Yury Chernoff, Professor and Director of the Center for Nanobiology of the Macromolecular Assembly Disorders (NanoMAD)
Ph.D.,Biology, St. Petersburg State University (Russia), 1985
Office: Boggs 1-107
Yeast molecular genetics: genetic control of protein biosynthesis, folding and aggregation; prions and protein-based inheritance; chaperones and stress response
Prions were initially identified as proteins in an unusual conformation that cause neurodegenerative diseases in mammals, including humans. Infection depends on the prion's ability to convert an unmodified non-prion protein, encoded by the same host maintenance gene, into the prion conformation. Prion proteins form ordered fibrous aggregates, resembling those involved in other neural inclusion diseases, such as Huntington's disease or Alzheimer's disease. Moreover, many non-prion proteins can form amyloids in specific conditions. It is thought that amyloids represent one of the ancient types of the protein fold.
Some yeast non-Mendelian heritable elements, such as [URE3], [PSI+] or [RNQ+], closely resemble mammalian prions. This shows that heritable information can be coded in protein structures, in addition to information coded in the DNA sequence. Therefore, prions provide a basis for the protein-based inheritance in yeast (and possibly in other organisms).
Protein aggregates behave as "molecular tumors" at the subcellular level. While most aggregated proteins form "non-malignant tumors", prions form the "malignant tumors" that can spread to other cells. We have shown that the ability of the yeast prions to spread depends on the chaperone helpers producing the infectious "seeds". In this way, prions use the cellular stress defense systems to their own advantage. Chaperones could become potential targets in counteracting the prion diseases and other aggregation-related disorders.
Our current research is focused on the following topics: 1) role of the specific chaperones of the Hsp70 and Hsp100 groups, proteolytic systems and cytoskeletal assembly networks in formation and propagation of yeast prions; 2) molecular evolution of yeast prion proteins, and mechanisms of the so-called "species barrier" that prevents transmission of the amyloid state between related proteins of divergent amino acid sequences; 3) using yeast as a model system for studying mechanisms of aggregation and toxicity of proteins involved in mammalian neural inclusion diseases.
Cashman, N.R. and Y.O. Chernoff (2012) A special focus issue on the materials of Prion 2011 meeting in Montreal, Canada. Prion 6:95-6. Link
Antony, H., A.P. Wiegmans, M.Q. Wei, Y.O. Chernoff, K.K. Khanna and A.L. Munn (2012) Potential roles for prions and protein-only inheritance in cancer. Cancer Metastasis Rev 31:1-19. Link
Gong, H., N.V. Romanova, K.D. Allen, P. Chandramowlishwaran, K. Gokhale, G.P. Newnam, P. Mieczkowski, M.Y. Sherman and Y.O. Chernoff (2012) Polyglutamine toxicity is controlled by prion composition and gene dosage in yeast. PLoS Genetics 8:e1002634. Epub 2012 Apr 19. Link
Liebman, S.W. and Y.O. Chernoff (2012) Prions in yeast. Genetics 191:1041-72. Link
Kiktev, D.A., J.C. Patterson, S. Müller, B. Bariar, T. Pan and Y.O. Chernoff (2012) Regulation of chaperone effects on a yeast prion by cochaperone Sgt2. Mol Cell Biol 32:4960-70. Epub 2012 Oct 8. Link
Chernoff Y.O. (2011) Mutations and natural selection in the protein world. J Mol Biol Oct 28;413(3):525-6. Epub 2011 Aug 10. Link
Chernova, T.A., A.V. Romanyuk, T.S. Karpova, J.R. Shanks, M. Ali, N. Moffatt, R.L. Howie, A. O'Dell, J.G. McNally, S.W. Liebman, Y.O. Chernoff and K.D. Wilkinson (2011) Prion induction by the short-lived, stress-induced protein Lsb2 is regulated by ubiquitination and association with the actin cytoskeleton. Mol Cell 43:242-252. Link
Kiktev, D.A., Y.O. Chernoff, A.V. Archipenko and G.A. Zhouravleva. (2011) Identification of genes influencing synthetic lethality of genetic and epigenetic alterations in translation termination factors in yeast. Dokl Biochem Biophys 438:117-119.
Bruce, K.L. and Y.O. Chernoff. (2011) Sequence specificity and fidelity of prion transmission in yeast. Semin Cell Dev Biol 22:444-451. Link
Newnam, G.P., J.L. Birchmore and Y.O. Chernoff. (2011) Destabilization and recovery of a yeast prion after mild heat shock. J Mol Biol 408:432-448. Link