Biomedical Engineering ETDs

Publication Date

Fall 8-19-2020

Abstract

Candida spp. pathogens continue to be a major health care burden with high mortality and exceeding a billion dollars in terms of healthcare cost. Candidainfection ranges from superficial dermatological infection to more serious blood stream infection in debilitated patients. One of the major lines of innate immune defense against Candidais phagocytosis. Dectin-1 is the antifungal receptor in myeloid cells responsible for most immune responses against fungi including phagocytosis. We looked into the signaling pathway coordinating this mechanical process downstream of Dectin-1. We found that Dectin-1 activation gives rise to a significant mechanical force generation mediated through RHOA-ROCK-MyosinII pathway. Further we found out, that this RHOA-ROCK-MyosinII activation can help in early, large recruitment of tetrameric antifungal receptor DC-SIGN to fungal contact site. Finally, we developed and characterized polyacrylamide substrates and a magnetic bead-based system for studying importance of stiffness and nanoscale mechanical forces in C. albicans pathogenesis.

Language

English

Keywords

Candida albicans, mechanical force, immune recognition, receptor transport, mechanobiology tools

Document Type

Dissertation

Degree Name

Biomedical Engineering

Level of Degree

Doctoral

Department Name

Biomedical Engineering

First Committee Member (Chair)

Aaron Neumann

Second Committee Member

Tione Buranda

Third Committee Member

Judy Cannon

Fourth Committee Member

Rama Gullapalli

Fifth Committee Member

Andrew Shreve

Project Sponsors

NIH, STMC

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