Division of Molecular Medicine Faculty
Name: Kelly LaPara
Mail: 420 Washington Ave SE, MMC 194, Minneapolis, MN 55455
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, diabetes, nonalcoholic fatty liver disease (NAFLD/NASH), 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 stable isotope tracer based NMR and mass spectrometry-based untargeted metabolomics 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. Complex in vivo phenotyping methodologies are strategically aligned with these sophisticated chemical profiling platforms to generate high resolution phenotypic pictures. 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, diabetes, NAFLD/NASH, heart failure/CHF, and metabolic maladaptations that can occur in any disease state.
Dr. Curtis Hughey, PhD, completed his doctoral studies at the University of Calgary in Biochemistry and Molecular Biology. During his doctoral training he received a Canadian Institutes of Health Research Doctoral Scholarship and the Izaak Walton Killam Memorial Scholarship to study the use of stem cell therapy to promote in vivo insulin sensitivity in mouse models of diet-induced obesity and heart failure. With an interest in the genetic and environment regulation of in vivo glucose control, Dr. Hughey then pursued a postdoctoral fellowship at Vanderbilt University. While at Vanderbilt, he received a Canadian Diabetes Association Postdoctoral Fellowship to test the role of liver energy state in the regulation of glucose production during exercise. This work employed a metabolic flux analysis technique that uses stable isotopes, mass spectrometry, and computational modeling to quantify in vivo metabolic fluxes. An emerging research focus for the Hughey Laboratory at the University of Minnesota is to define the role of transmethylation in the metabolic reprogramming that occurs in non-alcoholic fatty liver disease and hepatocellular carcinoma.
Metabolic dysregulation underlies many public health challenges of modern society. The overarching objective of research in the Hughey Laboratory is to identify pathways within complex metabolic networks that can be used for early identification of disease or targeted to prevent or treat metabolic diseases. To accomplish this aim, studies combine the use of stable isotopes, mass spectrometry, and computational modeling to quantify in vivo metabolic fluxes in genetically-engineered mice. Many studies also employ provocative stimuli such as exercise and diet to challenge metabolic networks. Areas of focus are: The role of dysregulated hepatic transmethylation in the metabolic programming that promotes non-alcoholic fatty liver disease and hepatocellular carcinoma. Regulation of hepatic glucose formation during acute exercise and in response to habitual exercise.
In 2014, Dr. Puchalska obtained her PhD degree from the Faculty of Chemistry, Department of Analytical Chemistry and Chemical Engineering at the University of Alcalá (Spain). She joined Dr. Crawford's group in 2015 to exploit the field of mass spectrometry-based metabolomics and lipidomics to study metabolism on a systems level. She joined Division of Molecular Medicine at the University of Minnesota Medical School in 2017, where she leads cutting-edge research that utilizes mass spectrometry approaches to reveal essential information regarding the metabolism. Her research focus is to prevent the progression of nonalcoholic fatty liver disease (NAFLD), which is tightly linked to the obesity and Type 2 Diabetes epidemics increasing in prevalence.
Utilization of mass spectrometry approaches to reveal essential information regarding the metabolism; Prevention of the progression of nonalcoholic fatty liver disease (NAFLD), which is tightly linked to the obesity and Type 2 Diabetes epidemics
Mass spectrometry-based metabolomics and lipidomics
Non-alcoholic fatty liver disease
Honors and Recognition
Dr. Wernimont received her MD and PhD as part of the Medical Scientist Training Program at the University of Wisconsin School of Medicine and Public Health. For her PhD, she studied basic mechanisms of T cell activation. Afterwards, she completed her residency in Obstetrics and Gynecology and fellowship in Maternal-Fetal Medicine at the University of Iowa, as part of their Physician Scientist Training Program. Dr. Wernimont joined the University of Minnesota in 2020 and her research is currently funded through the NIH Reproductive Scientist Development Program. In addition to caring for patients with complicated pregnancies, she has a strong research interest in improving care delivery for pregnant patients with diabetes and fetal growth abnormalities.
Administrative Phone: 612-301-3408
Administrative Email: firstname.lastname@example.org
Administrative Fax: 612-301-3415
Dr. Wernimont’s research interests are directed towards improving outcomes for people with pregnancies complicated by diabetes and obesity. In her clinical research, she has worked to develop
and identify better ways to deliver care for patients with diabetes in pregnancy. Towards this end, she recently created the University of Minnesota Obstetric Measures (UMOMs) database that includes over
70,000 patients and 100,000 deliveries from the MHealth/Fairview System. She has used this database to examine timing of delivery in pregnancies complicated by diabetes and how providers define “poor
glucose control.” She is currently leading a multi-department effort to establish a biorepository for systematic collection of maternal, placental, and neonatal samples to support translational research across the perinatal spectrum at the University of Minnesota to link with clinical data within the UMOMs database. The resulting biorepository is termed UMOM:GOPHER (University of Minnesota Obstetric Measures--Gestational Outcomes and Pediatric HEalth Repository). In her basic science, Dr. Wernimont studies how the maternal nutritional-metabolic environment impacts placental development, function and long-term health outcomes. Using both human placental specimens and trophoblast cell lines, Dr. Wernimont combines cutting edge metabolomics and transcriptomics to define the mechanisms by which changes in nutrient availability impact trophoblast differentiation. The long term goal of this work is to develop novel strategies to improve pregnancy health and childhood outcomes in pregnancies complicated by diabetes.
Diabetes and obesity in pregnancy; Fetal Growth Abnormalities