Research Topics
| D KirschnerSummaryAffiliation: University of Michigan Country: USA Publications
Research Grants
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Detail Information
Publications
Resistance, remission, and qualitative differences in HIV chemotherapyD E Kirschner
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109 0620, USA
Emerg Infect Dis 3:273-83. 1997..Also the virus population rapidly rebounds when treatment is stopped even after extended periods of remission...- Toward a multiscale model of antigen presentation in immunityDenise E Kirschner
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Immunol Rev 216:93-118. 2007..In addition, we begin to address how such models can be used to answer questions about mechanisms of infection and new strategies for treatment and vaccines... - Mycobacterium tuberculosis as viewed through a computerDenise Kirschner
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109 0260, USA
Trends Microbiol 13:206-11. 2005..tuberculosis as a human pathogen. Our goal is to stimulate experimentation and foster collaborations between theoretical and experimental scientists... - Mathematical and computational approaches can complement experimental studies of host-pathogen interactionsDenise E Kirschner
Department of Microbiology and Immunology, 6730 Medical Science Bldg II, University of Michigan Medical School, Ann Arbor, MI, USA
Cell Microbiol 11:531-9. 2009..g. seconds to lifetimes). In sum, when combined, these compatible approaches offer new opportunities for understanding host-pathogen interactions... - On the global dynamics of a model for tumor immunotherapyDenise Kirschner
Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor, MI 48109 0620, USA
Math Biosci Eng 6:573-83. 2009..This model was extensively studied using numerical simulation, however no global analytical results were originally presented. In this work we explore the global dynamics to show under what conditions tumor clearance can be achieved... - Influence of backward bifurcation on interpretation of r(0) in a model of epidemic tuberculosis with reinfectionBenjamin H Singer
Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor, MI 48109 0620
Math Biosci Eng 1:81-93. 2004..In particular, when reinfection is present the basic reproductive number, R(0), does not accurately describe the severity of an epidemic... - Role of the thymus in pediatric HIV-1 infectionD E Kirschner
Department of Microbiology, University of Michigan Medical School, Ann Arbor 48109 0620, USA
J Acquir Immune Defic Syndr Hum Retrovirol 18:95-109. 1998..We find that infection in the thymus not only can supplement peripheral infection but can help explain the faster progression in pediatric cases, as well as the early and high viral burden... - Model of HIV-1 disease progression based on virus-induced lymph node homing and homing-induced apoptosis of CD4+ lymphocytesD Kirschner
Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor, Michigan, USA
J Acquir Immune Defic Syndr 24:352-62. 2000..These results lead to a recalculation of the CD4+ lymphocyte dynamics during highly active antiretroviral therapy, and also suggest new targets for therapy... - A model to predict cell-mediated immune regulatory mechanisms during human infection with Mycobacterium tuberculosisJ E Wigginton
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
J Immunol 166:1951-67. 2001..A balance in Th1 and Th2 immune responses governed by IFN-gamma, IL-10, and IL-4 facilitate this down-regulation. These results are further explored through virtual deletion and depletion experiments... - Identification of key processes that control tumor necrosis factor availability in a tuberculosis granulomaMohammad Fallahi-Sichani
Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA
PLoS Comput Biol 6:e1000778. 2010..Ultimately, these modeling and experimental results can help identify new strategies for TB disease control/therapy... - Effect of multiple genetic polymorphisms on antigen presentation and susceptibility to Mycobacterium tuberculosis infectionStewart T Chang
Program in Bioinformatics, Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
Infect Immun 76:3221-32. 2008..Furthermore, the model allows polymorphisms to be ranked by effect, providing a new tool for designing association studies... - The timing of TNF and IFN-gamma signaling affects macrophage activation strategies during Mycobacterium tuberculosis infectionJ Christian J Ray
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109 0620, USA
J Theor Biol 252:24-38. 2008..We examine implications of these results in establishment of latent Mtb infection... - Dendritic cell trafficking and antigen presentation in the human immune response to Mycobacterium tuberculosisSimeone Marino
Department of Microbiology and Immunology, University of Michigan Medical School, 6730 Medical Science Building II, Ann Arbor, MI 48109, USA
J Immunol 173:494-506. 2004..This will induce the most protective T cell response... - Multiple mechanisms allow Mycobacterium tuberculosis to continuously inhibit MHC class II-mediated antigen presentation by macrophagesStewart T Chang
Department of Microbiology and Immunology, University of Michigan Medical School, 6730 Medical Science Building II, Ann Arbor, MI 48109-0620, USA
Proc Natl Acad Sci U S A 102:4530-5. 2005..In addition, based on a sensitivity analysis of the model, we identify other cellular processes that may be targeted by such pathogens to accomplish the same effect, representing potentially novel mechanisms... - The role of delays in innate and adaptive immunity to intracellular bacterial infectionSimeone Marino
Dept of Microbiology and Immunology, University of Michigan Medical School, 6730 Med Sci Bldg II, Ann Arbor, MI 48109 0620, USA
Math Biosci Eng 4:261-88. 2007..This allows us to evaluate completely the role of all parameters in the model. This includes identifying effects of stability switch parameters on infection outcome... - Characterizing the dynamics of CD4+ T cell priming within a lymph nodeJennifer J Linderman
Department of Chemical Engineering, Center for Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA
J Immunol 184:2873-85. 2010..Finally, we identify several pathogen-targeted mechanisms that, if altered in their efficiency, can significantly effect the generation of primed CD4+ T cells... - Synergy between individual TNF-dependent functions determines granuloma performance for controlling Mycobacterium tuberculosis infectionJ Christian J Ray
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
J Immunol 182:3706-17. 2009..Results suggest that bacterial numbers are a strong contributing factor to granuloma structure with TNF. Finally, TNF-dependent apoptosis may reduce inflammation at the cost of impairing mycobacterial clearance... - TNF and IL-10 are major factors in modulation of the phagocytic cell environment in lung and lymph node in tuberculosis: a next-generation two-compartmental modelSimeone Marino
Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor, MI 48109 0620, USA
J Theor Biol 265:586-98. 2010..Our results suggest that TNF is a major mediator of recruitment of phagocytes to the lungs. In contrast, IL-10 plays a role in balancing the dominant macrophage phenotype in LN and lung... - The human immune response to Mycobacterium tuberculosis in lung and lymph nodeSimeone Marino
Department of Microbiology and Immunology, University of Michigan Medical School, 6730 Medical Science Building II, Ann Arbor, MI 48109 0620, USA
J Theor Biol 227:463-86. 2004..Then we use the model to predict key processes determining these different disease trajectories (i.e. identify bifurcation parameters), suggesting directions for further basic science study and potential new treatment strategies... - The importance of an inter-compartmental delay in a model for human gastric acid secretionSimeone Marino
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 48109 0620, USA
Bull Math Biol 65:963-90. 2003..This suggests that gastric acid secretion homeostasis likely depends strongly on the delay in gastrin transport from the antrum to the corpus... - Contribution of CD8+ T cells to control of Mycobacterium tuberculosis infectionDhruv Sud
Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, 48109, USA
J Immunol 176:4296-314. 2006..We also determined the minimum levels of effector memory cells of each T cell subset (CD4(+) and CD8(+)) in providing effective protection following vaccination... - Differences in reactivation of tuberculosis induced from anti-TNF treatments are based on bioavailability in granulomatous tissueSimeone Marino
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA
PLoS Comput Biol 3:1909-24. 2007..Alternatively, the dose and timing of anti-TNF therapy could be modified. Anti-TNF therapy will likely lead to numerous incidents of primary TB if used in areas where exposure is likely... - A comparison of random vs. chemotaxis-driven contacts of T cells with dendritic cells during repertoire scanningThomas Riggs
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109 0620, USA
J Theor Biol 250:732-51. 2008..Our results suggest that, within a LN T-zone, a random search strategy is optimal for a rare cognate T cell to find its DC match and maximize production of activated T cells... - The dual role of dendritic cells in the immune response to human immunodeficiency virus type 1 infectionIan B Hogue
Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor, MI, USA
J Gen Virol 89:2228-39. 2008.... - The coreceptor mutation CCR5Delta32 influences the dynamics of HIV epidemics and is selected for by HIVA D Sullivan
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109-0620, USA
Proc Natl Acad Sci U S A 98:10214-9. 2001..Also, we show that HIV can provide selective pressure for CCR5Delta32, increasing the frequency of this allele... - Requirement for multiple activation signals by anti-inflammatory feedback in macrophagesJ Christian J Ray
Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor, MI 48109-0620, USA
J Theor Biol 241:276-94. 2006..This model will be useful for evaluating macrophage control of intracellular pathogens in addition to the biochemical mechanisms examined here... - Predicting differential responses to structured treatment interruptions during HAARTSeema H Bajaria
Department of Microbiology and Immunology, Department of Biomedical Engineering, The University of Michigan Medical School, Ann Arbor, MI 48109-0620, USA
Bull Math Biol 66:1093-118. 2004..Simulations predict that short-term viral suppression with varying interruption strategies does not guarantee long-term clinical benefit... - A methodology for performing global uncertainty and sensitivity analysis in systems biologySimeone Marino
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109 0620, USA
J Theor Biol 254:178-96. 2008.... - Measuring emigration of human thymocytes by T-cell receptor excision circlesPing Ye
Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor, MI, USA
Crit Rev Immunol 22:483-97. 2002..Our findings suggest that T-cell dynamics are key to the accuracy of TREC concentrations as a useful measurement of human RTEs... - Reconstitution of thymic function in HIV-1 patients treated with highly active antiretroviral therapyPing Ye
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Clin Immunol 106:95-105. 2003..We further predict that protease inhibitors have high levels of efficacy directly suppressing viral replication within the thymus, while reverse transcriptase inhibitors have low efficacy... - Reevaluation of T cell receptor excision circles as a measure of human recent thymic emigrantsPing Ye
Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109-0620, USA
J Immunol 168:4968-79. 2002..Therefore, we suggest that T cell turnover should be examined together with TREC concentration as a measure of RTE. If peripheral T cell division remains relatively unchanged, then TREC concentration indeed reflects thymic output... - Peptide length-based prediction of peptide-MHC class II bindingStewart T Chang
Program in Bioinformatics, University of Michigan Ann Arbor, MI, USA
Bioinformatics 22:2761-7. 2006..For several datasets and at least two algorithms these modifications consistently improved prediction accuracy. AVAILABILITY: http://malthus.micro.med.umich.edu/Bioinformatics.. - New insights into mathematical modeling of the immune systemPenelope A Morel
Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA
Immunol Res 36:157-65. 2006..These are collaborative studies between experimental immunologists, mathematicians, and computer scientists... - Tumor necrosis factor blockade in chronic murine tuberculosis enhances granulomatous inflammation and disorganizes granulomas in the lungsSoumya D Chakravarty
Department of Medicine and Microbiology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, F406, Bronx, NY 10461, USA
Infect Immun 76:916-26. 2008.... - Chemokine and cytokine mediated loss of regulatory T cells in lymph nodes during pathogenic simian immunodeficiency virus infectionShulin Qin
Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15260, USA
J Immunol 180:5530-6. 2008.... - Virologic and immunologic events in hilar lymph nodes during simian immunodeficiency virus infection: development of polarized inflammationBeth A Fallert
Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
J Acquir Immune Defic Syndr 47:16-26. 2008.... - Increased expression of interferon-inducible genes in macaque lung tissues during simian immunodeficiency virus infectionTodd M Schaefer
Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA
Microbes Infect 8:1839-50. 2006.... - The thymus during HIV disease: role in pathogenesis and in immune recoveryPing Ye
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
Curr HIV Res 2:177-83. 2004..Immunologic interventions aiming at restoring thymic function in AIDS patients are also reviewed...
Research Grants
- The dynamics of granuloma formation in tuberculosisDenise Kirschner; Fiscal Year: 2005..The ability to synthesize the data generated by the experiments in the models allows for an understanding of the dynamics of granuloma formation as more than the sum of its parts. ..
- Chemokine Dynamics in the HIV-1/SIV Infected LungDenise Kirschner; Fiscal Year: 2006..End of Abstract) ..
- "MSM" A multi-scale approach for understanding antigen presentation in immunityDenise Kirschner; Fiscal Year: 2007..tuberculosis as well as for other pathogens. ..
- MODELING CELLULAR IMMUNITY DURING HIV AND TB INFECTIONSDenise Kirschner; Fiscal Year: 2002..Key parameters governing these interactions will be identified through mathematical sensitivity analyses. These results will incorporate, and be tested against, known clinical and experimental data. ..