Research
Research within the Division of Molecular Medicine is dedicated to defining the metabolic determinants of chronic diseases. Genetically modified animal models and studies in human subjects are combined with sophisticated isotopic tracing, computational flux modeling, and metabolomics approaches to allow our research to fully encompass the complexities of integrated physiology in health and disease. Our researchers aim to leverage the knowledge acquired from our experimental investigations to prevent, identify, and treat metabolic diseases including insulin resistance, nonalcoholic fatty liver disease, liver cancer, and cardiovascular disease.
PUBLICATIONS
Crawford and Puchalska Lab
|
2023 |
|
Ketones and the Heart: Metabolic Principles and Therapeutic Implications |
|
2022 |
|
Krebs takes a turn at cell differentiation Artifactual fatty acid dimers mimic FAHFA signals in untargeted metabolomics pipelines Acute aerobic exercise reveals FAHFAs distinguish the metabolomes of overweight and normal weight runners Ketone body oxidation increases cardiac endothelial cell proliferation |
|
Metabolic and Signaling Roles of Ketone Bodies in Health and Disease Diminished ketone interconversion, hepatic TCA cycle flux, and glucose production in D-β-hydroxybutyrate dehydrogenase hepatocyte-deficient mice Determination of ketone bodies in biological samples via rapid UPLC-MS/MS |
|
2020 |
|
Mitochondrial pyruvate carriers are required for myocardial stress adaptation. Pimozide Alleviates Hyperglycemia in Diet-Induced Obesity by Inhibiting Skeletal Muscle Ketone Oxidation. Nonalcoholic Steatohepatitis: A Review. |
|
2019 |
|
Ketogenic therapies for lymphedema? Pyruvate Carboxylase Wields a Double-Edged Metabolic Sword. Application of Stable Isotope Labels for Metabolomics in Studies in Fatty Liver Disease. The failing heart utilizes 3-hydroxybutyrate as a metabolic stress defense. Hepatocyte-Macrophage Acetoacetate Shuttle Protects against Tissue Fibrosis. |
|
2018 |
|
Transport-exclusion pharmacology to localize lactate dehydrogenase activity within cells. Lipidomics reveals a systemic energy deficient state that precedes neurotoxicity in neonatal monkeys after sevoflurane exposure. Isotope Tracing Untargeted Metabolomics Reveals Macrophage Polarization-State-Specific Metabolic Coordination across Intracellular Compartments. Refueling the Failing Heart: A Case for Sodium-Glucose Cotransporter 2 Inhibition in Cardiac Energy Homeostasis. Ketone bodies as epigenetic modifiers. Hepatic ketogenic insufficiency reprograms hepatic glycogen metabolism and the lipidome. Intra- and inter-subject variability for increases in serum ketone bodies in patients with type 2 diabetes treated with the sodium glucose co-transporter 2 inhibitor canagliflozin. |
|
2017 |
|
Circulating acylcarnitine profile in human heart failure: a surrogate of fatty acid metabolic dysregulation in mitochondria and beyond. Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics. |
|
2016 |
|
Comprehensive and Quantitative Analysis of Polyphosphoinositide Species by Shotgun Lipidomics Revealed Their Alterations in db/db Mouse Brain. Lactate metabolism is associated with mammalian mitochondria. The Failing Heart Relies on Ketone Bodies as a Fuel. |
|
2015 |
|
The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. |
|
2014 |
| Ketogenesis prevents diet-induced fatty liver injury and hyperglycemia. Cotter DG, Ercal B, Huang X, Leid JM, d'Avignon DA, Graham MJ, Dietzen DJ, Brunt EM, Patti GJ, Crawford PA. Clin Invest. 2014 Dec;124(12):5175-90. doi: 10.1172/JCI76388. Epub 2014 Oct 27.PMID: 25347470. Cardiomyocyte-specific deficiency of ketone body metabolism promotes accelerated pathological remodeling. Impairments of hepatic gluconeogenesis and ketogenesis in PPARα-deficient neonatal mice. X13CMS: global tracking of isotopic labels in untargeted metabolomics. |
|
2013 |
|
Role of choline deficiency in the Fatty liver phenotype of mice fed a low protein, very low carbohydrate ketogenic diet. Impact of peripheral ketolytic deficiency on hepatic ketogenesis and gluconeogenesis during the transition to birth. PGC-1β and ChREBP partner to cooperatively regulate hepatic lipogenesis in a glucose concentration-dependent manner. Ketone body metabolism and cardiovascular disease. Metabolic stress in the myocardium: adaptations of gene expression. Successful adaptation to ketosis by mice with tissue-specific deficiency of ketone body oxidation. |
|
2012 |
|
Liver-specific PGC-1beta deficiency leads to impaired mitochondrial function and lipogenic response to fasting-refeeding. Low-carbohydrate ketogenic diets, glucose homeostasis, and nonalcoholic fatty liver disease. |
|
2011 |
|
Altered systemic ketone body metabolism in advanced heart failure. Hepatic steatosis, inflammation, and ER stress in mice maintained long term on a very low-carbohydrate ketogenic diet. Obligate role for ketone body oxidation in neonatal metabolic homeostasis. |
|
2010 |
|
Akt2 deficiency promotes cardiac induction of Rab4a and myocardial β-adrenergic hypersensitivity. Adaptation of myocardial substrate metabolism to a ketogenic nutrient environment. Epitope mapping in cell surface proteins by site-directed masking: defining the structural elements of NTPDase3 inhibition by a monoclonal antibody. Coordinated regulation of the metabolome and lipidome at the host-microbial interface. |
|
2009 |
|
Regulation of myocardial ketone body metabolism by the gut microbiota during nutrient deprivation. |
Hughey Lab
|
2022 |
|
Integrating the contributions of mitochondrial oxidative metabolism to lipotoxicity and inflammation in NAFLD pathogenesis Disrupted liver oxidative metabolism in glycine N-methyltransferase-deficient mice is mitigated by dietary methionine restriction |
|
2021 |
|
Multitissue 2H/13C flux analysis reveals reciprocal upregulation of renal gluconeogenesis in hepatic PEPCK-C-knockout mice. |
D. Andre d'Avignon
D. Andre d'Avignon, PhD, Senior Researcher, Crawford and Puchalska lab
Sneha Jena
Sneha Jena, Researcher, Wernimont lab
Siyuan Liu
Siyuan Liu, Hughey Lab
Renee Mahr
Renee Mahr, Researcher, Wernimont Lab
Dr. Sereen Nashif
Sereen Nashif, Maternal Fetal Medicine Fellow, Wernimont Lab
Alisa Nelson
Alisa Nelson, Postdoctoral Associate, Crawford and Puchalska lab
Ferrol Rome
Ferrol Rome, Researcher, Hughey lab
Rumina Todorova
Rumina Todorova, Researcher, Crawford and Puchalska lab
Eric Queathem
Eric Queathem, PhD thesis student, Biochemistry, Molecular Biology, and Biophysics Program, Crawford and Puchalska lab
OUR TEAM
SHARED RESOURCES AND CORE FACILITIES
The research goals of the Division are supported by strong shared resources and core facilities at the University of Minnesota.