BBS Faculty Member - Paul Yu

Paul Yu

Department of Medicine

Brigham and Women's Hospital
Thorn Biosciences 1203A
20 Shattuck Street
Boston, MA 02115
Tel: 857-307-0395
Fax: 617-278-5509
Email: pbyu@bics.bwh.harvard.edu
Visit my lab page here and here.



The focus of Paul Yu’s laboratory is to determine how signaling via the bone morphogenetic protein (BMP) signaling pathway contributes to the pathophysiology of disease, and more broadly, how it directs the remodeling of mesenchymederived tissues. We have examined models of disease thought to entail gain-of-function in the BMP signaling pathway.

These include vascular and valvular calcification, and ectopic ossification of skeletal muscle and connective tissues, which we have studied in small animals using models of atherosclerosis and fibrodysplasia ossificans progressiva (FOP). These diseases are thought to represent a spectrum of heterotopic ossification (HO) disorders. We are interested in (i) the mechanisms by which BMP signals may synergize with other inflammatory or osteogenic stimuli in order to drive endochondral bone formation, and (ii) the progenitor populations that are recruited in order to form endochondral tissues. Second, we have studied a disease thought to entail loss-of-function in the BMP signaling pathway, idiopathic pulmonary arterial hypertension (IPAH). Loss-of-function mutations in the gene encoding the BMP type II receptor (BMPR2) have been detected in the majority of individuals with familial IPAH, and in a proportion of individuals with sporadic IPAH. We have modeled this disease with conditional BMPR2 knock-out mice, examining their pulmonary vascular function in vivo and their tissues in vitro for evidence of aberrant BMP-mediated function. To facilitate these studies we are developing novel pharmacologic tools for probing BMP and TGF-β signaling pathways. This effort has yielded pharmacophores which are being refined for enhanced selectivity within the BMP signaling pathway. These molecules have gained widespread use as probe compounds for interrogating BMP and TGF-β signaling pathways, and hold promise as therapies for BMP signaling gain-of-function diseases.



Last Update: 8/28/2013



Publications

Yu PB et al., Nat Chem Biol 2008, 4(1):33-41.

Yu PB et al., Nat Med 2008, 14(12):1363-9.

Steinbicker AU et al., Blood 2011, 117(18):4915-23.

Derwall M et al., ATVB 2012, 32(3):613-22

Mohedas AH et al., ACS Chem Biol 2013, 8(6), 1291-1302.

Bagarova J et al., Mol Cell Biol 2013, 33(12):2413-24.

Sanvitale CE et al., PLoS One 2013, 8(4);e62721.

Malhotra R et al., Pulm Circ, 2013, June-July.



© 2013 by the President and Fellows of Harvard College