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The pancreas is one of the earliest, and most commonly affected, organs in patients with cystic fibrosis (CF). Studying the pathogenesis of pancreatic disease is limited in CF patients, due to its early clinical onset, co-morbidities and lack of tissue samples from the early phases of disease. In recent years, several new CF animal models have been developed that have advanced our understanding of both CF exocrine and endocrine pancreatic disease. Additionally, these models have helped us to better define the influence of pancreatic lesions on CF disease progression in other organs, such as the gastrointestinal tract and lung.

Background: Preeclampsia, a devastating gestational hypertensive disorder, is characterized by low circulating renin relative to normal pregnancies. Vasopressin plays an important role in selected low-renin hypertensive states. Therefore, we hypothesized a role for vasopressin in preeclampsia. Methods: Copeptin, a biologically inert, 4 kDa pro-segment of vasopressin with a stable and slow plasma elimination rate, is secreted in a 1:1 molar ratio with vasopressin. In this case-control study, copeptin was measured in banked maternal plasma throughout pregnancy from women who did or did not develop preeclampsia. Results: Maternal plasma copeptin was significantly elevated in all trimesters in pregnancies that did (n=51) or did not (n=30) develop preeclampsia (first trimester: 903 vs. 2045 pg/mL, p=0.008; second trimester: 706 vs. 1806, p=0.02; third trimester: 822 vs. 1890, p=0.0006). While controlling for covariates such as age, BMI, chronic hypertension, twin gestation, diabetes, and history of preeclampsi...

We have described a novel mouse model of non-melanoma skin cancer driven by skin-specific expression of Zmiz1. These mice spontaneously developed keratoacanthomas and we have morphologically distin...

Preeclampsia is a cardiovascular disorder of late pregnancy that is, commonly characterized by hypertension, renal structural damage and dysfunction, and fetal growth restriction. Prevailing etiologic models of this disorder include T‐cell dysfunction as an initiating cause of preeclampsia. Indoleamine 2,3‐dioxygenase (IDO), an enzyme that mediates the conversion of tryptophan to kynurenine, has been linked to preeclampsia in humans, and is known to regulate T‐cell activity and an endothelial‐derived relaxing factor. To test the hypothesis that IDO is causally involved in the pathogenesis of preeclampsia, mice deficient for IDO (IDO‐KO) were generated on a C57BL/6 background. IDO‐KO and wild‐type C57BL/6 mice were bred, and preeclampsia phenotypes were evaluated during pregnancy. Pregnant IDO‐KO mice exhibited pathognomonic renal glomerular endotheliosis, proteinuria, pregnancy‐specific endothelial dysfunction, intrauterine growth restriction, and mildly elevated blood pressure compared to wild‐type mice. Together these findings highlight an important role for IDO in the generation of phenotypes typical of preeclampsia. Loss of IDO function may represent a risk factor for the development of preeclampsia. By extension, increased IDO activity, reductions in IDO reactants, or increases in IDO products may represent novel therapeutic approaches for this disorder., Indoleamine 2,3 Dioxygenase (IDO) has been implicated in the T‐cell dysregulation and early pathogenesis of the devastating pregnancy‐related hypertensive disease, preeclampsia. We demonstrate that chronic deficiency in IDO in a IDO‐KO mouse model recapitulates many of the essential phenotypes of human preeclampsia including renal damage. This novel model will help dissect the role of IDO and T cells in the early pathogenesis of preeclampsia.