Working to generate patient-specific thymus function using human pluripotent stem cells in directed differentiation approaches that mimic developmental differentiation cues in 2D or 3D cell culture environments.
René Maehr, PhD
Associate Professor of Molecular Medicine
PhD in Pathology, Vrije Universiteit, Amsterdam, Netherlands
Postdoc, Harvard University, Cambridge, Massachusetts
Diplom, Albert Ludwig University of Freiburg, Germany
Type 1 Diabetes Research
We are investigating how normal differentiation of the thymic epithelial cell lineage is regulated and recapitulating that process with pluripotent stem cells. We envisage that this approach will unlock the potential of patient-specific pluripotent stem cells for the study and, eventually, treatment of human immune syndromes.
The thymus is a primary lymphoid organ that regulates the 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 declines in adaptive immunity.
In an approach we call Applied Developmental Biology, we merge approaches and technologies from various disciplines of biology
Immunology
Stem Cell Biology
Human pluripotent stem cells are used to study the molecular basis of cell fate decisions in the endodermal lineage. In addition, the use of induced pluripotent stem cells allows for capturing a disease-associated, potentially susceptibility-conferring genotype in a stem cell. With differentiation approaches, we explore stem cell-based models of immune syndromes.
Developmental Biology
Mouse models are utilized to elucidate the molecular basis of thymus organogenesis. For example, we applied high-throughput single-cell RNA-seq technologies to draft a developmental cell atlas of thymus organogenesis.
Functional Genomics
Massive parallel sequencing approaches are used to determine transcriptomic and chromatin states guiding cellular differentiation and function. Hypotheses developed from computational analysis of those datasets are tested with CRISPR technologies.
Selected Publications