Researchers in the School of Pharmacy and Pharmaceutical Sciences will lead four grants totaling more than $ 10 million to examine the effects of drug toxicity on cognitive disorders in older adults with HIV, develop urgent therapies to life-threatening infections, explore the disease of obesity, and craft new treatments for chronic obstructive pulmonary disease (COPD).
The studies will be led by Brian Tsuji, professor of pharmacy practice and associate dean for clinical and translational sciences; Qing Ma, associate professor of pharmacy practice; and Jun Qu, professor of pharmaceutical sciences.
The five-year $ 4 million award presented to Ma from the National Institute on Aging in the National Institutes of Health (NIH) is the largest active R01 ─ a competitive grant that supports mature health-related research ─ at the School of Pharmacy and Pharmaceutical Sciences, as well as the second largest active R01 at the university.
Influence of prescribed drugs on mental health in HIV patients
Drug toxicity from overprescription is a growing issue among older adults with HIV, who often must undergo antiretroviral therapy and take medications for other chronic conditions, particularly cognitive and mood disorders such as depression.
Ma, together with Scott Letendre, professor of medicine at the University of California San Diego, will lead an investigation of the underlying mechanisms behind concurrent use of multiple medications on neurotoxicity, cognition and depression.
The study will examine data and specimens from nearly 20,000 comprehensive medical and neurobehavioral assessments collected over more than 20 years from the National NeuroAIDS Tissue Consortium.
“Our research will provide valuable data on how aging interacts with prescribed drugs to increase the risk of neurotoxicity and central nervous system complications,” says Ma.
“The identification of these pharmacological factors would be substantially beneficial to public health,” he adds. “The results may also inform future interventions to prevent and treat cognitive and mood disorders in people with HIV as they age.”
New line of defense against superbugs
Drug-resistant bacteria, or superbugs, are an urgent threat to public health around the globe. Resistant to all antibiotics, these bacteria can cause a variety of illnesses, from pneumonia to wound infections.
Tsuji, through a $ 3.9 million award from the National Institute of Allergy and Infectious Diseases (NIAID), will lead an investigation of Carbapenem-resistant Enterobacteriaceae (CRE), a drug-resistant bacteria that can kill up to half of patients who develop bloodstream infections, according to the Centers for Disease Control and Prevention (CDC).
The study will center on a strain of CRE that produces New Delhi Metallo-β-lactamases (NDM), an enzyme that breaks down the Carbapenem class of antibiotics and renders it ineffective. Carbapenem antibiotics are often considered the last line of defense against superbugs.
“NDM-producing CRE are concerning as they have rapidly spread worldwide and can efficiently coexist with a plethora of other drug-resistant genes,” says Tsuji, whose research focuses on developing groundbreaking treatments to fight superbugs. “It is critical to prepare therapeutics for the future occurrence of NDM strains that harbor a diverse array of resistance genes in hospitals.”
The researchers aim to develop treatments that consist of combinations of three and four antibiotics. They will also examine the bacteria’s genetics to understand why individual antibiotics and previous drug combinations failed.
The new award builds on Tsuji’s previous research on combination therapy to combat superbugs, completed under a $ 4.4 million grant from the NIAID. If successful, the innovative therapies will be tested in future clinical trials.
Exploring proteins behind COPD and obesity
Qu is co-principal investigator on a three-year, $ 1.2 million grant from the U.S. Department of Defense to craft new therapies for COPD.
Nearly 16 million people in the U.S. have been diagnosed with COPD and the disease is the third-leading cause of death in the nation, according to the CDC.
The research will examine the key relationships between microbes, immune cells and lungs cells to better develop treatments for the disease. Qu’s lab will focus on creating a novel strategy for surveying the proteins within mucus and saliva samples based on his recently developed groundbreaking technique in quantitative proteomics.
The study is led by Sanjay Sethi, 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 co-principal investigator on a four-year, $ 1 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases in the NIH to study the pathology of obesity.
The prevalence of obesity in both children and adults in the U.S. has increased to epidemic proportions. To better understand the disease, researchers will use targeted mass spectrometry to develop standardized tests that monitor the hormones and proteins closely associated with obesity, including insulin, and pro- and anti-inflammatory markers.
As one of the world leaders in liquid chromatography–mass spectrometry-based targeted protein quantification, Qu has developed a number of novel methods that enhanced the sensitivity and accuracy of protein analysis.
“Obesity has become one of the leading global risks for mortality in the world,” Qu says. “Unfortunately, many of the current tests for monitoring the disease are not reproducible due to the lack of standardization. This project aims to develop tests that can easily transfer to other clinical laboratories to enable precise monitoring of obesity, thus facilitating better personalized patient care.”
The research is also led by Wei-Jun Qian, a bioanalytical chemist in the Biological Sciences Division of Pacific Northwest National Laboratory.