Welcome to the Morrison Laboratory!
Research Program Overview
Emerging infections are a global public health threat. In the 21st century alone, we already have experienced devastating outbreaks of infectious disease, including diseases caused by mosquito-borne (e.g., chikungunya and Zika viruses) and respiratory RNA viruses (e.g., SARS-CoV-2). Our laboratory seeks to improve our knowledge of the molecular pathogenesis of these infections (i.e., what are the critical host-pathogen interactions that contribute to protection or pathology?) by addressing questions at the interface of immunology and virology/parasitology.
Arthropods, including mosquitoes, sand flies, and ticks, often bite humans to obtain blood meals. During feeding, these arthropods can transmit infectious microbes, such as RNA viruses and protozoan parasites, to humans that cause devastating diseases (e.g., chikungunya, dengue, leishmaniasis, and malaria). Mosquito-transmitted RNA viruses include flaviviruses, such as dengue, West Nile, and Zika viruses, bunyaviruses, such as Rift Valley fever virus, and alphaviruses, such as chikungunya, Mayaro, Ross River, and Venezuelan equine encephalitis viruses. Chikungunya, Mayaro, and Ross River viruses, and other related arthritogenic alphaviruses, cause explosive epidemics that can involve thousands to millions of infected patients. Chikungunya, which translates as “disease that bends up the joints”, is characterized by an abrupt onset of fever with severe joint pain, and the pain may persist for weeks to years. Chronic chikungunya joint disease may result from persistent viral infection in musculoskeletal tissues. To investigate the molecular pathogenesis of arbovirus infections, we use genetic strategies, molecular and cellular approaches, and mouse models of acute and chronic infection. Using these systems, we study viral interactions with the host innate and adaptive immune response. We are particularly interested in defining mechanisms of activation and resolution of virus-induced inflammatory responses, immunological mechanisms that control virus clearance versus virus persistence, and viral genetic determinants that counteract host anti-viral responses and promote persistent infection. The mouse models we use enable us to utilize transgenic and knockout strains to study the role of specific host genes in the disease process and investigate the genetics of host susceptibility to acute and chronic infection. Additionally, due to the availability of well-established reverse genetics system for the viruses, we are able to manipulate the genome of the virus to define genetic determinants of phenotypes and to engineer novel recombinant viruses to expand our experimental approaches (e.g., engineering the virus to express a fluorescent protein in infected cells or to encode heterologous TCR epitopes). Taken together, these advantages provide highly tractable systems to establish mechanisms by which viral interactions with the host lead to disease. In addition, we utilize cell culture-based and animal infection models to test novel vaccines, anti-virals and immunomodulatory therapeutics against acute and chronic viral infection.
Arthropod-transmitted protozoan parasites include Leishmania (the causative agents of leishmaniasis), Trypanosoma (the causative agents of Sleeping sickness and Chagas’ disease) and Plasmodium (the causative agents of malaria). Leishmaniasis is a major global health problem that affects more than 12 million people worldwide. Leishmania parasites are endemic in Asia, the Middle East, sub-Saharan Africa, and South America. These obligate intracellular parasites are transmitted to humans by infected sand flies and cause a spectrum of clinical manifestations that includes cutaneous leishmaniasis (localized lesions of the skin), mucocutaneous leishmaniasis (mucosal lesions; nose, mouth, throat) and visceral leishmaniasis (parasite infection and disease in visceral organs including the liver, spleen, bone marrow, and lymphatic system). We aim to define interactions between leishmania parasites and host cells that influence host innate and adaptive immune responses, and ultimately parasite clearance versus persistence. In addition, we aim to determine the parasite-encoded factors that dictate parasite resistance or susceptibility to oxidative/nitrosative stress, a major host defense mechanism employed by infected macrophages. To accomplish these goals we use cell culture and murine infection models. We also use a variety of genetic tools to manipulate the genome of these organisms.
Ultimately, we seek to use the new knowledge gained from our studies to improve our ability to prevent and treat these diseases, as well as diseases caused by newly emerging infectious agents such as SARS-CoV-2, through the development of vaccines as well as pathogen- or host-targeted therapeutics.