John P. McGovern Award – Eugene Toy, M.D.

Eugene Toy, M.D., clinical associate professor in the Department of Obstetrics, Gynecology and Reproductive Sciences, has been named the winner of the John P. McGovern Award as the outstanding clinical teacher – for the second time.

The John P. McGovern Award is given annually to the outstanding clinical faculty member as chosen by the senior class, and faculty may not be selected consecutively. The award is made possible by an endowment from the McGovern Foundation.

Toy, who has been on faculty at the Medical School since 1996, has been the clerkship director of the obstetrics/gynecology junior rotation at St. Joseph Medical Center since 1997 and assistant course director for the third-year obstetrics/gynecology clerkship since 2000. He also is the residency program director of the Methodist Hospital obstetrics/gynecology program.

He received the McGovern Award in 2002 and is the creator and lead author of 15 books for the Case Files series, in which he has partnered with Medical School faculty in both clinical and basic science disciplines.

Previous recipients include Octavio Pinell, M.D., 2006, 2004, 2001, 1999, 1997, 1995; Alberto Puig, M.D., Ph.D., 2007, 2005; Frank Arnett, M.D., 2003, 2000; Toy, 2002; Edward Yeomans, M.D., 1998; John F. Donnelly, M.D., 1996, 1993, 1990; James T. Willerson, M.D., 1994; John M. Passmore, M.D., 1992; Herbert L. DuPont, M.D., 1991.

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Blood-clotting protein modified for people with hard-to-treat Hemophilia

Medical School pathologists have developed a chemically modified protein that may help people with a hard-to-treat form of a genetic bleeding disorder known as Hemophilia A. The discovery and the results of pre-clinical tests appear in the May 2 issue of the Journal of Biological Chemistry.

With a shortage of the blood-clotting protein Factor VIII (FVIII), people with Hemophilia A typically receive injections of FVIII derived from plasma or produced synthetically to control potentially life-threatening episodes of bleeding. Unfortunately as many as one in three people with Hemophilia A produce inhibitor antibodies, which attack the externally-administered FVIII and negate its blood-clotting benefits.

To combat this problem, scientists in the laboratory of Dr. Sudhir Paul developed a chemically modified version of FVIII which during laboratory tests neutralized these inhibitor antibodies, thus paving the way for the correction of the blood-coagulating process. The modification is called electrophilic FVIII analog (E-FVIII).

“It’s a two-step process,’’ said Paul, the senior author. “The E-FVIII permanently inactivates the antibodies that inhibit blood clotting in 20 to 30 percent of patients receiving Factor VIII replacement therapy. Once the antibodies are cleared, additional FVIII can be injected.” The study involved blood donated by eight people with FVIII-resistant Hemophilia A.

Today, people with FVIII-resistant Hemophilia A have limited treatment options, said co-author Dr. Keri Smith, assistant professor of pathology and laboratory medicine. Those options include bypass therapy or multiple FVIII injections. Both are prohibitively expensive and often ineffective to meet emergency blood-clotting needs.

E-FVIII might provide a more economically feasible method of treating inhibitor antibodies, Smith said.

There is no cure for Hemophilia A, and it primarily affects males. About one of every 7,000 males born in the United States has this condition. A person with hemophilia bleeds longer than a person without hemophilia.

Stephanie Planque, who is lead author and is working toward her Ph.D. degree, helped conceive the chemical inactivation principle behind the study. The modified FVIII analog was produced by pathology faculty Dr. Hiroaki Taguchi and Dr. Yasuhiro Nishiyama, using newly developed synthesis methods. Dr. Miguel Escobar, of the department of pediatrics and internal medicine and the Gulf States Hemophilia and Thrombophilia Center, led the clinical aspects of the work, and Dr. Kathleen Pratt, at the Puget Sound Blood Center and Division of Hematology, University of Washington, Seattle, contributed a genetically-produced protein that helped the study reach its conclusions.

According to Paul, the next step involves clinical trials. “E-FVIII is a first generation reagent. Future genetic and chemical manipulations may help develop improved E-FVIII analogs,” Paul wrote in the paper.

Work was supported by the Hemophilia Associations of New York and Georgia and the National Institutes of Health. The study is titled “Covalent Inactivation of Factor VIII Antibodies from Hemophilia A Patients by an Electrophilic FVIII Analog.”

-R. Cahill

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Internal Medicine resident wins Young Investigator Award

Dr. Mihail Chelu, a resident enrolled in the Clinical Investigator Pathway of the Department of Internal Medicine, has received the International Young Investigator Award for basic research at the Heart Rhythm 2008 Conference.

The Young Investigators Awards are designed to recognize and encourage the work of young investigators and the institutions where they work and study.

His winning paper “CaMKII phosphorylation of defective ryanodine receptors predisposes to atrial fibrillation” was based upon research funded by the 2007-2008 Michael Bilitch Fellowship in Cardiac Pacing and Electrophysiology from the Heart Rhythm Society. Chelu was co-sponsored by Dr. Xander H.T. Wehrens, an assistant professor in the Department of Molecular Physiology and Biophysics at Baylor College of Medicine and Dr. David D. McPherson, professor and director of the Division of Cardiology.

After completing his internal medicine residency, Chelu will enter a cardiology fellowship in July 2009.

The Heart Rhythm Society is the international leader in science, education, and advocacy for cardiac arrhythmia professionals and patients, and is the primary information resource on heart rhythm disorders. Its mission is to improve the care of patients by promoting research, education, and optimal health care policies and standards.

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