NIH awards $6M to identify scleroderma genes

Within five years, Medical School researchers expect to have identified the genetic clues to scleroderma, a chronic, often progressive, autoimmune disease.

The National Institutes of Health awarded Dr. Maureen Mayes a $6 million, five-year grant to conduct a genome-wide association study. The study’s goal is to identify gene regions that influence a patient’s susceptibility to a serious form of scleroderma known as systemic sclerosis.

Scleroderma, a condition that causes the immune system to attack its own body, affects an estimated 300,000 patients nationwide, mostly women ages 25-55. The disease can result in thickening and tightening of the skin and, in systemic cases, causes serious damage to internal organs, oftentimes targeting the lungs.

“I’ve been studying scleroderma for 20 years, and to see the research field mature to the point where we can do this genotyping, and at the end of five years have an answer is very exciting,” said Mayes, principal investigator and professor of internal medicine in the Division of Rheumatology and Clinical Immunogenetics. “Right now we don’t know what causes scleroderma, and there is no cure. With this genetic information, we can change that. We can develop better treatments and improve or eliminate symptoms.”

For the first phase of the research, which is supported in part by the UT Center for Clinical and Translational Sciences, Mayes and collaborators will study the genes of 1,500 patients with scleroderma, plus 3,000 in a control group. Most patients from scleroderma centers at the Medical School, Johns Hopkins School of Medicine, and Fred Hutchinson Cancer Research Center have already been identified, and Mayes estimates that the genotyping can be completed as soon as the end of this year. Dr. Olga Gorlova, a co-investigator at The University of Texas M. D. Anderson Cancer Center, will then conduct an in-depth statistical analysis of the genome-wide association scan.

During the second phase of the study, to validate the results from the first patient group, Mayes will lead efforts to collect and analyze another 1,500 genetic samples from patients at 10 scleroderma centers in the United States and Canada. Genetic data from a control group of 3,000 healthy individuals will be used for comparison.

“This is the tip of the iceberg. With this study, we’ll be able to identify gene regions, and from those regions, we will be able to identify specific genes,” Mayes said. “This provides us a map to the pathways that cause scleroderma, and if we know the pathways, we could interrupt them and prevent disease.”

In addition, the study could help investigators identify genes that are markers of severe disease, as well as genes that are indicators of mild disease that is not likely to progress. This, Mayes said, would help physicians determine the best course of treatment. For those with genes that indicate mild disease, rheumatologists could treat their symptoms, which often include joint pain and heartburn. Physicians could pursue a more aggressive approach to treatment, including chemotherapy, for patients with genes that are identified to increase likelihood of severe disease.

“The goal is to improve their quality of life, and one of the most important ways we can do that is to first identify and learn more about the genes that influence scleroderma,” Mayes said.

Patients who would like to participate in the study may register by calling 1.800.736.6864. Local participants who qualify will have their blood drawn once at the Clinical Research Unit at Memorial Hermann – Texas Medical Center.

-M. Raine

Walters named Kroc Fellow

Dr. Edgar (Terry) Walters, professor of integrative biology and pharmacology, has been named the first holder of the Ray A. and Robert L. Kroc Faculty Fellowship.

Holders of the three-year fellowship must achieve excellence in research and graduate education in the areas of neuroscience and/or endocrinology and be a faculty member of any of the UT Health Science Center schools with an appointment as a regular faculty member of the Graduate School of Biomedical Sciences.

Walters, who has been on faculty at the Medical School since 1982, is past director and current co-director of the Graduate School’s Program in Cell and Regulatory Biology, and just finished serving as president of the Graduate School faculty. Some of his research in neuronal injury, pain, and memory involves the marine snail Aplysia, whose large and accessible neurons enable single-cell experimental manipulations.

Walters was nominated by Dr. George Stancel, dean of the GSBS, and a committee who evaluated all of the nominees. He said that his first reaction to finding out he was the recipient of the fellowship was surprise.

“I had never heard of the Kroc fellowship (since it was new), I did not know that the GSBS had fellowships for faculty members, and, although my research has been continuously funded for nearly 25 years, I don’t have the kind of huge laboratory or extremely prolific publication record that typically attracts unsolicited awards,” he said. “I like to think that my research is notable more for the novelty and significance of our hypotheses about relationships between injury and memory than for the quantity of our papers.”

The endowment was originally set up as the Ray A. and Robert L. Kroc Lectureship in 1985 by the Kroc Foundation, which was established in 1969 with the purpose of awarding gifts to institutions to support research in the areas of diabetes, multiple sclerosis, and other endocrine or neurological diseases. The gift, which established the endowment, was the foundation’s last gift -- the foundation was then dissolved.

In 2007, Dean Stancel determined that the lectureship was not useful to the GSBS and the endowment was changed to the Ray A. and Robert L. Kroc Faculty Fellowship. The purpose of the fellowship is the same as for the lectureship—to further research in diabetes and other endocrine diseases as well as research in multiple sclerosis and other neurological diseases.

“My second response, of course, was gratitude to the Kroc Foundation and to the Graduate School – gratitude for the honor and gratitude for the funding that comes with the fellowship. Those of us who have spent considerable time working with GSBS students and faculty do it because we love education and because we value the accomplishments and efforts of the Graduate School. None of us receive any salary from the Graduate School, and none of us expect any rewards other than the satisfaction that comes from mentoring and teaching enthusiastic students as they begin their scientific careers. I think it would be great if this award, and perhaps others like it, could help to encourage scientifically active faculty to devote a little more time to the equally important mission of graduate education,” he said.

Walters received his Ph.D. in physiology from Columbia University and completed postdoctorate training in neurophysiology at Columbia and the University of Pittsburgh.

He said the award could not have come at a better time.

“At the same time that my Medical School department, Integrative Biology and Pharmacology, is entering an exciting growth phase under the dynamic leadership of our new chair, Dr. John Hancock, my research is expanding from studies of injury- and memory-related plasticity in very simple nervous systems to investigate related phenomena associated with spinal cord injury in mammals,” he said. “I am immediately putting these funds to use in helping to recruit an outstanding trainee to my laboratory. Knowing that I had just received the Kroc Faculty Fellowship made the difference in my decision a couple of weeks ago to offer a postdoctoral position to a terrific young scientist who will extend investigations begun by a Ph.D. student in my lab who just successfully defended his dissertation.

“A potential third use of the Kroc Faculty Fellowship is to support scholarly efforts. Because of recent funding cutbacks at the NIH and the consequent pressure to spend more time collecting and publishing primary data (not to mention writing grant proposals), less and less time is available for thinking about the broader context of our research, for systematically developing and generating hypotheses, and for exploring and communicating the intellectual background and ramifications of our scientific ideas. The Kroc Faculty Fellowship can help to support stimulating scholarly activities, for example by permitting the fellow to attend meetings with scientists in potentially overlapping fields,” he said.

- D. Brown

Study: Need to lower high blood pressure after stroke should not rule out clot-busting drug

Patients who require aggressive therapy to lower their blood pressure following a stroke do not appear to be at a higher risk for bleeding or other adverse outcomes after receiving anti-clotting therapy, according to a study done by researchers at the Medical School.

The research findings, which are published in the September issue of Archives of Neurology, could translate to a treatment option for as many as 10 percent of patients with acute ischemic stroke who previously would have been ineligible to receive tissue plasminogen activator (tPA) because of high blood pressure.

Dr. Sean Savitz, co-director of the Stroke Program and an attending neurologist at Memorial Hermann - Texas Medical Center, said high blood pressure can increase the risk of bleeding if tPA—the only proven therapy for acute ischemic stroke—is used to dissolve the stroke-causing clot in the brain. Because of that risk, patients with high blood pressure who otherwise would have qualified to receive tPA were left with no stroke treatment options, said Savitz, one of the study’s authors.

The researchers set out to answer whether aggressively lowering the patient’s blood pressure and then administering tPA could be done without increasing the risk of bleeding or causing other adverse events.

Dr. Sheryl Martin-Schild, then of the Medical School and now of Tulane University Health Sciences Center, New Orleans, and colleagues reviewed the medical records of 178 patients with acute ischemic stroke who received intravenous tPA within three hours at Memorial Hermann - TMC. Of these, 50 required treatment for lowering blood pressure before beginning tPA therapy. This included 24 (48 percent) who received the medication nicardipine, either alone or in combination with the drug labetalol.

“We observed several important differences between patients who required blood pressure–lowering treatment and those who did not,” the authors wrote. “They had more severe strokes and their blood glucose concentration was higher, predicting they would have a worse outcome if all other factors were equal. As expected, they more frequently had a history of hypertension.”

After controlling for these factors—including age, baseline stroke severity and blood glucose levels—there were no differences between patients who received antihypertensive treatments and those who didn’t in adverse events, poor outcomes, or stroke severity scores at discharge.

“Overall, the results of the present study provide the first experimental support for the revised American Heart Association guidelines allowing tPA therapy in patients requiring aggressive blood pressure management and also provides support for the use of nicardipine in patients with acute ischemic stroke who are eligible for thrombolytic therapy,” the authors concluded. “Aggressive control of severely elevated blood pressure is feasible and should not automatically exclude otherwise eligible patients with acute ischemic stroke from receiving thrombolytic therapy.”

This study was supported by a training grant from the National Institutes of Health to the Medical School’s Stroke Program.

-M. Raine

Medical School research retreat postponed

The Medical School’s ninth annual Research Retreat, which was set for Sept. 25, has been postponed due to Hurricane Ike.

The Office of Research Affairs will keep the Medical School community apprised of the new day and time, which is dependent upon the keynote speaker’s availability.

 

CCTS announces third round of career development award winners

Four assistant professors at the Medical School have been awarded Career Development Awards in the third round of K12 awards provided by the Center for Clinical and Translational Sciences. Two are supported by K12 funds, and two by the Dean’s office. These four awardees join seven prior awardees at UT Houston since the first K12 awards were funded in February of 2007.

The award provides 50-75 percent salary support for up to three years and $10,000-$15,000 in research funds per year for junior investigators to conduct clinical or translational research studies under the mentorship of senior faculty mentors.

The recipients are:

Dr. Jerrie Refuerzo, assistant professor of obstetrics, gynecology, and reproductive sciences, received funding for her proposal, “Developing, Evaluating and Applying Nanotherapeutics to Improve the Treatment of Outcome of High-risk Pregnancies.” Refuerzo will work with mentor Dr. Mauro Ferrari, professor and director for the Center for NanoMedicine.

Dr. Nitin Tandon, assistant professor of neurosurgery, will study “A Cross-modal Synthetic Approach to Eloquent Cortical Regions” under the mentorship of Dr. Ponnada Narayana, professor of diagnostic and interventional imaging.

Dr. KuoJen Tsao, assistant professor of pediatric surgery, will study “The Role of Anti-reflux Surgery for Gastroesophageal Reflux Disease in Premature Infants with Bronchopulmonary Dysplasia.” Tsao will work with his mentors Dr. Kevin Lally, professor and chair of the Department of Pediatric Surgery, and Dr. Kathleen Kennedy, professor of pediatrics.

Dr. Susan Wootton, assistant professor of pediatrics - infectious diseases, will study “GI Shedding of Human Influenza Virus in Hospitalized Children.” Wootton will work with her mentors Dr. James Murphy, adjunct professor of pediatrics, and Dr. Pedro Piedra, professor of pediatrics at Baylor College of Medicine.

Dr. Erik Sulman, assistant professor at M. D. Anderson Cancer Center, also is a recipient of this award. A member of the Radiation Oncology Department, he will study “Functional Analysis of Podoplanin in the Treatment Resistance of Glioma Stem Cells.” Sulman will work with his mentor, Dr. Kenneth Aldape, professor of pathology at M. D. Anderson Cancer Center. He joins five prior awardees at M. D. Anderson since February 2007.

Blood drive a success

Twenty-five donors gave blood at the Medical School’s annual Sept. 11 blood drive in the Leather Lounge. The Gulf Coast Regional Blood Center blood drive was cut short due to the evacuation of many in anticipation of Hurricane Ike, but the donations were provided just ahead of the storm when they were needed most.

An upcoming blood drive will be set for Oct 8 at the UT Professional Building. More details to come.

 

AMA/TMA chapter hosting voter registration drive

The Medical School’s American Medical Association/Texas Medical Association chapter is hosting a voter registration drive at noon through Oct. 6 in the Leather Lounge. A driver’s license or the last four digits of your Social Security number are needed to register. Cookies, voter guides, early voting dates, healthcare plan recommendations, and a polling booth simulation will be available.

For those who want to vote here but are not registered to vote in the surrounding area, they must apply for an absentee ballot where they are registered or register in the county where they would like to vote.