- ASSOCIATE PROFESSOR Microbiology
- ASSISTANT PROFESSOR Medicine, Infectious Diseases
M.S., University of Salamanca
Ph.D., Mount Sinai School of Medicine of the City University of New York
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Evasion of innate immunity by dengue virus (DENV)Specific Clinical/Research Interests Mechanisms of evasion of immunity by dengue and influenza viruses; human immunology in viral infections. Generation of recombinant viruses.
Current Students: Sarah Pagni (PhD Student), Rebecca Hamlin (MDPhD student)
Postdoctoral Fellows: Sebastian Aguirre, Ana Maestre, Kevin Maringer, Irene Ramos
Research Personnel: Dabeiba Bernal-Rubio
Past Members: Juan R. Rodriguez, PhD, Timothy Savage, MS, Phoenix Bell (MS)
Summary of Research Studies:
The main focuses of study in the Fernandez-Sesma laboratory are the interactions of important human pathogens with primary human immune cells.
- Dengue virus (DENV)is an important human pathogen for which there is no vaccine or treatment available. Dengue is a flavivirus transmitted to humans by the bite of the mosquito aedes aegipti. We are studying the role of different primary human cells, such as dendritic cells (DCs) and macrophages in the initiation or evasion of immunity by DENV. We have analyzed the pattern of gene expression and cytokine secretion in different primary cells after DENV infection and have recently shown that the DENV protease complex (NS2B/3) is crucial for the inhibition of type I IFN production by DENV in primary human DCs, an important step in the generation of the innate and adaptive immune responses by this virus. We are currently studying how primary isolates of DENV are able to initiate or evade immune responses in human primary cells.
- We are also studying adaptation of DENV to human and mosquito cells as part of a DARPA funded multi-investigator project led by Dr. Raul Andino at UCSF. Our laboratory is interested in innate immune evasion by this virus as a measure of adaptation and fitness.
Innate immunity to influenza virus and HIV
- Influenza virus is another important human pathogen that causes epidemics yearly in humans as well as occasional pandemics. Influenza virus has been shown by us and others to inhibit important elements of immunity such as the type I interferon (IFN) system as well as the ability of DCs to get activated. As part of our NIH funded Center for research in influenza pathogenesis (CRIP) http://www.mssm.edu/research/centers/center-for-research-on-influenza-pathogenesis/, lead by Dr. Adolfo Garcia-Sastre, in the department of Microbiology at MSSM, http://www.mssm.edu/profiles/adolfo-garcia-sastre#bot, which is one of the Centers of excellence for influenza research (CEIRS) we are using recombinant influenza viruses with specific mutations in several virulence genes, such as the NS1 and HA, among others, and analyzing the ability of different influenza viruses to interfere with different aspects of immunity in primary human systems.
- Human Immunodeficiency virus (HIV), is responsible for one of the most devastating current human epidemics. Our newest project is the study of global innate immune responses to HIV-1 infection in primary human cells. We were recently awarded with an NIH program project grant (HIV immune networks team, or HINT) www.hint.org, with Dr. John Young at the Salk Institute as the principal investigator. This is a multi-investigator program project to study the interactions between HIV and innate immunity. It combines systems biology, molecular virology, innate immunity and viral immunology components. Our project, in collaboration with Dr. Viviana Simon, in the department of Microbiology at MSSM, http://www.mssm.edu/profiles/viviana-a-simon#bot, focuses on the interactions between HIV and primary immune cells (DCs, macrophages and T cells) that may account for the generation of weak adaptive immunity to HIV in patients.
Aguirre S, Maestre AM, Pagni S, Patel JR, Savage T, Gutman D, Maringer K, Bernal-Rubio D, Shabman RS, Simon V, Rodriguez-Madoz JR, Mulder LC, Barber GN, Fernandez-Sesma A. DENV Inhibits Type I IFN Production in Infected Cells by Cleaving Human STING.. PLoS Pathogens 2012 Oct; 8((10)): e1002934doi: 10.1371/journal.ppat.1002934. Epub 2012 Oct 4.
Chiang C, Engel A, Opaluch A, Ramos I, Maestre A, Secundino I, De Jesus P, Nguyen Q, Welch G, Bonamy G, Miraglia L, Orth A, Nizet V, Fernandez-Sesma A, Zhou Y, Barton G, Chanda S. Cofactors required for TLR7- and TLR9-dependent innate immune responses. . Cell Host and Microbe 2012 March 15; 11(3): 306-318.
Berger A, Sommer AF, Zwarg J, Hamdorf M, Welzel K, Esly N, Panitz S, Reuter A, Ramos I, Jatiani A, Mulder LC, Fernandez-Sesma A, Rutsch F, Simon V, König R, Flory E. SAMHD1-deficient CD14+ cells from individuals with Aicardi-Goutières syndrome are highly susceptible to HIV-1 infection. PLoS pathogens 2011 Dec; 7(12).
Varga ZT, Ramos I, Hai R, Schmolke M, García-Sastre A, Fernandez-Sesma A, Palese P. The influenza virus protein PB1-F2 inhibits the induction of type I interferon at the level of the MAVS adaptor protein. PLoS pathogens 2011 Jun; 7(6).
Ramos I, Bernal-Rubio D, Durham N, Belicha-Villanueva A, Lowen AC, Steel J, Fernandez-Sesma A. Effects of receptor binding specificity of avian influenza virus on the human innate immune response. Journal of virology 2011 May; 85(9).
Ashour J, Morrison J, Laurent-Rolle M, Belicha-Villanueva A, Plumlee CR, Bernal-Rubio D, Williams KL, Harris E, Fernandez-Sesma A, Schindler C, García-Sastre A. Mouse STAT2 restricts early dengue virus replication. Cell host & microbe 2010 Nov; 8(5).
Rodriguez-Madoz JR, Belicha-Villanueva A, Bernal-Rubio D, Ashour J, Ayllon J, Fernandez-Sesma A. Inhibition of type I IFN response in human dendritic cells by dengue virus infection requires catalytically active NS2B3 complex. J. Virol 2010 Oct; 84(19): 9760-9774.
Rodriguez-Madoz JR, Bernal-Rubio D, Kaminski D, Boyd K, Fernandez-Sesma A. Dengue virus inhibits the production of type I interferon in primary human dendritic cells. J. Virol 2010 May; 84(9): 4845-4850.
Haye K, Bourmakina S, Moran TM, Garcia-Sastre A, Fernandez-Sesma A. The NS1 protein of a human influenza virus inhibits type I interferon production and the induction of antiviral responses in primary human dendritic and respiratory epithelial cells. J. Virol 2009; 83(13): 6849-6862.
Phipps-Yonas H, Seto J, Sealfon SC, Moran TM, Fernandez-Sesma A. Interferon- pretreatment of conventional and plasmacytoid human dendritic cells enhances their activation by influenza virus. PLoS Pathogens 2008 Oct 31; 4(10): e1000193.
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.
Below are financial relationships with industry reported by Dr. Fernandez-Sesma during 2012 and/or 2013. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
Equity (Stock or stock options valued at greater than 5% ownership of a publicly traded company or equity of any value in a privately held company)
- Vivaldi Biosciences Inc.
Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website at http://icahn.mssm.edu/about-us/services-and-resources/faculty-resources/handbooks-and-policies/faculty-handbook. Patients may wish to ask their physician about the activities they perform for companies.
Annenberg Building Floor 15 Room 15-06
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New York, NY 10029
Annenberg Building Floor 15 Room 06
1468 Madison Avenue
New York, NY 10029