscience letters 2016 Aug; 629: 99-104.
Tan PS, Nakagawa S, Goossens N, Venkatesh A, Huang T, Ward SC, Sun X, Song WM, Koh A, Canasto-Chibuque C, Deshmukh M, Nair V, Mahajan M, Zhang B, Fiel MI, Kobayashi M, Kumada H, Hoshida Y. Clinicopathological indices to predict hepatocellular carcinoma molecular classification. Liver international : official journal of the International Association for the Study of the Liver 2016 Jan; 36(1): 108-118.
Chikina MD, Gerald CP, Li X, Ge Y, Pincas H, Nair VD, Wong AK, Krishnan A, Troyanskaya OG, Raymond D, Saunders-Pullman R, Bressman SB, Yue Z, Sealfon SC. Low-Variance RNAs Identify Parkinson's Disease Molecular Signature in Blood. Movement disorders : official journal of the Movement Disorder Society 2015 Mar; 30(6): 813-821.
King LY, Canasto-Chibuque C, Johnson KB, Yip S, Chen X, Kojima K, Deshmukh M, Venkatesh A, Tan PS, Sun X, Villanueva A, Sangiovanni A, Nair V, Mahajan M, Kobayashi M, Kumada H, Iavarone M, Colombo M, Fiel MI, Friedman SL, Llovet JM, Chung RT, Hoshida Y. A genomic and clinical prognostic index for hepatitis C-related early-stage cirrhosis that predicts clinical deterioration. Gut 2014 Aug; 64(8): 1296-1302.
Tulchin N, Ornstein L, Dikman S, Strauchen J, Jaffer S, Nagi C, Bleiweiss I, Kornreich R, Edelmann L, Brown K, Bodian C, Nair VD, Chambon M, Woods NT, Monteiro AN. Localization of BRCA1 protein in breast cancer tissue and cell lines with mutations. Cancer cell international 2013 Jul; 13(1): 70.
Jiang K, Ren C, Nair VD. MicroRNA-137 represses Klf4 and Tbx3 during differentiation of mouse embryonic stem cells. Stem cell research 2013 Sep; 11(3): 1299-1313.
Nair VD, Ge Y, Kim J, Okawa Y, Balasubramaniyan N, Chikina M, Troyanskaya OG, Sealfon SC. Involvement of histone demethylase LSD1 in short-time scale gene expression changes during embryonic stem cell cycle progression. Mol Cell Biol 2012; 32(23): 4861-4876.
Nair VD, Olanow CW. Differential modulation of Akt/glycogen synthase kinase-3beta pathway regulates apoptotic and cytoprotective signaling responses. J Biol Chem 2008 May; 283(22): 15469-15478.
Nair VD, Mcnaught KS, González-Maeso J, Sealfon SC, Olanow CW. p53 mediates nontranscriptional cell death in dopaminergic cells in response to proteasome inhibition. J Biol Chem 2006 Dec; 281(51): 39550-39560.
Nair VD. Activation of p53 signaling initiates apoptotic death in a cellular model of Parkinson's disease. Apoptosis 2006 Jun; 11(6): 955-966.
Verma V, Mann A, Costain W, Pontoriero G, Castellano JM, Skoblenick K, Gupta SK, Pristupa Z, Niznik HB, Johnson RL, Nair VD, Mishra RK. Modulation of agonist binding to human dopamine receptor subtypes by L-prolyl-L-leucyl-glycinamide and a peptidomimetic analog. J Pharmacol Exp Ther 2005 Dec; 315(3): 1228-1236.
Nair VD, Yuen T, Olanow CW, Sealfon SC. Early single cell bifurcation of pro- and antiapoptotic states during oxidative stress. J Biol Chem 2004 Jun; 279(26): 27494-27501.
Nair VD, Sealfon SC. Agonist specific transactivation of phosphoinositide 3-kinase signaling pathway medaited by the dopamine D2 receptor. J Biol Chem 2003 Nov; 278(47): 47053-47061.
Nair VD, Olanow CW, Sealfon SC. Activation of phosphoinositide 3-kinase by D2 receptor prevents apoptosis in dopaminergic cell lines. Biochem J 2003 Jul; 373(1): 25-32.