Ahmed Mahmoud

Heart failure is the leading cause of death in the world due to the inability of the adult mammalian heart to regenerate following injury. Lower vertebrates, such as zebrafish are capable of complete and efficient regeneration of the myocardium following injury. Similarly, we demonstrated that neonatal mice are capable of regenerating their hearts within a short period after birth but lose this potential in the first week of life. Adult mammals lack this cardiac regeneration potential, thus our overarching goal in the laboratory is to dissect the molecular underpinnings of regeneration in the neonatal heart so that we can explore potential avenues to activate this process in adult humans.

Our goals are to identify the transcriptional and epigenetic networks that govern cardiomyocyte dedifferentiation and proliferation through studying evolutionarily conserved mechanisms of regeneration. These studies could aid in converting adult cardiomyocytes to a more proliferative and regenerative state. In addition, we aim to identify the microenvironment signals that regulate mammalian heart regeneration by studying the interplay of nerves as well as extracellular factors during mammalian heart regeneration. We use multidisciplinary approaches including genomics, proteomics, and mouse genetics in addition to molecular and cellular technologies to address these questions.

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Mahmoud, A.I., O’Meara, C.C., Gemberling, M., Zhao, L., Bryant, D.M., Zheng, R., Gannon, J.B., Cai, L., Choi, W., Egnaczyk, G.F., Burns, C.E., Burns, C.G., MacRae, C.A., Poss, K.D., Lee, R.T. Nerves regulate cardiomyocyte proliferation and heart regeneration. Developmental Cell, 2015 Aug 24;34(1):1-13.

Mahmoud, A.I., Porrello, E.R., Kimura, W., Olson. E.N., Sadek, H.A. Surgical models for cardiac regeneration in neonatal mice. Nature Protocols, 2014 Feb;9(2):305-11.

Mahmoud, A.I., Kocabas, F., Muralidhar, S.A., Kimura, W., Koura, A.S., Thet, S., Porrello, E.R., Sadek, H.A. Meis1 regulates postnatal cardiomyocyte cell cycle arrest. Nature, 2013 May 9;497(7448):249-53.

Porrello, E.R., Mahmoud, A.I., Simpson, E., Johnson, B.A., Grinsfelder, D., Canseco, D., Mammen, P.P, Rothermel, B.A., Olson, E.N., Sadek, H.A. Regulation of neonatal and adult mammalian heart regeneration by the miR-15 family. Proc. Natl. Acad. Sci., U.S.A, 2013 Jan 2;110(1):187-92.

Porrello, E.R.,Mahmoud, A.I., Simpson, E., Hill, J.A., Richardson, J.A., Olson, E.N., Sadek, H.A. Transient regenerative potential of the neonatal mouse heart. Science, 2011 Feb 25;331(6020):1078-80.