As a physician-scientist caring for patients with acute and chronic disease, including cancer, I am acutely aware of the burden caused by these conditions and the need for improved therapeutic treatment options. My laboratory developed an adrenal specific (AS-Cre) mouse strain, that has led to a number of discoveries, including the process of zonal transdifferentiation whereby the adrenal cortex undergoes continuous functional zonation during postnatal development (Dev Cell 2013). Additional studies have elucidated the role of the circadian clock in adrenal homeostasis (Endocrinology 2018), the role of TASK channels in regulating aldosterone release (Hypertension 2018) and a ZNRF3-dependent Wnt/β-catenin signaling gradient required for adrenal homeostasis, in collaboration with the Hammer Lab (Genes and Development 2019). We have recently reported on the essential role of b-Catenin (Cell Reports 2020), FGFR2 (Nature Commun 2020) and rosette biology (Nature Commun 2020) in postnatal adrenal homeostasis and the cooperative role of b-Catenin and p53 in the initiation of adrenal cortical carcinoma (Oncogene 2020). In parallel studies, my laboratory identified an elusive intestinal stem cell and is investigating the role in intestinal crypt dynamics in cancer initiation. I also direct the Human and Mouse Intestinal Enteroid Core of the NIH-funded (P30) Harvard Digestive Diseases Center, which has led to a number of new discoveries using both primary mouse and human gastrointestinal tissues including the description of new mechanisms underlying C. Diff. colitis (Nature 2016), new pore-forming toxins in enterococcus (Cell 2022), and a strategy to convert gastrointestinal stem cells into functional insulin-producing beta cells, ex vivo (Cell Stem Cell 2016, Nature Cell Bio in press) and enteroendocrine cells, in vitro (Nature Commun 2022). We also contributed to defining the essential role of WNT2B in the human intestine (AJHG 2018) and more recently have defined a new disorder arising from WNT2B deficiency in the adrenal cortex in both mice and humans (to be submitted).