Ilhem Messaoudi, Ph.D.

“…In coming decades, many forces will shape the US economy and society, but in all likelihood no single factor will have as pervasive an effect as the aging of the population…” Chairman Ben Bernanke, 2008

Aged individuals experience increased morbidity and mortality from infectious diseases. This is especially evident in cases of emerging diseases such as SARS and West Nile Virus, where most of the patients that succumb to disease are over the age of 50. This increase in susceptibility is mediated by the age-related decline in immunity commonly referred to as immune senescence. Since the proportion of aged individuals is rapidly increasing, understanding the defects in the immune systems of this vulnerable population will undoubtedly help us design interventions to improve immunity and increase the efficacy of vaccinations that could alleviate disease complications. The emphasis of my laboratory is to further our understanding of mechanisms underlying age-related T cell immune deficiencies using nonhuman primate animal models. More specifically work in my laboratory is focused on three areas:

  1. Elucidating immunological deficiencies that underlie varicella zoster virus (VZV) reactivation
  2. Understanding the interplay between menopause and immunity in aged women
  3. Determining how diet-induced obesity accelerates immune senescence

VZV reactivation and 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 VZV are not very 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 identify aspects of immune senescence that contribute to herpes zoster. Furthermore, we are identifying viral genes that can either be used in subunit vaccines against herpes zoster, or be deleted to create a safer and more efficacious attenuated vaccine. 
Ovarian senescence and its impact on immunity:
Several studies have shown that female sex hormones modulate immune function in women. However, despite intense research, we do not fully understand the impact of menopause on immune senescence. Due to increasing life expectancy, women in the United States can expect to live about one third of their life after menopause. To gain a better understanding of the impact of menopause on immune function, we are studying the effect of surgical menopause and different hormone therapy regimens on immune function in adult and middle-aged female rhesus macaques.
The impact of obesity on immune senescence:
In the last decade, obesity has become one of the most serious public health crises in the United States for both children and adults. Abnormalities in immune function are likely to be associated with, or even the cause of, obesity related diseases such as cardiovascular disease, diabetes, cancer, poor wound healing, and diminished responses to vaccination. However, the relationship between metabolism and immunity is poorly understood. Recently, together with Dr. Grove’s laboratory, we have determined that a diet high in fat and sugars results in premature aging of the immune system. The project is focused on understanding the molecular mechanisms underlying this diet-induced accelerated immune senescence.


Biography

Dr. Ilhem Messaoudi is an assistant scientist at the center and at the Vaccine and Gene Therapy Institute, OHSU. She received her B.Sc. in Biochemistry from Lafayette College (Easton, Pennsylvania) in 1996. She obtained a joint doctorate degree in immunology from The Weill Graduate School of Medical Sciences of Cornell University and Memorial Sloan Kettering Cancer Center in 2001. During her graduate tenure, she studied factors that influence the efficacy of the CD8 T cell response to viral infection. Dr. Messaoudi carried out her post-doctoral training in Dr. Janko Nikolich-Zugich’s laboratory at Oregon Health and Science University, Oregon National Primate Research Center where she focused on the characterization of changes in the phenotype and function of T cells with age in both mice and non-human primates.

Key Publications

  1. Messaoudi I., Guevara-Patino J., LeMaoult J., Dyall R., and Nikilocih-Zugich J..  Direct link between mhc polymorphism, T cell avidity and diversity in immune defense. 2002 Science 298:1797-1800.
  2. Messaoudi I., LeMaoult J., Guevara-Patino J.A., Metzner B.M., Nikolich-Zugich J. Age-Related CD8 T-Cell Clonal Expansions (TCE) Constrict CD8 T-Cell Repertoire and Have the Potential to Impair Immune Defense. 2004 J. Exp. Med. 200(10):1347-58.
  3. Messaoudi I., Warner J., Nikolich-Zugich D., Fischer M., and Nikolich-Zugich J. Molecular, cellular and antigen requirements for development of age-associated T cell clonal expansions in vivo. 2006 J. Immunol 176(1): 301-8
  4. Messaoudi I., Warner J., Fischer M., Park B., Hill B., Mattison J., Lane M. A., Roth G. S., Ingram D. K., Picker L. J.,  Douek D. C.,  Mori M., and Nikolich-Zugich J. Delay of T cell senescence by caloric restriction in aged long-lived non-human primates. 2006. Proc Natl Acad Sci U S A. 103(51):19448-53.
  5. Messaoudi I, Fischer M.B., Warner J., Park B., Mattison J., Ingram D.K., Totonchy T., Mori M., and Nikolich-Zugich J. Optimal window of caloric restriction onset limits its beneficial impact upon T cell senescence in primates. Aging cell, (6):908-19
  6. Messaoudi I., Barron A., Wellish M., Engelmann F., Legasse A., Planer S., Gilden D., Nikolich-Zugich J., and Mahalingam R. Simian Varicella Virus Infection of Rhesus Macaques Recapitulates Essential Features of Varicella Zoster Virus Infection in Humans. PLoS Pathogens, in press
  7. Ilhem Messaoudi, Jennifer E. Young, Ricki J. Colman, April M. Handy, George S. Roth, Donald K. Ingram, Julie A. Mattison. Aging and the effect of calorie restriction in rhesus monkeys. In press

 

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