| 161 | Kenneth L. van Golen, Ph.D. | <p>Associate Professor</p>
<p>Senior Research Scientist, The Helen F. Graham Cancer Center </p> | (302) 831-2669 | (302) 831-2281 | klvg@udel.edu | 320 Wolf Hall | Helen F Graham Christiana Care Research Institute | Department of Biological Sciences Wolf Hall University of Delaware Newark, DE 19716 | <ul>
<li><strong>B.S.</strong> - Michigan State University
</li><li><strong>Ph.D.</strong> - University of Texas, Health Science Center
</li><li><strong>Postdoctoral</strong> - University of Michigan </li></ul> | <p></p><ul><li>BISC612 Advanced Cell Biology</li><li>BISC605/606 Advanced Human Physiology</li><li>BISC400 Special Topics: Signal Transduction<br></li></ul> <p></p> | <p>Since 1996 my research has been focused on understanding the biology of a unique and aggressive form of breast cancer known as Inflammatory Breast Cancer (IBC). IBC accounts for approximately 5% of breast cancers annually but is responsible for 10% of breast cancer deaths in the U.S.A. IBC is a "lumpless" breast cancer and is hallmarked by distinct changes in the appearance of the breast, particularly the skin, resembling an infection. This disease typically affects younger women and has been reported in girls as young as 12 years old. IBC has a 42% and 18% 5- and 10-year-disease-free survival rate, respectively. In comparison to non-inflammatory breast cancers which have 90% and 83% 5- and 10-year-disease-free survival rates.</p><p>In 1999 my laboratory found that RhoC GTPase, a member of the Rho subfamily of the Ras-superfamily of monomeric G-proteins, is overexpressed and active in IBC.  RhoC drives the invasive and metastatic capabilities of IBC and is also a prognostic marker for particularly aggressive breast cancers. Much of my research over the years has focused on RhoC biology and its role in IBC progression. </p><p>Currently, my laboratory is concerned with studying various aspects of IBC biology with a main focus on what makes this disease so aggressive and invasive. Studies in my laboratory have expanded from focusing on RhoC GTPase to scientific model development, microenvironment interactions, unique signal transduction pathways and development of new therapeutic agents. My laboratory remains as one of approximately two dozen laboratories worldwide that are focused on IBC research. In addition, I am one of the Founders and current Vice President of the IBC-International Consortium (IBC-IC;  <a href="https://ibcic.org/">https://ibcic.org/</a>).<br></p> | <p><strong>The role of the platelet derived growth factor receptor alpha in inflammatory breast cancer progression- </strong>Our previous research has demonstrated a significant increase in expression of the platelet derived growth factor receptor alpha (PDGFRA) in IBC versus non-IBC tumors. We also demonstrated that the level of expression of PDGFRA is predictive of patient survival. Currently, we are determining how this receptor affects IBC tumor cell growth and survival. We are also working on repurposing a drug currently in the clinic for gastrointestinal stromal tumors to as a therapy for IBC.</p><p><strong>Development of natural inhibitor of RhoC GTPase to prevent metastasis- </strong>The natural compound Ambrosin is derived from a plant that grows in the Nile river delta. In a collaborative project it was determined X-ray crystallography that Ambrosin is predicted to interact specifically with RhoC GTPase. Our preliminary data has demonstrated that RhoC activity is specifically inhibited by this compound. We are currently developing this as an anti-metastatic compound. </p><p><strong>Understanding the etiology of inflammatory breast cancer skin metastases- </strong>About 25% of IBC patients develop prolific skin metastases post-radiation treatment. We have demonstrated that radiation causes a localized increase in TGF-beta expression by normal skin cells which stimulated residual IBC cells to become motile and migrate. We are currently exploring the molecular mechanisms of this form of metastases and developing agents to block TGF-beta signaling.</p><p><strong>Intracellular bacteria as a possible causative agent of inflammatory breast cancer- </strong>The cause of IBC is currently unknown. Genetic disposition imparted by family history does not seem to play a role. There has been speculation in the field of an infectious agent as a cause of the disease. Preliminary findings from our laboratory suggest potential infection of an intracellular bacteria.<br></p> | | <p><strong>KL van Golen</strong>, S Davies, ZF Wu, YF Wang, CD Bucana, H Root, S Chandrasekharappa, M Strawderman, SP Ethier, SD Merajver. " A novel putative low-affinity IGF-binding protein, LIBC, and RhoC GTPase correlate with the inflammatory breast cancer phenotype". Clin. Cancer Res. 5: 2511-2519, 1999.</p><p><strong>KL van Golen</strong>, ZF Wu, XT Qiao, LW Bao, and SD Merajver. "RhoC GTPase a novel transforming oncogene for human mammary epithelial cells that partially recapitulates the inflammatory breast cancer phenotype." Cancer Res. 60: 5832-5838, 2000.<br></p><p>CG Kleer, KA Griffith, MS Sabel, G Gallagher,<strong> KL van Golen,</strong> Z-F Wu and SD Merajver, "RhoC GTPase is a Novel Tissue Biomarker Associated with Biologically Aggressive Carcinomas of the Breast." Breast Cancer Res. Treatment 93(2): 101-110, 2005.</p><p>HL Lehman, SJ Van Laere, CM van Golen, PB Vermeulen, LY Dirix and <strong>KL van Golen</strong>. "Regulation of inflammatory breast cancer cell invasion through Akt1/PKBalpha phosphorylation of RhoC GTPase." Molecular Cancer Res. 10(10): 1306-1318, 2012. doi: 10.1158/1541-7786.MCR-12-1073. PMID:22896661</p><p>HL Lehman, EJ Dashner, M Lucey, P Vermeulen, L Dirix, S Van Laere and <strong>KL van Golen</strong>, "Modeling and characterization of inflammatory breast cancer emboli grown <em>in vitro</em>." Int. J. Cancer, (ePub), 2012. 132(10): 2283-94, 2013. doi: 10.1002/ijc.27928. PMID:23129218.</p><p>MS Joglekar, WO Elbazanti, MD Weitzman, HL Lehman and <strong>KL van Golen</strong>. Caveolin-1 Mediates Inflammatory Breast Cancer Cell Invasion via the Akt1 Pathway and RhoC GTPase. J Cell Biology 116(6): 923-933, 2015. doi:10.1002/jcb. 25025. PMID: 25559359.</p><p>Joglekar-Javadekar M, Van Laere S, Bourne M, Moalwi M, Finetti P, Vermeulen PB, Birnbaum D, Dirix LY, Ueno N, Carter M, Rains J, Ramchandran A, Bertucci F, <strong>van Golen KL</strong>. Characterizaiton and Targeting of Platelet Derived Growth Factor Receptor Alpha (PDGFRA) in Inflammatory Breast Cancer (IBC). Neoplasia, 19(7): 564-573, 2017.</p><p>Link to full bibliography: <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=van+golen+k">https://www.ncbi.nlm.nih.gov/pubmed/?term=van+golen+k</a></p> | | | <img alt="Dr. Kenneth Van Golen" src="/content-sub-site/PublishingImages/people/klvg/IMG_0640.jpg" style="BORDER:0px solid;" /> | |
