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Assistant Professor
of Chemistry/Biochemistry
Otto Professor in Chemistry
Office: Science
Center 261
Phone: (319) 352-8679
Fax: (319) 352-8606
Email: shawn.ellerbroek@wartburg.edu |
Education
B.A., 1995, University of Iowa
Ph.D., 2000, Northwestern University
American Cancer Society Postdoctoral Fellow 2001-2004
Courses Taught
CH 113 Principle of Chemistry
CH 130 Hot Topics in Science and Medicine
CH 325 Biochemistry
CH 425 Advanced Biochemistry
CH 455 Methods of Biochemical Research
CH 456 Student Originated Research
Areas of Research Interest
I am interested in the studying mechanisms of cell movement and invasion. There are three main student-driven research projects currently underway in my laboratory.
The role of Lysophosphatidic Acid on Ovarian Cancer Cell Surface Localization of Plasminogen Activator (uPA)
Ovarian cancers frequently remain undetected until late stages when prognosis is poor. Researchers looking for more accurate and reliable methods of early detection have identified lysophosphatidic acid (LPA) as a potential causative agent of ovarian cancer progression. It has been suggested that recruitment of enzymes to the surface of cells is indispensable for effective cell invasion. We are actively studying the mechanisms involved in LPA stimulation of cell surface binding of uPA, an enzyme that contributes to the break down of tissue barriers during cancer cell invasion. This work employs a combination of molecular biology, cell culture, and enzyme assays.
Role of Residue 43 in RhoA/B/C Function
RhoA, RhoB, and RhoC are small intracellular GTPases that share over 80% sequence identity. As GTPases, all three Rho proteins become “activated” in the cell when they bind a GTP molecule. These proteins are then inactivated through their intrinsic ability to hydrolyze bound GTP into GDP (hence the name “GTPase”). Over expression of all three Rho proteins causes most cells to become contractile, leading to the early (and wrong) hypothesis that the proteins must have redundant functions towards cell movement. Recently, increased RhoC expression has been identified as a prominent indicator of cancer progression. This fanfare has turned a number of heads towards the interesting question, why are there three such closely related Rho proteins anyway?
Rho exchange factors are large proteins that activate Rho GTPases. Over the course of studying a novel Rho exchange factor, we noticed that it activated RhoA and RhoB, but not RhoC. We further observed that amino acid #43 was different in RhoC (an isoleucine) compared to RhoA and RhoB (which have Valines), and this structural difference may be the impediment in the ability of our protein to activate RhoC. We are currently extending the above observations through an analysis of exchange factor activity against normal and Rho proteins mutated at this current residue. Along with our collaborator at Birmingham-Southern College, Dr. Gretchen Repasky, we hope to gain a better understanding of the function of this critical residue. This work involves a combination of molecular biology, protein purification, cell culture, and enzyme assays.
Putative Role of Matrix Metalloproteinase-9 in Neurite Outgrowth; Establishment of a Neurogenesis Model System
The overall objective of this proposal is to examine proteolytic events associated with neuronal differentiation of PC12 cells as a model for a damaged or regenerating nerve system. Rat pheochromocytoma (PC12) cells are a cell line that traces back to the medulla of a Sprague Dawley rat and thus able to differentiate into neurons upon stimulation with Nerve Growth Factor (NGF). Based on a recent study, we are interested in examining whether matrix metalloprotease-9 (MMP-9) proteolytic activity is required for neurite outgrowth. This work involves a combination of three-dimensional cell culture and confocal microscopy.
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