Kenneth L. van Golen, Ph.D.

Teaching

  • BISC612-Advanced Cell Biology
  • BISC 850 - Advanced Topics in Biology: The Rho GTPases

Research Interests

The main interest of my laboratory is to understand the biology of Inflammatory breast cancer (IBC).  IBC is an extremely aggressive form of breast cancer that is phenotypically unique form of breast cancer.  IBC is hallmarked by distinct changes in the skin changes that resemble an infection or mastitis.  IBC affects younger women (typically in thier late 20's or early 30's) and progresses rapidly.  The rapid progression of the disease is thought to occur because of the propensity of the tumor cells to invade and reside in the dermal lymphatic vessels of the skin overlying the breast. 

In 1999 our laboratory found that RhoC GTPase, one member of the Rho family, was overexpressed in inflammatory breast cancer.   Later, we found that RhoC over expression was a prognostic marker for metastasis in small breast tumors (<1 cm in size). Since then we have begun to look at how RhoC confers a metastatic phenotype to inflammatory breast cancer and how it interacts with other Rho GTPases. Our studies have expanded to include pancreatic cancer and prostate cancer bone metastasis.

The Rho GTPases comprise a group of 23 small GTP binding proteins that play a significant role in nearly every cellular process. One of the most characterized roles of the Rho proteins is their ability to reorganize the cell cytoskeleton. Signals from the extracellular environment, transduced through growth factor receptors and/or cell adhesion molecules leads to the coordinated activation of Rho proteins and reorganization of the cytoskeleton. In turn, this leads to changes in cells shape, polarity, migratory and invasiveness.

The potent ability of the Rho proteins to affect cell migration and invasion has many implications for the dissemination and spread of cancer and in normal processes such as development and immunity. RhoC GTPase is associated with metastatic spread and thus appears to be a metastatic switch.   Interestingly, RhoC is 91% homologous on the protein level to RhoA GTPase, yet the two proteins have completely different functions in the cell.  One of our goals is to understand what makes these two GTPases distinct from one another.

A complete understanding of how the Rho proteins, particularly RhoC, can influence progression of a cancer cell to become metastatic is key to the development of anti-metastatic therapies.  Aside from IBC our laboratory also has interests in understanding the mechansims underlying prostate cancer skeletal metastasis. 

Current Projects

  • Understanding the molecular mechanisms of inflammatory breast cancer metastasis - The goal of this project is to understand how inflammatory breast cancer metastasizes.  We have developed an in vitro model of IBC emboli formation that accurately resembles IBC emboli in the patient.  Using this model we are beginning to unravel the molecules and signaling pathways involved in IBC metastasis.  In particular we are studying the role of RhoC with Akt/Protein Kinase B and with the scaffolding molecule caveolin-1.  We are also studying the role of platelet derived growth factor alpha in conferring a survival advantage to IBC cells.
  • The role of Rho GTPases in prostate cancer bone metastasis - The goal of this project is to understand the contribution of individual Rho GTPases during the process of binding to bone marrow endothelial cells, tumor cell diapedesis (transendothelial cell migration) and invasion through the bone stroma.
  • Determining the differences between RhoA and RhoC GTPases-  Since RhoA and RhoC share 91% homology we are using an advanced genetic and imaging approach to understand the differences in the spatial and temporal activation of the proteins. 

Selected Publications

Associate Professor
Senior Research Scientist, The Helen F. Graham Cancer Center

Phone: (302) 831-2669

Fax: (302) 831-2281

Email: klvg@udel.edu

Office: 320 Wolf Hall

Address:
Department of Biological Sciences
Wolf Hall
University of Delaware
Newark, DE 19716

Education

  • B.S. - Michigan State University
  • Ph.D. - University of Texas, Health Science Center
  • Postdoctoral - University of Michigan