Andre Terzic, M.D., Ph.D.

Location

Summary

• Cardioprotective and cardioregenerative medicine
• Genetics of cardiac disease and stress tolerance
• Bioenergetic signaling, nucleocytoplasmic communication and ion channel biology

Cardiac adaptation to stress is mandatory for survival. What cellular processes secure adaptation and safeguard myocardial function in response to demand is fundamental in the understanding of evolutionary preservation, disease incidence and outcome. The priority of this multidisciplinary research program is in deciphering molecular pathways of stress tolerance, and the identification of the genetic basis of maladaptation in human disease. This ongoing work has evolved on the principle of metabolomic matrix networks and biocatalysis applied to the pathogenetics of cardiac disease, such as heart failure. Originally initiated by the dissection of transcellular conduits of energetic signalization, using transgenesis and the innovative systems biology approach of metabolic flux imaging coupled to live nanoscale readout of cellular wellbeing, this integrative research at the interface of biophysics, biochemistry, physiology and medicine, has led to the discovery of the vital role for membrane metabolic sensors in decoding signs of energetic distress. Normally integrated with cellular energetic pathways, the proper function of metabolic decoders is found essential in securing a high-fidelity homeostatic feedback mechanism that adjusts organ function to meet demand. Failure in metabolic decoding, typified by genetic mutations in the ATP-sensitive potassium channel heteromultimeric protein complex or due to abnormal signal transmission to the channel site, increases the susceptibility for poor outcome establishing a novel paradigm in disease pathogenesis. The promise that lies ahead is in the translation of these fundamental principles of stress adaptation, established for the heart and tested in discrete patient cohorts, into broader diagnostic and therapeutic screens applied to diverse disease entities and the population at large. In particular, the ability to early detect for each individual the defining genetic basis of disease susceptibility and to treat by targeted stem cell-based repair deficits in diagnosed stress intolerance, provides a real opportunity for the further advancement of cardiovascular medicine in the decade ahead.