Description of Research Expertise

RESEARCH INTEREST: Determinants for the development of succesful antiviral immune responses.

KEYWORDS: Virus-host interaction, innate immunity, respiratory viruses, lung immunity.

RESEARCH DETAILS:
The understanding of the processes that lead to the efficient generation of an immune response is critical for the development of therapies and vaccines against threatening pathogens. My group studies the events that occur early during the virus-host interaction and that determine the successful transition from the less specific initial innate immune response to the more specific adaptive immune response. We work with a number of mouse models of respiratory infection including influenza virus, respiratory syncytial virus, human metapneumovirus, and the mouse pathogen Sendai virus. We have strong virology and immunology components and use multiple techniques in vitro and in vivo to gather an inclusive mechanistic understanding of the processes that determine the successful development of anti-viral immunity. Our work extends to the study of strategies for the improvement of vaccines and to the analysis of determinants of virus persistence. Current projects are:
1. Cellular sensors of virus infection: The signaling initiated by the binding of pathogen-specific motifs to sensor molecules present in the host is critical for the initiation of the immune response. Pathogens, on the other hand, have developed strategies to counteract immune recognition so that they can grow and spread successfully. We are interested in the identification of cellular mechanisms for the detection of pathogenic viruses. We are currently focused on the study of the cellular response mediated by the viral sensors RIG-I and MDA5. We are particularly interested in investigating the specific role of each of these molecules in mediating the recognition and immune response to virus infection.
2. Viral triggers of dendritic cell maturation: Proper maturation of dendritic cells determines the effective transition from innate to adaptive immunity. The characterization of viral elements capable of triggering dendritic cell maturation can provide with novel adjuvant molecules to be used in vaccination. We discovered that defective viral genomes that are generated during the replication of viruses at high titer greatly enhance the stimulatory ability of standard virus stocks. Defective viral genomes potently activate dendritic cells through a unique mechanism different from that utilized by standard viruses. We are interested in characterizing the viral motifs responsible for this activity. We are also evaluating Sendai virus defective genomes as natural adjuvants for vaccination.
3. Lung innate immunity. We have shown that soon after a respiratory infection the lung communicates with cells developing in the distal bone marrow via type I IFNs that are produced in the lung and transported through the blood. Cells instructed in the bone marrow by type I IFNs become resistant to virus infection and respond more efficiently to viral cues when recruited to the lung therefore enhancing the innate immune response and facilitating the clearance of the virus. Studies to further characterize the innate systemic response to a respiratory infection are undergoing with a focus in the identification of molecular signals to distal cells and their consequence for anti-viral immunity.

LAB PERSONNEL:
Undergraduate Students:
-Emily Dunay (Vagelos Program for Molecular and Life Sciences)

Graduate Students:
-Sabrina Tsang (CAMB, MVP, UPenn)
-Won-keun Kim (Visiting Scholar, Graduate student at Mount Sinai School of Medicine, NY).

Postdocs:
-Xiomara Mercado-López Ph.D.

Technicians:
-Deepika Jain (Research Specialist-Lab Manager)
-Karla Tapia (Research Specialist)

Visit http://www.lopezlab.org for more information