Maternal obesity alters uterine NK activity through a functional KIR2DL1/S1 imbalance.

In pregnancy, uterine natural killer cells (uNK) play essential roles in coordinating uterine angiogenesis, blood vessel remodeling and promoting maternal tolerance to fetal tissue. Deviances from a normal uterine microenvironment are thought to modify uNK function(s) by limiting their ability to establish a healthy pregnancy. While maternal obesity has become a major health concern due to associations with adverse effects on fetal and maternal health, our understanding into how obesity contributes to poor pregnancy disorders is unknown.

Maternal obesity drives functional alterations in uterine NK cells.

Over one-fifth of North American women of childbearing age are obese, putting these women at risk for a variety of detrimental chronic diseases. In addition, obesity increases the risk for developing major complications during pregnancy. The mechanisms by which obesity contributes to pregnancy complications and loss remain unknown.

An Integrated Analysis of Heterogeneous Drug Responses in Acute Myeloid Leukemia That Enables the Discovery of Predictive Biomarkers.

Many promising new cancer drugs proceed through preclinical testing and early-phase trials only to fail in late-stage clinical testing. Thus, improved models that better predict survival outcomes and enable the development of biomarkers are needed to identify patients most likely to respond to and benefit from therapy. Here, we describe a comprehensive approach in which we incorporated biobanking, xenografting, and multiplexed phospho-flow (PF) cytometric profiling to study drug response and identify predictive biomarkers in acute myeloid leukemia (AML) patients.

ADAM12-directed ectodomain shedding of E-cadherin potentiates trophoblast fusion.

Trophoblasts, placental cells of epithelial lineage, undergo extensive differentiation to form the cellular components of the placenta. Trophoblast progenitor cell differentiation into the multinucleated syncytiotrophoblast is a key developmental process required for placental function, where defects in syncytiotrophoblast formation and turnover associate with placental pathologies and link to poor pregnancy outcomes. The cellular and molecular processes governing syncytiotrophoblast formation are poorly understood, but require the activation of pathways that direct cell fusion.

A disintegrin and metalloproteinase 12 (ADAM12) localizes to invasive trophoblast, promotes cell invasion and directs column outgrowth in early placental development.

During pregnancy, stromal- and vascular-remodeling trophoblasts serve critical roles in directing placental development acquiring pro-invasive characteristics. The A Disintegrin and Metalloproteinase (ADAM) family of multifunctional proteins direct cellular processes across multiple organ systems via their intrinsic catalytic, cell adhesive and intracellular signaling properties. ADAM12, existing as two distinct splice variants (ADAM12L and ADAM12S), is highly expressed in the human placenta and promotes cell migration and invasion in several tumor cell lines; however, its role in trophoblast biology is unknown.