University of California, Riverside

School of Medicine



Faculty Biographies


Ilhem Messaoudi

ASSOCIATE PROFESSOR OF BIOMEDICAL SCIENCES

 Ilhem Massaoudi

University of California, Riverside
Riverside, CA 92521

Tel: (951) 827-7774
E-mail: ilhem.messaoudi@ucr.edu
Office: 311 School of Medicine Research Building

Education and Training

  • B.S., Biochemistry, Lafayette College, Easton, PA, 1996
  • Ph.D., Immunology, Cornell University Graduate School of Medical Sciences, and Memorial Sloan-Kettering Cancer Center joint Immunology Program, New York, NY, 2001
  • Postdoctoral Fellow, Vaccine and Gene Therapy Institute, Oregon Health and Science University, 2006

Research Summary

Research efforts in the Messaoudi laboratory are focused on three general areas: 1) the impact of age on immune response to viral infections; 2) modulation of immune function by nutritional intake and sex steroids levels; and 3) uncovering mechanisms of pathogenesis during infection with emerging and re-emerging infectious agents.

1. Immune senescence and viral infections

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 on influenza infection in rhesus macaques: influenza infection results in ~36,000 death annually most in individuals over the age of 65. We are examining the impact of age on disease severity and immune response to pandemic H1N1 influenza infection using a rhesus macaque model of infection. We have recently showed that CD4 T cell responses are delayed in aged macaques. Current research efforts are focused on understanding the mechanisms underlying this delay.

2. Modulation of immune function by nutritional intake and sex steroids

a) Impact of chronic ethanol consumption on immune function: In collaboration with Dr. Kathy Grant (Oregon National Primate Research Center- ONPRC), we have recently shown that chronic ethanol self-administration in a macaque model results in profound alterations in the plasma cytokine levels and cytokine production by gut-resident T cells. We also have evidence that moderate ethanol consumption enhances immune response to vaccination while excessive ethanol intake dampens immunity. Current experiments are aimed at uncovering the mechanism underlying the biphasic effect of ethanol on immune response to vaccination and the alteration in cytokine/growth factor production with a special emphasis on the role of microRNAs.

b) Impact of high fat and calorie diet on immune senescence: Several studies suggest that obesity is associated with diminished capacity to respond to infection. However, the mechanisms underlying this increased susceptibility are poorly understood. We have shown that a diet high in fat and fructose leads to a loss of circulating naïve T cells, increased inflammatory cytokine production and reduced T cell proliferative capacity. Future studies are aimed at understanding the impact of maternal diet on the immune system of the neonate and the infant in collaboration with Dr. Nicole Marshall.

c) 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 ovarian steroids affect immune function and the impact of androgen supplementation on immune senescence in aged male macaques in collaboration with Dr. Henryk Urbanski.

3. Pathogenesis of emerging and re-emerging infections:

a) Viscerotropic yellow fever disease: In collaboration with Dr. Mark Slifka (VGTI, OHSU), we are investigating the mechanisms of virulence of yellow fever virus. To that end, we have developed a rhesus macaque model using infection with the wild type DAKH1279 YFV strain that recapitulates the development of lymphopenia, viscetropic disease and multi-organ failure seen in fatal yellow fever cases. Ongoing research is examining the basis for virulence of WT strain by examining differences in host gene expression following vaccination with the attenuated strain 17D or infection with DAKH1274. Moreover, we are assessing the immunogenicity and efficacy of novel vaccines against YFV and Dengue using a new inactivated vaccine platform developed by Dr. Slifka.

b) Defining immune correlates of protection against lethal EBOV infection: In collaboration with Dr. Feldmann (Rocky Mountain Laboratories), we are examining the immune correlates of protection against filovirus infections (Ebola and Marburg). More specifically, we are characterizing the immune response generated by the recombinant Vesicular Stomatitis Virus (VSV) vaccine. Our recent studies demonstrated that antibodies are necessary and sufficient for protection. Although this vaccine is highly efficacious, it is unlikely to garner FDA approval as VSV can infect livestock, therefore future studies are aimed at understanding the exact type of antibodies required for protection in order to design new vaccine platforms that are more likely to garner FDA approvals.

Selected Publications

  • 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. (2006) Delay of T cell senescence by caloric restriction in aged long-lived non-human primates. Proc Natl Acad Sci US. 103(51): 19448-53.
  • Messaoudi I, Fischer M.B., Warner J., Park B., Mattison J., Ingram D.K., Totonchy T., Mori M., and Nikolich-Zugich J. (2008) Optimal window of caloric restriction onset limits its beneficial impact upon T cell senescence in primates. Aging Cell 7(6): 908-19.
  • Messaoudi I., Barron A., Wellish M., Engelmann F., Legasse A., Planer S., Gilden D., Nikolich- Zugich J., and Mahalingam R. (2009) Simian Varicella Virus Infection of Rhesus Macaques Recapitulates Essential Features of Varicella Zoster Virus Infection in Humans. PLoS Pathogen, 5(11): e1000657.
  • Engelmann F., Barron A., Neuringer M., Urbanski H., Kohama S., and Messaoudi I. (2010) Surgical menopause accelerates immune senescence and reduced immune response to vaccination. AGE, 33(3): 275-89.
  • Haberthur K., Engelmann F., Barron A., Legasse A., Dewane J., Fischer M., Kerns A., Brown M., and Messaoudi I. A critical role for CD4 T cells in a nonhuman primate model of VZV infection. (2011) PLoS Pathogens. 7 (11): e1002367.
  • Meyer C., Kerns A., Barron A., Kreklywich C., Streblow D., and Messaoudi I. Simian Varicella Virus Gene Expression During Acute and Latent Infection of Rhesus Macaques. (2011) Journal of Neurovirology. 17 (6): 600-12.
  • Hammarlund E., Amanna I.J., Dubois M.E., Barron A., Engelmann F., Messaoudi I., and Slifka M.K. A flow cytometry-based assay for quantifying non-plaque forming strains of yellow fever virus. (2012) PLoS One. 7 (9): e41707.
  • Josset L., Engelmann F., Haberthur K., Kelly S., Park B., Kawoaka Y., García-Sastre A., Katze M.G., and Messaoudi I. Increased viral loads and exacerbated innate host response in aged macaques infected with 2009 pandemic H1N1 influenza A virus. (2012) J. Virol. 86(20): 11115-27.
  • Andrea Marzi, Flora Engelmann, Friederike Feldmann, Kristen Haberthur, W. Lesley Shupert, Douglas Brining, Dana P. Scott, Thomas W. Geisbert, Yoshihiro Kawaoka, Michael G. Katze, Heinz Feldmann1, and Ilhem Messaoudi. Antibodies are necessary for rVSV/ZEBOV-GP mediated protection against lethal Ebola virus challenge in nonhuman primates. PNAS in press.
  • Christine Meyer, Amelia Kerns, Kristen Haberthur, Jesse Dewane, Joshua Walker, Wayne Gray, and Ilhem Messaoudi. Attenuation of the adaptive immune response in rhesus macaques infected with simian varicella virus lacking open reading frame 61. Journal of Virology, in press.

More Information 

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900 University Ave.
Riverside, CA 92521
Tel: (951) 827-1012

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