harrod lab

The Harrod lab is led by Kevin Harrod, Ph.D.

Infections of the respiratory tract are the most common cause of human malady worldwide. Dr. Kevin S. Harrod’s laboratory is focused toward understanding mechanisms of infectious disease leading to pulmonary dysfunction and chronic lung disease.  

We utilize a technology-forward approach to elucidate molecular targets for therapeutics and prophylaxis against respiratory pathogens, and to elucidate new cellular pathways important in pathogenesis, host defense or prevention.  Our predominant focus is on common respiratory viruses such as influenza, RSV, hMPV, and coronaviruses, but recent advances have allowed us to bridge our expertise to bacterial pathogenesis, the lung microbiome and sepsis.  We have identified novel therapeutic targets using integrated high-throughput screening platforms coupled with in silico applications to yield novel information in disease pathogenesis.  Systems biology and omics approaches are commonplace in our laboratory with an emphasis on integration of these techniques with new experimental models. The laboratory is often comprised of molecular biologists, microbiologists, bioinformaticists, and physician-scientists to bring together multiple expertise and experiences within biomedical research. 

Dry-iceViruses continue to cause the vast majority of respiratory infection in individuals of both resource-rich and research-poor nations. Despite this impact, few antivirals have been developed and scant numbers are in clinical trials. The mutagenic potential of RNA viruses, the most common viruses of the respiratory tract, suggest that resistance is likely attainable soon after antivirals are utilized in mass production.  One approach is the use of re-purposed therapies for treating the common sequelae of respiratory infection, pneumonia and bronchitis.  Using loss-of-function gene-targeting approaches, we have identified classes of molecules called matrix metalloproteinases (MMPs) that facilitate influenza pathogenesis, for which pharmaceutical antagonists have already been developed.  We are currently developing single-drug and combinatorial therapies to mitigate influenza-mediated lung disease in outbreak and highly pathogenic scenarios.

Respiratory syncytial virus (RSV, and a related virus, human metapneumovirus (hMPV) are most common causes of hospitalization in infants and young children.  Despite this impact, currently no vaccines or therapies are approved for most cases of RSV or hMPV infection.  Importantly, sustainable and durable memory immunity is not generally observed in children.  The reasons for this are unclear.  We have explored the early innate events that confer immune mechanisms critical to memory immunity.  Notably, early innate immune responses are subverted by these viruses, rendering a less-than-optimal innate response that is needed for a strong adaptive immune response.  Our lab continues to explore these mechanisms to identify interventions that may yield better immunity and immunization strategies in pediatric populations.

Pneumococcal carriage is the single leading predictor of pneumococcal infection in both children and adults.  The interaction of pneumococcals and the lung microbiome are poorly understood.  Together with the Bill and Melinda Gates Foundation, we have set out to understand the impact of biomass combustion as a fuel source for cooking in the home in resource-poor cultures.  As a surrogate of exposure to biomass fuels, we have identified pneumococcal and commensal bacteria as biomarkers that could lead to the evaluation of new cookstove technologies in resource-poor settings.  This work is our first foray into microbiome investigations and the use of next-generation deep sequencing technologies for exploring lung health and disease.

Lastly, sepsis and bacteremia are leading cause of death in the ICU.  Currently, markers of early sepsis diagnosis are severely inaccurate.  We have combined our expertise in advanced infection model development with emerging advance in omics technologies to identify molecular signatures in the metabolome of sepsis patients that can exceed prediction of current clinical standards.  We continue to develop target “metatype” approaches that can further provide “next-generation diagnostics” for reducing sepsis morbidity and mortality in intensive care settings.