Associate Professor Rennolds Ostrom of UTHSC Receives $165,000 Grant for Cell Function Research

A $165,000 grant from the American Heart Association will allow Dr. Rennolds Ostrom and his research team to understand basic biochemical and cell biological processes that govern how cells respond to hormones in the blood and signals from the brain.

A $165,000 grant from the American Heart Association will allow Dr. Rennolds Ostrom and his research team to understand basic biochemical and cell biological processes that govern how cells respond to hormones in the blood and signals from the brain.

Rennolds Ostrom, PhD, associate professor in the Department of Pharmacology at the University of Tennessee Health Science Center (UTHSC), has received a grant totaling $165,000 from the American Heart Association for research focused on understanding basic biochemical and cell biological processes that govern how cells respond to hormones in the blood and signals from the brain. [Read more...]

Dr. Alessandro Iannaccone Invited to Write Editorial in Lancet to Comment on Phase 1B Trial of Hereditary Retinal Degeneration

Iannaccone_labcoat_library_2012_resized cropped

Dr. Alessandro Iannaccone

Despite a tremendous increase in the research efforts and progress to find treatments and cures for hereditary retinal degenerations, therapeutic options able to restore significantly vision remain to date limited. But the scenario is changing.

Alessandro Iannaccone, MD, MS, Director of the Retinal Degenerations and Ophthalmic Genetics Service and Associate Professor of Ophthalmology at the Hamilton Eye Institute of the University of Tennessee Health Science Center (UTHSC), was invited by Lancet to comment, alongside with Dr. Marco Zarbin, MD, PhD, FARVO, Professor and Chair of the Department of Ophthalmology at the Rutgers-New Jersey Medical School, on a recent Phase 1B clinical trial of a special form of retinal degeneration due to a specific enzymatic defect in the retina that reflects thing changing scenario.

Dr. Iannaccone, who also serves on the Scientific Advisory Board of Foundation fighting Blindness (FFB) and is the President of the FFB Mid-South chapter of Memphis, was asked to comment on a new approach to treating Leber congenital amaurosis (LCA) with mutations in either the RPE65 or the LRAT genes. LCA is a very early onset form of a condition known better as retinitis pigmentosa (RP). These forms of LCA are characterized by enzymatic defects that cause early-onset severe visual loss and nystagmus due to a deficiency of the vitamin A metabolite, 11-cis-retinal, in photoreceptors. The 11-cis-retinal molecule is the so-called “chromophore” of the rod visual pigment, rhodopsin. “When the retina does not receive enough 11-cis-retinal or cannot recycle effectively the one it has, our night vision is greatly incapacitated”, commented Iannaccone. “In the case of these forms of LCA, the protein portion of the visual pigment, called opsin, can reach normally the outer segment of the photoreceptor, but the cells cannot use it because it is not complexed with enough 11-cis-retinal to form the actual visual pigment, rhodopsin, and night vision is very poor despite only limited degeneration of the photoreceptors themselves. The at least partial structural integrity of photoreceptors in these forms of LCA is behind the success that gene therapy has also had in the RPE65-linked form of LCA”. Patients from the UTHSC Retinal Degenerations and Ophthalmic Genetics Service at the Hamilton Eye Institute have been successful participants in such trial.

Now a pharmacological approach to bypassing the enzymatic defects in these forms of LCA has been devised and tested in a human Phase 1B trial. An orally administered synthetic retinoid, 9-cis-retinyl acetate, was used to provide an alternate form of the chromophore to photoreceptors and tested to assess its safety and its preliminary efficacy. The results have been very encouraging. “This trial is extremely encouraging and points to a rapidly changing scenario in the development of therapeutic approaches for RP, LCA and related diseases.”

But some notes of caution are warranted. “Interpreting Phase 1B clinical trials that are not designed to assess efficacy can prove tricky, so we need to be careful not to overstate the results of this otherwise very promising study,” remarked Iannaccone. “This is especially important when a largely pediatric population is treated, and visual function testing is performed on children. Some of the tests of visual function one needs to use to assess efficacy can be particularly variable, especially in children, whose attention span and comprehension of the test can be limited and can increase significantly during the trial. In these specific forms of LCA in which there is an enzymatic deficiency in the retina precluding proper provision of 11-cis-retinal to photoreceptors, there is also a very delayed ability to adapt to changes in lighting conditions. This too can impact greatly our ability to measure correctly changes in visual function in these patients, and potentially confound the outcome of such trials. Emphasis is usually placed on letting patients adjust to darkness for long enough, but not as much emphasis is placed on letting them adjust long enough to light.”

Dr. Iannaccone highlighted this important issue in the Lancet editorial, showing how increasing durations of light adaptation before running a visual field test can impact dramatically the size of a patient’s visual field and the quality of the vision measured within it. “We have to be extremely careful at controlling as precisely as possible these variables. The last thing anyone wants to do is to claim huge therapeutic successes when, in fact, the perceived benefits may have been due, at least in part, to a poorly controlled confounding variable as essential as the time spent adjusting to the light of the testing instrument before running the test. This is not as critical in normal subjects, but in patients with retinal degenerations, and especially in these specific LCA patients, it is essential.” Dr. Iannaccone noted how, in his experience, this issue is often seen in RP patients in his clinic, and especially in patients with another unique related disorder, known as choroideremia. “Since 9-cis-retinyl acetate carries also a potential risk for a neuro-ophthalmological complication known as pseudotumor cerebri, it is especially important that claims of efficacy for this treatment be made with a great deal of caution.”

There is still much appeal for treatments that can provide across-the-board help for these patients. Although hereditary retinal degenerations as a whole are estimated to affect only one in 3,500 to 4,000 people and fall in the category of the orphan diseases, there are over 200 genes that can cause these conditions. This is a huge genetic heterogeneity for such rare diseases. Thus, broad-spectrum, non-specific treatments that can favorably impact these conditions remain essential to treat these diseases. But to cure them,” remarked Iannaccone, “we now understand that a molecularly driven and genetically specific approach may be indispensable, and this Phase 1B trial with 9-cis-retinyl acetate is an excellent example of that. This is the fruit of bed-to-bench-to-bed translational research at its best, and represents the future of retinal degenerations therapeutics.” Trials and studies that Dr. Iannaccone is presently involved with at the Hamilton Eye Institute fall in the same conceptual framework. “I am very excited about the latest developments in this field. The first gene for RP was cloned just in 1990, and we have come a very long way in a short time. I have been working in this field for nearly 25 years, and the fruit of hard, at times unrewarding, work are truly coming to fruition now. It comes as no surprise to me that the National Eye Institute has also identified finding treatments and cures for retinal degenerations as one of its top programmatic priorities, and it is great to be at the forefront of this field.”

 

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The link to the Lancet editorial in question can be found at:

 

http://www.ncbi.nlm.nih.gov/pubmed/25030841

 

Assistant Professor Dong Wang of UTHSC Receives $308,000 Grant for Heart Attack Research

With the help of a $308,000 grant from the American Heart Association, Dr. Dong Wang and his research team will be able to further explore ways to improve the treatment of patients with heart attack and ischemic heart disease.

With the help of a $308,000 grant from the American Heart Association, Dr. Dong Wang and his research team will be able to further explore ways to improve the treatment of patients with heart attack and ischemic heart disease.

Dong Wang, PhD, MD, assistant professor in the Department of Medicine at the University of Tennessee Health Science Center (UTHSC), has received a grant totaling $308,000 from the American Heart Association. [Read more...]

Associate Professor Ae-Kyung Yi of UTHSC Receives $1.6 Million Grant for Arthritis Research

Ae-Kyung Yi PhD

With a newly funded grant from the NIH, Dr. Yi and her research team will be able to develop novel and specific therapeutic approaches to rheumatoid arthritis and other complex autoimmune diseases.

Ae-Kyung Yi, PhD, associate professor in the Departments of Pediatrics, and Microbiology, Immunology and Biochemistry at the University of Tennessee Health Science Center (UTHSC), has received a grant totaling $1.6 million from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, a subsidiary of the National Institutes of Health. [Read more...]

Assistant Professor Kristen O’Connell of UTHSC Receives $1.6 Million Grant for Obesity Research

A $1.6 million grant from the NIH will enable Dr. Kristen O’Connell and her research team to identify the changes that high-calorie diets have on the neural circuits that control appetite and food intake.

A $1.6 million grant from the NIH will enable Dr. Kristen O’Connell and her research team to identify the changes that high-calorie diets have on the neural circuits that control appetite and food intake.

Kristen O’Connell, PhD, assistant professor in the Department of Physiology at the University of Tennessee Health Science Center (UTHSC), has received a grant totaling $1,607,325 from the National Institute of Diabetes and Digestive and Kidney Diseases, a subsidiary of the National Institutes of Health. [Read more...]

UTHSC Medical Student and Department of Surgery Residents Win Majority of Awards at Tennessee Chapter of the American College of Surgeons Meeting

The Annual Meeting of the Tennessee Chapter of the American College of Surgeons was recently held August 8 – 10, 2014 at Paris Landing State Park in Buchanan, TN. Participants from East Tennessee State University, Vanderbilt University, UT Chattanooga, UT Knoxville, and UTHSC took part in the Resident Paper Competition in the four categories of Cancer, Trauma, Basic Science, and Clinical Science. Of the eight awards, UTHSC won five of them.

Oncology Category:
1st Place:         Elena Paulus, M.D., Surgery Resident “Understanding Disparities in Breast Cancer Care in Memphis, TN”|
2nd Place:        Rodrigo Interiano, M.D., Surgery Resident “Safety and Diagnostic Accuracy of Tissue Biopsies in Children with Cancer”

Trauma Category:
1st Place:         Leah Hendrick, 4th Year Medical Student “Early Femur Fixation Benefits Both High and Low Risk Patients”
2nd Place:        Rodrigo Interiano, M.D. “Utility of MRI of Abdomen in Evaluation of Pediatric Pancreatic Injuries”

Basic Science Category:
1st Place:         Nathan Hinkle, M.D., Surgery Resident “P13K the Right Target: Effects of Chemotherapy and Targeted P13K Inhibition on Neuroblastoma Angiogenesis

We are extremely proud of these individuals and are grateful to our faculty for the guidance they provided on these excellent research papers.

 

Five UT Researchers Among Thomson Reuters’ “World’s Most Influential Scientific Minds”

UTHSC's Dr. Karen C. Johnson

Karen C. Johnson, MD, MPH

UTHSC's Dr. David Nelson 2

David Nelson, PhD

Five University of Tennessee researchers, including two from the University of Tennessee Health Science Center (UTHSC), have made the list of the “world’s most influential scientific minds” of the last decade as determined by the most frequently cited articles.

[Read more...]

Professor Teresa Waters, PhD, Named Chair for Department of Preventive Medicine in UTHSC College of Medicine

Dr. Teresa Waters

Dr. Teresa Waters

David M. Stern, MD, executive dean of the University of Tennessee Health Science Center (UTHSC) College of Medicine, has announced the appointment of Teresa Waters, PhD, as the new chair for the Department of Preventive Medicine in the UTHSC College of Medicine. [Read more...]