Vikas Kumar, Ph.D.

Assistant Professor

   

Director for Mass Spectrometry and Proteomics Core Facility
Department of Genetics, Cell Biology and Anatomy
985875 Nebraska Medical Center, DRC 1044
Omaha, NE 68198-5875
402.559.3157
Email


Education:
PhD, University of Otago NZ, 2011
Postdoc, Boston University School of Medicine, 2012

Research:

Cardiovascular/Muscular Proteomics and Redox Regulation

Our lab in collaboration with Dr. Lie Gao’s lab is interested in the understating role of change in protein expression and oxidative post-translational modifications (OPTMs) to cardiovascular and muscle physiology and pathophysiology. The capacity for OPTMs to alter protein function can be accounted for by reversible or irreversible modifications. Reversible OPTMs can modulate physiological protein function and are enzymatically reducible and, therefore, reversible. The sulfur-containing amino acids methionine (Met) and cysteine (Cys) are the known oxidized amino acids that are enzymatically reduced and shown to regulate physiological redox signaling events. Whereas irreversible OPTMs are persistent and typically occur through non-enzymatic processes. That can lead to protein inactivation and structural changes and ultimately require protein degradation and re-synthesis for reversal. These include the hydroxylation of aromatic groups and aliphatic amino-acid side chains, nitration of aromatic amino-acid residues, oxidized lipid adduction, conversion of amino-acid residues to carbonyl derivatives, and higher oxidation states of thiol groups. Although these are often associated with progressive protein and cellular dysfunction, irreversible modifications have been observed during normal physiologic responses.

Nrf2/Keap1 plays a crucial role in the exercise-induced benefits of cardiac and skeletal muscle and activation of this system ameliorates sarcopenia with aging. We are using state of art mass spectrometry-based proteomics to study the whole protein profile, and redox proteome, followed by in-depth bioinformatics analyses to create the integrative network maps of Nrf2/Keap1 signaling. Overall, we employ unique transgenic models, mass spectrometry-based proteomics, and bioinformatics analyses to address our hypotheses. We expect that the data obtained from these multidisciplinary approaches will develop a more sophisticated understanding of Nrf2/Keap1-activated signaling networks underlying exercise benefits on cardiac and skeletal muscle and therefore highlight novel therapeutic targets for the development of enhanced therapeutic strategies for muscle wasting in aging and other pathological conditions, such as cancer, chronic heart failure, and chronic kidney disease.

Publications listed in PubMed

Publications:

  1. Bhat, A., Abu, R., Jagadesan,S., Vellichirammal,N.N., Pendyala, V.V., Yu, L., Rudebush,T., Guda,C., Zucker,I.H., Kumar, V. #, and Gao, L#. (2023). Quantitative proteomics identifies novel Nrf2-mediated adaptative signaling pathways in skeletal muscle following exercise training. Antioxidants doi: 10.3390/antiox12010151.
  2. Abu, R., Yu, L., Kumar, A., Gao, L. #, and Kumar, V#. (2021). A Quantitative Proteomics Approach to Gain in Sight into NRF2-KEAP1 Skeletal Muscle System and Its Cysteine Redox Regulation. Genes. doi: 10.3390/genes12111655.
  3. Alqarzaee, A.A., Chaudhari, S.S., Islam, M.M., Kumar, V., Zimmerman, M.C., Saha, R., Bayles, K.W., Frees, D., and Thomas, V.C. (2021). Staphylococcal ClpXP protease targets the cellular antioxidant system to eliminate fitness-compromised cells in the stationary phase. Proc Natl Acad Sci U S A. doi: 10.1073/pnas.2109671118.
  4. Cho,E., Zhang, P., Kumar, V., Kavalchuk, M., Zhang, H., Huang, Q., Duncan,J.S., and Wu, J. (2021) Phosphorylation of RIAM by Src Promotes IntegrinActivation by Unmasking the PH Domain of RIAM.  Structure. doi: 10.1016/j.str.2020.11.011.
  5. Kurimchak, A.M.#, Kumar, V.#, Herrera-Montávez, C., Johnson, K., Srivastava, N., Devarajan, K., Peri, S., Cai, K., Mantia-Smaldone, G., and Duncan, J. (2020). Kinome Profiling of Primary Endometrial Tumors Using Multiplexed Inhibitor Beads and Mass Spectrometry Identifies SRPK1 As Candidate Therapeutic Target. Mol Cell Proteomics. doi: 10.1074/mcp.RA120.002012.
  6. Gao, L.#; Kumar, V.#; Vellichirammal, N.N.; Park, S.Y.; Rudebush, T.L.; Yu, L.; Son, W.M.; Pekas, E.J.; Wafi, A.M.; Hong, J.; Xiao,P.; Guda, C.; Wang, H.J.; Schultz, H.D.; Zucker. I.H. (2020). Functional, proteomic and bioinformatic analyses of Nrf2- and Keap1- null skeletal muscle. J Physiol. doi: 10.1113/JP280176.
  7. Kurimchak, A. M.; Herrera-Montavez, C.; Brown, J.; Johnson, K.J.; Sodi, V.; Srivastava, N.; Kumar, V. ; Deihimi,S.; O’Brien, S.; Peri, S.; Mantia-Smaldone, G.M.; Jain, A.; Winters, R.M.; Cai,Q. K.; Connolly, D.C.; Chernoff, J.; and Duncan, J. S. (2020). Functional proteomics interrogation of the kinome identifies MRCKA as a therapeutic target in high-grade serous ovarian carcinoma. Sci Signal. 13: eaax8238.
  8. Nagarkoti, S., Dubey, M., Awasthi, D., Kumar, V., Chandra, T., Kumar, S. and Dikshit, M. (2018) S-Glutathionylation of p47phox sustains superoxide generation in activated neutrophils. Biochim Biophys Acta. 1865(2):444-454.
  9. Vikram, A., Lewarchik, C.M., Yoon, J.Y., Naqvi, A., Kumar, S., Morgan, G.M., Jacobs, J.S., Li, Q., Kim, Y.R., Kassan, M., Liu, J., Gabani, M., Kumar, A., Mehdi, H., Zhu, X., Guan, X., Kutschke, W., Zhang, X., Boudreau, R.L., Dai, S., Matasic, D.S., Jung, S.B., Margulies, K.B., Kumar, V., Bachschmid, M.M., London, B. and Irani, K. (2017). Sirtuin1 regulates cardiac electrical activity by deacetylating the cardiac sodium channel. Nat Med. 23: 361-67.
  10. Kumar, S., Kim, Y.R., Vikram, A., Naqvi, A., Li, Q., Kassan, M., Kumar, V., Bachschmid, M.M., Jacobs, J.S., Kumar, A. and Irani, K. (2017). Sirtuin1-regulated lysine acetylation of p66Shc governs diabetes-induced vascular oxidative stress and endothelial dysfunction. Proc Natl Acad Sci U S A. 114: 1714-19.
  11. Behring, J.B.#, Kumar, V.#, Whelan S.A., Chauhan, P., Siwik, D.A., Costello, C.E., Colucci, W.S., Cohen, R.A., McComb, M.E., and Bachschmid, M.M. (2014). Does reversible cysteine oxidation link the Western diet to cardiac dysfunction? FASEB J. 28: 1975-87.  
  12. Kumar, V., Kleffman, T., Hampton, M.B., Cannell, M.B. and Winterbourn, C.C. (2013). Redox proteomic investigation of thiol proteins in mouse heart during ischemia/reperfusion using ICAT reagents and mass spectrometry. Free Radic Biol Med. 58: 109-17.
  13. Burgoyne, J.R., Haeussler, D.J., Kumar, V., Ji, Y., Pimental, D.R., Zee, R.S., Costello, C.E., Lin, C., McComb, M.E., Cohen, RA, and Bachschmid M.M. (2012). Oxidation of HRas cysteine thiols by metabolic stress prevents palmitoylation in vivo and contributes to endothelial cell apoptosis. FASEB J. 26: 832-841.
  14. Kumar, V., Kitaeff, N., Hampton, M.B., Cannell, M.B. and Winterbourn, C.C. (2009). Reversible oxidation of mitochondrial peroxiredoxin 3 in mouse heart subjected to ischemia and reperfusion. FEBS lett. 583: 997-1000.
  15. Singh, D.K., Kumar, D., Siddiqui, Z., Basu, S.K., Kumar, V. and Rao, K.V.S. (2005). The strength of receptor signaling is centrally controlled through a cooperative loop between Ca2+ and an oxidant signal. Cell. 121: 281-93.