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UGA pharmacy researchers receive, continue NIH grants totaling more than $4.9 million

June 6, 2012

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Athens, Ga. - This spring, the National Institutes of Health awarded four faculty in the University of Georgia College of Pharmacy new and continued grant funding in excess of $4.9 million for up to five years.

UGA's Azza El-Remessy was awarded a new grant to study molecular mechanisms of diabetic retinopathy. Pharmacy faculty able to continue receiving NIH support as transfer grants were Lakshman Segar, researching vascular phenotypic regulation by growth factors, insulin and glucose; Dexi Liu, looking at image-guided hydrodynamic gene delivery; and Han-Rong Weng, studying glial-cytokine-neuronal interactions in neuropathic pain.

El-Remessy, an associate professor of clinical and administrative pharmacy and head of the college's clinical and experimental therapeutics program in Augusta, received $315,000 for the first year of funding on a five-year research project grant, or R01, from NIH to study molecular mechanisms of diabetic retinopathy. The grant's overall total is just over $1.57 million.

Diabetic retinopathy, or DR, is the leading cause of blindness in working-age adults in the U.S. Characterized by neurodegeneration, glial reactivity, inflammation and acellular capillary formation, it can eventually lead to retinal neovascularization and blindness.

"Given the limited and invasive treatments available only for advanced stages of DR, there is a great need to identify novel molecular targets for earlier therapeutic intervention," El-Remessy said. "Our long-term goal is to identify such targets for DR by probing the relationships between glial inflammation and vascular injury."

Segar, an associate professor of clinical and administrative pharmacy, will receive $946,682 with a possible additional $167,000 in funding over the next three years to study the role of platelet-derived growth factors, insulin and glucose transporters on the phenotypic characteristics of vascular smooth muscle cells. The R01 grant from the NIH/National Heart, Lung and Blood Institute received initial funding two years ago when Segar was a faculty member at Pennsylvania State University College of Medicine. He joined the UGA pharmacy faculty last year.

"The overall goal of this project is to gain new understanding into the mechanisms of coronary artery disease," Segar said. "The specific objective is to investigate how platelet-derived growth factor regulates glucose transport and insulin receptor signaling to influence phenotypic changes in vascular smooth muscle cells. The development of vascular complications in nondiabetic and diabetic patients correlates closely with increased VSMC glucose metabolism and dysregulated insulin receptor signaling."

Liu, a professor and head of the department of pharmaceutical and biomedical sciences, is working on a research project that ultimately seeks the development of a safe and effective method for gene therapy.

Liu transferred two NIH grants from the University of Pittsburgh after he joined the UGA faculty in July 2011. The first grant, entitled "Image-guided Hydrodynamic Gene Delivery" is from the National Institute of Biomedical Image and Bioengineering and was awarded for the development of an image-guided, site-specific gene delivery system. Funding continued this spring for the grant's fifth year. The annual budget is $613,572.

The second grant, "Computer-Assisted Hydrodynamic Gene Delivery for Hemophilia Gene Therapy," is a R01 grant from the National Heart, Lung and Blood Institute for the demonstration of the safety and effectiveness of an image-guided, computer-controlled injection device for treatment of hemophilia, using dogs as an animal model. The grant is in its third year. The original award was for $840,284. An additional $387,878 was transferred for a multi-year total of $1,228,162.

"We developed the concept of hydrodynamic gene delivery some time ago and have been working on its clinic applications," Liu said. "Our goal is to combine the technology of image-guided catheter insertion with our recently developed computer-controlled injection system to achieve site-specific gene delivery for gene therapy. Current research focuses on optimization of various parameters for safe and effective gene transfer using pigs, dogs and baboons as animal models. We are at the last stage of testing before we move to the clinic."

Weng joined the College of Pharmacy faculty in 2011 as an assistant professor of pharmaceutical and biomedical sciences. Previously, he worked at the University of Texas M.D. Anderson Cancer Center where he had been principal investigator on a four-year R01 grant. The last two years of his $583,638 NIH study on glial-cytokine-neuronal interactions in neuropathic pain was transferred this spring.

How dysfunctional glial cells—which provide support and protection for neurons in the brain and in other parts of the nervous system—lead to abnormal pain signaling in the spinal dorsal horn in neuropathic pain remains a mystery, he said. Activation of glutamate receptors by glutamate is a key step for acute pain transmission and activation of signal transduction pathways leading to initiation and maintenance of pathological pain.

"We hypothesize that activation of glial cells induced by nerve injury results in dysfunction of glial glutamate transporters, which leads to abnormal activation of ionotropic glutamate receptors in the spinal dorsal horn and behavioral hypersensitivity," he said.