My laboratory routinely models human pancreatic development in vitro by differentiating human pluripotent stem cells (hPSC) into early pancreatic progenitors (ePP). Using a protocol that tightly adheres to developmental logic, abundant PDX1+ ePP cells emerge after two weeks of in vitro culture. These ePP cells, which we can also isolate, culture and expand clonally, display a molecular signature that significantly overlaps with the developing human pancreatic primordium.

In the last several years, we have employed a suite of modern molecular, biochemical and bioinformatics approaches to establish the gene regulatory network downstream of PDX1 –
​a “pancreatic roadmap”. This work has revealed a number of poorly described (RFX6) or hitherto uncharacterised (TSHZ2 and TSHZ3) pancreatic regulatory genes that we are functionalising in vitro with CRISPR/Cas9 gene-edited hPSC lines. PDX1 is also expressed in adult b cells, where it is required for b cell maturation and survival. Interestingly, several PDX1 target genes that emerged from our studies on ePPs are also expressed in b cells, which we additionally posit function like PDX1 in the adult islet to maintain normoglycemia and are thus prone to dysregulation in diabetes. We are currently testing this hypothesis using an extended differentiation platform to generate b-like cells in vitro and in animal models (mouse and zebrafish).

Lastly, my lab is aptly called the “Endodermal Development and Differentiation” lab. In keeping with this nickname, we have begun in recent years to diversify our interests and study endodermal organ systems beyond the pancreas. These include a disease-modeling project using patient-derived hiPSC and differentiation into the lung lineage as well as an exciting study on intestinal homeostasis involving a novel centrosomal protein.​