One of our goals it to define pharmacology for enhancing maintenance and repair of adult tissues.Our work uncovered that MEK inhibitor precludes both proliferation and differentiation of mouse and human myogenic progenitors; and that pERK activation resets stem cell epigenome to youthful states.
Search for clinically relevant MAPK inducers yielded FGF-6 and FGF-19 and small peptides, e.g. oxytocin, that activate MAPK are capable of rapid and robust enhancement of old tissue repair. US Patent No. 9,758,763. 2017. The novel pro-myogenic FGFs and oxytocin are not oncogenic; and oxytocin is likely to enhance memory and cognition and combat osteoporosis, emphasizing the multi-functional positive role of youthful calibration of signal transduction. Multi-prong (TGF-beta and MAPK) pathway calibration might be more beneficial for tissue health and repair, because strong attenuation of TGF-beta alone inhibits oxytocin receptor; which is also a new side-effect of various viral infections (uncovered on our recently published work).
(Conboy lab→Stanford
postdoc→ CEO Juvena).
This work has lead to new bio-tech Juvena and in the Conboy lab we focus on development of novel pharmaceuticals for simultaneous “rejuvenation” of muscle, brain, bone, liver, etc. mammalian tissues.
- Elabd C, Cousin W, Upadhyayula P, Chen RY, Chooljian MS, Li J, Kung S, Jiang KP and Conboy IM. Oxytocin is an age-specific circulating hormone that is necessary for muscle maintenance and regeneration. Nature Communications. 2014; 5:4082, PMID 24915299
- Yousef H, Conboy MJ, Mamiya H, Zeiderman M, Schlesinger C, Schaffer DV, Conboy IM. Mechanisms of action of hESC-secreted proteins that enhance human and mouse myogenesis. Aging. 2014 Aug;6(8):602-20.PMID: 25109702
- Li J, Han S, Cousin W, Conboy IM. Age-specific functional epigenetic changes in p21 and p16 in injury-activated satellite cells. Stem Cells. 2015 Mar;33(3):951-61. PMID: 25447026.
- Liu Y, Conboy I. Unexpected evolutionarily conserved rapid effects of viral infection on oxytocin receptor and TGF-β/pSmad3. Skelet Muscle. 2017 May 15;7(1):7. PMID: 28506310