My research focuses on three main topics:
At the Microscopy and Microanalysis meeting in Albuquerque, NM. From L-R: Pops, Jon Blaize, Laura L’Amoreaux (not a graduate student), John Misigah, Janto Tachjadi, and Kristin Kane (doctoral student of Dr. Greg Cheplick).
1. The retinal pigment epithelium
The retinal pigment epithelium (RPE) sits along the posterior neural retinal, between the photoreceptors and the choriocapillaris. The RPE are in intimate contact with the photoreceptors, but no junctional complexes are present between the two cell types. Tight junctions do occur between adjacent RPE cells, thereby creating the blood-retinal barrier. The RPE themselves have long apical microvilli, which surround the outer segments of the photoreceptors. In addition to serving as the blood-retinal barrier, the RPE serve other functions as well. My laboratory is most interested in the RPE role in phagocytosis of outer segments. Doctoral student Jonathan Blaize is working on this project to determine the role(s) that hepatocyte growth factor (HGF) and its cognate receptor cMet have in preparing the RPE for phagocytosis.
2. Choroidal and retinal neovascularization
While the RPE are important in the regulation of the homeostasis of the neural retina, they also produce and respond to a plethora of growth factors. These include vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1). The homeostasis of the retina includes regulation of the choriocapillaris, the capillary-rich area of the sclera near the RPE. Lack of homeostasis of the blood vessels leads to neovascularization, as is seen in proliferative diabetic retinopathy (PDR) and retinopathy of prematurity (ROP). Doctoral student Janto Tachjadi has proposed to test the hypothesis that IGF1 modifies VEGF's effect of angiogenesis by regulating VEGF pathway.
3. Neuroendocrine regulation of insulin/glucagon homeostasis
In a collaboration with Dr. Abdeslem El Idrissi, we are investigating the GABAergic and somatostatinergic pathways related to insulin and glucagon homeostasis. In the endocrine pancreas, a rise in plasma glucose initiates an electrogenic release of insulin and GABA from pancreatic beta cells. The insulin moves to the plasma where it works on distant targets. The GABA binds to GABAA receptors on the alpha cells, hyperpolarizing the alpha cell and preventing glucagon release. The GABA also influences the release of glutamate, which diffuses to delta cells and stimulates the release of somatostatin. Somatostatin then targets both alpha and beta cells to restore the electrogenic potential and resets the beta cell for the next rise in glucose concentration.
4. Development of an imaging/probing technique for neurons using atomic force microscopy
The idea is relatively simple: functionalize an AFM tip with an neurotransmitter, then probe the surface of neurons (or other neuroendocrine cells) loaded with calcium flux indicators. Using the Asylum Research AFM, we can image the calcium flux while obtaining surface detail of the cells.