Office Address
Minneapolis, MN 55455
United States
Douglas
Mashek
Professor
Biochemistry, Molecular Biology, and Biophysics
The Mashek laboratory has broad interests in understanding the biochemical basis of metabolic diseases (Type 2 Diabetes, NAFLD, obesity), cancer, and aging, and how interventions such as diet influence these processes. A central theme of our laboratory that connects these diverse research areas is lipid droplet biology. These organelles represent the primary storage form of energy in nearly all cell types and their excess in most tissues is a sign of metabolic stress/dysfunction. Our findings to date have led us down numerous research avenues, discussed below, that further explore the biochemistry and cell biology of lipid droplets in a variety of cell types (liver, muscle, adipose) as well as translational studies tightly intertwined with lipid droplet biology. Our laboratory employs a wide range of experimental techniques ranging from basic biochemistry, molecular biology, enzymology, and cell biology to animal models to clinical trials.
Research statement
The Mashek laboratory has broad interests in understanding the biochemical basis of metabolic diseases (Type 2 Diabetes, NAFLD, obesity), cancer, and aging, and how interventions such as diet influence these processes. A central theme of our laboratory that connects these diverse research areas is lipid droplet (LD) biology. These organelles represent the primary storage form of energy in nearly all cell types and their excess in most tissues is a sign of metabolic that further explore the biochemistry and cell biology of lipid droplets in a variety of cell types (liver, muscle, adipose) as well as translational studies tightly intertwined with lipid droplet biology. Our laboratory employs a wide range of experimental techniques ranging from basic biochemistry, molecular biology, enzymology, and cell biology to animal models to clinical trials. Ongoing areas of emphasis include how LDs cause inflammation, how LD interactions with other organelles compartmentalize metabolism and signaling, how LD breakdown is beneficial and conveys similar benefits to fasting or caloric restriction, how LDs mediate the differential effects of dietary fats, and how nutrient-sensing nodes (sirtuins) mediate the effects of LDs on cell function.
Selected publications
Najt CP, Adhikari A, Heden TD, Gansemer ER, Rauckhorst AJ, Cui W, Markowski TW, Higgins L, Kerr EW, Boyum MD, Alvarez J, Brunko S, Mehra D, Puchner EM, Taylor EB, Mashek DG. Organelle interactions compartmentalize hepatic fatty acid trafficking and metabolism. Cell Reports 2023;42(5):112435
Shang L, Aughey E, Kim H, Heden TD, Wang L, Najt CP, Esch N, Brunko S, Abrahante JE, Macchietto M, Mashek MT, Fairbanks T, Promislow, Neufeld TP, Mashek DG. Systemic lipolysis promotes physiological fitness in Drosophila melanogaster. Aging 2022;14(16):6481-6506.
Cui W, Sathyanarayan A, Lopresti M, Aghajan M, Chen D, Mashek DG. Lipophagy-derived fatty acids undergo extracellular efflux via lysosomal exocytosis. Autophagy 2020;19:1-16.
Najt CP, Khan SA, Heden TD, Witthuhn BA, Perez M, Mead LE, Franklin MP, Karanja KK, Graham MJ, Mashek MT, Bernlohr DA, Parker L, Chow LS, Mashek DG. Lipid droplet-derived monounsaturated fatty acids traffic via PLIN5 to allosterically activate SIRT1. Molecular Cell 2020;77(4):810-824.
Chow L, Manoogian E, Alvear A, Fleischer JG, Thor H, Dietsche K, Wang MS, Hodges J, Nair KS, Panda S, Mashek DG. Time restricted eating effects on body composition and metabolic measures in humans who are overweight: a feasibility study. Obesity 2020;28(5):860-869.