CHEMISTRY > BIOCHEMISTRY > ELLERBROEK

Dr. Shawn M. Ellerbroek 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

Publications

Biochemistry Web Links

Biochemistry Student Research Projects

I am interested in the studying mechanisms of cell movement and invasion. There are four major student projects currently underway in my laboratory as outlined below.

The role of Epidermal Growth Factor (EGF) on Ovarian Cancer Cell Surface Localization of Matrix Metalloproteinase-9 (MMP-9)
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 epidermal growth factor (EGF) as a potential causative agent of ovarian cancer progression. We have previously established that EGF stimulates ovarian cancer cell invasion through the activity of an enzyme, matrix metalloproteinase-9, that can break down tissue barriers to cancer cell invasion. It has been suggested that recruitment of enzymes such as MMP-9 to the surface of cells is indispensable for effective cell invasion. In support, we found that EGF stimulates binding of MMP-9 to ovarian cancer cells. We are currently investigating mechanisms of MMP-9 surface association through biochemical analysis of MMP-9 binding to ovarian and breast cancer cells under varying conditions, including that of MMP-9 over-expression.

Analysis of RhoA phosphorylation in fibroblasts and neuronal cells
During cancer metastasis, tumor cells migrate to new sites in the human body and grow uncontrollably. A large group of molecules within a cancer cell; termed proteins, work together to promote tumor cell movement and subsequent migration. Among these molecules, RhoA has emerged as a key regulatory protein of the cellular migration event. Evidence suggests that RhoA needs to be at certain places within a cell at specific times for it to effectively orchestrate cellular movement. Where RhoA goes, and what it does when it arrives, may be controlled by a process termed phosphorylation.

RhoA phosphorylation involves chemically modifying the RhoA protein on an amino acid residue (serine 188). Experimental evidence indicates that RhoA phosphorylation inhibits its activity, possibly by altering its cellular localization. The dynamics of RhoA phosphorylation is entirely unknown, as the scientific community has lacked a suitable reagent to discern phosphorylated from unphosphorylated RhoA in the cell. In collaboration with colleagues at the University of North Carolina at Chapel Hill and Pharmingen, we have tackled this problem by recently creating a reagent (a monoclonal antibody) that only binds phosphorylated, not but not unmodified, RhoA. The goal of this project is to use this novel antibody to elucidate where and when RhoA is phosphorylated during resting and spreading states of fibroblast and neuronal cells.

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.

Neuronal Expression of XPLN
Rho GTPases are indispensable regulators of cell movement, an event critical to cancer cell metastasis. My collaborators and I have cloned and characterized multiple activators of Rho GTPase proteins, including a RhoA activator we named XPLN (pronounce Zeppelin, after the rock band). Over the course of studying XPLN, we created a reagent, called a polyclonal antibody, to study its expression in tissues. In a collaborative effort with Dr. Melville in the biology department, students are currently using this antibody to study XPLN expression in neuronal tissues. Future work includes analyzing XPLN expression during different stages of mouse development or under oxidative stress induced by methamphetamines.

Student Research Presentations

“Behavioral diagnostic methods for the detection of carcinoma” Paper presented at the Chicago Society for Neuroscience Meeting and The National Conference on Undergraduate Research, University of North Carolina at Ashville.
Advisors: Dr. John Melville, Dr. Shawn Ellerbroek, and Dr. Cynthia Bane

Student Research Grants

2007-8 Academic Year Undergraduate Research Fellowship ($2,200):
“Cellular Exchange of RhoA, RhoB, and RhoC Proteins Mutated at Residue 43”
Student Investigator: Chris Goetzinger
Faculty Investigator: Dr. Shawn Ellerbroek

2007-8 McElroy Student Research Grant ($2,000): “Lysophosphatidic Acid Stimulation of Cell Surface uPAR Expression Through NF-kB Activity”
Student Investigator: Kyle Huegel
Faculty Investigator: Dr. Shawn Ellerbroek

2006-7 Academic Year Undergraduate Research Fellowship ($2,561.80): “The role of Epidermal Growth Factor (EGF) on Ovarian Cancer Cell Surface Localization of Matrix Metalloproteinase-9 (MMP-9)” Jessica Viner and Dr. Shawn Ellerbroek, Wartburg College

2006-7 McElroy Student Research Grant ($2,000): “Analysis of endogenous RhoA phosphorylation in fibroblasts” Julie Schweinfurth and Dr. Shawn Ellerbroek, Wartburg College

Courses Taught
CH 111 General 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
CH 461 Science Seminar

Student Research Posters

American Society of Biochemistry Molecular Biology (ASBMB) Washington, D.C. (2007)

“A Novel Monoclonal Antibody Against Phosphorylated RhoA”
Julie Schweinfurth, Kim Chaffin, Adi Dubash and Shawn Ellerbroek

“Role of Residue 43 in Activation of RhoA, RhoB, and RhoC”
Justin Peters and Shawn Ellerbroek

Wartburg College Undergraduate Poster Session (2007)

LPA Stimulation of UPAR Expression Through NF-KB
By Audra Schutte, Megan Buege, and Devon Hunerdosse
Advisor: Dr. Shawn Ellerbroek

A Novel Monoclonal Antibody Against Phosphorylated RhoA
By Julie Schweinfurth, Adi Dubash, and Kim Chaffin
Advisor: Dr. Shawn Ellerbroek

Role of Residue 43 in Activation of RhoA, RhoB, and RhoC
By Justin Peters
Advisor: Dr. Shawn Ellerbroek

Annual Meeting of the Animal Behavior Society, Snowbird, Utah. (2006)

“Behavioral diagnostic methods for the detection of bladder cell carcinoma”
Laura Durant, John Melville, Eric Cassmann, Cynthia Bane, Shawn Ellerbroek, and Roy M. Ventullo.

Regional Meeting of the Society for Neuroscience, Chicago , IL. (2006)

"The sensitivities of biochemical and behavioral diagnostic methods for the detection of bladder cell carcinoma."
Laura Durant, Eric Cassmann, Cynthia Bane, Shawn Ellerbroek, and Johnathan Melville.

Wartburg College Undergraduate Poster Session (2006)

“Exploration of the potential role of Prohibitin 3’ untranslated region acting as an siRNA” by Stephanie Egts
Advisor: Dr. Shawn Ellerbroek

“Identification of XPLN in Adult Mouse Brain” by Berenice Arias
Advisors: Dr. John Melville and Dr. Shawn Ellerbroek

“The Sensitivities of Biochemical and Behavioral Diagnostic Methods for the Detection of Bladder Cell Carcinoma” by Laura Durant and Eric Cassmann
Advisors: Dr. John Melville, Dr. Shawn Ellerbroek, and Dr. Cynthia Bane

“MMP-9 Binding to Invasive Ovarian Cancer Cells” by Delford Dohery, Matt Fox, Kyle Hilsabeck
Advisor: Dr. Shawn Ellerbroek

5th Annual Grinnell College Howard Hughes Medical Institure Symposium

“MMP-9 Binding to Invasive Ovarian Cancer Cells” Delford Dohery, Matt Fox, Kyle Hilsabeck, and Dr. Shawn Ellerbroek (2006)