February 13, 2017

Drs. Bradley Ford, Siegfried Janz, Kevin Legge and Ashutosh Mangalam were each awarded $30,000 Medical Research Initiative Grants from the Roy J. Carver Charitable Trust. The Medical Research Initiative Grant Program is an annual Carver College of Medicine competition designed to provide seed money for investigators whose preliminary findings show great promise. Exciting new ideas and the potential for attracting extramural funding are key factors in the selection process. The grant titles and descriptions for each are below:

Rapid Antibiotic Resistance Profiling of Uropathogens 

Drs. Bradley Ford and James McNamara, an Associate Professor in Internal Medicine, were awarded a grant to extend their novel nuclease probe technology from rapid diagnosis of urinary tract infection (UTI) to rapid susceptibility testing. The goal is to develop this technology for rapid diagnostic and susceptibility testing in order to guide appropriate prescription of antibiotics before patients are finished with a clinic visit.

 About one in five bacteria that cause UTI are currently resistant to the two most commonly-used drugs to treat these infections. Currently, bacterial resistance takes a minimum of two days to identify, which is  two-thirds of the time it takes to complete a typical course of treatment. Ideally, the new nuclease probe testing technology will be available at the point of care to confirm the diagnosis of a UTI and guide  therapy by immediately identifying antimicrobial resistance.

Transgenic Mouse Model of Human KSHV-associated B-lymphocyte Disorders

Dr. Siegfriend "Siggy" Janz, and collaborators Drs. Carol Holman, Xuefang Jing and Ramakrishna “Rama” Sompallae were awarded the grant to to enhance our understanding of the mechanism by which a  Kaposi sarcoma-associated herpesvirus (KSHV)-encoded homolog of cellular interleukin-6 (IL-6), designated viral IL-6 (vIL-6), promotes severe and often fatal B-cell proliferations, such as plasmablastic multicentric Castleman’s disease and primary effusion lymphoma. Our ability to treat these conditions is limited at best at this juncture, and findings from this study may provide avenues for novel therapies.

Nanoparticle Vaccination Against Influenza Virus

Drs. Kevin Legge and Thomas Waldschmidt were awarded the grant to further develop their novel nanoparticle-based vaccine designed to protect against influenza virus infection. The study is being done in collaboration with Dr. Balaji Narasimhan at Iowa State University.

Seasonal influenza A virus (IAV) remains a major cause of respiratory illness worldwide with significant morbidity and mortality. At present however, the only available vaccine is an inactivated formulation given intramuscularly. While this vaccine induces strong antibody titers in the circulation, it does not invoke local T cell and B cell immunity at the site of infection (the respiratory track). In order to achieve such immunity, Drs. Legge, Waldschmidt and Narasimhan have developed a biocompatible nanoparticle-based IAV vaccine that can be safely administered intranasally. Preliminary studies have demonstrated this vaccine to not only induce potent antigen-specific T cell and B cell responses in the upper and lower airway, but to protect against both homologous and heterologous influenza A viruses. The funds from this grant will be used to further validate the nanovaccine in preclinical models.

Deciphering the Mechanism of Obesity Induced Inflammation in Multiple Sclerosis
Utilizing Human Leucocyte Antigen (HLA) Class-II Transgenic Mice

Dr. Ashutosh Mangalam was awarded the grant to build upon recent findings in his laboratory showing that multiple sclerosis (MS) patients with active disease have higher BMI and gut microbial dysbiosis compared to healthy controls. Obesity has been linked to MS; however, the mechanism is not well understood. In preliminary studies, Dr. Mangalam’s laboratory has obtained data suggesting that obesity might induce conversion of regulatory Treg cells into inflammatory Trogue cells, leading to a pro-inflammatory environment and increased disease severity.

The preliminary findings have led to the hypothesis that high fat diet induced obesity shifts the immune response from anti- to pro-inflammatory through modulation of gut microbiota. Dr. Mangalam will utilize ‘humanized’ mice expressing transgenic HLA-class II molecules that predispose towards MS in order to test this hypothesis.