Pharmacology

Biography

Tetsuro Wakatsuki obtained MS in Mechanical Engineering and PhD in Biophysics at the Washington University, St. Louis. He was a faculty member of Washington University School of Medicine and Medical College of Wisconsin. Since 2012 he took a full time Chief Scientific Officer position at InvivoSciences, Inc. which he co-found in 2001. He is an honorary scientist at University of Wisconsin, Madison and conducting NIH-funded research projects with scientists in various academic institutions including University of Michigan, Ann Arbor. Several of his inventions have been allowed worldwide and one of the patented technologies received the Edison Award in 2012.

Research Interest

American healthcare system spends >$200 billion in cardiovascular treatment. Inter-individual variability in efficacy and toxicity response is rather large for cardiovascular treatments. InvivoSciences has developed an in vitro disease model that recapitulates individual patient’s cardiomyopathy in engineered heart tissues (EHTs) using the patient-derived cells. Automated cell culture and novel cardiomyocyte-differentiation protocol improved the productivity and reproducibility for generating patient-specific disease models for drug and diagnostics development. The application of our technology to establish a patient-specific disease model for a rare disease, Muscular Dystrophy (MD), will be discussed. While the exon skipping treatment could finally overcome skeletal muscle wasting of Duchenne muscular dystrophy (DMD), it depends on skeletal muscle’s high regenerative capacity. Therefore, the limited regenerative capacity of cardiac muscle encounters challenges for treating DMD heart failure, which was recognized only recently. Mass-produced micro-scale EHTs from patient-derived cardiomyocytes using induced pluripotent stem cell technology recapitulate a patient-specific DMD heart failure phenotype in vitro and screen compounds for drug discovery. A detection of slowly developing DMD cardiac phenotypes in EHTs was required to comprehensively analyze their excitation-contraction-energy coupling (ECEC) by measuring their action potential, calcium transient, cardiac contractility, and mitochondrial metabolism by a high-throughput assay device under various stress conditions. Combining multi-scale (i.e., molecule to whole body) computational models of human physiology with the ECEC analysis of EHTs will predict clinical outcomes (e.g., cardiotoxicity and efficacy) of a potential treatment at the preclinical stage. The project will support discovery of disease mechanisms to identify potential targets for therapy.