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Grant program rewards novel research ideas

BY: DOUG CAMPBELL

1/29/1999 - Seven Vanderbilt University Medical Center investigators have been awarded funds through an innovative new program to provide seed money to support novel avenues of research.

The investigators are studying topics ranging from how protein interacts with muscle chloride channels to new ways to prevent youth violence, and they are the first group to be awarded funding through the VUMC Intramural Discovery Grants Program.

This initiative, announced last year, consists of three different types of funding mechanisms intended to stimulate the development of new ideas. What makes the new program remarkable is the source of the funds ‹ Vanderbilt itself.

According to Lee E. Limbird, Ph.D., associate vice chancellor for Research, experience with endeavors such as the Diabetes Center and the Cancer Center has shown that wise investment in intramural funding results in pilot data being secured that leads to substantial grant awards from the National Institutes of Health or various disease-focused foundations.

The goals of the program are twofold ‹ to increase VUMC's success in acquiring grants, and to foster risk-taking and the embrace of entirely new ideas and novel approaches to scientific discovery.

"We received 59 applications, and awarded as many grants as we could possibly fund," said Jan Lotterer, director of the program."

A total of $225,000 was awarded. Two interdisciplinary grants, three pilot and feasibility studies, and two bridges to independence were awarded.

The seven investigators, and their areas of research, chosen as the first awardees of the VUMC Intramural Grants Program are:

o Melanie Lutenbacher, Ph.D., assistant professor of Nursing ‹ "Application of two Measures of Effectiveness to Program Planning for Youth Violence Prevention." The overall purpose of this project is to promote community collaboration in the area of program planning for youth violence prevention by providing community leaders with scientific and applied measures of program effectiveness.

o Dr. Elizabeth Yang, assistant professor of Pediatric Hematology-Oncology ‹ "The Role of the Cell Death Gene BAD in Keratinocyte Differentiation and Apoptosis." Apoptosis, or programmed cell death, is essential to normal development and homeostasis. BAD is a potent pro-apoptotic molecule which heterodimerizes with BCL2 and BCL-xL and counters their anti-apoptotic function. This project seeks to precisely define the expression pattern of BAD in differentiating and apoptotic keratinocytes and to determine the causal relationship between BAD expression and differentiation using epidermal tissue and keratinocyte cultures.

o Patricia Hebert, Ph.D., associate professor of Preventive Medicine ‹ "Interindividual Variability in Estrogen Metabolism in Postmenopausal Women." This project will describe and examine the environmental and genetic factors which influence the concentration of estradiol in the serom of post-menopausal women who are receiving estrogent replacement therapy.

o Carol L. Beck, Ph.D., research fellow in Medical Nephrology ‹ "Protein Interactions with Muscle Chloride Channels." In previous work, mutations in the gene encoding the skeletal muscle chloride channel (CIC-1) have been determined to be the molecular defect in hereditary myotonia found in fainting goats. Many of these mutations occur in proline rich regions of the molecule, suggesting that disruption of protein-protein interactions may occur. Knowledge gained from this project is expected to contribute to the understanding of myotonia congenita, muscle excitation and the role of protein-protein interactions in modulating muscle function. These findings may have future relevance to other inherited conditions of skeletal muscle, especially diseases associated with abnormal cytoskeletal proteins.

o Amit S. Kalgutkar, Ph.D., research associate in Biochemistry ‹ "Structural Analogs of APHS." Recently, the first account of selective covalent modification of COX-2 by a novel inactivator, APHS, was reported. This proposal presents strategies in the design of non-acetylating analogs of APHS as selective COX-2 inhibitors, which use this novel binding site. These compounds may be devoid of potential side effects associated with selective COX-2 covalent modifiers.

o Steven K. Hanks, Ph.D., associate professor of Cell Biology ‹ "Pathogenesis of Familial Juvenile Nephronophthisis." The long-term objective of this project is to understand the nature of the cellular defects underlying the pathogenesis of familial juvenile nephronophthisis (NPH), a common genetic cause of kidney failure in children. Although clinical and histological observations indicate NPH results from a loss of normal excretory tubule function, the pathogenesis of the disease remains poorly understood.

o Eric Delpire, Ph.D., assistant professor of Anesthesiology ‹ "Characterization of Na-K-2CL Cotransport Knock-out Mouse." Analysis of the Na-K-2CL cotransporter expression in the developing and adult central nervous system has permitted the flourishing of new ideas and new concepts are waiting to be thoroughly tested. The purpose of this project is to characterize a phenotype of mice associated with deletion of the gene and to study intracellular cl-regulation in control, heterozygote and homozygote neurons. This addresses the role of this cotransporter in promoting the biological responses to the neurotransmitter GABA.

The second round of competition for the VUMC Intramural Program Grants will have a deadline of April 9 and a start date of July 1.

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