Associate Professor of Chemistry/Biochemistry
B.A., 1995, University of Iowa
Ph.D., 2000, Northwestern University
American Cancer Society Postdoctoral Fellow 2001-2004
CH 113 Principle of Chemistry
CH 130 Hot Topics in Science and Medicine
CH 205 Introductory Organic Chemistry
CH 325 Biochemistry
CH 425 Advanced Biochemistry
CH 455 Methods of Biochemical Research
CH 456 Student Originated Research
GM 359 Tanzania: Culture and Current Issues
ID 359 Tanzania and the Global AIDS Crisis
Wartburg Biochemistry Student Publications:
Areas of Research Interest
I am interested in studying mechanisms of cell movement and invasion. Two main student-driven research projects are currently underway in my laboratory as outlined below.
Lysophosphatidic Acid Regulation of Urokinase Plasminogen Activator Receptor (uPAR) Function
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 breakdown of tissue barriers during cancer cell invasion, to its receptor uPAR. This work employs a combination of molecular biology, cell culture, and enzyme assays.
Role of Residue 188 in RhoA and RhoC Function
RhoA and RhoC are small intracellular GTPases that share over 85% sequence identity. Both of these Rho proteins become "activated" in the cell when they bind a GTP molecule. The proteins are then inactivated through their intrinsic ability to hydrolyze bound GTP into GDP (hence the name "GTPase"). Increased RhoC expression has been identified as a prominent indicator of cancer progression and raised the interesting question, how are these closely related proteins uniquely regulated?
We have observed that RhoA contains a serine residue at position 188, whereas RhoC contains an arginine. Kinase-catalyzed addition of a negatively charged phosphoryl group to serine 188 of RhoA (phosphorylation) promotes RhoA removal from membranes, thereby inhibiting its activity. Phosphorylation may destabilize the interface between RhoA and the negatively charged inner plasma membrane through charge repulsion while increasing binding to its natural inhibitor, Rho-GDI.
We predict the presence of an arginine at position 188 of RhoC promotes enzyme activity. First, position 188 is directly comparable between the two enzymes (two residues away from the carboxyl-localized prenylated cysteine). Second, the arginine residue cannot be phosphorylated. Third, arginine is a basic residue that carries a positive charge at normal physiological pH; this residue may in fact electrostatically stabilize RhoC association with the negatively charged inner cell membrane, thereby promoting activity. We therefore postulate that mutating RhoA residue 188 from a serine to an arginine will promote membrane association and increase RhoA activity. Conversely, mutating RhoC residue 188 from an arginine to a serine will have the opposite effect.