The mammalian heart has evolved an extensive array of adaptive mechanisms to meet the body’s beat-to-beat physiological requirements. Recent data from human genetic studies have demonstrated that many critical genes and pathways regulating cardiac growth in health and disease remain poorly defined. For example, the early ‘stress responders’ that initiate and facilitate cardiac adaptation are speculative, and the detailed molecular basis of physiological (reversible) myocardial growth remains to be elucidated. This latter point is particularly salient, as exercise-derived cardiac growth is a bulwark against most forms of postnatal cardiac disease. Specifically, a large body of data describes the key pathways and regulators of pathological (irreversible) myocardial hypertrophy. Yet, the mechanistic link between the heart’s irreversible commitment to pathological hypertrophy is poorly defined.     

The global mission of my current and future research program is to systematically map out and identify the critical molecular events that are essential for perinatal heart development and striated muscle adaptation, with an emphasis on the molecular regulation of growth, differentiation, and regeneration. My research is focused on identifying new potential targets for pharmacological agents and clinical strategies that may result in improved therapies for cardiac dysfunction and failure. So far, my research has contributed through the discovery(1) and characterization(1–4) of MLIP and most recently identified the first human variants of MLIP that are associated with pediatric muscular dystrophy(5) with cardiac dysfunction appearing in young adults (unpublished). Understanding MLIP function has the potential to transform our understanding of fundamental cardiac biology and open new translatable opportunities.

References

1.        Ahmady, E., Deeke, S. A., Rabaa, S., Kouri, L., Kenney, L., Stewart, A. F. R., and Burgon, P. G. (2011) Identification of a novel muscle A-type lamin-interacting protein (MLIP). J. Biol. Chem. 286, 19702–13

2.        Ahmady, E., Blais, A., and Burgon, P. G. (2021) Muscle Enriched Lamin Interacting Protein (Mlip) Binds Chromatin and Is Required for Myoblast Differentiation. Cells. 10, 615

3.        Cattin, M.-E., Wang, J., Weldrick, J. J., Roeske, C. L., Mak, E., Thorn, S. L., DaSilva, J. N., Wang, Y., Lusis, A. J., and Burgon, P. G. (2015) Deletion of MLIP (Muscle-enriched A-type Lamin-interacting Protein) Leads to Cardiac Hyperactivation of Akt/Mammalian Target of Rapamycin (mTOR) and Impaired Cardiac Adaptation. J. Biol. Chem. 290, 26699–26714

4.        Cattin, M.-E., Deeke, S. A., Dick, S. A., Verret-Borsos, Z. J. A., Tennakoon, G., Gupta, R., Mak, E., Roeske, C. L., Weldrick, J. J., Megeney, L. A., and Burgon, P. G. (2018) Expression of murine muscle-enriched A-type lamin-interacting protein (MLIP) is regulated by tissue-specific alternative transcription start sites. 293, 19761–19770