Cardiovascular Innovation Institute opens; Williams named as scientific director

Louisville's Cardiovascular Innovation Institute, or CII, formally opened its doors Jan. 13 and named internationally respected bioengineering researcher Stuart Williams, Ph.D., as the facility's new scientific director.

His appointment must be confirmed by the institute's board of directors.

The new CII building (foreground) joins UofL's Health Sciences Center Research Tower on the downtown medical campus.

Professor and chairman of biomedical engineering at the University of Arizona since 1997, Williams also directs the Arizona Research Laboratories' division of biomedical engineering and holds joint appointments in the university's departments of materials science and engineering, surgery and physiology.

"Dr. Williams brings tremendous expertise in translational research and a stellar track record of scientific research to Louisville," said Laman Gray Jr., M.D., CII medical director and a University of Louisville professor of surgery.

"Dr. Williams work is an outstanding fit for the CII and the University of Louisville," added UofL President James Ramsey, Ph.D. "As a leader, a scientist and an entrepreneur, his expertise in biomedical engineering and materials science will complement the work being done by several of our distinguished faculty. I look forward to seeing the progress he will bring the institute in the future."

A partnership between the University of Louisville and Jewish Hospital, the institute seeks to improve care for patients with advanced heart disease, so they may live longer, richer lives. It will build on the success of both institutions' work with ventricular assist devices and artificial hearts.

UofL President James Ramsey, Ph.D., presents Sen. Mitch McConnell with a framed photo of the institute.

The institute will focus on testing, clinical evaluation and development of bio-adaptive heart innovations and combination therapies, including heart-assist devices, gene therapies, biofeedback sensors and related technologies. This will be done through a collaboration between UofL's Health Sciences Center and the Department of Bioengineering at the university's J.B. Speed School of Engineering.

The interior of the new Cardiovascular Innovation Institute features a glass-ceiling atrium.

CII features expanded research facilities plus training and administrative space equipped with the latest technology. Funding for the facility includes a $15 million investment from Jewish Hospital, $6.2 million in federal earmarks secured by Sen. Mitch McConnell, $4.2 million invested by the University of Louisville, a $5 million grant from Kosair Charities, $5.5 million from the Kentucky Cabinet for Economic Development and the Department of Commercialization and Innovation and $1.5 million from the Gheens Foundation.

Diphtheria toxin and immune factor fight melanoma

A drug containing parts of the diphtheria toxin appears to prompt the immune system to recognize and kill cancer cells in patients with advanced skin cancer, a team of researchers at UofL's James Graham Brown Cancer Center has discovered.

Preliminary results of a phase II clinical trial, presented Nov. 9 at an international symposium in Prague, Czech Republic, showed that five out of seven human patients with stage IV melanoma experienced significant regression or stabilization of both tumors and the spread of cancer.

Jason Chesney, M.D., Ph.D., associate director for translational research at the Brown Cancer Center and an assistant professor of medicine at the University of Louisville School of Medicine, presented one of only 10 projects at the conference, which was sponsored by the European Organization for Research and Treatment of Cancer, the National Cancer Institute and the American Association for Cancer Research.

His was selected from almost 800 peer-reviewed research presentations.

"The immune system that attacks cancer cells in humans depends on a balance between T-cells, which recognize and attack tumor cells, and suppressive or regulatory T-cells, which turn off activated immune cells in order to prevent autoimmune disease," Chesney said.

In research with mice, Chesney's team discovered that the drug denileukin diftitox targets and depletes regulatory T-cells, allowing particular T-cells in the immune system known as CD8 + T lymphocytes to attack and kill the melanoma cells.

This success led to testing of the drug in human patients.

Chesney and his colleagues gave seven patients with stage IV melanoma 9 or 12 micrograms of the drug per kilogram of body weight daily for four days, every three weeks for four cycles. Five patients who received the higher dose experienced significant regression of several metastatic tumors.

All of the patients are still alive after 12 months, and the phase II trial is continuing to examine the effectiveness of the drug, Chesney said at a news briefing. Stage IV melanoma patients normally have a median life expectancy of about eight months.

"To our knowledge, this is the only trial to study the effects of regulatory T-cell depletion in human cancer patients," he said.

"The results demonstrate that depleting these cells in patients with melanoma may allow the immune system to activate and successfully kill cancer cells. These patients have survived longer than the median average life expectancy of a patient with stage IV melanoma.

"We believe that, in the future, this approach to therapy may prove to be useful in all types of cancer."

UofL cancer drug shows promise in clinical trials

A second patient with late-stage renal cancer is responding well to a new drug discovered by University of Louisville researchers in a Phase I clinical trial being conducted at UofL's James Graham Brown Cancer Center.

After being treated with a drug derived from guanine-rich oligonucleotides (GROs) -- a compound discovered by UofL faculty Paula Bates, Ph.D., Donald Miller, M.D., Ph.D., and John Trent, Ph.D. -- the patient's tumors have shrunk 70 percent, according to Damien Laber, M.D., principal investigator in the trial.

"Across the board, patients are responding well with fewer side effects than other available treatments," Miller said. "This particular patient's results are very exciting, because the patient had relapsed after three prior therapies with common cancer drugs."

A compound discovered by UofL's Donald Miller, M.D., Ph.D., (inset); and John Trent, Ph.D., and Paula Bates, Ph.D., (above) has shrunk tumors by up to 70 percent in clinical trials, investigators report. The compound also has fewer side effects than other cancer drugs.

Miller, director of the James Graham Brown Cancer Center and associate vice president for health affairs at UofL, presented full data from the trial Oct. 1 at the European Society of Medical Oncology annual conference in Istanbul, Turkey.

The clinical trial at the Brown Cancer Center includes 12 patients with renal cancer and five with lung cancer. The trial is sponsored by Antisoma PLC, which acquired Louisville-based Aptamera in October 2005. Aptamera was founded by Bates, Miller and Trent to bring GRO-based therapies to market.

GROs are short pieces of synthetic DNA that work by binding tightly to a specific protein present on the surface of cancer cells, interfering with tumor growth. Because the compounds select cancer cells over normal cells, GRO-based therapies have fewer side effects than many traditional cancer drugs.

"This is just one of many targeted drugs in the pipeline at the Brown Cancer Center and UofL, and we are doing everything we can to move these new therapies from the lab to the patients as swiftly as possible," Miller said.

Diabetes treatment also stops sepsis, study finds

A drug developed to treat diabetes also can stop sepsis, a severe and often fatal reaction of the immune system to infection, a University of Louisville researcher has found.

The drug, sorbinil, appears to block an enzyme that throws the body into overdrive to fight infection, said cardiology professor Aruni Bhatnagar, Ph.D.

Sepsis occurs when the immune system shifts into high gear, causing widespread inflammation and driving up body temperature, breathing and heart rate.

Aruni Bhatnagar, Ph.D.

The condition kills nearly one third of the 700,000 Americans it strikes each year.
Bhatnagar's research team found that sorbinil dramatically boosted the chance of recovery in mice with acute infections. About 40 percent of the mice treated with the drug after infection survived, while none of the untreated mice survived.

"We believe this drug holds promise for treating high-risk patients such as children, new mothers, people who undergo prolonged surgery and people with mechanical heart-assist devices," he said.

A research paper on the finding appears in the current online issue of the journal Circulation.

The team used a genetic silencing technique developed by Nobel Prize-winning scientists Andrew Fire and Craig Mello to prove that sorbinil blocks the enzyme triggering sepsis.

Future research on the enzyme could lead to new treatments for other immune disorders such as heart inflammation, hepatitis and pancreatitis, Bhatnagar said.

Scientists at University of Texas-Galveston, University of Texas-San Antonio and University of California-San Francisco also took part in the study.

Scientific team develops vaccine that prevents lung cancer development in mice

A team of researchers at UofL's James Graham Brown Cancer Center has discovered that vaccinating mice with embryonic stem cells can prevent lung cancer.

Their findings, presented Nov. 7 at an international cancer symposium in Prague, Czech Republic, suggest that it could be possible to develop embryonic stem cell vaccines that prevent cancers in humans at high risk of developing cancer.

John Eaton, Ph.D., deputy director of the Brown Cancer Center, and Robert Mitchell, Ph.D., assistant professor of biochemistry and molecular biology at the University of Louisville School of Medicine, presented the findings at the conference.

The vaccine, Eaton said during a news briefing, has been tested in two ways: by implanting lung cancer cells after vaccination and by using a model of lung cancer that mimics cancer caused by smoking.

John Eaton, Ph.D.

"Our results raise the exciting possibility of developing a vaccine capable of preventing the appearance of various types of cancers in humans, especially those with hereditary or environmental predispositions for developing disease," said Eaton, James Graham Brown professor of cancer biology. Such cancers could include breast cancer, colon cancer or lung cancer caused by smoking and other environmental factors.

He warned, however, that the work is still in its early stages and that, while the
results in mice look promising, it could be some time before this approach is tested
in humans.

Eaton and Mitchell found that, in the case of implanted lung cancer cells, the vaccine had a consistent effectiveness rate of 80-100 percent in preventing tumor outgrowth. All non-vaccinated control animals developed tumors.

The researchers tried the experiment again four months (equivalent to 10 human years) after the initial vaccination. Mice given lung cancer cells did not develop tumors, suggesting that the effect of the vaccination is long lasting.

In a model of lung cancer development that mimics smoking, mice vaccinated after exposure to carcinogens developed almost no tumors. The few that did appear were much smaller than those in non-vaccinated mice.

"Our progress over the next few years will depend, to a large extent, on whether we can attract significant funding," Eaton said. The team's work is supported by a pilot grant from the Brown Cancer Center and by a grant from the Kentucky Lung Cancer Research Program.

New university research lab named in honor of the Barnstable Brown Foundation

Derby tradition mingled with biomedical research Nov. 6 as the University of Louisville dedicated a new diabetes research lab on its Health Sciences Campus.

The Barnstable Brown Research Laboratory, part of UofL's Institute for Cellular Therapeutics, was named to honor the Barnstable Brown Foundation, which raises funds for diabetes research through its Kentucky Derby party.

"Years before healthcare professionals began talking about the diabetes epidemic and its effects in Kentucky, the Barnstables and Browns took up the cause of finding a cure for this devastating disease," said UofL President James Ramsey, Ph.D.

"We are proud to have been among the organizations they have chosen to support."

Researchers at the lab will focus on learning how to harness T-cells, which normally help the body fight infectious diseases, said Thomas Mitchell, Ph.D., associate professor of microbiology and immunology.

Thomas Mitchell, Ph.D.

T-cells turn against the body in people with Type I diabetes and begin killing the cells in the pancreas that make insulin, said Mitchell, who also occupies UofL's Barnstable Brown Gala Chair in Diabetes Research. Mitchell's team is trying to learn how to manipulate T-cells to keep them focused on preventing infection, he said.

"No single scientist or research team can cure diseases alone," Mitchell said. "It takes support from the community, of which the Barnstable Brown Derby Eve Gala is a joyful and pioneering example."

Novel drug therapies used during third Louisville hand transplant procedure

A 54-year-old Michigan man became the third person to undergo a hand transplant at Jewish Hospital in Louisville and the first to receive treatment with only two anti-rejection drugs. Normally three drugs are necessary.

David Savage lost his dominant right hand in a work-related accident more than 30 years ago.

On Nov. 29, A team of 32 physicians from Jewish Hospital, Kleinert, Kutz Hand Care and the University of Louisville worked 16 hours to attach the donor hand.

Suzanne Ildstad, M.D., director of the University of Louisville's Institute for Cellular Therapeutics, Jewish Hospital Professor of Transplantation and a member of the surgical team, noted that for the first time with a hand transplant, surgeons used a strategy to reduce the number of immunosuppressive drugs.

Suzanne Ildstad, M.D., director of UofL's Institute for Cellular Therapeutics, said the transplant employed innovative strategies for reducing the required number of immunosuppressive drugs.

It may sound trivial that a person normally has to take three drugs to suppress rejection after transplant, Ildstad said, but the toxicity of those drugs, which include steroids, adversely affects the patient's long-term quality of life.

Savage took steroids only for the first two days after surgery.

University Hospital receives Medal of Honor from Health and Human Services

University Hospital was recognized for superior medical care Dec. 7 when it was awarded the Medal of Honor from the U.S. Department of Health and Human Services for substantially increasing organ donation rates.

University Hospital was one of 187 hospitals out of 787 nationwide to receive the distinguished award.

By partnering with the Kentucky Organ Donor Affiliates (KODA) in the ongoing "Donate Life" campaign, University Hospital was able achieve, and sustain, a donation rate of at least 75 percent of eligible donors for 2005.

By contrast, the national average donation rate in all hospitals was 59 percent in 2005. In 2004, it was 55 percent.

The record gains followed the Health Resources Services Administration's launch in 2003 of the Organ Donation Breakthrough Collaborative.

That initiative brought together donation professionals and hospital leaders to identify and share best practices to maximize organ donation rates.

Heather Huddleston of Rep. Anne Northup's office presents James Taylor, president and CEO of University Hospital, with the Medal of Honor during a ceremony Dec. 7.

The goal was to achieve organ donation rates of 75 percent or more for at least a year. Staff from the Health Resources Services Administration and the organ procurement organizations helped participating hospitals identify, adapt, test and implement practices known to produce high donation rates.

"As we celebrate University Hospital's outstanding accomplishments, let us remember that behind each number is a human face: an individual who has made a gift of life by becoming an organ donor, and the people who have benefited from the live-saving, life-enhancing transplant," said Kenneth Moritsugu, the acting U.S. surgeon general.

Heather Huddleston, a field representative for Rep. Anne Northup, presented the award to James Taylor, University Hospital president and CEO, and Larry Cook, M.D., UofL's executive vice president of health affairs

"University Hospital doctors, nurses and support staff never stop fighting for our patients," Taylor said. "The exemplary dedication and teamwork that they display every day to save lives is also used to increase the quality and length of life for so many more."

Martínez-Maldonado named university's executive vice president for research

Nephrologist Manuel Martínez-Maldonado, M.D., has been selected as the executive vice president for research at the University of Louisville.

President and dean of Ponce School of Medicine in his native Puerto Rico from 2000 to 2006, Martínez-Maldonado boasts a long list of academic and administrative positions.

He has been professor of medicine, vice provost and vice president for research at Oregon Health Sciences University (OHSU) in Portland; vice chair of the Department of Medicine at Emory University Medical School; and director of internal medicine and ambulatory care at the Atlanta VA Medical Center.

Martínez- Maldonado, M.D.

He also has held professorships at Baylor College of Medicine, the University of Puerto Rico, Emory University and OHSU, and has taught at Harvard and Vanderbilt universities.

Martínez-Maldonado has authored numerous scientific publications. His research interests are the regulation of blood pressure and the effect of high blood pressure on the kidneys. He also focuses on the renin angiotensin system, a hormone system that helps regulate long-term blood pressure and blood volume in the body and which is controlled primarily by the kidneys.

He is a member of the Institute of Medicine of the National Academy of Sciences and a foreign honorary member of the American Academy of Arts and Sciences.

Also a published poet, Martínez-Maldonado said UofL's tremendous growth, not only in research and the health sciences, but also university-wide, was a contributing factor to his accepting the post.

"A great university must have great arts and sciences departments," he said, adding that what happens on the Belknap Campus is of critical importance to the success
of UofL.

Martínez-Maldonado noted that he arrived at Baylor, Oregon, Emory and Ponce when they were "trying to achieve new goals" and that he was able to help further them.
"I know I can help" UofL do the same, he said.

"It will be a real delight to work with Dr. Ramsey and all the vice presidents," he said. "I look forward to that interaction."

UofL President James Ramsey, Ph.D., praised Martínez-Maldonado, as well as his predecessor, Nancy Martin, Ph.D.

"Dr. Martínez-Maldonado brings a distinguished career of research and administration to this post," Ramsey said. "As executive vice president for research for the past 10 years, Dr. Nancy Martin did an outstanding job in building our research program.

"I believe Martínez-Maldonado will build skillfully upon our research successes."

New dean instrumental in bringing collection of rare books to School of Medicine

Edward Edward Halperin, M.D., M.A., officially came on board as dean of the University of Louisville School of Medicine on Nov. 1.

Between the announcement of his appointment and his arrival in Louisville, he has been busy with all of the activities normally associated with moving a home and office - a list of things to do that can seem overwhelming.

But Halperin hasn't limited himself to boxes and crates - between his acceptance of the job at UofL and his resignation from Duke University, he has been busy working on behalf of the UofL School of Medicine.

In the months of September and October, Halperin traveled to Columbia University in New York City and the University of Pennsylvania in Philadelphia to give talks to pre-med students about why they should consider applying to medical school at UofL.

"I believe it is essential that we cast a wide net for outstanding Kentucky students studying at Ivy League schools and for top out-of-state UofL medical students," he said.

Halperin was also instrumental in bringing to Louisville a gift of rare books and folios from the estate of G.S.T. Cavanagh, a noted collector and dealer of antiquarian medical books.

Approximately 100 volumes will come to UofL's Kornhauser Medical Library and several will be available as gifts for UofL medical students receiving academic awards.

The collection includes first editions of works by noted scientific and medical authors Sir Humphrey Davey, Joseph Priestly and Oliver Wendell Holmes.

Other notable works include a set of volumes by Charles Mayo and Howard Kelly and a full set of Bell's "Textbook of Surgery."

Cavanagh joined the Duke University School of Medicine in 1962 as director of the Medical Center Library and ended his career as curator of the Trent Collection of the History of Medicine.

"I first encountered Mr. Cavanagh as a young member of the Duke faculty in the early 1980s," said Halperin. "I was working on some manuscripts in the History of Medicine Reading Room and dictating notes into my handheld Dictaphone. He told me he would have 'none of that noise' in the library and threw me out."

During the subsequent years, Halperin became friends with Cavanagh through his scholarly work on the history of medicine and when Cavanagh died, Halperin spoke at his memorial service.

He praised Cavanagh as a "fine scholar, mentor and distinguished bookman," adding that, "It's a real pleasure to bring a little bit of that legacy to UofL."

Heart association recognizes UofL's cardiology chief

The American Heart Association's Scientific Council on Basic Cardiovascular Sciences bestowed its Distinguished Achievement Award on UofL cardiologist Roberto Bolli, M.D., during a recognition dinner at Chicago's Art Institute in November.

Roberto Bolli, M.D.

The award recognizes individuals who have made major contributions to the scientific council over a continuing period of time. Recipients also are required to have made substantial professional contributions to the field, including the contribution of new knowledge and leadership in national or international organizations. The award is presented only once every three years.

Bolli holds the Jewish Hospital Heart and Lung Institute Distinguished Chair in Cardiology and is director of the Division of Cardiology and UofL's Institute for Molecular Cardiology. His research focuses on preventing the damage caused during heart attacks by studying latent ischemic preconditioning, in which heart muscle exposed to brief periods of stress becomes resistant to the tissue death that might be caused by a heart attack.

Autism specialist receives lifetime achievement award

Peter E. Tanguay, M.D., an emeritus professor of psychiatry at the University of Louisville, was awarded the George Tarjan Award for Contributions in Mental Retardation by the American Academy of Child and Adolescent Psychiatry during a ceremony and public honors lecture held Oct. 26 at the AACAP's meeting in San Diego, Calif.

Tanguay was recognized for his internationally known work in the field of autism and related disorders.

He was an expert consultant on the 1998 film "Rain Man" starring Dustin Hoffman, which won four Academy Awards.

The Tarjan Award, named for the late George Tarjan, M.D., recognizes an academy member who has made significant contributions to the understanding or care of those with mental retardation and developmental disabilities.

Tarjan, a pioneer in the field of autism and related disorders, mentored Tanguay during the first two decades of his academic career at the University of California Los Angeles.

Tanguay's honors lecture focused on his recent work in converting the diagnostic criteria for autism and related disorders from a category-based approach to one that recognizes these disorders as a spectrum.

Tanguay joined UofL in 1994 as the Ackerly Endowed Professor of Child and Adolescent Psychiatry.

Tanguay received his M.D. from the University of Ottowa, Ontario, and completed his residency at UCLA. He is a past director of the American Board of Psychiatry and Neurology and is a fellow of the American College of Psychiatrists.