RESEARCH
Our research program sits at the intersection of rheumatology, exercise physiology, skeletal muscle biology, metabolism, immunology, cardiovascular health, and aging with the overarching goal of understanding the molecular mechanisms through which physical activity and energy balance influence human health, resilience, and disease. A central focus of our work is identifying how exercise and metabolic interventions alter molecular pathways that contribute to inflammation, chronic disease, physical function, and healthy aging. Through translational studies spanning basic biology, clinical trials, and population-based research, we seek to define the biological mechanisms that connect lifestyle factors to disease prevention and improved health outcomes.
Our research helped pioneer the concept of exercise as a biologically active and potentially disease-modifying intervention in rheumatic disease. Beginning in 2008 and supported by NIH and ACR/RRF career development awards, Dr. Huffman identified skeletal muscle as a critical mechanistic link between inflammation, physical inactivity, metabolic dysfunction, and disability in rheumatoid arthritis (RA). This work challenged the traditional view of skeletal muscle as merely a target of disease and instead demonstrated its active role in regulating systemic pathways that influence inflammation, metabolism, and functional outcomes.
This conceptual framework led to a series of studies examining whether exercise-induced adaptations in skeletal muscle can modify RA disease activity and related comorbidities. These investigations included high-intensity interval training, exercise in a pre-clinical RA model, and a comprehensive remotely delivered exercise and weight loss program. Collectively, these studies demonstrated that exercise-induced improvements in RA disease activity are accompanied by favorable molecular changes within skeletal muscle, providing mechanistic evidence for exercise as a therapeutic strategy.
Beyond rheumatology, our laboratory has a longstanding involvement in major multidisciplinary studies examining the fundamental biology of exercise, metabolism, and aging. Participation in the Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE: PI William Kraus) provided an important foundation for understanding how defined doses and intensities of exercise influence cardiometabolic health through molecular and metabolic responses. Huffman’s contributions include work highlighting the impacts of hormone therapy on post-menopausal training responses and identification of a novel skeletal muscle succinate node important for insulin sensitivity responses.
Our research also extends from exercise to the study of energy balance and human aging through the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) program Dr. Huffman and Kraus co-lead the CALERIE Research Network that promotes use of CALERIE data and biospecimens to investigate molecular mechanisms of geroscience, including proteomic approaches (PI Daniel Belsky) and the legacy effects of a two-year calorie-restriction intervention on hallmarks of healthspan and aging (PI Sai Das). Recent work has also investigated biological pathways associated with preservation of strength during calorie-restriction-induced weight loss.
Dr. Huffman participates in the NIH Molecular Transducers of Physical Activity Consortium (MoTrPAC), including the North Carolina Consortium Clinical Site. MoTrPAC is a large-scale national effort designed to identify the molecular signals through which exercise communicates across cells, tissues, and organ systems. Using deeply phenotyped participants, controlled endurance and resistance training, and comprehensive blood, skeletal muscle, and adipose tissue biospecimen collections, the consortium is generating unprecedented insight into the molecular mechanisms underlying the systemic benefits of exercise. Dr. Huffman leads a working group, “Luna,” that plans to address how hormonal variation across the life impacts exercise responses.
Our translational research program spans the continuum from molecular physiology to clinical disease. Across our major research efforts, we seek to understand how exercise, energy balance, and aging influence human biology and health. STRRIDE investigates how exercise dose and training influence cardiometabolic physiology; CALERIE expands this framework to energy balance, healthspan, and biological aging; MoTrPAC aims to identify the molecular transducers responsible for the systemic benefits of physical activity; and our RA research applies these discoveries directly to inflammatory disease. Together, these complementary research programs are advancing a unified understanding of how lifestyle-related biological pathways can be leveraged to prevent disease, improve function, and promote healthy aging.
Dr. Huffman is co-Director of the Human Physiology Testing Core | Duke Molecular Physiology Institute | Duke Molecular Physiology Institute.
SUMMARY
Kim M. Huffman, MD, PhD is a tenured Associate Professor in the Department of Medicine, Division of Rheumatology. Her research seeks to define the molecular mechanisms for beneficial effects of physical activity and to translate these findings to beneficial interventions for aging-related and rheumatologic diseases.
MD, Medical University of South Carolina, Charleston, SC
PhD, Medical Scientist Training Program, Medical University of South Carolina, Charleston, SC
MHSc, Duke University School of Medicine, Durham, NC
Where I see patients.
James R. Urbaniak, MD, Sports Sciences Institute
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