Stanislav Kholmanskikh, Ph.D.
Assistant Research Professor of Neuroscience
Overview
My research focus is regulation of neuronal cytoskeleton during normal development and disease. I have been especially interested in dissecting the functions of neuronal migration gene Lis1 that appears to impact all three major cytoskeletal components, including motor proteins, microtubules and actin. While role of Lis1 as part of cytoplasmic dynein motor is well established, data from our lab indicates prominent role Lis1 plays in the regulation of actin and microtubule cytoskeleton likely in a dynein-independent manner. We have established that Lis1 promotes actin polymerization at the leading edge of migrating cells via downregulation of RhoA and concomitant upregulation of Rac1 and Cdc42 activity. We also showed that contrary to its effects in a mixture of purified proteins, in vivo Lis1 promotes microtubule dynamics.
Our current efforts include defining the pathway that links Lis1 to the activity of small Rho GTPases and microtubule dynamics. We also continue to investigate the mechanisms by which human mutations cause neurological disease, and how their normal proteins function in health, particularly with respect to cytoskeletal regulation and subcellular protein localization.
Recent Publications
- Jason D. Gray, Stanislav Kholmanskikh, Bozena S. Castaldo, Alex Hansler, Heekyung Chung, Brian Klotz, Shawn Singh, Anthony M. C. Brown, and M. Elizabeth Ross, "LRP6 exerts non-canonical effects on Wnt signaling during neural tube closure," Human Molecular Genetics 22 (21), 4267-4281 (2013);
- Jean-Baptiste Riviere, Bregje W. M. van Bon, Alexander Hoischen, Stanislav S. Kholmanskikh, Brian J. O'Roak, Christian Gilissen, Sabine Gijsen, Christopher T. Sullivan, Susan L. Christian, Omar A. Abdul-Rahman, Joan F. Atkin, Nicolas Chassaing, Valerie Drouin-Garraud, Andrew E. Fry, Jean-Pierre Fryns, Karen W. Gripp, Marlies Kempers, Tjitske Kleefstra, Grazia M. S. Mancini, Malgorzata J. M. Nowaczyk, Conny M. A. van Ravenswaaij-Arts, Tony Roscioli, Michael Marble, Jill A. Rosenfeld, Victoria M. Siu, Bert B. A. de Vries, Jay Shendure, Alain Verloes, Joris A. Veltman, Han G. Brunner, M. Elizabeth Ross, Daniela T. Pilz, and William B. Dobyns, "De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome," Nat Genet 44 (4), 440-444 (2012);
- S. S. Kholmanskikh, H. B. Koeller, A. Wynshaw-Boris, T. Gomez, P. C. Letourneau, and M. E. Ross, "Calcium-dependent interaction of Lis1 with IQGAP1 and Cdc42 promotes neuronal motility," Nat Neurosci 9 (1), 50-57 (2006);
- S. S. Kholmanskikh, J. S. Dobrin, A. Wynshaw-Boris, P. C. Letourneau, and M. E. Ross, "Disregulated RhoGTPases and actin cytoskeleton contribute to the migration defect in Lis1-deficient neurons," J Neurosci 23 (25), 8673-8681 (2003).