Shannon Hilchey, Ph.D.

Research Overview

My research for the last 17 years has been in the immunobiology of regulatory T cells, T follicular helper cells, and B cell differentiation, in both mice and human subjects. My specific expertise includes developing and applying innovative immunological research methods to study immunobiology in primary human samples, especially normal lymphocytes and lymphomas.  My research has included genotypic-phenotypic characterization of lymphocyte cellular subsets by combined transcriptomics and flow cytometry. I have specific expertise in research human B and T cell research where cell numbers are typically limiting. In particular, as the Technical Director of the Lymphoma Lab at the James P. Wilmot Cancer Center from 2004-2013, I have published several key studies using novel T cell functional assays with single cell RNAseq from fine needle aspirate (FNA) lymph node biopsies of lymphoma patients. Over the last 5 years, I have developed my own independent research work, with a focus on multidisciplinary transcriptomic and proteomic analysis of B cell differentiation and migration. This work has evolved from collaborations with Drs. Juilee Thakar and Martin Zand, including an RO1 (R01-AI134058-01A1) in which we propose to characterize and model the molecular mechanisms by which changes in oxygen levels modulate human B cell migration. The work involves defining and modeling how human B cells respond to infection or vaccination upon encountering different oxygen levels as they are activated/differentiate within the developing germinal center of the draining lymph node and migrate from the lymph node (1-5% oxygen) to the peripheral blood (5-13% oxygen) ultimately ending up in the bone marrow (5-7%). These studies will fill a critical gap in our understanding of human B cell responses, specifically the effects differing oxygen levels have on human B cells as they migrate within and from one anatomical compartment to another. We are now extending this work into HIV vaccination. My prior work involved studies directly related to the current proposal, including complex parallel flow cytometry, ELISpot, ELISA, RNAseq, and proteomics analysis. Lastly, throughout my tenure at the University of Rochester, I have successfully collaborated with a number of other researchers and produced several peer-reviewed publications, including publications with Dr. Thakar performing high-resolution proteomics and transcriptomics studies.

Grants

Modeling of HIF-1-alpha Regulation of B Cell Migration

R01-AI134058-01A1

Major Goals: This project proposes to characterize and model the molecular mechanisms by which changes in oxygen levels modulate human B cell migration. The work involves defining and modeling how human B cells respond to infection or vaccination upon encountering different oxygen levels as they are activated/differentiate within the developing germinal center of the draining lymph node and migrate from the lymph node (1-5% oxygen) to the peripheral blood (5-13% oxygen) ultimately ending up in the bone marrow (5-7%). These studies will fill a critical gap in our understanding of human B cell responses, specifically the effects differing oxygen levels have on human B cells as they migrate within and from one anatomical compartment to another.

Modeling Mechanisms of Adjuvanted Influenza Vaccine Induced IgG Repertoire Diversity and Heterosubtypic Immunity

R01-AI129518-01

Major Goals: The goal of this study is to model the B cell molecular somatic mutation events that occur when MF59 adjuvant is used in seasonal influenza vaccination.  The work involves both murine and human experiments to with influenza vaccination.  Multi-dimensional data regarding IgG cross reactivity with vaccine strains, as well as influenza strains with related hemagglutinin sequences, will be linked to immune repertoire sequences of vaccine responsive B cell IgG complementarity determining regions, and correlated with protein sequences.  This data will be used to model and validate sequence emergence, and how MF59 adjuvant results in broader influenza reactivity than unadjuvanted vaccines.

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