Jeff Hogan

Activities

Infectious diseases have plagued humans and animals for thousands of years and have altered the course of history countless times. Although advances such as vaccines, therapeutics, and antibiotics have helped in this regard, recent outbreaks of disease such as SARS coronavirus (SARS-CoV) and the novel H1N1 influenza virus outbreak in 2009 highlight the fact that additional research and treatments are of great need. With this in mind, our laboratory focuses on studying the interactions of the host and pathogen. By better understanding these processes, we aim to develop novel approaches to prevent the diseases, transmission, and mortality associated with viral and bacterial infections.

Vaccination represents one of the most important public health tools available. In this regard, we are working together with Dr. Eric Lafontaine to develop protein-based vaccines against the gram-negative bacteria Burkholderia mallei (Bm) and Burkholderia pseudomallei (Bp). These bacteria are endemic to areas near the equator including Southeast Asia and Northern Australia and can be isolated from the soil (Bp) or from an equine reservoir (Bm). Although the infections can manifest in multiple forms depending upon the route of infection, the most severe form of disease occurs during inhalation which results in pneumonia and subsequent bacteremia. The first step in this process is adherence to host cells, allowing entry of bacteria into the cytoplasm for replication and dissemination. Our approach to vaccine development for both Burkholderia mallei and pseudomallei is to target this mechanism, and we hypothesize that immune responses against bacterial proteins which facilitate binding to host cells can prevent or slow the entry of bacteria and subsequent replication. Recent data with one such candidate vaccine suggest that these bacterial adhesins are highly immunogenic and can provide protection against aerosol challenge.

While vaccines are excellent tools to protect naïve individuals, they are not generally effective for persons already infected or displaying signs of clinical disease. In this regard, our lab is also interested in the development of novel therapeutics for treatment. To address this need, we have employed a wide range of strategies including RNA interference (RNAi), random mutagenesis, and screening of chemical compound libraries to identify potentially useful treatments for SARS-CoV, influenza virus, and poxviruses. We are currently investigating the cellular genes and proteins required for SARS-CoV replication using both siRNAs and a lentiviral vector-based shRNA expression platform. To date, we have identified several cellular genes that are important in the lifecycle of SARS-CoV and influenza virus replication, and these may represent novel drug targets for intervention strategies. In order to gain a better understanding of poxvirus replication, we have made use of a custom-designed siRNA library that targets the majority of the known and predicted viral genes. These studies have led to the identification of over 17 different viral genes that are required for poxvirus replication, and given us insights into the complex replication cycle of this large DNA virus. Future studies will explore the feasibility of siRNA-mediated therapeutic use in vivo.