Last year, four faculty researchers in the UB School of Pharmacy and Pharmaceutical Sciences were awarded nearly $12 million in combined National Institutes of Health grant funding to advance novel therapies to combat several serious threats to human health including HIV, cancer, obesity and superbugs.
But what might be as impressive as the total dollar amount is the fact that the UB School of Pharmacy and Pharmaceutical Sciences remains so competitive despite its much smaller size than similar programs around the country.
“The School of Pharmacy is very small overall,” explains Joseph Balthasar, BS '91, PhD '96, professor, pharmaceutical sciences. “We have fewer than 20 faculty pursuing basic science research; several of our peer schools have more than 60 faculty in basic science areas. So for us to be as competitive as we are in respect to federal funding is really notable.”
Despite its size, the institution has earned a reputation for excellence that dates back decades and has produced an impressive array of groundbreaking therapeutic discoveries.
“Our pharmacy school is ranked No. 14 nationwide,” says Qing Ma, PharmD, PhD, associate professor of pharmacy practice. “We have a very long tradition that is evident to the NIH reviewers. We also have a very good, supportive environment for career development here. We will have a brilliant future because we are trying very hard to build that clinical and translational pharmacology.”
“The most impressive feat of these grants isn’t not just the dollar amount, but more the cutting-edge nature and timing of them,” says Brian Tsuji, PharmD, professor of pharmacy practice and associate dean for clinical and translational sciences. “All the grants are focused on new therapeutic approaches to fight really urgent threats. Our investigators are coming up with novel therapeutics to treat real medical needs, fill substantial gaps, help patients who are very sick, and think outside the box at a time when traditional therapies weren’t working.”
Ma was awarded a five-year, $4 million award by the National Institute on Aging in the NIH to study drug toxicity in older adults with HIV. The grant is the largest active R01—a competitive grant that supports mature health-related research—at the UB School of Pharmacy and Pharmaceutical Sciences, and the second largest active R01 at the university.
Using data and specimens from nearly 20,000 comprehensive medical and neurobehavioral assessments collected over more than 20 years from the National NeuroAIDS Tissue Consortium, Ma and Scott Letendre, MD, professor of medicine at the University of California San Diego, will look at the underlying mechanisms of drug toxicity from over-prescription, as older HIV patients take a host of medications to manage HIV, plus many other chronic conditions and mood disorders.
“The question we want to answer is, ‘How can we change drug dosing to minimize toxicity while maintaining therapeutic effects?’” says Ma. “If we can identify certain drug categories, or at least have some initial evidence that polypharmacy might be the cause of a neurocognitive disfunction, then figure out how to optimize the medical approach, we can apply those skills to other scenarios. Maybe polypharmacy is what makes the elderly become vulnerable to Alzheimer’s or dementia. The HIV medication study model is a baby step that we can expand later to other categories.”
Balthasar earned a $1.8 million R01 grant from the National Cancer Institute (NCI) to investigate three new approaches to enhance the uptake and distribution of antibodies in solid tumors. The first approach looks at ways to help antibodies make their way deeper into the core of a cancerous mass, rather than binding tightly to the outer cells and preventing their penetration inward. The second uses cells’ natural recycling systems to circulate pH-dependent antibodies within a tumor. The third uses nanobody-enzyme conjugates to break down the matrix that weaves between the cells of tumors enough to let antibodies get through, but not so much that it creates toxicity.
Balthasar’s work develops “platform strategies,” meaning his findings in these studies could be applied to a whole range of anti-cancer antibodies currently in development and use.
“We’re developing adjuvant agents that are designed for co-administration with current drug therapies to make them work better,” says Balthasar. “The findings could be applied to all antibodies used to treat solid tumors, which make up about 90% of cancers.”
Tsuji won a $3.9 million award from the National Institute of Allergy and Infectious Diseases (NIAID) to lead an investigation of a drug-resistant bacteria that can be deadly in half of patients who develop bloodstream infections, according to the Centers for Disease Control and Prevention (CDC).
The Carbapenem-resistant Enterobacteriaceae (CRE) superbug in Tsuji’s study, which is prevalent in New York City and global locales including Thailand, India and China, produces a specific enzyme that makes the bacteria fully resistant to every existing antibiotic. To combat this, Tsuji and his team are investigating how a multipronged attack by a combination of several drugs might be enough to disarm the CRE.
“Most infections are treated in a single or traditional fashion,” explains Tsuji. “We’re using existing drugs that are already approved to develop a practical approach. Using a cocktail of three or four drugs, we try to overwhelm the bacteria’s individual resistance mechanisms to each individual drug. It’s finding the magical sweet spot of the right drugs, the right combo and the right concentration.”
Jun Qu, PhD, professor of pharmaceutical sciences, was awarded a three-year, $1.2 million grant from the U.S. Department of Defense to develop new treatments for Chronic Obstructive Pulmonary Disease (COPD), a combination of diseases with common symptoms that affect the lungs. Qu will use his recently developed, groundbreaking technique in quantitative proteomics to examine mucus and saliva samples for biomarkers that can help pinpoint the specific type of disease within the COPD category.
Qu shares the co-principal investigator role with Sanjay Sethi, MD, professor and chief of the Division of Pulmonary, Critical Care and Sleep Medicine in the Jacobs School of Medicine and Biomedical Sciences at UB.
Qu is also the co-principal investigator on a four-year, $1 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases to study hormones and proteins associated with obesity in order to standardize and improve testing, monitoring and treatment.
“In both studies, if we can measure biomarkers, we can inform the diagnostics and the therapeutics,” says Qu. “Doctors might be able to predict how disease will advance in a specific patient, take preventative measures and personalize treatment.”