Sergei Y. Sokol
- PROFESSOR Developmental and Regenerative Biology
Ph.D. in Biochemistry, Harvard University
Training Areas(s): CAB, MCBDS*, NEU
Member, Black Family Stem Cell Institute
Dr. Sokol's research is focused on signaling molecules regulating cell polarity and cell movements during vertebrate development. He also studies molecular mechanisms regulating neuronal differentiation of neural stem/progenitor cells.
Cell polarity in vertebrate development, neural development, axis specification, Wnt signaling, morphogenetic movements
Polarity is a fundamental cell property that is essential for cell functions and is required for cell maintenance and differentiation. In embryonic development, cell polarity is reflected in asymmetric division of stem cell progenitors and developmental fate decisions. The frog Xenopus laevis makes an important in vivo vertebrate system to study cell polarity in various developmental contexts. Using both frog and mouse embryos, we are studying biochemical mechanisms that generate cell and tissue polarity. Our group would like to understand how developmental polarity is acquired and how communication between embryonic cells leads to their differentiation and assembly into specific tissues.
Several aspects of cell polarity and fate are controlled by the secreted growth factors of the Wnt family that are related to the proto-oncogene Wnt1. Our previous work demonstrated the structural and functional conservation of the Wnt pathway in vertebrates during formation of the Spemann organizer, a special signaling center in the embryo responsible for neural induction and head development. In vertebrate embryos, Wnt proteins are responsible for dorso-ventral and antero-posterior axis polarity, cell proliferation and cell death. Consistent with their important roles, many components of the canonical Wnt pathway are mutated in colon carcinomas, melanomas, liver, breast and skin tumors. In addition, Wnt signaling regulates morphogenetic cell movements and accompanying cytoskeletal changes during gastrulation. Since this pathway is distinct from the canonical beta-catenin pathway, we want to learn how different proteins relay Wnt signals to different targets.
In embryonic development, different cell types often differentiate as a result of asymmetric division of stem/progenitor cells. The apical Par protein complex, consisting of the PDZ-containing proteins Par-6 and Par-3 and atypical protein kinase C (aPKC), functions to control asymmetric divisions and establish cell polarity in a variety of cell types. The basolateral determinants PAR-1 and Lgl play equally important roles at the opposite side of epithelial cells. These proteins are highly conserved from worms to humans and function to regulate cell polarity in many embryonic tissues. Our studies demonstrate that Lgl is required for cell polarity and asymmetric cell division during primary neurogenesis in Xenopus ectoderm and its localization may be controlled by Wnt signaling. We are using the cell biological and embryological approaches in the frog Xenopus laevis and the advantages of the genetic approach in mice to study cell polarity and asymmetric division of neural progenitor cells. We would like to learn how the subcellular localization of Lgl and Par proteins regulates the self-renewal and differentiation of neural stem/progenitor cells. The knowledge of molecular mechanisms regulating neuronal differentiation should have implications on stem cell research and regenerative medicine.
For more information, please visit the Sokol Laboratory website.
Gloy J, Hikasa H , Sokol SY. Frodo interacts with Dishevelled to transduce Wnt signals. Nature Cell Biol 2002; 4: 351-357.
Lisovsky M, Itoh K , Sokol SY. Frizzled receptors activate a novel JNK-dependent pathway that may lead to apoptosis. Curr Biol 2002; 12: 53-58.
Sokol SY, Brott BK. A vertebrate homologue of the cell cycle regulator Dbf4 is a Wnt inhibitor required for heart development. Dev. Cell 2005; 8: 703-715.
Itoh K, Brott BK, Sokol SY, Ratcliffe MR, Bae G. Nuclear localization is required for Dishevelled function in Wnt/b-catenin signaling. J. Biol 2005; 4: 3.
Dollar G, Sokol SY, Mlodzik M, Weber U. Regulation of Lethal giant larvae by Dishevelled . Nature 2005; 437: 1376-1380.
Kibardin A, Sokol SY, Ossipova O. Metastasis-associated kinase modulates Wnt signaling to regulate brain patterning and morphogenesis. Development 2006; 133: 2845-2854.
Ossipova O, Sokol SY, Green JB, Tabler J. PAR-1 specifies ciliated cells in vertebrate ectoderm downstream of aPKC. Development 2007; 134: 4297-4306.
Sokol SY. A role for Wnts in morphogenesis and tissue polarity. Nature Cell Biol 2000; 1: E124-E126.
Sokol SY. Wnters in La Jolla. Development 2007; 134: 3393-3399.
Hikasa H, Ezan J, Itoh K, Li X, Klymkowsky MW, Sokol SY. Regulation of TCF3 by Wnt-Dependent Phosphorylation during Vertebrate Axis Specification. Dev Cell 2010;(19): 521-532.
Hikasa H, Sokol S. Phosphorylation of TCF proteins by homeodomain-interacting protein kinase 2. J Biol Chem 2011; 286(14): 12093-100.
Sokol S. Wnt signaling through T-cell factor phosphorylation. Cell Res 2011 May;.
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Dr. Sokol did not report having any of the following types of financial relationships with industry during 2012 and/or 2013: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
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