- Ophthalmology and Visual Sciences
- Adjunct Faculty
- Department of Neuroscience
- Adjunct Faculty
- Rockefeller Neuroscience Institute (SOM)
- PhD, Weimann Institute of Science, Rehovot, Israel
- BS, B.S. in Biology, Moscow State University, Moscow, USSR (Russia)
- Brooks, C., Snoberger, A., Belcastro, M., Murphy, J., Kisselev, O., Smith, D., Sokolov, M. (2018) “Archaeal Unfoldase Counteracts Protein Misfolding Retinopathy in Mice.” Journal of Neuroscience 38(33) 7248-7254, (PMID: 30012684)
- Brooks, C., Murphy, J., Belcastro, M., Heller, D., Kolandaivelu, S., Kisselev, O., Sokolov, M. (2018) “Farnesylation of the Transducin G Protein Gamma Subunit Is a Prerequisite for Its Ciliary Targeting in Rod Photoreceptors.” Frontiers in Molecular Neuroscience 11 (16) PMCID: PMC5787109
- Wright ZC, SIngh RK, Alpino R, Goldberg AF, Sokolov M, Ramamurthy V. ARL3 regulates trafficking of prenylated phototransduction proteins to the rod outer segment. Hum Mol Genet (2016) [Epub ahead of print].
- Sinha S, Belcastro M, Datta P, Seo S, Sokolov M. Essential role of the chaperonin CCT in rod outer segment biogenesis. Invest Ophthalmol Vis Sci (2014) 55(6): 3775-85. PMCID: PMC4062400.
- Gao X, Sinha S, Belcastro M, Woodard C, Ramamurthy V, Stoilov P, Sokolov M. Splice isoforms of phosducin-like protein control the expression of heterotrimeric G proteins. J Biol Chem (2013 Sep 6); 288(36):25760-8.
- Sinha S, Majumder A, Belcastro M, Sokolov M, Artemyev NO. Expression and subcellular distribution of UNC119a, a protein partner of transducin α subunit in rod photoreceptors. Cell Signal (2013 Jan) 25(1): 341-8. doi: 10.1016/j.cellsig.2012.10.005.
- Belcastro M, Song H, Sinha S, Song C, Mathers PH, Sokolov M. Phosphorylation of phosducin accelerates rod recovery from transducin translocation. Invest Ophthalmol Vis Sci (2012 May 1) 53(6): 3084-91. doi: 10.1167/iovs.11-8798.
- Yang J, Wang L, Song H, Sokolov M. Current understanding of usher syndrome type II. Front Biosci (2012 Jan 1) 17:1165-83.
- Posokhova E, Song H, Belcastro M, Higgins L, Bigley LR, Michaud NA, Martemyanov KA, Sokolov M. Disruption of the chaperonin containing TCP-1 function affects protein networks essential for Rod outer segment morphogenesis and survival. Mol Cell Proteomics. 2010 Sep 17.
- Edrington TC, Sokolov M, Boesze-Battaglia K. Peripherin/rds co-distributes with putative binding partners in basal rod outer segment disks. Exp Eye Res (2011) 92(5):439-42.
1989 B.S. in Biology, Moscow State University, Moscow, USSR (Russia)
1997 Ph.D. in Biochemistry, Weizmann Institute of Science, Rehovot, Israel
1997-1998 Structure and function of the chloroplast ATP synthase complex, University of Kansas, Lawrence, KS
1998-2004 G protein-mediated signaling of vertebrate photoreceptors, Harvard Medical School, Boston, MA
2004-2011 Assistant Professor, Ophthalmology and Biochemistry, Sensory Neuroscience Research Center, West Virginia University
2011- 2021 Associate Professor, Ophthalmology, Biochemistry and Neuroscience, West Virginia University
2021 - Professor, Departments of Ophthalmology, Biochemistry, and Neuroscience, West Virginia University
Available Research Projects:
1. Treating neurodegenerative diseases by xenogeneic molecular chaperones
Unicellular organisms (microbes) experience massive protein misfolding during heat shock (temperature spike). Misfolded proteins are cytotoxic and could perturb proteostasis over time unless re-folded or purged. Thus, the survival of microbes critically depends on the network of molecular chaperones orchestrating the folding and degradation of nascent or damaged proteins.
Some types of chaperones are common for all living cells, however some of them are specific for microbes and absent in mammals. One could argue that homeothermic mammals hardly ever experience heat shock. Yet, mammalian neurons are known to be vulnerable to protein misfolding caused by mutations, as observed in neurodegenerative diseases.
My lab uses cross-species genetics to explore therapeutic potential of microbial chaperones in mammals. Specifically, we are pursuing new strategies against neurodegenerative diseases caused by protein misfolding. We have generated transgenic mice expressing a molecular chaperone from thermophilic archaea. We are testing the potency of this archaeal chaperon to counteract the development of currently incurable blinding disease, retinitis pigmentosa. In addition, we are developing viral vector for the chaperone delivery, and adopting different types of microbial chaperones for the treatment.
2. Chaperonin system of rod photoreceptors
Chaperonins are ring-shaped ATPase complexes found in all living cells including prokaryotes, archaea, and eukaryotes. Chaperonins are responsible for the folding of cytosolic proteins in their central cavity. When a chaperonin encapsulates its protein substrate, it segregates it from intracellular molecular environment, which facilitates its correct folding. Chaperonin’s activity is integrated into the cellular chaperone network.
Procaryotic GroEL/ES complex is the most studied chaperonin. Its eukaryotic counterpart, chaperonin containing t-complex protein 1, commonly abbreviated as CCT or TRiC, is structurally more complex, which makes it more difficult to study. The known CCT/TRiC substrates are actin, tubulin, and heterotrimeric G proteins. Other CCT/TRiC substrates in specialized mammalian cells remain unknown, because CCT/TRiC was predominantly studied in yeasts.
One of our projects focuses on the function of CCT/TRiC in specialized mammalian neurons. Our goal is to identify new CCT/TRiC substrates, and to determine how the selection of substrates is regulated. We also seek to decipher the response of the chaperonin system to neurodegenerative conditions. Towards this goal, we genetically introduced epitope tag into CCT/TRiC, which allows us to purify intact chaperonin complex from the cells. We are using this model to analyze proteins that interact with CCT/TRiC, including its substrates and regulatory co-factors.