I was honored with the opportunity to work under Dr. Cecelia C. Yates this summer at the University of Pittsburgh and develop my skills as a biomedical researcher because of the support from the Summer Research Opportunity Program in Pathology (SROPP) sponsored by the American Society for Investigative Pathology (ASIP). It was an invaluable experience and training opportunity for my future research career.
The Yates’ Lab focuses on the dynamic roles that macrophages and fibroblasts play in excessive scar formation during tissue remodeling. This area of research was new to me and I was surprised to find that currently, most fibrosis related diseases are treated with anti-inflammatory medications and only slows progression. This knowledge prompted a sense of purpose and satisfaction within me as I investigated the specific interplay that exists between macrophages (inflammation modulators) and fibroblasts (extracellular matrix modulators) to better understand the cellular mechanisms that go awry in a diseased state.
Interestingly, it has been found that as the polarization of macrophages alters their cytokine and chemokine release patterns, this shifts fibroblasts behavior through paracrine pathways, resulting in a distinct composition and micro-environment within the ECM. Previously, the Yates lab reported that the mechanism by which macrophage phenotypes differentially alter fibroblasts’ pro-and anti-fibrotic matrix production, is regulated, in part, by CXC-type chemokines in the absence of TGFÎ². From that data, my summer project sought to uncover the means by which macrophages-secreted chemokines drive or inhibit fibroblast to myofibroblast-phenoconversion and matrix production. This project allowed me to create a model system that mimics the cells’ interstitial cross-talk between macrophage-specific phenotype and fibroblast.Â The data derived from this project points to macrophage-specific phenotype-fibroblast crosstalk dependency on proper tissue repair.
In addition to working in the lab, the research-focused atmosphere at the University of Pittsburgh contributed significantly to the multi-faceted training I received this summer. I had the opportunity to attend workshops hosted by Pitt’s Health Science Library that introduced Bioinformatics software analysis to me such as CLC Genomics Workbench, Correlation Engine, and Ingenuity Pathways Analysis. It was astonishing to experience and appreciate the vast amount of research capabilities that are right at the touch of my fingertips. Additionally, I attended weekly collaborative lab meetings and data and journal clubs. Most often, I heard from researchers mapping fibroblast populations from normal patients and patients with scleroderma using Single-cell RNA sequencing (scRNA-seq) methods. I was delighted to receive in-depth bioinformatics exposure this summer and learn from experts about techniques directly applicable to the research I was conducting.
I am going to be a senior Neuroscience major at the University of Pittsburgh this fall and look forward to continuing my work with Dr. Yates. I plan to extend the scope of my project by using different knockout cell lines and different signaling molecules t to find more specific modes of the interplay between macrophages and fibroblasts.
This unique experience as an SROPP student was exceptional in that it broadened my scope of knowledge of different research approaches and techniques. It also has solidified my desire to pursue pathological research. I am incredibly fortunate to have had the opportunity to work under Dr. Yates and could not have accomplished what I did without her elite mentorship and enthusiasm for research to encourage me. Having the responsibility for my research project forced me out of my comfort zone and led me to ask questions I didn’t know I had. Overall, I look forward to continuing investigating possible treatments in wound healing and fibrosis and am excited to capitalize on the skills I learned this summer and exercise them further. I owe tremendous gratitude to the American Society for Investigative Pathology and the University of Pittsburgh’s Department of Pathology and School of Nursing for this unique career-building opportunity.