Postdoctoral Researcher

The Holmes Lab is looking for a postdoctoral researcher to join our lab to carry out research projects related to innate immunity and pathogenesis in arthritogenic alpha virus infections. Our research focuses on defining the tissue tropism of emerging arthritogenic alphaviruses and determining how cells that are permissive to infection influence virus dissemination and disease progression.

Our most recent published work demonstrated that, in contrast to established paradigms, there are two phases of alpha virus transport through the lymphatics at early times of infection, one that precedes viral replication, and a second that requires replication in the skin which enables transit to the bloodstream (Holmes AC et al, doi: 10.1016/j.celrep.. We found that skin-infiltrating Ly6

Chi monocytes promote infection of several non-hematopoietic cell types in the skin. Unexpectedly, in contrast to the skin, lymph node-associated monocytes are refractory to virus infection. Our work highlighted that there is an underappreciated role for cell-free, fluid-phase lymphatic trafficking during early alpha virus dissemination and that there may be tissue-specific signals that govern monocyte permissiveness to alpha virus infection. Our aim is to identify and define the mechanisms that drive monocyte heterogeneity in arthritogenic alpha virus infections.

In a forthcoming manuscript (Holmes AC et al, submitted, PLoS Pathogens), we have identified a subset of platelet‑derived growth factor alpha‑positive (PDGFRα+) skeletal muscle mesenchymal cells that are infected via the major arthritogenic alpha virus entry receptor, matrix remodeling‑associated protein 8 (MXRA8). Infection of this PDGFRα+ cell subset increases local vascular permeability to mediate virus spread directly to the bloodstream in a manner that is dependent on vascular endothelial growth factor ( VEGF ) signaling.

Our aim is to define the molecular events that underlie the VEGF signaling cascade during arthritogenic alpha virus infections and determine how virus disseminates across the vasculature.

Duties will include:

• The candidate will be trained on and perform in vitro and in vivo experiments related to arthritogenic alpha virus infections
• The candidate will carry out qRT- PCR on mouse tissues
• The candidate will carry out flow cytometry
• The candidate will carry out microscopy and imaging of mouse tissues
• The candidate will generate and maintain primary cell lines from mice and commercially available cell lines and carry out arthritogenic alpha virus infections in both primary cells and cell lines
• The candidate will develop projects involving methods such as single-cell and spatial RNAseq
• The candidate will prepare manuscripts for publication
• The candidate will be required to work at both BSL
  -2 and BSL
  -3 and will receive the appropriate institutional safety training

We are a new lab supported by funding from the Howard Hughes Medical Institute ( HHMI ) and are looking to grow! The lab is committed to the success of all members and provides mentorship and opportunities for research and career development. We are located at the Jacobs School of Medicine and Biomedical Sciences in downtown Buffalo, NY.

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