NF1 Signal Transduction and Vascular Dysfunction
Abstract
We have made strong progress on each of the proposed Aims. We have continued our evaluation of the signals and mechanisms involved in dysfunctional morphogenesis with strong evidence both chemical and genetic accumulating that the PI3Kinase and mTOR axis play a critical role. While this is associated with proliferative augmentation it is not clear that enhanced proliferation is required. Rapmycin was surprisingly unique in its potency to inhibit the NF1 induced mTOR activation and to reverse the dysfunctional morphogenesis. Data continues to accumulate suggesting an interplay between TGFb-related signaling and the morphogenic defects seen following loss of NF1. Finally the development of a novel mouse model of induced loss of NF1 in the adult mouse vasculature on a haploinsufficient background led to a surprise finding of rapid development of leukemia. This may suggest important control of the HSC niche by NF1.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2015
- Accession Number
- ADA620935
Entities
People
- Kevin Pumiglia
Organizations
- Albany Medical College