Dr. Kraus’ research group focuses on understanding the biological mechanisms whereby exercise training results in health benefits, and then translating that knowledge into clinical practice. The work spans basic science to cell culture to integrative physiology in human subjects. A second, but integrated line of work seeks to use multiplatform molecular data from human subjects to understand the molecular architecture of human atherosclerotic cardiovascular disease.
Our work on the mechanisms of exercise training has centered on our human studies that range from those in healthy individuals (adolescents in the Durham Elite Athletes Study) to those with established atherosclerotic disease (cardiovascular and peripheral vascular disease (AMNESTI), heart failure (HF-ACTION) and healthy aged (FIT for LIFE). In work spanning over 15 years we have been studying the effects of different modes, intensities and amounts of exercise on cardiometabolic risk factors (STRRIDE studies, funded by the NIH) (1,2,3,4,5,6,7). We are using this work to develop science around the role of energy cycling and energy balance on health during the lifespan, in particular on stem cell health. This work is being translated into a clinical program to promote healthy aging.
We have been investigating the utility of molecular markers to predict responses to exercise exposures of different types as outlined above. It is clear that approximately half of the variability in this response is heritable: that is, it is in one’s genes. Collaboratively, we have helped to develop a gene score that predicts improvements in cardiovascular fitness with exercise training (8). We are applying this to other cardiometabolic outcomes and incorporating genomics and metabolic data. Soon, in combination with the information gleaned from our previous work, we should be in a position to be able to recommend the right exercise, for the right person, at the right time—“personalized lifestyle medicine.” To this end are also interested in the effects of exercise when used in combination with drug therapy on health outcomes—a little studied area that is in demand for much more work. The entire enterprise, we call Lifestyle Medicopharmacogenetics. The STRRIDE clinical data and biorepository feeds this work.
We are proud to be part of an initiative that is housed in the Department of Biomedical Engineering to develop cellular models of multi-tissue physiologic integration “on a chip”. This builds upon over 15 years of collaborative work that seeks to tease out the specific biological signals (mechanical, electrical, paracrine, hormonal and metabolic) that signals muscle to modify phenotype (metabolic and fiber type) characteristics in response to chronic exercise (9,10,11). In our current work, we are using the multi-tissue chip technology to understand the mechanisms responsible for muscle adaptation to environmental cues (12).
Finally, a major effort within the Molecular Physiology Institute is to develop and understand molecular signatures (metabolite, genomic, genetic) which when combined with clinical information, provide strong predictive classifiers, or signatures, for cardiovascular disease (13,14,15). This work is built upon several robust clinical cohorts, bio-repositories and data repositories that have been assembled to develop this science, among them CATHGEN, GENECARD, CARRIAGE Family, and HF-ACTION. Understanding predictive molecular signatures will lead to new therapeutic strategies for prevention of cardiometabolic diseases.