Article

Duke Molecular Physiology Institute Leads Bench-to-Bedside Research

Assumes leadership role in developing new disease detection strategies and their translation to underlying disease mechanisms

Images of cellular molecules

Almost seven years after its creation, the Duke Molecular Physiology Institute (DMPI) has become a leading research hub by leveraging physiologic profiling and biological analyses  known as multi-omics to develop new disease detection strategies, novel therapies, and insights into disease mechanisms

Image of director of DMPI
Christopher Newgard, PhD, Director of DMPI

Christopher B. Newgard, PhD, institute director and author of studies associated with the role of branched-chain amino acids in cardiometabolic diseases, conceived the idea to consolidate molecular physiological research while serving as director of the Sarah W. Stedman Nutrition and Metabolism Center. Newgard maintains his role as director of the Stedman Nutrition and Metabolism Center.

Beginning in 2011, Newgard spent two years gathering data to justify what he identified as a opportunity for synergy as well as a need for a more collaborative research environment. “During those years, I was a bit of a nuisance in the office of the School of Medicine dean,” Newgard says.

When Duke leaders approved the idea in 2013, DMPI was created by bringing the teams from the Stedman Nutrition and Metabolism Center and Duke Center for Human Genetics together with researchers who were “natural clinical al ies,” Newgard says. The team moved into a renovated Carmichael Building in downtown Durham with attractive new research space for its current team of 40 faculty.

Duke University Medical School Dean Mary E. Klotman, MD, praised the institute’s track record. “DMPI serves as a model for leveraging across disciplines and integrating top PhD and physician scientists in this case to come up with novel insights to metabolic diseases,” Klotman says.

Newgard acknowledges that many Duke entities consider their research translational. “But the institute has a unique flavor because although we often begin with the clinical, our team has the experience to perform comprehensive molecular profiling and then define biomarkers,” Newgard says. “That’s the starting point of our journey back to basic mechanisms.”

Five distinct research pillars exist within DMPI, but the strength of the Institute, Newgard says, is the collaborative opportunities that emerge when the scientists and physicians share ideas in a common physical environment. The fields of research are:

  • Basic research: Pursuing cellular and molecular discoveries of pathogenesis.
  • Metabolomics and proteomics: Identifying and interpreting the underlying metabolic etiology of disease, and the ways in which this is regulated by changes in protein amount and modification.
  • Genomics and epigenetics: Finding the genomic and heritable factors that cause disease. 
  • Computational biology: Developing integrative analytical foundations for research.
  • Clinical translation: Constructing the most effective, translational interface between bench and bedside.
    DMPI serves as a model for leveraging across disciplines and integrating top PhD and physician scientists in this case to come up with novel insights to metabolic diseases.
    Duke University Medical School Dean Mary E. Klotman, MD

    The collaboration between physicians and clinical researchers is the key to the growth and success of DMPI, Newgard says. “The unity of the work is the most powerful aspect of the Institute,” Newgard says. “We have an equal number of PhDs, who perform basic mechanistic research, and MDs who serve as the conduit to engage in and promote the clinical side of the research. Moreover, our MD and PhD principal investigators are constantly influencing developments in our core labs and vice versa.”

    When DMPI was created, several well-established Duke researchers joined the new enterprise as faculty members, including:

    • David D. D’Alessio, MD, chief of the Endocrinology, Metabolism and Nutrition Division and a leading researcher into the causes of type 2 diabetes, particularly abnormal insulin secretion.
    • Michael S. Freemark, MD, Chief of the Division of Pediatric Endocrinology and Diabetes within the Pediatrics Department.
    • William E. Kraus, MD, cardiologist and medical director of the Duke Cardiac Rehabilitation Program, a researcher and specialist in heart disease prevention and rehabilitation and Co-Director of the DMPI translational research section.
    • Svati H. Shah, MD, MHS, cardiologist and vice-chief, Translational Research, Duke Cardiology Division. Shah directs the Duke Adult Cardiovascular Genetics Clinic. She is co-Director (with Dr. Kraus) of the DMPI translational research section, and associate dean of genomics and director of the Precision Genomics Collaboratory.
    • Laura Svetkey, MD, MHS, director of the Duke Hypertension Center and director of clinical research at the Stedman Nutrition and Metabolism Center.