Florian Douam

Assistant Professor of Virology, Immunology & Microbiology
Assistant Director of Graduate Studies for Virology, Immunology & Microbiology

See BU Profile for more information and publications.

Determinants of Immune Outcomes in Human RNA Virus Infections

 Viral diseases mainly stem from the immune system’s failure to eliminate a virus infection or from an excessive immune response. Our laboratory is interested in unraveling cell- and tissue-specific mechanisms regulating the ability of the immune system to effectively resolve an infection, leading to long-lasting immunity, or to drive acute (during infection) and post-acute (following active infection resolution) immunopathologies. To support such investigations, we utilize a variety of human RNA viruses, including mosquito-borne orthoflaviviruses (e.g., yellow fever virus) and human coronaviruses (e.g., SARS coronaviruses) in multiple infection contexts, from cell culture layers to animal models. We particularly strive to adopt a human-centric, integrative approach to viral immunology by synergizing advanced human cell-based systems and organoids with innovative mouse models engrafted with human tissues and/or human genes (i.e., humanized mice). With this approach, we seek to unravel new molecular insights that will guide the creation of advanced vaccines and immunotherapy strategies for current and future viral diseases.

Our investigations are centered around four research axes:

1. Immunoregulatory mechanisms driving protection from respiratory virus infections: We develop and leverage mouse models, including genetically humanized, genetic knock-out, and mice engrafted with a human immune system and/or human lung tissues, to investigate human and mouse immune mechanisms driving the resolution of respiratory viral infection in the lung. We are also interested in defining the contribution of biological sex and sex hormones to governing protective lung antiviral immunity.
2. Human skin responses to arthropod-borne virus transmission: We employ advanced humanized mice and organoid systems to model human skin responses to viruses transmitted by mosquito bites (e.g., Dengue virus, Zika virus). We utilize these experimental platforms to elucidate crucial epithelial and hematopoietic processes in the human skin that define the effective transmission of these viruses from the mosquito salivary glands to the human cutaneous environment, their dissemination from the skin to peripheral tissues, and the resulting immunopathologies. We also aim to explore how mosquito and viral factors regulate these events.
3. Molecular basis of acute and post-acute viral immunopathologies: We develop cell-culture-based systems and mouse models to uncover cell- and tissue-specific mechanisms regulating acute immunopathology during different RNA virus infections. We are especially interested in viral-mediated mechanisms regulating cellular entry and tropism, evasion of cell-intrinsic immune defenses, and cellular stress and inflammation. Additionally, by developing humanized mouse models recapitulating persisting and systemic inflammatory syndromes following the resolution of viral infections, we also aim to elucidate molecular drivers and hematopoietic dysregulation defining post-acute viral immunopathologies.
4. Broadly acting vaccines for viral infectious diseases: We synergize various multi-antigen expression cassettes, genetic platforms (mainly virus-like particles and self-amplifying RNA), nucleotide modifications (in collaboration with the BU Biomedical Engineering department), and vaccination regimens to develop innovative immunization strategies with broad antiviral activity. We are also interested in leveraging our vaccines as tools to uncover fundamental immunological mechanisms governing specific or broadly acting immunity against infectious diseases.