09/10/13, Honors & Other Things - Almanac, Vol. 60, No. 4

The Perelman School Medicine has received a $12 million grant over five years from the National Institutes of Health to head up a multi-institutional study looking at the biology of asthma and other airway diseases. The goal of the research is to find new, druggable targets in the smooth muscles of the airway that could lead to more effective bronchodilators that prevent or reverse lung constriction for longer periods of time.

Current, long-term therapies for asthma keep the airways open for 12 hours to prevent attacks but at the same time desensitize a key cell surface receptor known as the G-coupled protein receptor (GCPR), limiting their efficacy. Here, researchers will devise new therapeutics that sustain such receptors, and increase efficacy to 96 hours or more.

"Our approach has been to investigate novel targets and molecules with the hopes of finding bronchodilators that won't lose activity and remain effective in severe asthma and other airway diseases, like COPD. We want longer-lasting treatment options," said Dr. Reynold A. Panettieri, Jr., director of the Asthma Section in the division of Pulmonary, Critical Care and Allergy, and principal investigator for the NIH grant. "This grant will propel our research even further, as the team, under the Airways Biology Initiative here at Penn, work towards much-needed and new approaches to managing asthma, a particular area of interest that affects 26 million Americans a year."

Bronchodilators are medications that relax the bronchial muscles for obstructive lung diseases, like asthma. Today, the disease costs the US about $56 billion in medical costs, lost work days, and even early deaths—some of which are caused by current medications. COPD, or chronic obstructive pulmonary disease, costs the US almost $30 billion, not including lost productivity.

Past studies by researchers from the Initiative have uncovered new mechanisms in the airway smooth muscles that can be exploited.

The new research endeavor will elaborate on these discoveries and investigate other unique molecules that promote bronchodilation, new agonists to bitter taste receptors and antagonists to GCPR to prevent bronchoconstriction.

Other institutions involved in the research include Thomas Jefferson University, the University of Southern Florida, Johns Hopkins University and the University of Arkansas. The Program Project Grant (PPG) was awarded by the NIH's National Heart, Lung and Blood Institute.

The Program Project Grant is more complex in scope and budget than the individual research grant. While individual research grants are awarded to support the work of one principal investigator who, with supporting staff, is addressing a scientific problem, Program Project Grants are available to a group of several investigators with differing areas of expertise who wish to collaborate in research by pooling their talents and resources. PPGs represent synergistic research programs that are designed to achieve results not attainable by investigators working independently.

The National Cancer Institute has awarded $10.3 million over five years to a group of Penn researchers to investigate the early events of Kaposi's sarcoma associated herpesvirus infection and its implication for developing therapeutics in treating associated cancers.

Dr. Erle S. Robertson, professor of microbiology, at the Perelman School of Medicine, heads the team of Penn faculty who will be conducting the research.

"This funding comes at an opportune time when funding is extremely limited from the NIH and provides support to pursue a difficult area of research not previously explored due to lack of funding or difficulty in obtaining funding," said Dr. Robertson. "The program will explore the early events after infection with the oncogenic herpesvirus in primary cells and allows for breakthroughs which are likely to be fundamental to our understanding of the events that lead to a successful infection which goes on to a transformed state."

Kaposi's sarcoma associated herpesvirus (KSHV) is associated with a number of human cancers, in particular AIDS associated Kaposi sarcoma (KS) and pleural effusion lymphomas, as well as Multicentric Castlemen's Disease.

KSHV was identified 15 years ago and has been tackled mostly on a level of the individual investigator. This award brings together three groups of investigators, which includes Drs. Paul Lieberman (The Wistar Institute) and Yan Yuan (Penn Dental School), within the Penn community to join their scientific expertise to address the mechanism of KSHV-mediated oncogenesis.

The overall goal is to investigate the mechanism of viral control by encoded antigens during the early stages of infection of primary B cells. The fundamental cellular processes targeted during these early stages will provide new information as to the strict requirements for successful establishment of latency by the virus.

The success of these projects will allow for a more comprehensive view of KSHV infection and pathogenesis and provide new clues for the development of strategies to prevent and treat KSHV associated cancers, endemic and in the HIV population.

In addition, the accumulation of new information on KSHV biology will be critical for the broader area of herpesvirus biology to gain insights into the mechanism of oncogenesis associated with other viruses, including Epstein Barr virus.

(Left to right) Frank Scott, Vesselin Tomov, David Goldberg, Kimberly Forde, Rotonya Carr, Marie-Pier Tetreault, Christina Twyman-St. Victor, Blair Madison; Not present: Meenakshi Bewtra, Gregory Sonnenberg and Andrew Rhim.

Eleven researchers from the Division of Gastroenterology at the Perelman School of Medicine have been awarded a total of $6.1 million in grants from the National Institutes of Health. This year's awards include ten K series career advancement grants and one Early Independence Award (a K series equivalent grant). The grants given to the 11 assistant professors, instructors and research associates will be used over the next two to five years to explore a range of topics related to GI health including chronic liver diseases, Hepatitis C, inflammatory bowel disease, esophageal diseases, colon cancer, pancreatic cancer and cancer treatment.

"We are so proud of the high-caliber research being conducted by these young investigators," said Dr. Anil K. Rustgi, chief of the division of Gastroenterology. "It's an honor to have their efforts recognized by the NIH. These awards are a result of the focus and hard work each of them has demonstrated, but also they reflect the dedication of their mentors' and our Division's cohesive approach to career and professional development. We are excited to see the valuable contributions their research will make to the fields of Gastroenterology and Hepatology, and look forward to the establishment of their independent careers."

The NIH's K awards are designed to promote the career development of specific groups of individuals based on their past training and career stage. The objective of these programs is to bring candidates to the point where they are able to conduct their research independently and are competitive for additional grant support.

Among recipients of the groups' K series career awards is Dr. Rotonya Carr, who earlier this year was also named the recipient of the Harold Amos Medical Faculty Development Award from the Robert Wood Johnson Foundation.

The other Penn GI researchers who received awards are Drs. Meenakshi Bewtra, Kimberly Forde, David Goldberg, Blair Madison, Frank Scott, Gregory Sonnenberg, Marie-Pier Tetreault, Vesselin Tomov and Christina Twyman-St. Victor. Dr. Andrew Rhim, a K series award recipient and former researcher at Penn Medicine, is now on faculty at the University of Michigan.