Peter Crawford's Research Focus
Obesity and cardiovascular disease are among the leading causes of morbidity and mortality worldwide. Our research focuses on the interplay between intermediary metabolism and these disease processes. Derangements in the processing of carbohydrates, fats, and amino acids are central drivers of disease pathogenesis, but the roles of another metabolic fuel class, ketone bodies, are less well understood. We use novel genetic mouse models with engineered deficiencies in ketone body metabolism to study the metabolic shifts that occur in response to obesity, cardiovascular disease, and dynamic environmental challenges. From these models, we have developed new perspectives of how metabolism adapts in obesity and cardiomyopathy, how these adaptations ultimately prove deleterious, and how innovative and personalized nutritional and pharmacological therapies may mitigate these adverse responses. We leverage recent advances in NMR and mass spectrometry technologies to study metabolism on a systems level, and we also employ established techniques in molecular cell biology and biochemistry to reveal phenotypic shifts at the cellular level. In addition to our mouse studies, we perform studies in humans to learn how alterations of ketone metabolism and related pathways may serve as diagnostic biomarkers and therapeutic targets for obesity-related disease, cardiac dysfunction, and metabolic maladaptations that can occur in the neonatal period.
Peter Crawford's Bio
Dr. Crawford was an undergraduate in the biological sciences at Duke University, where he graduated in 1991. As an M.D./Ph.D. student at Washington University (1999 graduate), he made numerous contributions to the field of nuclear receptor biology in the laboratory of Jeffrey Milbrandt. He underwent clinical training in internal medicine and cardiology at Barnes-Jewish Hospital, and then performed postdoctoral studies in the laboratory of Jeffrey Gordon, where he used gnotobiotic mice to unveil mechanisms through which the gut microbiome and the host-microbial interface regulates mammalian energy expenditure, fuel utilization, organ function, and systems physiology. He initiated his independent research program in the Center for Cardiovascular Research at Washington University in 2007, developing novel mouse models and exploiting penetrating chemical profiling methods to develop an understanding of the fundamental connections between metabolism and physiology. Dr. Crawford and his lab joined the Sanford-Burnham Medical Research Institute at Lake Nona in the summer of 2014.
Dr. Crawford's research goals focus on the roles of intermediary metabolism in systemic integrated physiological homeostasis. Through his research training he became an architect/phenotypic analyst of novel genetic mouse models that exhibit complex metabolic dysfunction, which allowed Dr. Crawford and his colleagues to reveal diverse and fundamental mechanisms of metabolic regulation. His laboratory developed a platform for metabolic analysis that includes the development of novel germline and tissue-specific mouse strains that are unable to appropriately metabolize ketone bodies, which are key integrators of mitochondrial oxidative substrate metabolism. The laboratory’s metabolic analysis of these strains includes extensive NMR and mass spectrometric metabolomic methods to map and quantify 13C-labeled metabolites. Together the tools and approaches developed and used in the lab offer a unique window into the metabolic adaptations and maladaptations in nonalcoholic fatty liver disease, obesity/metabolic syndrome, the neonatal period, and myocardial disease.