The Mackow lab investigates viral cell targeting and the regulation of vascular, pulmonary and CNS cell functions. We explore viral mechanisms of vascular permeability, age dependent neurovirulence and innate and adaptive immune regulation as potential virulence determinants and therapeutic targets. Using recombinant approaches we define pathogenic viral protein functions, modify and attenuate viruses and use recombinant viruses to evaluate mechanisms of viral pathogenesis in murine models that mimic human disease. Our studies are aimed at revealing novel therapeutics and potential vaccines for preventing viral pulmonary and neurodegenerative diseases and extend to defining roles for cell senescence in age-dependent human CNS diseases.

Our lab investigates mechanisms of Flavivirus (FV: Powassan virus, Zika virus, Dengue virus), SARS-CoV2 and Hantavirus (HV) pathogenesis. One focus is on viral regulation of vascular endothelial cell (EC) functions that dynamically control pulmonary edema and permeability of the blood brain barrier (BBB). We further analyze mechanisms of POWV neuroinvasion via the blood CSF barrier (BCSFB) using in vitro and in vivo approaches. We study CNS cell responses that direct spongiform encephalitis, age-dependent lethality and long term neurologic damage. Roles for innate and adaptive responses in viral persistence and pathogenesis are being evaluated for use as attenuation and therapeutic targets.