The translational interface between bench and bedside

The Clinical Translational Research Section bridges basic science and patient-centered outcomes by “forward” translating laboratory findings into clinical research and “retro” translating molecular discoveries from human cohorts to mechanistic experimentation in tractable cell and animal models. We take a bench-to-bedside-to-bench approach to facilitate the discovery, validation, and qualification of novel biochemical and genetic biomarkers for diagnosing disease, predicting progression, and monitoring response to therapy.  Researchers in the DMPI clinical translation section have expertise in both basic and clinical sciences.  Our research encompasses cell biology and metabolism, genetics and genomics, and the pathophysiology of underlying disease.  Research also includes clinical trials in pharmacological treatments as well as dietary, psychosocial, and exercise interventions for prevention and treatment of disease and improving quality of life.  We provide a unique combination of physiological and biochemical techniques in order to better detect biomarkers of human disease and prediction of long-term outcomes.

We employ a broad range of techniques to study normal human physiology and human disease.  Measures of physical function include walk and strength testing, cardiopulmonary exercise testing with gas exchange analysis, energy balance (accelerometers, pedometers, heart rate monitors, activity monitors, doubly labeled water, resting metabolic rate), body composition (computed tomography, BodPod, caliper measures), organ composition (computed tomography, SPECT-CT, bone scintigraphy, MRI), and dynamic metabolic measures (oral glucose tolerance tests, frequently sampled intravenous glucose tolerance tests, hyperinsulinemic/euglycemic and isoglycemic clamps, hepatic glucose output, and metabolic flux measured with stable isotopes).  Vascular health is evaluated using structural (carotid intimal medial thickness, ankle brachial index, pulse wave velocity and reflection), functional (blood flow and compliance, endothelia function, tissue perfusion), and biochemical analyses (nitric oxide bioavailability and free radical damage). 

Diet and physical activity research utilizes dietary records and self-report measures of physical function, physical activity, quality of life, sleep and activities of daily living.  Exercise training studies are conducted with well-defined and well-documented exercise exposures varying in intensity, amount, and modality.  Biospecimens can be collected including blood, urine, and synovial fluid as well as tissue samples such as fat and muscle.  We are also developing dynamic measures of energy metabolism using magnetic resonance spectroscopy.

The Clinical Translational Research Section houses the Biomarkers Core Laboratory which conducts various measures of metabolism including lipoprotein composition, and proteins of immune status and disease state. Most recently, this research team has applied proteomic analysis of joint fluid in knee OA to identify potential new biomarkers of OA progression (1). Samples collected in our physiology intervention studies form the basis of an extensive sample and data repository that is developed in collaboration with our colleagues in the basic science, metabolomics, genomics & epigenetics, and computational biology sections to develop biomarkers of human disease and predictors of long-term outcomes.

Recent accomplishments include establishment of the STRRIDE studies as the standard for the dose-effects of exercise on cardiometabolic health (2). We have participated in the development of a gene panel that predicts acquisition of a training response to chronic aerobic exercise (3).  We have developed an innovative intervention for exercise training in the elderly and established oral nitrate therapy as a potential intervention to be used with exercise for treatment of various cardiovascular conditions (4,5).

DMPI Cores used by the Clinical Translation Group: Biomarkers and Human Physiology Testing