Steven H Kleinstein PhD

Associate Professor of Pathology

Research Interests

Computational immunology; Systems biology; Disease/tissue/pathway/process modeling and simulation; Statistical and model-based analysis of experimental and clinical data

Current Projects

A major current focus area for our research is the response to influenza infection and vaccination. As part of the multi-institutional Program for Research on Immune Modeling and Experimentation (PRIME), we are developing mathematical models to understand how pathogen and host variation, cytokine environment and genetics shape the dendritic cell response to influenza virus. We are also studying the influenza vaccination response as part of the NIH/NIAID Human Immunology Project Consortium (HIPC).

Another broad research theme focuses on the question: “What mechanisms underlie the ability of our immune system to continually adjust to the rapidly changing pathogenic environment?” My lab specifically works on B cell affinity maturation, and we have made significant advances in understanding germinal center population dynamics, Immunoglobulin (Ig) germline receptor diversity, somatic hypermutation and selection dynamics. Our methods and website for detecting selection are widely used by the community, and have broad applicability not only for understanding the response to pathogens, but also to determine the role of antigen-driven selection in autoimmunity and B cell cancers.

Information on additional projects is available from our lab website:
http://clip.med.yale.edu

Research Summary

Our group combines techniques from dynamic modeling, systems biology and bioinformatics to better understand the immune response.

Extensive Research Description



Selected Publications

  • Yaari G, Uduman M and Kleinstein SH. Quantifying selection in high-throughput Immunoglobulin sequencing datasets. Nucleic Acids Research. 2012. doi:10.1093/nar/gks457. PMID: 22641856
  • Kerfoot SM, Yaari G, Patel J, Johnson K, Gonzalez D, Kleinstein SH, and Haberman AM. Inter-follicular germinal center B cell and T follicular helper cell development precedes follicular Tfh maintenance. Immunity. 2011. Jun 24;34(6):947-60. PMID: 21636295.
  • Christopher R. Bolen, Mohamed Uduman and Steven H. Kleinstein. Cell Subset Prediction for Improving Blood Genomic Studies. BMC Bioinformatics. 2011. Jun 24;12(1):258. PMID: 21702940.
  • Mohamed Uduman, Gur Yaari, Uri Hershberg, Jacob A. Stern, Mark J. Shlomchik and Steven H. Kleinstein. Detecting selection in Immunoglobulin sequences. Nucleic Acids Research. 2011. Jul;39:W499-504. PMID: 21665923.
  • Zaslavsky E*, Hershberg U*, Seto J, Pham, AM, Marquez S, Duke JL, Wetmur JG, tenOever BR, Sealfon SC, Kleinstein SH. Antiviral response dictated by choreographed cascade of transcription factors. The Journal of Immunology. 2010. Mar 15;184(6):2908-17. PMID: 20164420, PMCID: PMC2856074.
  • Steven H. Kleinstein. "Getting Started in Computational Immunology". PLoS Computational Biology (2008) 4(8): e1000128 doi:10.1371/journal.pcbi.1000128
  • Two levels of protection for the B cell genome during somatic hypermutation. Man Liu, Jamie L. Duke, Daniel J. Richter, Carola G. Vinuesa, Christopher C. Goodnow, Steven H. Kleinstein and David G. Schatz. Nature (2008) Feb 14451(7180):841-5.
  • Anja E. Hauser, Tobias Junt*, Thorsten R. Mempel*, Michael W. Sneddon*, Steven H. Kleinstein*, Sarah E. Henrickson, Ulrich H. von Andrian, Mark J. Shlomchik, and Ann M. Haberman." Definition of Germinal-Center B Cell Migration In Vivo Reveals Predominant Intrazonal Circulation Patterns". Immunity (2007) Vol. 26, 655-667.

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