​Immune cell ontogeny & functionality

We investigate how growth factors and tissue-derived signals shape the development and function of myeloid cell lineages including macrophages, mast cells, dendritic cells, and neutrophils.

Using amphibians as comparative models, we examine how these immune cells develop, interact with tissues, and respond to their physiological environment to influence immune defenses, inflammation, repair, and regeneration.

Growth factor-driven cell fates: Frog bone marrow-derived precursor cells differentiated into macrophages with growth factors, colony stimulating factor-1 (CSF1) or interleukin-34 (IL34). Granulocytes differentiated with colony stimulating factor-3 (CSF3) give rise to neutrophils whereas stem/mast cell factor (SCF) drives mast cell production

Tissue Surveillance, Repair & Regeneration

Why do some animals repair wounds without scarring, while others develop persistent fibrosis? 

​​Our work examines how immune cells shape the outcome of infections and tissue injury, the later focusing on the tradeoffs between inflammation, scar formation and regenerative repair.

We investigate how key immune cell populations interact with infected and/or damaged tissues to influence return to homeostasis,

By defining how immune cell states and their communication with epithelial, stromal and other tissue-specific cell types change over the course of infections and repair, we aim to understand species specific differences in pathogen susceptibilities and why some injuries resolve through fibrosis and scarring, whereas others support regeneration. 
  

A) Altering wound macrophages impacts repair: Deposition of collagen I and III in recombinant (r)CSF1- and rIL34-administered wounds.   Our findings suggest that while macrophages differentiated with CSF1 are more prominently involved in the inflammatory phase of wound repair, IL34-macrophages predominate the later reparative phase of these responses, promoting fibroblast activation and collagen deposition.

B) Developmental stage-dependent repair efficacies: Juvenile frogs undergo scarless regeneration of skin wounds, including reformation of architecture and glands. Adult frog wounds resolve in fibrotic scars.   Our work indicates that juvenile frogs rely more heavily on IL34-derived macrophages during wound repair whereas adult frogs rely on CSF1-macrophage responses.

Control of Host-Microbiome-Pathogen Interface

There is a global rise in invasive fungal diseases, threatening biodiversity and human health. The amphibian pathogen Batrachochytrium dendrobatidis (Bd) is a prime example of this, causing major amphibian population declines. While both amphibian host immunity and skin microbiomes influence Bd resistance, how these systems interact remains unclear. We are examining how the skin-resident immune compartment and microbial communities jointly determine disease outcomes in amphibians. 

Skin-resident immune cells dictate host-microbiome-pathogen interfaces: We developed a way to enrich mast cells in X. laevis skin (arrows). These skin mast cells promote skin mucus gland (m) filling (blue) and prevent Bd-infection associated pathologies including reducing pathogen loads, preventing epithelial (Ep) thickening and skin microbiome dysbiosis.