Hello there! My name is Carole Zhuoxian Yan, I am from Hunan Province, China. I graduated from Central South University with a major in clinical medicine and completed a three-year rotation in the Burns and Plastic Surgery department at Xiangya Hospital during my master’s studies. My experience in this field has provided me with a solid foundation in clinical practices and patient care, especially concerning burn injuries and surgical treatments. My previous research focuses on the molecular mechanisms of the recovery of deep II°burn-injured dermis. I have been exploring the functions of miRNA/mRNA m6A modification in burns.
During my rotation, I treated many patients with burns or surgery-induced scarring. Scarring significantly impacts a patient’s appearance, function, and psychological well-being, often necessitating surgical intervention. The difficulty in healing and the frequent recurrence of keloid made a profound impression on me, inspiring me to investigate the mechanisms of scar formation and explore the possibility of preventing scars through medication. Therefore, I applied for a PhD under Professor Killugudi Swaminatha Iyer and Associate professor Mark Fear, and during our discussions, we found our research interests aligned perfectly. The ARC program’s generous scholarship and resources made joining the team an excellent opportunity, so I accepted the olive branch without hesitation.
My project focuses on skin fibrosis disease and its immunomodulation. Short-lived accumulation of monocyte-derived macrophages in a single injury can achieve scar-less healing. For instance, if a burn wound heals within 10 days, it is virtually scarless. Additionally, children heal faster and are less likely to scar than adults, likely due to immune factors, making immunomodulation a critical target for treating scarring. Macrophages are key regulatory cells of the immune system, with multiple subtypes identified. Using single-cell sequencing and spatial transcriptomics, we have identified scar-associated macrophages in various organs, including the liver and lung. We hypothesize that these macrophages significantly contribute to dermal fibrosis. Therefore, my research focuses on understanding macrophage-fibroblast cross-talk in skin fibrosis and exploring therapeutic targeting.
The first aim is to profile macrophages’ immune heterogeneity and their spatial distribution, particularly the distance between them and fibroblasts in keloid tissue. We aim to identify specific markers of scar-associated immune cells in the skin. The second aim is to investigate and validate fibroblast-macrophage crosstalk in skin fibrosis. We will co-culture macrophages and fibroblasts, modulate macrophage phenotype and function using different inducible factors, and characterize changes in ECM deposition. The third aim is to identify potential therapeutic targets in the fibroblast-macrophage interaction pathways to ameliorate or prevent fibrosis.
I aim to establish a simple and practical macrophage-fibroblast co-culture system that closely mimics the human environment and serves as a platform for anti-scarring drug screening. This project requires multidisciplinary exchange and collaboration across medicine, bioinformatics, biochemistry, biophysics, materials science, and other fields. The ARC Research Center provides these resources and opportunities. With experience in scarring research from Associate professor Mark Fear, biochemistry and materials research from ProfessorKillugudi Swaminatha Iyer, biophysics insights from
Associate professor Yu Suk Choi, and drug develope and screening from Assistant professor Wolfgang Jarolimek, along with industry support for 3D printing equipment, I am confident in the project’s success. This comprehensive guidance and support from various mentors strengthen my confidence in achieving the project goals.
