Aging limits stemness and tumorigenesis in the lung by reprogramming iron homeostasis.

Aging is associated with a decline in the number and fitness of adult stem cells . Aging-associated loss of stemness is posited to suppress tumorigenesis , but this hypothesis has not been tested . Here, using physiologically aged autochthonous genetically engineered mouse models and primary cells , we demonstrate aging suppresses lung cancer initiation and progression by degrading stemness of the alveolar cell of origin.

Developing SHP2-based combination therapy for KRAS-amplified cancer.

Gastroesophageal adenocarcinomas (GEAs) harbor recurrent amplification of KRAS, leading to marked overexpression of WT KRAS protein. We previously demonstrated that SHP2 phosphatase, which acts to promote KRAS and downstream MAPK pathway activation, is a target in these tumors when combined with MEK inhibition. We hypothesized that SHP2 inhibitors may serve as a foundation for developing novel combination inhibitor strategies for therapy of KRAS-amplified GEA, including with targets outside the MAPK pathway.

A STAT5B-CD9 axis determines self-renewal in hematopoietic and leukemic stem cells.

The transcription factors signal transducer and activator of transcription 5A (STAT5A) and STAT5B are critical in hematopoiesis and leukemia. They are widely believed to have redundant functions, but we describe a unique role for STAT5B in driving the self-renewal of hematopoietic and leukemic stem cells (HSCs/LSCs). We find STAT5B to be specifically activated in HSCs and LSCs, where it induces many genes associated with quiescence and self-renewal, including the surface marker CD9.