Nikolas Nikolaidis
Evolutionary Biochemistry of Cellular Stress Response
In our laboratory, we study how proteins differentiate in order to perform specialized functions. In particular, we are using theoretical and experimental approaches to investigate:
a) The origin, long-term evolution, and functional differentiation of molecules involved in the innate and adaptive immune systems. We are studying the Immunoglobulin (Ig)-like domains, which play a pivotal role in the immune response of vertebrates. We are using bioinformatics and phylogenetic methods to study the evolutionary relationships of the Ig-like domains. On the basis of these studies we generate hypotheses, which we test by molecular biology and biochemistry techniques.
b) The functional diversification of stress response proteins. We are studying the heat shock proteins (hsps), which as a major component of the stress response pathway are important for cell survival and homeostasis. We are using comparative genomics/proteomics to reveal conserved and new functional partners of the hsps in evolutionarily key species. We test the physiological importance of these interactions by examining how environmental or molecular perturbations affect the cellular response, adaptation, and survival.
Selected publications (Click for full list)
Bilog, A. D., Smulders, L., Oliverio, R., Labanieh, C., Zapanta, J., Stahelin, R. V., & Nikolaidis, N. (2019). Membrane localization of HspA1A, a stress inducible 70-kDa heat-shock protein, depends on its interaction with intracellular phosphatidylserine. Biomolecules, 9(4). doi:10.3390/biom9040152
Hoffman, M., Palioura, D., Kyriazis, I. D., Cimini, M., Badolia, R., Rajan, S., . . . Drosatos, K. (2021). Cardiomyocyte Kruppel-like factor 5 promotes de novo ceramide biosynthesis and contributes to eccentric remodeling in ischemic cardiomyopathy. Circulation, 143(11), 1139-1156. doi:10.1161/CIRCULATIONAHA.120.047420
Kourtidis, A., Dighera, B., Risner, A., Hackemack, R., & Nikolaidis, N. (2022). Origin and evolution of the multifaceted adherens junction component Plekha7. Front Cell Dev Biol, 10, 856975. doi:10.3389/fcell.2022.856975
Nguyen, P., Hess, K., Smulders, L., Le, D., Briseno, C., Chavez, C. M., & Nikolaidis, N. (2020). Origin and evolution of the human Bcl2-associated athanogene-1 (BAG-1). Int J Mol Sci, 21(24). doi:10.3390/ijms21249701
Ramirez, M. S., Penwell, W. F., Traglia, G. M., Zimbler, D. L., Gaddy, J. A., Nikolaidis, N., . . . Tolmasky, M. E. (2019). Identification of potential virulence factors in the model strain Acinetobacter baumannii A118. Front Microbiol, 10, 1599. doi:10.3389/fmicb.2019.01599
Rodman, N., Martinez, J., Fung, S., Nakanouchi, J., Myers, A. L., Harris, C. M., . . . Ramirez, M. S. (2019). Human pleural fluid elicits pyruvate and phenylalanine metabolism in Acinetobacter baumanini to enhance cytotoxicity and immune evasion. Front Microbiol, 10, 1581. doi:10.3389/fmicb.2019.01581
Smulders, L., Altman, R., Briseno, C., Saatchi, A., Wallace, L., AlSebaye, M., . . . Nikolaidis, N. (2022). Phosphatidylinositol monophosphates regulate the membrane localization of HSPA1A, a stress-inducible 70-kDa heat shock protein. Biomolecules, 12(6). doi:10.3390/biom12060856
Smulders, L., Daniels, A. J., Plescia, C. B., Berger, D., Stahelin, R. V., & Nikolaidis, N. (2020). Characterization of the relationship between the chaperone and lipid-binding functions of the 70-kDa heat-shock protein, HspA1A. Int J Mol Sci, 21(17). doi:10.3390/ijms21175995