Steven H. Kleinstein appointed Anthony N. Brady Professor of Pathology

Kleinstein has made fundamental contributions to immunology through the development and application of innovative computational methods.
Steven H. Kleinstein
Steven H. Kleinstein

Steven H. Kleinstein, who through his research on computational immunology has made fundamental contributions to immunology through the development and application of innovative computational methods, was recently appointed the Anthony N. Brady Professor of Pathology.

He completed his Ph.D. in computer science at Princeton University. In 2006, he was recruited to join the faculty of the Yale School of Medicine’s Department of Pathology, with a secondary appointment in 2014 in the Department of Immunobiology. He was awarded tenure in both departments in 2015 and promoted four years later to professor with tenure.

He also serves as co-director of graduate studies for the Program in Computational Biology and Bioinformatics (CBB).

A longstanding focus of his work has been somatic hypermutation (SHM) and B cell affinity maturation, the core of adaptive immunity. His lab developed the widely used Immcantation framework, which is based on foundational computational methods he devised, including the identification of clonally related B cells (Journal of Immunology, 2017; PLoS Computational Biology, 2020), integration of the resulting lineages (PNAS, 2019), detection of immune selection, and inference of migration/differentiation networks (PLoS Computational Biology, 2022). Kleinstein has applied these methods in collaborative studies to gain important biological insights into human infection, vaccination, and autoimmunity. For example, he demonstrated that B cells traffic across the blood-brain barrier in multiple sclerosis (MS) patients (Science Translational Medicine in 2014). He also helped discover a new niche for B cell development in the brain (Science, 2021).

In the broader area of adaptive immunity, he has made significant contributions to understanding germinal center population dynamics, SHM targeting, antigen-driven selection, and V gene germline diversity. He showed how influenza vaccination elicits immune responses (Nature, 2020; Elife, 2021). His group was the first to use population dynamic models in conjunction with in vivo multi-photon imaging to directly test the hypothesis of cyclic re-entry as the mechanism underlying affinity maturation (Immunity, 2007). Moving beyond physiological responses, he helped demonstrate that SHM represents a risk for genomic instability (Nature, 2008). His research has been supported by the National Institutes of Health, the Defense Advanced Research Projects Agency, and the U.S.-Israel Binational Science Foundation (BSF). He has more than 145 publications.

Over the past years, Kleinstein’s achievements have been recognized by his selection as Executive Committee member of the Adaptive Immune Receptor Repertoire (AIRR) Community, member of the Scientific Advisory Board (SAB) of the International iReceptor Plus Consortium, member of the NIH/DAIT Advisory Panel for the Bioinformatics Integration Support Contract (BISC), member of the External Advisory Committee (EAC) for the NIH/National Institute of Allergy and Infectious Diseases (NIAID) Malaria Vaccine Immunity and Efficacy Program, and his service as an editorial board member for the Journal of Theoretical Biology. He led the cross-center “signatures” project , co-led the data standards effort and currently co-leads the national data coordinating center for the NIH/NIAID Human Immunology Project Consortium (HIPC). He currently serves as co-leader of the Data Analysis Working Group of the NIH/NIAID Immunophenotyping assessment in a COVID-19 cohort (IMPACC) network.

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