Thomas M Moran, PhD
- PROFESSOR | Microbiology
Research Topics:Antigen Presentation, B Cells, Cellular Immunity, Cytokines, Dendritic Cells, Immune Antagonism, Immunoglobulin Genes, Immunological Tolerance, Immunology, Infectious Disease, Inflammation, Interferon, T Cells, Transplantation, Vaccine Development, Viruses and Virology
Dr. Moran has published widely on immunity to virus infection using both mouse models and studies in human subjects. In addition he has led studies aimed to understand changes that occur in immune functions of women during pregnancy. He served as the Overall Director of the NIH funded Center for Investigating Viral Immunity and Antagonism (CIVIA). CIVIA focused on studies of human immunology and infectious disease by advancing technological methodologies, supporting inventive research, serving as a conduit for collaboration and promoting exchange of scientific information. Among other projects, a recent study funded by CIVIA profiled the immune response of patients receiving the live-attenuated influenza virus vaccination. Dr. Moran served as overall PI for the Viral Immunity in Pregnancy study (VIP) that recently concluded. This was a study of changes that occur in women during pregnancy with an emphasis on understanding the enhanced susceptible to infection. Data from the two cohorts of the VIP study-immune response changes during pregnancy (60 patients) and influenza vaccination during pregnancy (350 patients) were recently published.
Dr. Moran is the Director of the Center for Therapeutic Antibody Development (CTAD) here at Mount Sinai School of Medicine. The center has been active for more than 15 years and during this time produced many monoclonal antibodies against various infectious agents cell surface receptors and other cell associated proteins. CTAD has a close collaboration with Medical Research Council-Technology division in London to produce and develop human or humanized monoclonal antibodies. A number of collaborative projects are in progress primarily to develop monoclonal antibodies withtherapeutic applications. Technology has been developed and is currently being used by CTAD to produce human monoclonal antibodies by V gene cloning as well as fusion of human B cells expanded by various methods in vitro.
Multi-Disciplinary Training AreasImmunology [IMM], Microbiology [MIC]
PhD, Boston University
Influenza virus infection in mouse model systems
Virus–host interaction studies: The Moran lab studies the interaction of the mammalian immune system with viral and bacterial pathogens. Studies using a mouse model of influenza virus infection have documented the kinetics and mechanisms by which the virus inhibits the initiation of immunity. Other studies have analyzed the interaction of influenza virus with dendritic cells, the key intermediaries between innate and adaptive immunity. A systems biology approach attempting to model the key interaction of seasonal and pandemic influenza viruses with DCs in a collaboration with Dr. Stuart Sealfon (Prime study) is in progress.
Viral Infection in mice during pregnancy
Women in the later stages of pregnancy are very susceptible to severe influenza virus infection. We have studied changes in the immune response of women in our human study called Viral Immunity during Pregnancy (VIP). A mouse model was developed to test hypothesis generated based upon the human data. In this model the pregnant mice were shown to have a reduction in both innate and adaptive response to influenza virus infection. This is consistent with our observation in humans.
Live Attenuated Influenza Virus Vaccine in Humans
In this study subjects were given the FluMist vaccine and there responses and seroconversion measured. Surprisingly a very small percentage of subjects had antibodies in their blood as a result of the vaccine. However, a local mucosal response was documented by the rise in antibodies and cytokines in nasal washes. Subjects with the low levels of G-CSF, a growth factor involved in phagocyte activation and recruitment, were significantly more likely to seroconvert.
Viral Infection in Pregnancy (VIP)
The VIP study utilized blood collected from women in the three trimesters of pregnancy to study aspects of innate and adaptive immunity. Blood samples collected in the post partum period were used as controls. The study showed that immunological functions such as T cell activation and NK cell function were reduced in the later stages of pregnancy. Cells numbers and cytokines in blood changed indicative of an increase in barrier functions. These data suggested that elements of the immune response involved in recovery from infection are compromised during pregnancy but the increase in barriers may make pregnant women less likely to become infected.
Bacterial coinfection in influenza infected mice
Human data has shown that a significant proportion of the deaths that occur during influenza virus pandemics results from bacterial coinfection. Studies are ongoing to try to understand the reasons for the rapid growth of bacteria such as Streptococcus pneumoniae in animals concurrently infected with influenza virus. Influenza infected mice die when inoculated with bacterial doses that have no effect on healthy animals. Our data has shown that type 1 interferon is responsible as animals lacking the type 1IFN receptor are resistant to the bacteria. Cells in the lungs are inhibited from producing IL17 when type 1 interferon, released in response to the virus, is present. IL17 is known to be an important cytokine clearance of bacterial infection. The exact mechanism for what the loss of IL17 does is currently being investigated
Center for Therapeutic Antibody Discovery(CTAD)
Dr. Moran is the Director of the Center for Therapeutic Antibody Discovery(CTAD) here at Mount Sinai School of Medicine. The center has been active for more than 15 years and during this time produced many monoclonal antibodies against various infectious agents cell surface receptors and other cell associated proteins. CTAD has a close collaboration with Medical Research Council-Technology division in London to produce and develop human or humanized monoclonal antibodies. A number of collaborative projects are in progress primarily to develop monoclonal antibodies with therapeutic applications. Technology has been developed and is currently being used by CTAD to produce human monoclonal antibodies by V gene cloning as well as fusion of human B cells expanded by various methods in vitro. CTAD collaborates with many other faculty members in the production of conventional and therapeutic antibodies. Current projects involve the generation of Mab to pancreatic, lung, and breast cancer. Diagnostics are being developed to identify human papilloma virus infected cells in the head and neck region and insulin producing cells in the pancreas.
Brimnes MK, Bonifaz L, Steinman RM, Moran TM. Influenza virus-induced dendritic cell maturation is associated with the induction of strong T cell immunity to a coadministered, normally nonimmunogenic protein. The Journal of experimental medicine 2003 Jul; 198(1).
Bonifaz LC, Bonnyay DP, Charalambous A, Darguste DI, Fujii S, Soares H, Brimnes MK, Moltedo B, Moran TM, Steinman RM. In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination. The Journal of experimental medicine 2004 Mar; 199(6).
Escribese MM, Kraus T, Rhee E, Fernandez-Sesma A, López CB, Moran TM. Estrogen inhibits dendritic cell maturation to RNA viruses. Blood 2008 Dec; 112(12).
Moltedo B, López CB, Pazos M, Becker MI, Hermesh T, Moran TM. Cutting edge: stealth influenza virus replication precedes the initiation of adaptive immunity. Journal of immunology (Baltimore, Md. : 1950) 2009 Sep; 183(6).
Wang TT, Tan GS, Hai R, Pica N, Petersen E, Moran TM, Palese P. Broadly protective monoclonal antibodies against H3 influenza viruses following sequential immunization with different hemagglutinins. PLoS pathogens 2010 Feb; 6(2).
Moltedo B, Li W, Yount JS, Moran TM. Unique type I interferon responses determine the functional fate of migratory lung dendritic cells during influenza virus infection. PLoS pathogens 2011 Nov; 7(11).