Much of our work has been focused on establishing new paradigms in multi-tissue stem cell aging, rejuvenation and regulation by conserved morphogenic signaling pathways. It has been over 10 years since we reported that the Delta/Notch pathway (previously known for regulation of embryonic development of flies and mice alike) plays an age-specific key role in repair and maintenance of postnatal muscle.
The precise progression of muscle precursor cells along themyogenic lineage, is due to a transition from Notch signaling to Wnt signaling where crosstalk between these two pathways occurs via GSK3beta.
We later determined that the main age-elevated pathway that inhibits activation of adult stem cells is TGF-beta/pSmad. The prominent roles of Notch, Wnt and TGF-beta, as well in the regulation and aging of multiple post-natal tissues and in pathologies have since been shown to be conserved between mouse and human, confirmed and extrapolated by us and by many labs. US patent 7,837,993.
Current work focuses on novel small sample proteomics for defining the pathway interactions and their key age-specific changes and examining tissue-to-tissue conservation, e.g. uncovering the molecular and functional biomarkers of youth-health versus aging-disease.
- Conboy IM, Conboy MJ, Smythe GM, Rando TA. Notch-mediated restoration of regenerative potential to aged muscle.Science. 2003 Nov 28;302(5650):1575-7.PMID:14645852
- Brack AS, Conboy IM(equal contribution), Conboy MJ, Shen J, Rando TA. Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis.Cell Stem Cell. 2008 Jan 10;2(1):50-9.
- Yousef H, Conboy MJ, Morgenthaler A, Schlesinger C, Bugaj L, Paliwal P, Greer C, Conboy IM, Schaffer D. Systemic attenuation of the TGF-β pathway by a single drug simultaneously rejuvenates hippocampal neurogenesis and myogenesis in the same old mammal. Oncotarget. 2015 May 20;6(14):11959-78.PMID:26003168
- This body of work is reviewed in Cell Cycle. 2012 Jun 15;11(12):2260-7. PMID: 22617385