Research

Research in the Maehr laboratory is aimed to understand the molecular mechanisms that underlie the formation and proper function of the thymus, a primary lymphoid organ that regulates development of T lymphocytes. Dysfunction of thymus-mediated tolerance and failures in thymus organogenesis have been linked to autoimmunity and immune deficiencies, respectively. In addition, rejuvenation of thymus function could address acquired, and age-related decline in adaptive immunity.

A major direction of the laboratory is to study how normal differentiation of the thymic epithelial cell lineage is regulated, and how this differentiation process can be recapitulated with pluripotent stem cells. We envisage that this approach will unlock the potential of patient-specific pluripotent stem cells for study, and eventually treatment strategies, of human immune syndromes.

We combine next generation sequencing-based assays with molecular tools (e.g. CRISPR-technologies) and high-throughput screening, to address basic and translational questions in disease-relevant systems, such as mouse models and human pluripotent stem cells (hPSCs).

More information on our research:

One of our long-term goals is to recapitulate thymus function in patient-specific systems, to study the molecular basis of immune syndromes and pursue development of innovative treatment strategies. To be able to generate patient-specific thymus function, we utilize human pluripotent stem cells in directed differentiation approaches that mimic developmental differentiation cues in 2D or 3D cell culture environment. We utilize innovative cell culture screening approaches as well as developmental mouse models to elucidate the basis of cellular differentiation of early thymus-resident cells.

For example, recently we conducted a single cell RNA-seq based analysis of thymus organogenesis to draft a developmental cell atlas and molecular roadmap for our pluripotent stem cell differentiation efforts (Immunity, in press).

 

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