Faculty

Host-Pathogen Interactions in Persistent Infectious Diseases

     The work in my laboratory focuses mainly on questions related to host-pathogen interactions in infectious diseases. This means defining both the immune responses and the microbial characteristics that lead to infection and disease. In particular, our main focus is studying persistent infections - infections that the host is not able to clear. The persistent pathogens we focus on include both bacteria (e.g. Helicobacter pylori and Mycobacterium tuberculosis) and HIV-1. Such pathogens have evolved strategies to evade or circumvent the host-immune response and our goal is to understand the complex dynamic involved in host-pathogen interactions, together with how perturbations to this interaction (via treatment with chemotherapies or immunotherapies) can lead to prolonged or permanent health of the patient. Drug-resistance and the effects of treatment can be efficiently studied in this setting.

     Currently, our research focus is on the role of the host response in pathogenesis. The R01s funding our work aim to examine the immune responses in both HIV and TB infections in the lung . There are unique structures, granulomas, that are involved in the immune response to M. tuberculosis and we are developing methods to better understand their formation and function. In our HIV-1 studies, we are exploring the lung environment as an indicator of overall infection progression. This data could have a profound impact on our understanding the different disease trajectories seen in patients infected with persistent pathogens. We apply a host of computational tools from deterministic mathematical models to more discrete stochastic ones such as Agent Based Models and PDEs to examine spatial questions as well. Our broader goal is to develop a paradigm for understanding host-pathogen interactions leading to the pathogenesis of these persistent pathogens.
 

Selected Publications:

     Chang, ST, Ghosh, D, Kirschner, D and Linderman, JL. Peptide length-based prediction of peptide-MHC class II binding.  Bioinformatics, 22:2761-2767,  2006.

     Marino, S, Sud, D, Flynn,J  Kirschner, D. Differences in reactivation of tuberculosis induced from anti-TNF treatments are based on bioavailability in granulomatous tissue (to appear PLOS Computational Biology 2007).

     Blaser, M and Kirschner, D. The equilibria that allow bacterial persistence in human hosts. Nature. Vol 449, pps 843-849. 18 October 2007.

     Riggs, T, Walts, A, Perry, N, Lynch, J, Meyers, A, Flynn, JL, Linderman, JJ, Miller, M and Kirschner, D. A comparison of random vs. chemotactic directed motion of T cells during T cell repertoire scanning. In press, The Journal of Theoretical Biology, 2007.

     Ray, JCJ, Chan, J and Kirschner, D. Competing requirements for macrophage function contribute to intracellular survival of Mycobacterium tuberculosis (in press) The Journal of Theoretical Biology, 2008.

Dr. Kirschner's publication page