Dr. Messaoudi is a Professor and Chair in the Department of Microbiology, Immunology and Molecular Genetics at the University of Kentucky, College of Medicine. Dr. Messaoudi obtained her Bachelor of Science from Lafayette College and her PhD from Weill Graduate School of Biomedical Sciences (Cornell University)/Memorial Sloan Kettering Cancer Center. This was followed by a post-doctoral fellowship at the Vaccine and Gene Therapy Institute at Oregon Health and Science University. After completing her postdoctoral training, Dr. Messaoudi held faculty positions at Oregon Health and Science University and the University of California (Riverside and Irvine campuses) before moving to the University of Kentucky. The Messaoudi laboratory uses a combination of experimental and computational approaches to address fundamental questions related to immunity and host defense: ) Impact of advanced age on immune fitness and ability to respond to infection; 2) Modulation of immunity at the maternal-fetal interface by maternal obesity or substance use disorder; 3) Impact of chronic ethanol consumption on immune functions; and 4) Pathogenesis of emerging and re-emerging pathogens.
B.Sc Biochemistry, Lafayette College, Easton, PA
PhD, Cornell University, New York, NY – Field of study: Immunology
Postdoctoral training, Oregon Health & Science University, Portland, OR – Field of study: Immunology, Host-microbe interactions
Inflammation is a physiological process that occurs due to the presence of infection or as a result of tissue injury. Throughout one’s life, the immune system is responsible for the identification of pathogens as well as damaged/transformed cells. The ability of the immune system to respond to microbial and cellular insults is influenced by several factors including age and nutrition. While the immune system can eliminate some of the pathogens, several microbes can manipulate the immune system to establish a chronic infection or overwhelm it. The goals of research efforts in the Messaoudi laboratory are to understand how these factors impact the ability of the immune system to function adequately by using a systems biology approach combining next generation sequencing techniques and functional immunology assays. Specifically, research is focused on four general areas: 1) Impact of advanced age on immune fitness and ability to respond to infection; 2) Modulation of immunity at the maternal-fetal interface by maternal obesity or substance use disorder; 3) Impact of chronic ethanol consumption on immune functions; and 4) Pathogenesis of emerging and re-emerging pathogens.
1) Impact of advanced age on immune fitness and ability to respond to infection
A) Mechanisms of increased susceptibility to pulmonary Nontuberculous Mycobacterial disease in the elderly: Mycobacterium avium (MAC) and other non-tuberculous mycobacteria (NTM) can cause chronic, insidious, and often debilitating lung disease necessitating complicated and extensive multi-drug antibiotic therapy that can be life-long. While NTM are ubiquitous in the environment and human exposure throughout life is frequent, pulmonary disease is found almost exclusively among the elderly. We established a rhesus macaque model that recapitulates the hallmarks of human pulmonary MAC disease, and we are leveraging this animal model to:  identify age-associated changes in immunological parameters, inflammatory markers, microbial community and  uncover age-mediated alterations in immune responses and lung microbial communities that are associated with susceptibility to and development of chronic NTM pulmonary disease.
B) Mechanisms of varicella zoster virus reactivation and herpes zoster onset: 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. We have developed the first nonhuman primate animal model that recapitulates hallmarks of VZV infection in humans and we are using this animal model to:  understand how VZV hijacks T cells to disseminate to sensory ganglia and  identify key elements of the anti-VZV immune response that control viral reactivation.
2) Modulation of maternal-fetal immunity by maternal nutritional status or substance use disorder
A successful pregnancy requires carefully coordinated changes in the immune system that facilitate placentation, promote fetal tolerance and growth, and induce labor. Deviations from this tightly regulated “immune clock of pregnancy” can lead to increased risk of gestational diabetes, pre-eclampsia, and complications during labor. Pre-pregnancy maternal obesity and opioid use are emerging as two leading threats to mother and infant health as they are both associated with adverse outcomes. Maternal obesity is associated with increased incidence of several chronic diseases such as asthma and metabolic disease. On the other hand, maternal opioid use disorder is associated with neonatal opioid withdrawal syndrome (NOWS) and long-term neuro-cognitive defects such as attention-deficit disorder. Moreover, perturbations of maternal environment are associated with increased susceptibility to microbial infections indicating defects in immune responses. We are investigating the impact of maternal obesity or opioid use on the immune clock of pregnancy and on placental and fetal immunity.
3) Impact of chronic ethanol consumption on immune function
We have recently shown that chronic ethanol self-administration in a macaque model results in profound changes in production of immune mediators, composition of microbial communities, and response to vaccination. Defects in immune responses were mediated by dysregulation of microRNA expression and chromatin accessibility that result in large gene expression changes in circulating monocytes and splenic macrophages. Because monocytes are short-lived circulating cells under constant repopulation from the bone marrow, these observations suggest perturbations of the hematopoietic niche. We are using single-cell analyses of hematopoietic progenitors to investigate whether chronic alcohol consumption reprograms the epigenetic landscape of monocyte progenitors in the bone marrow, thus giving rise to circulating monocytes poised towards a hyper-inflammatory response.
4) Pathogenesis of emerging and re-emerging pathogens.
A) COVID-19: Using clinical samples and animal models of COVID-19, we are assessing how  aging and obesity leads to increased viral disease severity due to delayed/disrupted T cell and inflammatory responses following SARS-CoV-2 infection; and  SARS-CoV-2 infection disrupts nasal microbial and transcriptional landscape; and  vaccination modulates B and T cell repertoires in adults and pregnant women.
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 platform.
C) Filoviruses (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.