SARAH BOND, Cellular & Molecular Physiology
Michael Forgac, Adviser
Plasma Membrane V-ATPases and Cancer

I am investigating the role of surface vacuolar [H+]-ATPase (V-ATPase) activity in cancer. V-ATPases are ATP-dependent proton pumps located on intracellular membranes in all cells, where they serve the critical function of acidifying compartments such as endosomes and lysosomes. Recent reports reveal functional expression of V-ATPases on the plasma membrane of highly aggressive tumor cells. However, the contribution of surface V-ATPase activity to tumorigenesis is not known. I am testing the hypothesis that plasma membrane V-ATPases promote tumor cell survival by neutralizing the cytosol, and tumor cell metastasis by creating an acidic extracellular environment favorable for invasion.

MEGHAN LAVALLEY, Immunology
Linden Hu, Adviser
Host-pathogen Interaction in Lyme Arthritis

Borrelia burgdorferi, causes Lyme disease, a condition accompanied by arthritis. In mice, arthritis peaks 3-6 weeks after infection and then spontaneously resolves despite the continued presence of the organism. This phenomenon is accompanied by the development of antibodies against the B. burgdorferi protein Arp and administering anti-Arp antibodies promotes resolution of arthritis. I am working to understand the way anti-Arp antibodies work. Preliminary data suggests that Arp binds and sequesters a host anti-inflammatory protein, adrenomedullin, and that anti-Arp antibodies release adrenomedullin from Arp resulting in decreased inflammation. A better understanding of how B. burgdorferi utilizes host proteins to modulate pathogenesis may lead to better treatment strategies for Lyme disease.

BRANDI DAVIS, Biochemistry
Akiko Hata, Adviser
MicroRNAs and the Regulation of Smooth Muscle Cell Phenotype Switching

Upon vascular damage, smooth muscle cells (SMC) undergo a phenotypic switch characterized by a loss of contractile gene expression, increased proliferation and increased migration.  Following resolution of the injury, SMC “re-differentiate” and exhibit a contractile, non-proliferative phenotype.  Deregulation of this phenotype switching underlies many vascular disorders.  I am investigating the role of microRNAs, short RNAs that repress expression of genes, in the modulation of SMC phenotype switching.  To date I have identified microRNAs that are up-regulated when SMC differentiation is induced and found suggestions that these microRNAs may be required for SMC differentiation.  A better understanding of the role of microRNAs may lead to new therapeutic approaches in the treatment of vascular disorders.

PATRICIA GOODWIN, Neuroscience
Peter Juo, Adviser
Role of CDK5 in Synaptic Transmission

Our lab is interested in understanding molecular mechanisms that regulate synaptic transmission and uses C. elegans as a model system. I focus on cyclin dependent kinase-5 (CDK5), a molecule that seems to be involved in cell migration, axon outgrowth and neurodegeneration and regulates acetylcholine release at the neuromuscular junction. I have adopted a three-pronged approach and am analyzing the behavioral responses of cdk-5 mutants to the acetylcholine esterase inhibitor aldicarb and the effects of eliminating CDK-5 on the localization and abundance of synaptic components. I am also using an RNAi-based screen to identify potential targets and regulators of CDK-5. All of these approaches are designed to unravel the way CDK-5 functions at the synapse.