The Fernandez-Sesma group has developed and optimized human primary cell systems to study the interactions of DENV and other viruses with human primary immune cells, such as monocytes, dendritic cells (DCs) and macrophages and has recently developed a human tonsil system to study DENV infections. Using these systems her group identified the interferon (IFN) antagonist for DENV, the NS2B3 protease complex, which inhibits the production of this important antiviral cytokine in primary human cells by cleaving the adaptor molecule STING, and more recently we found that components of the viral protease also target cGAS for degradation in infected cells. The Fernandez-Sesma lab is currently characterizing the mechanisms of immune evasion by DENV and chikungunya viruses (CHIKV) in primary human systems and developing novel model systems to study these viruses.

Our research team also participates in several past and current multi-investigator projects on HIV, influenza and Dengue virus. Some of the past projects include a department of defense (DARPA) funded project together with several other investigators from other institutions to study evolution and fitness of DENV in mosquito and mammalian systems. We also participated in a NIH-funded multi-investigator program project to study innate immunity in HIV (HINT) (in which studying the role of those factors on HIV infections of primary human cells. Since 2015-2022 Dr Fernandez-Sesma led with Dr. Eva Harris an NIH/NIAID funded multi-investigator project as part of the Human Immunology Project Consortia (HIPC) named DHIPC. This project, aimed to understand how innate immune responses to DENV infection and vaccination influence adaptive immune responses induced using multi-OMICs approaches.

Of the current projects, one of them focus on influenza virus. One of them, Center for Research on Influenza Pathogenesis and Transmission (CRIPT), led by Dr. Garcia-Sastre focuses on influenza virus immune evasion strategies using human systems, and is one of the NIH/NIAID-funded Centers of Excellence of Influenza Research and Response (CEIRR). In particular, we study how influenza viruses of animal origin interact with cells of the human immune system as compared to human influenza viruses via their receptor binding properties. The Fernandez-Sesma lab also participate in one of the NIH-funded AViDD centers, namely QBRG-AViDD, led by Dr. Nevan Krogan , aiming to identify and characterize antiviral compounds against SASR-CoV-2 and other viruses, such as CHIKV and others. In 2022 Dr. Fernandez-Sesma and Dr. Viviana Simon were awarded a U19 grant named Viral Immunity and Vaccination (VIVA) as part of the HIPC and a top-notch group of investigators from ISMMS and from other institutions in which we will investigate the innate immune responses in humans after SARS-CoV2, influenza or dengue vaccines using OMICs technologies. As part of this project we are particularly interested in understanding serotype-specific  factors contributing to the immunogenicity of tetravalent dengue vaccines.