Alexei Korennykh,
Associate Professor
My long-term goal is to define how mammalian cells recognize and cleave non-coding RNA to maintain homeostasis and control their fate under normal conditions, during physiologic stresses, and in diseases. Present efforts in my laboratory focus on stress-activated RNA decay mediated by the human protein kinase/endoribonuclease RNase L, and by sensors of double-stranded RNA (dsRNA) that activate RNase L. The pathway of RNase L inhibits viral and bacterial infections, so major efforts in the field focus on the roles of RNase L in pathogen defense. RNase L is also a potent suppressor of proliferation, and a candidate tumor suppressor, which make RNase L-mediated RNA cleavage a mechanistically unique target for diagnostics and treatments of neoplastic and infectious diseases. To elucidate the biology of RNase L, we use biophysical, structural and genomic methods. My areas of training include protein/RNA recognition, protein kinase structure and function, cell biology, and macromolecular structure analysis. The unique advantage of our group, and a key innovative aspect of our work, is in applying our background in molecular mechanisms to an area of the human innate immune system, which lacks precise mechanistic understanding. Our work aims to address limitations in the field by obtaining a detailed structural and molecular understanding of the key proteins and protein complexes involved in RNA cleavage by RNase L, and by mapping the pathway of mammalian gene regulation by this receptor.
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