Dr. Lamitina’s research focuses on two areas, one basic science focused and one disease-centered. Both research areas capitalize on the experimental strengths of the model organism C. elegans. For over 20 years, his lab has studied the molecular genetics of the osmotic stress response, which is an important contributor to many physiological and pathophysiological states. Through an unbiased genetic screens, Dr. Lamitina has uncovered unexpected new pathways regulating this essential response in vivo, including the role of the extracellular matrix, non-canonical functions of a highly conserved glycosylation enzyme called O-GlcNAc transferase, and a newly discovered function of 3’ mRNA cleavage and polyadenylation.
Another area of research in the Lamitina involves the development of C. elegans models of neurodegenerative disease, particularly those involving repeat expansion mutations that can give rise to conditions such as Huntington’s disease or ALS/Frontotemporal Dementia. These repeats, which are often found in non-coding regions, are translated into long repetitive peptides, some of which cause neurodegeneration. The Lamitina Lab has developed C. elegans models of these peptides and performed genetic screens to understand their mechanisms of toxicity, which are conserved in mammalian neurons. Targeting of these genes, either genetically or pharmacologically, could lead to new therapies for these currently incurable diseases.
Snoznik, C., Mojsilovic-Petrovic, J., Rudich, P., Oosten, J., Kalb, R.G., Lamitina, T. The nuclear ubiquitin ligase adaptor SPOP is a conserved regulator of C9orf72 dipeptide toxicity. Proc Natl Acad Sci U S A, 2021, In Press.
Urso, S. Comely, M., Hanover, J.A., and Lamitina, T. The O-GlcNAc transferase OGT is a conserved and essential regulator of the cellular and organismal response to hypertonic stress. PLoS Genet. 2020 Oct 2;16(10):e1008821. doi: 10.1371/journal.pgen.1008821. PMID: 33006972
Rudich, P., Watkins, S., and Lamitina, T. PolyQ-independent toxicity associated with novel translational products from CAG repeat expansions. PLoS One. 2020 Apr 2;15(4):e0227464. doi: 10.1371/journal.pone.0227464. PMCID: PMC7117740
Rudich, P., Snoznik, C., Oosten, J., Monaghan, J., Pandey, U., Lamitina, T. Nuclear localized C9orf72-associated arginine containing dipeptides exhibit age-dependent toxicity in C. elegans. Human Molecular Genetics, 2017, Dec 15:26(24):4916-4928. PMCID: PMC5886095
Tanis, J.E., Ma, Z., Krajacic, P., He, L., Foskett, J.K., Lamitina, T. CLHM-1 is a Functionally Conserved and Conditionally Toxic Ca2+-Permeable Ion Channel in Caenorhabditis elegans. J. of Neuroscience, 2013 July 33(30):12275-86. PMCID: PMC3721838