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Arap, Pasqualini Earn O'Donnell Award from Texas Academy

Researchers honored for targeting attacks on cancer and obesity via vascular addresses

M. D. Anderson News Release 01/07/10

Two scientists who discovered that blood vessels supplying different organs and tissues have unique molecular signatures which may be exploited to develop highly targeted therapies will receive the 2010 Edith and Peter O'Donnell Award in Medicine from The Academy of Medicine, Engineering and Science of Texas.

The husband-and-wife team of Renata Pasqualini, Ph.D., and Wadih Arap, M.D., Ph.D., both professors in the David H. Koch Center for Applied Research in Genitourinary Cancers at The University of Texas M. D. Anderson Cancer Center, will be honored today at the TAMEST annual meeting in San Antonio.

"The O'Donnell Award recognizes Wadih Arap and Renata Pasqualini for their creativity, hard work and tenacity in developing this approach from breakthrough scientific insight all the way to an initial clinical trial," said Raymond DuBois, M.D., Ph.D., M. D. Anderson provost and executive vice president. "They are outstanding translational researchers and mentors for young scientists."

The O'Donnell Awards, named for TAMEST supporters and philanthropists Edith and Peter O'Donnell, recognize outstanding, innovative work by top Texas researchers in four categories: medicine, science, engineering and technology. The awards include a $25,000 honorarium, a citation and the opportunity to address the academy at its annual meeting.

Since they showed that blood vessels differ molecularly depending on their location, Arap and Pasqualini have focused on developing and applying their findings to practical clinical uses. These diverse signatures amount to vascular addresses that allow precise targeted destruction of the blood vessels that support tumors. The goal is to improve treatment efficacy and reduce side effects by selectively hitting the tumor or its blood supply, while sparing healthy tissues.

The first drug they designed to destroy the unique vasculature that supports prostate cancer is in a phase I clinical trial. A potential anti-obesity medication that attacks blood vessels that fuel fat is advancing through preclinical research and has been shown to reduce weight and improve the metabolic profile in obese mice and monkeys, with minor and reversible side-effects.

Translational research - the advancement of basic research discoveries to clinical use - is the driving force behind their scientific approach.

"We both desire that our work be translational, very practical," Arap said. "Knowledge for the sake of knowledge doesn't do it; we need to see it through to the clinic."

They are honored to have earned one of the rigorously vetted TAMEST awards. "Science is a lot about persistence in the face of rejection - rejection of grant applications, rejection of papers for publication, and great research going unrecognized," Pasqualini said. "An award such as this provides a rewarding and encouraging moment."

Arap and Pasqualini are celebrating their 10th year on the faculty of M. D. Anderson.

"People ask 'how can you possibly do it? I could never work with my spouse.' I can't imagine not," Pasqualini said. "It is really about sharing our accomplishments and failures to the fullest."

Since their initial discovery of vascular addresses, Arap, Pasqualini and their colleagues have developed a number of tools that provide platform technology for future discoveries.

They developed a phage display library to identify ligand-directed targeting agents. These small protein fragments recognize specific receptor proteins much like a key goes into a lock. Phage are viruses that are capable of infecting only bacteria, unless they come equipped with a ligand that homes in on its matching receptor. Upon binding, targeted phage are internalized specifically by cells bearing selective molecular addresses. Such viruses can also be engineered to deliver genes, imaging agents, and several other payloads, such as gold nanoparticles.

For the anti-obesity drug, phage screenings uncovered a ligand that binds to a protein which is uniquely expressed on the cell surface of blood vessels that supply white fat cells. They attached the ligand to a drug that forces cells to self-destruct, a combination that has shown great promise in animal studies.

The research team is developing a hybrid virus that delivers genes to tumors or tumor vasculature. The hybrid combines phage targeting with animal adeno-associated virus (AAV) infectiousness to successfully deliver genes for imaging or therapy, an approach so far successful in animal studies, including positive results when used to treat dogs with cancer. The AAVP vectors (AAV-phage chimeras) continue to advance in preclinical research.

TAMEST was founded in 2004 to provide broader recognition of the state's top achievers in medicine, engineering, and science, and to build a stronger identity for Texas as a center of achievement in these fields. Members include Texas Nobel Laureates and more than 200 members of the various national academies, such as the National Academy of Sciences. 01/07/10


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