The Totah lab is a translational, hypothesis driven lab with clinically relevant research projects. The lab studies cytochrome P450 enzymes involved in fatty acid metabolism especially arachidonic acid to epoxyeicosatrienoic acids (EETs) and the role these EETs play in maintaining the physiology and contribution to pathophysiology in the heart and kidney. The lab utilizes human tissue samples, animal studies, cell models and recombinantly expressed proteins to discover the effect of enzymes involved in the formation and metabolism of fatty acids and changes that occur during disease state. It uses transcriptomic analysis utilizying RNA-seq, quantitative proteomics and specific biomarkers to determine changes in the RNA and protein expression in healthy vs. diseased tissue. It also uses primary ventricular myocytes subjected to disease mimicking conditions of hypoxia, increased reactive oxygen species and chemical insult to reveal novel pathways involved in cardiac protection and uncover druggable targets to prevent and treat cardiac disease.
The Totah lab has active projects investigating the role of CYP2J2 and EETs in risk of sudden death and the diabetes induced cardiomyopathy. The lab is interested in determining the drug metabolism role of CYP2J2 in the heart and if inhibition by certain drugs can lead to cardiotoxicity.
In another project the lab is interested in the role CYP2J2 plays in metabolizing drugs locally in the kidney and its contribution to drug-arachidonic acid interaction and effect on kidney function, tumor generation, and chemotherapeutic resistance.
The other main research direction for the lab is to understand the importance of circulating hydrogen sulfide and chemistry involved in adducting proteins and signaling during cardiomyopathy. It has recently discovered the enzymes that methylate hydrogen sulfide to methane thiol and it is actively working to determine the role of hydrogen sulfide methylation in vivo and its effects on cellular function.