Professor, Molecular Biology and Biochemistry
School of Biological Sciences

Director, Center for Virus Research

Viral pathogenesis, host defense, modulation of immunity by nutrition and aging, impact of the microbiome on immunity

1) Women and Diversity Paper of the year. Society of Leukocyte Biology. September 2015
2) Dolph O Adams award. Society of Leukocyte Biology. October 2014
3) Brookdale Leadership in Aging Fellowship. Brookdale Foundation. July 2009
4) Nathan Schock Junior Investigator Award. Gerontological Society of America. September 2008
5) Junior Faculty Travel award. American Federation for Aging Research to attend the 2007 conference on Biomarkers of aging. August 2007
6) Junior Faculty Travel award. American Association of Immunologists to attend the annual meeting March 2007
7) Huang Foundation Trainee Achievement Award. American Association of Immunologists. February 2005
8) NIH Training grant award# 5T32 AI007472. Interactions at the microbe/host interface. October 2004
9) Travel Award to the 11th Summer Training Course In Experimental Aging Research. National Institute of Aging. June 2003
10) Travel award to the 8th Annual Meeting of Vaccine Development. Walter Reed Army Institute of Research. May 2002
11) Frank Lappin Horsfall Fellowship of Outsanding Achievement Awarded by the Memorial Sloan-Kettering Cancer Center. July 2000
12) Travel Award to the 6th Annual Meeting of Vaccine Development. Walter Reed Army Institute of Research. May 2000
13) Vincent du Vigneaud Award of Excellence. May 2000. Weill Graduate School of Biomedical Sciences at Cornell Univeristy
14) Pre-Doctoral Fellow of the Cancer Research Institute. July 1999 – July 2001

Inflammation is a physiological process that occurs due to the presence of infection, or as a result of tissue injury. Throughout one’s life, your immune system is responsible for the identification of viruses, bacteria and other foreign invaders, some of which are eliminated, while others are controlled. The ability of our immune system to respond to microbial pathogens is influenced by several factors including age and nutrition. Moreover, several microbes can manipulate our immune system to establish a chronic infection or overwhelm it. The goals of research efforts in the Messaoudi’s laboratory is to understand how these factors impact the ability of the immune system to function adequately. More specifically, research in the Messaoudi lab is focused on three general areas: 1) impact of advanced age on immune fitness and ability to respond to infection; 2) Modulation of immune function by alcohol use disorder and obesity; and 3) Subversion of the immune system by viruses.

1. impact of advanced age on immune fitness and ability to respond to infection:
a) Towards a better understanding of herpes zoster: The reactivation of varicella zoster virus (VZV) results in herpes zoster, more commonly known as shingles, which causes significant morbidity and sometimes mortality in the elderly. The immunological and virological bases for VZV reactivation are poorly understood. Furthermore, the currently available vaccines against varicella and zoster are not 100% efficacious. We have developed the first nonhuman primate animal model that recapitulates hallmarks of VZV infection in humans. We are using this animal model to: 1) identify key elements of the anti-VZV immune response that control viral replication and 2) characterize the pattern of viral gene expression to identify viral genes that can either be used in subunit vaccines against herpes zoster, or be deleted to create a safer attenuated vaccine.
b) Impact of age-related decline in sex steroids levels on immunity: Sex steroids modulate immune response during autoimmune disease, infection and vaccination. Increasing age leads to dramatic decreases in the circulating levels of sex steroids in both women and men. However, the impact of menopause/andropause on immune senescence remains poorly understood. We showed that menopause reduced immune response to vaccination and that estradiol treatment can partially rescue this loss. We are currently studying the mechanisms by which sex steroids affect immune function and the impact of androgen/estrogen supplementation on immune senescence in aged male and female macaques.

2. Modulation of immune function by alcohol use disorder and obesity:
a) Impact of chronic ethanol consumption on immune function: We have recently shown that chronic ethanol self-administration in a macaque model results in profound alterations in cytokine production and response to vaccination in a dose-dependent fashion. Current experiments are aimed at uncovering the mechanism underlying the biphasic effect of ethanol on immune response to vaccination and immune mediator production with a special emphasis on the role of epigenetics and small RNA on regulating gene expression.
b) Impact of maternal nutritional status on offspring immunity: Pre-pregnancy obesity is emerging as one of the biggest threats to infant health as it is associated with adverse health outcomes that range from increased fetal defects to neonatal infections and long-term complications such as asthma and cardiovascular disease. We are studying the impact of pre-pregnancy maternal BMI on offspring monocyte function, a cell type that plays a critical role in host defense and chronic inflammatory diseases.

3. Pathogenesis of emerging and re-emerging infections:
b) Viscerotropic yellow fever disease: We are investigating the mechanisms of virulence of yellow fever virus (YFV) using a rhesus macaque model that recapitulates the development of lymphopenia, viscerotropic disease and multi-organ failure seen in human fatal yellow fever cases. Ongoing research is examining the basis for virulence of YFV and assessing the immunogenicity and efficacy of novel vaccines against YFV and Dengue using a new inactivated vaccine platforms.
c) Filovirus (Ebola and Marburg) hemorrhagic disease: We are examining mechanisms of pathogenesis as well as the immune correlates of protection against filovirus infections (Ebola and Marburg) using macaque models that recapitulate the human disease. Specifically, we are investigating mechanism by which these viruses induce a dysregulated inflammatory response while simultaneously hampering the development of an effective antiviral immune response.

https://www.ncbi.nlm.nih.gov/sites/myncbi/1pI12_Ixqttk1/bibliography/46779521/public/?sort=date&direction=ascending

NIH/NIAID; NIH/NIAAA; Bill and Melinda Gates Foundation

American Association of Immunologists

Society for Leukocyte Biology

American Society of Microbiology

Cellular and Molecular Biosciences

Immunology and Pathogenesis

Center for Virus Research

Institute for Immunology

Link to this profile
https://faculty.uci.edu/profile/?facultyId=6320

Last updated
02/10/2021