Principal Investigator

Grant Title

Grant Sponsor

Amount
 

Mitchell, Chad

Fieldable In-vivo EPR Biodosimetry

DTRA

$267,419
 

Muldoon, Sheila

Genetic Testing for Malignant Hyperthermia

University of Pittsburgh MC

$10,691
 

Anders, Juanita

Optimization of Light Therapy Parameters for Translation to Treatment of Human Acute Spinal Cord Injury

Photothera

$25,000
 

Bowyer, Mark

Scientific Educational Validation Study of Rapid Fire/Sma  (CRADA)

Verefi Technologies, Inc.

$20,000
 

Liu, Alan

A Hybrid Simulator for Intracranial Hematoma Training

Verefi  Technologies, Inc.

$50,057
 

Namboodiri, Aryan

Acetate Supplementation as Therapeutic Approach to Canavan Disease

Jacob’s Cure

$25,000
 

Cantilena, Louis

Phase I Resource Center (PIRC)

NCCAM

$2,498,571
 

CDR Chad Mitchell, Ph.D., Assistant Professor in the Department of Radiology, received $267,419 from the Defense Threat Reduction Agency for a program entitled “Fieldable In-vivo EPR Biodosimetry”. Following a radiological or nuclear attack, military medical personnel will need to access the radiation dose received by casualties before they can be treated.At present, the most promising means for measuring such radiation doses after-the-fact involves the use of electron paramagnetic resonance (EPR) measurements in extracted teeth. While this method has been successfully demonstrated here at USUHS, the removal of teeth and subsequent chemical preparation introduce delays which would be unacceptable in the field.The purpose of this study is to modify existing technology which makes EPR measurements in the mouth of casualties believed to have received significant radiation doses. Experts at Dartmouth University lead the world in a wide range of EPR techniques including the measurement of radiation dose.While these in-vivo measurements require heavy equipment which can not be easily transported, it is believed that this equipment can be tailored to tooth enamel dosimetry and significantly reduced in size. This reduced system can then be optimized to fit the requirements of a fieldable system to provide forward deployed units with fast, accurate measurements of radiation dose. To ensure reliable results and the fieldability of the system, Drs. Romanyukha and Mitchell from USUHS will provide oversight including review of all scientific results, participation in design decisions, regulatory compliance, and financial management.

Dr. Aryan Namboodiri, Assistant Professor in the Department of Anatomy, Physiology and Genetics, received a grant for $25,000 from the Jacob’s Cure Foundation entitled “Acetate Supplementation as Therapeutic Approach to Canavan Disease”. Canavan disease (CD) is an autosomal-recessive neurodegenerative disorder caused by mutations in the gene coding for the enzyme aspartoacylase (ASPA). ASPA catalyzes deacetylation of N-acetylaspartate (NAA), an abundant (~10 mM) and nervous system-specific amino acid derivative. CD is characterized by spongiform degeneration of the brain resulting in severe psychomotor retardation, with most affected children dying before the age of 10. The precise pathogenesis of CD is currently unclear, but Dr. Namboodiri’s group has proposed that it results from a lack of NAA-derived acetate, which is required for myelin lipid synthesis. Their central hypothesis is that infants born with CD are normal at birth because ASPA activity is not essential until myelin synthesis is dramatically accelerated shortly after birth. Once myelination accelerates after birth, ASPA is required to liberate the acetate from NAA for the synthesis of acetyl CoA, which is used in the synthesis of the lipid portion of myelin. In this hypothesis, CD is thought to result from defective myelin synthesis caused by a deficiency in the supply of the NAA-derived acetate. A number of studies, including Dr. Namboodiri’s lab recent demonstration of the selective localization of ASPA inoligodendrocytes in the CNS, are consistent with the acetate deficiency hypothesis of CD. Furthermore, they have recently tested the acetate deficiency hypothesis in the murine model of CD (ASPA -/-) directly by 1) determining acetate levels in the brain and 2) studying the myelin-associated lipid synthesis. The results showed that acetate levels in the brains of CD mice were decreased by almost 80%, and that the synthesis of a number of myelin related lipids also decreased significantly. These results provided the first direct evidence in support of this hypothesis. A major implication of these findings is that acetate supplementation is likely to provide a simple and inexpensive therapeutic approach for CD. Toward this goal, they have made progress by showing that oral administration of glyceryl triacetate (GTA, Triacetin), an acetate precursor, and resulted in10-20 fold increases in acetate levels in the brains of mice in 1-2 hours. They propose to test whether or not acetate supplementation using GTA is effective as a treatment of CD using the Tremor Rat as a model system. The immediate goals of the new grant are to: 1) determine whether acetate supplementation in Tremor Rats prevents development of CD pathologies, or significantly improves motor function and 2) determine optimal conditions (dose, time course, and tolerability) for oral supplementation of acetate using GTA. Success in these endeavors could lead to a simple, noninvasive, and inexpensive method for the treatment of CD that can be administered by parents at home.

Dr. Juanita Anders, Associate Professor in the Department of Anatomy, Physiology and Genetics received a $25,000 grant from Photothera, Inc. entitled “Optimization of Light Therapy Parameters for Translation to Treatment of Human Acute Spinal Cord Injury.”The research will establish a specific set of optimized parameters based on 810 nm wavelength of light that will translate to effective treatment of human acute spinal cord injury.Two specific models of spinal cord injury will be examined at the lower thoracic spinal cord level, one model is the dorsal hemi section model and the other is a contusion model using the NYU spinal cord contusion system.Twenty one days post injury the spinal cords will be examined for effectiveness of light therapy as measured by quantitative morphometrics assessing the number and length of regrowing axons.Anterograde and retrograde tracing techniques and immunolabelling will be used to identify and track the regenerating neurons.

Dr. Sheila Muldoon, Professor, Department of Anesthesiology, received a small subcontract from the University Pittsburgh entitled “Genetic Testing For Malignant Hyperthermia.”Dr. Muldoon will be providing testing services to the University Pittsburgh in regard to malignant hyperthermia (MH).MH is a pharmacogenetic disease of the skeletal muscle intercellular calcium concentrations which become abnormally high. This elevation of calcium can lead to life threatening situation when MH patients are exposed to volatile anesthetic.

COL Mark Bowyer, MC, USAF, Assistant Professor in the Department of Surgery and a member of the Simulation Center received a $20,000 CRADA from Verefi Technologies, Inc., entitled “Prospective Randomized Trial Comparing Two Virtual Reality Laparoscopic Simulators: MIST-VR and Rapid Fire Smart Tutor.”Skills for minimally invasive surgery are difficult to acquire and underdevelopment of these techniques can result in suboptimal patient outcomes.Computer based simulation training has been recently shown to be a feasible means to acquire these skills and have been proven superior to conventional training approaches.The first computer based virtual reality simulator to demonstrate these benefits, the Minimally Invasive Surgical Trainer – Virtual Reality (MIST-VR) is currently the best validated simulator for MIS skills.However, it is far from the ideal solution for VR simulator training.COL Bowyer’s work describes a prospective, randomized, trail to compare the MIST – VR with a new computer based VR trainer know as Rapid Fire/Smart Tutor (RFST) which utilizes a real-time adaptable training environment to account for inter-trainee variability to minimize user frustration and optimize learning.

Dr. Alan Liu, Assistant Professor in the Department of Surgery and a member of the Simulation Center, received a $50,057 CRADA from Verefi Technologies, Inc. entitled “A Hybrid Simulator for Intracranial Hematoma Training.” Intracranial pressure due to battlefield injuries is a growing problem for the military and if left untreated this is life threatening.Key to the solution of this problem is proper training of the medical healthcare professional in the field. Dr. Liu is developing a training device that will allow the medical professional to be trained in treatment of intracranial hematomas using a virtual computer environment.

Dr. Louis Cantilena, Professor in the Department of Medicine, received a $2,498,571 contract from the National Center for Complementary and Alternative Medicine for a Phase I Resource Center. The objective of this contract is to establish the infrastructure of a Phase I Resource Center and conduct early phase clinical trails of NCCAM-sponsored botanical dietary supplement materials.The trials that Dr. Cantilena will be conducting clinical pharmacokinetics data and assess the dose range and tolerability of NCCAM selected dietary supplements.Information generated will guide decisions about the conduct and design of larger Phase II clinical trials.

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