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John Mittler has broad interests in ecology and evolutionary biology, and will be available to meet with faculty and students all day Monday (the Department will also spring for a free breakfast for some lucky person on both Monday and Tuesday). If you'd like to meet with John (and I encourage you to; he’s good value), please contact Mary Price (mary.price@ucr.edu; 232-9505), who is organizing his schedule.

Talk Abstract:

The major obstacles to HIV-1 treatment are the evolution of drug resistance and persistence of viruses within latently infected cells.   Longitudinal studies of the decline of latently infected cells during therapy suggest that these cells have a half-life of ~4 years.  This estimate, however, assumes that therapy is 100% effective.  To address this limitation, we have developed a novel method for estimating the longevity of viral reservoirs from changes in genetic divergence (i.e., distance from the founder virus) that occur during therapy.  Our method gives much shorter half-lives (median ~1 year), though this is still too long for viral eradication to be a realistic option using current therapies.  It may still be possible, however, to eradicate populations of viruses resistant to one- or two-drug “maintenance regimens” after a period of highly intense “induction therapy.”  Our models suggest that under a variety of biologically plausible conditions that 4-10 months of induction therapy are needed to maximize the probability of eradicating viruses resistant to the maintenance regimen.  This is longer than the 2-3 months used in early (unsuccessful) trails of induction-maintenance therapy.  Interestingly, our models suggest that the optimal time to intensify therapy is often several days to weeks after the start of regular, maintenance therapy.  This delay is a consequence of virus-target cell dynamics similar to that which occur in predator-prey systems.

Brief biography & research interests:

John Mittler received his B.A. in biophysics and applied mathematics from the University of California at Berkeley and his Ph.D. in biological sciences from the University of California at Irvine with Dr. Richard Lenski.  John also did postdoctoral research at Emory University with Dr. Bruce Levin and at Los Alamos National Laboratory with Dr. Alan Perelson.

Dr. Mittler's laboratory specializes in the population biology of microorganisms (although he maintains a secret interest in species coexistence). Examples of questions addressed in his laboratory include: (1) How can therapy regimens be optimized to reduce the probability that HIV-1 will evolve resistance to anti-retroviral drugs? (2) Can we create realistic mathematical models for the interactions between HIV-1 and the immune system? (3) How can compartments and reservoirs for viral and bacterial infections be identified and targeted? (4) How can cytokines and other immunodulatory agents be employed to reduce HIV-1 replication? (5) Can we create models to account for the ordered construction and evolution of the flagellum in Salmonella typhimurium?

Selected Publications:

Wang, K., Mittler, J. E., and Samudrala R. 2006. Comment on evidence for positive epistasis in HIV-1. Science 312:848.

Price, M. V. and Mittler, J. E. 2006. Cachers, scavengers, and thieves: a novel mechanism for desert rodent coexistence. American Naturalist 168:194206.

Liu, Y., Mullins, J. I., and Mittler, J. E. 2006. Waiting Times for the Appearance of Cytotoxic T-lymphocyte Escape Mutants in Chronic HIV-1 infection. Virology 347:140-146.

Mittler, J. 2005. Within-host dynamics and treatment of HIV-1 infection: Unanswered Questions and Challenges for Computational Biologists. Chapter 16 in Deterministic and Stochastic Models for AIDS Epidemics and HIV Infection with Interventions. Eds. Wu, H. and Tan W-Y. World Scientific Publisher.

Wang, K., Jenwitheesuk, E., Samudrala, S., and Mittler J. E. 2004. Simple linear model provides highly accurate genotypic predictions of HIV-1 drug resistance. Antiviral Therapy 9: 343-352.

Wang, K., Samudrala, R., and Mittler, J. E. 2004. Antivirogram or PhenoSense: a comparison of their reproducibility and an analysis of their correlation. Antiviral Therapy 9: 703-712.

Nickle, D. C., Learn, G. H., Rain, M. W., Mullins, J. I., and Mittler, J. E.  2002.  Curiously modern DNA for a 250 million-year-oldbacterium. Journal of Molecular Evolution 54:134-137.