Vladislav Golubkov

Vladislav Golubkov, Ph.D.[La Jolla]

  • Research

    Dr. Golubkov studies the role of proteolysis in cell migration and invasion in cancer and other diseases.

  • Biography

    Dr. Golubkov received his PhD in 1999.

Publications

 

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Vladislav Golubkov's Research Focus

Birth Defects, Cancer, Breast Cancer

Cell motility is implemented in diverse processes such as normal embryo development and cancer. Deregulated cell motility promotes congenital disorders, cancer progression and metastasis. Dr. Golubkov’s research is focused on understanding the molecular mechanisms regulating cell motility in pathology.

Vladislav Golubkov's Research Report

Vladislav Golubkov
Recently, we identified a new mechanism that regulates directional cell motility. It is well established that matrix metalloproteases (MMPs), especially the membrane type-1 MMP (MT1-MMP/MMP14), promote cell motility by proteolysis of extracellular matrix proteins, cell surface receptors and other signaling molecules. It is also well established that the Wnt/planar cell polarity (Wnt/PCP) pathway controls the orientation of cells in a tissue plane in such a way that all cells are oriented in the same front/back direction. We identified a link between these two regulators of cell motility: The proteolysis of protein tyrosine kinase 7 (PTK7), a PCP pseudokinase, by MT1-MMP. We demonstrated that the PTK7 proteolysis by MT1-MMP controls cell migration in early embryogenesis and regulates cancer cell directional motility and invasion. The full-length PTK7 is one of the major cell surface proteins expressed in normal breast epithelial cells and is a major cleavage target of MT1-MMP. The full-length PTK7 efficiently inhibits cell invasion and down-regulates the myosin light chain (MLC) phosphorylation, a downstream event in the Wnt/PCP pathway. MT1-MMP proteolysis of PTK7 reverses the inhibitory signal of the full-length PTK7 and this proteolytic event promotes cell invasion. Thus, PTK7 proteolysis by MT1-MMP is a proteolytic master switch that turns on the motility of cells. This ubiquitous mechanism is conserved in models as diverse as zebrafish embryogenesis and cancer cell invasion. It is likely that aberrations in the PTK7 signaling are detrimental to cell movements. Because both the pro-invasive MT1-MMP and the polarity regulating PTK7 are linked to embryogenesis and cancer, the precise understanding of the downstream signaling events of PTK7 proteolysis will result in a more comprehensive understanding of polarized collective cell motility in development and cancer.

About Vladislav Golubkov

Experience

Dr. Golubkov received his PhD from the Laboratory of Cytotechnology at the Institute of Theoretical and Experimental Biophysics, Russian Academy of Science. As a PhD student he developed novel approach to produce snake venom proteins for biotechnology applications by utilizing the snake secretory epithelial cell culture. After graduation from the PhD program in 1999, he moved to the United States to join Dr. Yanina Rozenbeg-Adler’s Targeted Artificial Gene Delivery (TAGD) group at the University of Southern California, Los Angeles (USC) to study the retargeting of gene therapy vectors by biophysical and chemical surface modifications. Later, in 2001, Dr. Golubkov joined Francis Markland’s laboratory at USC and studied the anti-tumor and anti-angiogenic properties of the snake venom disintegrin, contortrostatin. Dr. Golubkov continued to explore the molecular mechanisms of diseases in Dr. Alex Strongin’s laboratory at the Sanford-Burnham Medical Research Institute (2003-present) where he studies matrix metalloproteinases (MMPs) and other proteases in pathology, primarily in cancer.

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Education

2011-present, Research Assistant Professor, Sanford-Burnham Medical Research Institute (La Jolla, California).
2007-2011, Staff Scientist, Sanford-Burnham Medical Research Institute (La Jolla, California).
2003-2007, Postdoctoral associate, Sanford-Burnham Medical Research Institute (La Jolla, California).
2000-2003, Postdoctoral associate, Keck School of Medicine, University of Southern California (USC, Los Angeles, California).
1996-1999, Ph.D. (Cell Biology, Biophysics, 1999), Institute of Theoretical and Experimental Biophysics, Laboratory of Cytotechnology, Russian Academy of Science (Russia).

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