The Cahan laboratory, in the Department of Biomedical Engineering and the Institute for Cell Engineering at Johns Hopkins University, focuses on stem cell biology and cell fate engineering, with an emphasis on the development and diseases of the synovial joint. We use a combination of in vivo, in vitro, molecular, and computational approaches to achieve our goals. Graduate students in the Biomedical Engineering, BCMB, and Pathobiology PhD programs interested in rotating should to discuss.

Gene Regulatory Networks

Gene regulatory networks (GRNs), encoded in the genome of an organism, define the complete set of regulatory relationships among genes and gene products. GRNs govern the cell’s transcriptional output both at steady state and in response to perturbations, and thus act as major molecular determinants of cell-type identity. The study of GRNs is a central and unifying component of our research program. We are actively developing new algorithms to reconstruct GRNs, to measure their establishment, to infer their dynamics, and to model intercellular regulatory networks. We are especially interested in understanding how cell type specific GRNs are established during synovial joint development.

The assessment question

To what extent is a cell population, derived via directed differentiation of pluripotent stem cells or via direct conversion between somatic cells, equivalent to the desired cell type? We develop computational platforms that leverage the burgeoning universe of single cell data modalities to address this question. Doing so has allowed us to define common patterns of divergence between engineered populations and their in vivo counterparts, and to identify potential targets for intervention so as to yield improved cell engineering protocols.

The improvement problem

Several lessons have emerged from our applications of computational assessment of engineered cell populations. First, we found that cells derived by directed differentiation approached their in vivo target cell types more closely than those derived through direct conversion. Second, GRNs of the starting cell type frequently were maintained in engineered cells. Third, there was substantial improvement of target cell type GRN status when cell fate engineering was practiced in situ, or after engineered cells were transplanted into their native niche. Finally, we documented the aberrant establishment of GRNs of other cell types (neither the starting or the target) in engineered cells. These insights are guiding our lab's efforts to develop generic systems to improve cell fate engineering protocols. Most of these efforts are based on GRNs and involve devising algorithms that predict the identity and timing of transcriptional regulator, microRNA, and signaling pathway modulations.