Jennifer Durham, Cellular & Molecular Physiology, Ira Herman, Adviser
Endothelial βcap73 and Control of Pathological Angiogenesis

My thesis work focuses on the molecular mechanisms of pathological angiogenesis. Angiogenesis is the process by which blood vessels are remodeled; pathological angiogenesis plays a central role in tumor growth and in two blinding diseases, diabetic retinopathy and macular degeneration. Endothelial cell migration, critical for angiogenesis, is influenced by β-actin-filaments and over-expression of βcap73, a β-actin-specific binding protein is linked to defective cell migration. I am testing the hypothesis that over-expression of βcap73 in the retinal microvasculature will abrogate endothelial cell migration. My experiments will help determine if actin-mediated assembly processes offer a novel therapeutic approach to counter the pathologic angiogenesis.

Christine Graham, Neuroscience, Douglas Vetter, Adviser
Stress Responses and Inner Ear Function

I am investigating the role of a neuroendocrine, stress-response signaling pathway in the inner ear.  Urocortin, a neuropeptide that signals through two G protein coupled receptors, [I think there are some words missing here] corticotropin releasing hormone receptor 1 and 2 (CRHR1 and CRHR2), is one molecule known to be present in the efferent neurons descending from the brainstem to the cochlea.  The receptors that interact with urocortin are known to modulate stress in several other settings in the nervous system.  Through the use of mice that lack CRHR1, I am testing the hypothesis that signaling through CRHR1 plays a dual role in the cochlea, guiding the development of proper innervation structure and protecting against noise-induced trauma.

Jin-Hwan Han, Immunology, Thereza Imanishi-Kari, Adviser
AID, Somatic Mutation and Class Switch Recombination During B Cell Development

I am studying somatic hypermutation (SHM) and class switch recombination (CSR), important processes that create high affinity antibodies during an immune response. For many years it was thought that SHM and CSR are restricted to immune responses involving mature B cells acting with the help of T cells. My work has shown that CSR and SHM also occur during B cell development in a T cell-independent manner.  I hypothesize that self-reactive B cell receptors may be altered by SHM to prevent the development of autoimmunity. My immediate goal is to understand how an enzyme necessary for SHM and CSR, activation-induced cytidine deaminase (AID), is expressed and regulated during B cell development in normal and in autoimmune mice.

Joshua Russo, Cell, Molecular & Developmental Biology, John Castellot, Adviser
CCN5 and Control of Uterine Fibroids

I am investigating the possibility that secreted matricellular protein CCN5 may impact uterine fibroids or leiomyomas, non-malignant tumors of smooth muscle cells.  Leiomyoma is the most common tumor in women, affecting 20-25% of women of reproductive age and as many as 60% of women of African descent.  Over-expression of CCN5 can inhibit the motility and proliferation of smooth muscle cells and I am particularly interested in testing the hypothesis that CCN5 expression might ameliorate the condition.   I am working to develop an animal model of uterine leiomyoma to address the effects of CCN5 over-expression in vivo and also trying to determine the molecular pathway by which CCN5 exerts its affects.