Identification of progenitor melanocyte markers in human skin and characterization by engineered mouse models

Melanocytes are the pigment-producing cells in skin that originate from specialized pool of progenitor cells. These progenitor melanocytes are responsible for maintaining the melanocyte population over time and for regeneration, but they are rare, heterogeneous, and not fully defined in human skin. Understanding which molecular markers distinguish these progenitor populations—and how those markers relate to cell behavior—is foundational for unraveling normal pigmentation biology and early events in melanoma development. In this project, we first profile human skin to identify candidate progenitor melanocyte markers. Using high-resolution molecular techniques, we analyze human skin samples to detect gene expression patterns and protein markers that are enriched in cells with progenitor-like properties. These markers give us hypotheses about which cells are upstream in the lineage leading to mature melanocytes. To move beyond correlation, we use engineered mouse models in which the candidate markers can be traced or manipulated in vivo. These models allow us to track the lineage relationships of progenitor-marked cells over time—observing how they contribute to melanocyte maintenance, differentiation, and response to stress—and to assess how the expression of these markers correlates with behavior in a living tissue context. The mouse systems are genetically designed so that cells expressing a given marker can be labeled, followed, and, when needed, experimentally perturbed, providing a dynamic view of progenitor function. Students participating in this project will gain exposure to: - Human tissue analysis for marker discovery (e.g., sample processing, immunostaining, microscopy) - Single-cell analyses or targeted profiling approaches to detect and prioritize candidate progenitor markers - Genetically engineered mouse model work, including tissue collection, genotyping and interpretation of in vivo behavior of genetically modified mouse models - Comparative analysis between human marker expression and mouse model readouts to build translational insight This work bridges human molecular discovery with functional in vivo biology, helping to define the origins of melanocyte populations and providing a framework to understand how disruptions in progenitor dynamics might contribute to disease and cancer.