Gender	Male
E-mail	thomas.moran@mssm.edu
Education and Training	Ph.D., Boston University

Dr. Moran's role at Mount Sinai has been multifaceted. In addition to extensive research involving the investigation of virus interaction with the mammalian immune system, he has served as the Microbiology Course Director for three years and as the Co-director of Immunobiology for five years.  He is also currently the Microbiology Training Co-director for graduate studies.

Dr. Moran has established an on-site Hybridoma Core Facility, which has been operative for 15 years. Other institutional committees he has served on are the Institutional Animal Care and Use Committee (IACUC; 5 years), Shared Resource Facilities (SRF; 10 years), Biosafety, in-house granting as well as others. During his tenure, Dr. Moran has spearheaded the establishment of CIVIA, the Center for Investigation of Viral Immunity and Antagonism, a NIH funded project uniting researches from different disciplines.

Hybridoma Shared Research Facility

Center for Investigating Viral Immunity and Antagonism (CIVIA)

Education and Training	Ph.D., Boston University

Specific Clinical/Research Interests: Immune response to virus infection Viruses used: -Influenza, Newcastle Disease, and Sendai Models used: -mouse (in vivo, in-vitro, and ex-vivo) -human (in-vitro) cells isolated from human donors Cell types currently studied: -PBMC's, Monocytes, Dendritic cells, (cDCs & mDCs) Topics of interest: Effect of cytokine release on: -inflammation -trafficking Study of In VItro Immune response of cells isolated from pregnant donors to various laboratory viruses

Current Students: PhD: Chris Cotter, Won KeunKim, kester Haye, Tamar Hermesh, Bruno Moltedo, Hannah Phipps-Yonas, Tamar Hermesh, WonKeun Kim

Postdoctoral Fellows: Maria Escribese, Antonio Borderia, Marta Rodriguez, Wenjing Li

Research Personnel: Sharon Czelusniak, Luis Munoz, Martine Loubeau, Melissa Larrier, Bhakti Rawal, Karla Tapia

Summary of Current Research:
The major emphasis of the Moran lab is the investigation of the interaction of virus and the immune system. Dendritic cell maturation is a crucial step in the development of adaptive immunity. This work has been carried out in the mouse model using in vivo and in vitro systems. Our in vivo studies which are designed to monitor the kinetics of DC maturation provide a unique insight into the initation of adaptive immunity. The functionality of plasmacytoid and conventional DCs have also been explored in our laboratory. Migration studies of myeloid precursors of these cells are also being investigated using influenza virus, a well-adapted pathogen. Other ongoing studies of our lab, in collaboration with Dr. Carolina Lopez, involve the examination of the triggering of immunity by a particular species of defective interfering particles produced in Sendai virus. These molecules have enormous potential as immune enhancers.

The above studies have provided a foundation for the study of human immunity which uses cell populations collected from donor blood. At present, three types of DCs are studied: those present in circulating blood: CD11c positive DCs and plasmacytoid DCs as well as DCs generated in culture from CD14 positive monocytes. DCs are infected with recombinant influenza viruses and Newcastle disease viruses. The activation of these cells is measured by release of immunologically active proteins and genetic profiling analyzed by qRT-PCR. Using these techniques, we have identified genes that are activated in DCs after infection by virus that code for cytokines and chemokines, receptors and transcription factors. Of particular interest is the impact of viral antagonists on the maturation of DCs following exposure to virus. The interferon antagonist, NS1, found in all influenza viruses, has been shown to inhibit DC maturation as well as innate immune functions.

Dr. Moran is the Director of the Center for Investigation of Viral Immunity and Antagonism (CIVIA), an NIH funded project uniting researchers from different disciplines. CIVIA supports research on the human immune response to Category A-C pathogens (those which have been defined to pose the greatest bioterrorism threat). CIVIA developed tools for the rapid characterization of the pathogenic effect of these agents on the human immune system by combining cutting edge technology, clinical and research capabilities and educational outreach programs geared to these studies.

It is well documented that during pregnancy, autoimmune phenomena are usually reduced but infection by many pathogens (influenza, malaria, listeria) becomes more severe. It has not been clearly established how immunity is altered during following conception. Utilizing the technology developed in CIVIA has allowed the Moran lab to undertake an examination of the changes that occur in the immune syst em of women during different stages of pregnancy. In collaboration with the Departments of Obstetrics & Gynecology, a longitudinal study of their immunity is currently underway using NK cells, T Cells and mdcs isolated from the blood of pregnant donors. We hope to expand the study to include samples from patients with complications of pregnancy, such as pre-eclampsia, or IUGR (intrauterine growth retardation). The generation of information may provide clinically significant predictors of the aforementioned anomalies. We are also collaborating in a pilot study, with the Center for Advanced Medicine studying the transmission of Influenza in Healthy adults. Nasal, throat and blood samples collected from consenting patients and close contacts are analyzed for the efficacy of vaccination, as well as for various immune parameters.

The Hybridoma Shared Facility (HSRF) and CIVIA (The Center for Investigating Viral Immunity and Antagonism) are strongly affiliated with our lab. The HSRF offers investigators various services involving the production of custom-made monoclonal antibodies. These antibodies are produced in mice or hamsters, and are screened by numerous assay systems including ELISA, immunostaining, flow-cytometry and Western Blot analysis. Recently, genetic immunizations have been employed which may provide antibodies that are more useful when recognizing native conformational epitopes on the antigen provided by the investigator.

Borderia AV, Hartmann BM, Fernandez-Sesma A, Moran TM, Sealfon SC. Antiviral Activated Dendritic Cells: A Paracrine Induced Response State. J.Immunol;-in press.

Phipps-Yonas H, Seto J, Sealfron SC, Moran T, Fernandez-Sesma A. Interferon-b Pretreatment of Conventional and Plasmacytoid Human Dendritic Cells Enhances their Activation by Influenza Virus. Plos Pathogen;-in press.

Escribese MM, Kraus T, Rhee E, Fernandez-Sesma A, Lopez CB, Moran TM. Estrogen inhibits dendritic cell maturation to RNA viruses. Blood;-in press.

Friedman CS, O'Donnell MA, Legarda-Addison D. The tumor suppressor CYLD is a negative regulator of RIG-I-mediated anti-viral response. EMBO Reports;-in press.

Phipps-Yonas H, Ke J, Hartmann B, Ge Y, Sealfon S, Moran TM. A Comprehensive Evaluation Of Human Plasmacytoid Dendritic Cells Using Small Volumes Of Human Blood. J. Interferon and Cytokine Research;-in press.

Madan RP, Tan M, Fernandez-Sesma A, Moran TM, Emre S, Campbell A, Herold BC. A prospective, comparative study of the immune response to inactivated influenza vaccine in pediatric liver transplant recipients and their healthy siblings. Clin Infect Dis 2008; 46: 712-718.

Lopez CB, Moran TM. Host Immune Response to Influenza Virus. In: Yang D, editor. Host Gene Responses to RNA Viral Infection (2008). Vancouver, BC, Canada, World Scientific Publishing;.

Yount JS, Gitlin L, Moran TM, Lopez CB. MDA5 participates in the detection of paramyxovirus infection and is essential for the early activation of dendritic cells in response to Sendai Virus defective interfering particles. J Immunol 2008; 180: 4910-4918.

Hu J, Sealfon SC, Hayot F, Jayaprakash C, Kumar M, Pendleton AC, Ganee A. Chromosome-specific and noisy IFNB1 transcription in individual virus-infected human primary dendritic cells. Nucleic Acids Res 2007; 35: 5232-5241.

Fernandez-Sesma A, Moran TM. Role of the Influenza Virus NS1 protein in evasion of immunity. Future virology 2007; 2: 4.