Major questions in the Kohan Lab:
1. How do Foxp3+Tregs choose between lipoprotein triglyceride and plasma free fatty acids for fuel and does this metabolic flexibility change Treg function, proliferation, or maintenance of Foxp3?
2. What is the role of dysfunctional chylomicrons in Cystic Fibrosis metabolic disease, and does modulator therapy (Trikafta®) solve this intestinal defect?
3. What are the mechanisms of lymph versus portal partitioning during the absorption the nutrients, and is this regulated in health and disease?
Keywords: regulatory T cells (Tregs), lymph, chylomicrons, lipoproteins, lipid metabolism, small intestine
Email: akohan@pitt.edu
Website: https://kohanlab.com/
The long-term goals of my laboratory are to understand: (1) dietary lipid absorption and chylomicron synthesis, (2) the influence of chylomicrons in metabolic and inflammatory disease. To test physiologic and disease processes that arise from the small intestine, my lab has developed unique model systems and uses cellular metabolism approaches. My lab was the first lab to engineer the primary intestinal organoid culture system for studies of dietary lipid absorption [J Lipid Res 2017; J Lipid Res 2019].
Recently my lab has pioneered a unique 1-day mouse lymph cannulation model that enables the collection of flowing mesenteric lymph from live mice for 6-h after a duodenal nutrient infusion [J Vis Exp 2022; J Lipid Res 2022]. This makes my lab one of the only in the world to collect post-prandial lymph in >50ul quantities. We have now extended this mouse surgical model to include a quadruple cannulation, with cannulas in the duodenum, jugular vein, portal vein, and mesenteric lymph duct. To my knowledge, this has only ever been accomplished in rats, dogs, and pigs, and never with serial collections over the 6-h post-absorptive period.
Using these unique models, my lab has made several discoveries. My group has shown that apolipoprotein (apo) C-III, a significant cardiovascular risk factor, regulates intracellular lipid metabolism in enterocytes [J Lipid Res 2019], inhibits chylomicron secretion into the mesenteric lymphatics [Physiol Rep 2014], and is involved in aortic valve calcification [J Biol Chem 2021]. We’ve also discovered that chylomicrons shift Treg apoptosis, lipid uptake, and accumulation [BioRxiv 2019; Nat Comms 2022]. Most recently, we’ve used our cellular metabolism approaches to identify a new role for CFTR in the regulation of fatty acid transport and chylomicron synthesis in the small intestine [J Lipid Res, 2024]. I am also the Director of the Lipid Analytics Core in the Division of Endocrinology and Metabolism and direct the Metabolism Core for the University of Pittsburgh Cystic Fibrosis Research Center.
Major questions in the Kohan Lab:
1. How do Foxp3+Tregs choose between lipoprotein triglyceride and plasma free fatty acids for fuel and does this metabolic flexibility change Treg function, proliferation, or maintenance of Foxp3?
2. What is the role of dysfunctional chylomicrons in Cystic Fibrosis metabolic disease, and does modulator therapy (Trikafta®) solve this intestinal defect?
3. What are the mechanisms of lymph versus portal partitioning during the absorption the nutrients, and is this regulated in health and disease?
Keywords: regulatory T cells (Tregs), lymph, chylomicrons, lipoproteins, lipid metabolism, small intestine
Disclosures: None
Email: akohan@pitt.edu
Website: https://kohanlab.com/