- liver metabolism
- metabolic disease
- pioneer factors
- Foxa2
- nuclear receptors
- genomics
- computational biology
- epigenetics
- transcriptional regulation
Our laboratory is interested in investigating how cellular processes govern proper metabolic function and how abnormal physiology leads to metabolic disease. In particular, we aim to understand genetic and epigenetic mechanisms regulating liver metabolism. We are focusing on genome-wide chromatin changes underlying physiological dysfunction, which include chromatin accessibility, nuclear localization & dynamics, and genome organization. Our laboratory utilizes functional genomics, chromatin biology, physiology, and transcriptional regulation in a comprehensive approach to decipher molecular mechanisms in mammalian models of human metabolic disease (diabetes and diabetes-related metabolic dysfunction-associated steatotic liver disease, MASLD).
- Hao, Y., Han, L., Wu, A., Bochkis, I.M. Pioneer factor Foxa2 mediates chromatin conformation changes for activation of bile acid receptor FXR. CMGH 2024 17( 2), 237 – 249 doi: 10.1016/j.jcmgh.2023.10.009 PMID: 37879405
- Wei X, Murphy MA, Reddy NA, Hao Y, Eggertsen TG, Saucerman JJ, Bochkis IM. Redistribution of lamina-associated domains reshapes binding of pioneer factor FOXA2 in development of nonalcoholic fatty liver disease. Genome Res. 2022 Nov-Dec;32(11-12):1981-1992. doi: 10.1101/gr.277149.122. Epub 2022 Dec 15. PMID: 36522168..
- Kain J.*, Wei X.*, Reddy NA, Price AJ, Woods C, Bochkis IM. Pioneer factor Foxa2 enables ligand-dependent activation of type II nuclear receptors FXR and LXRα. Mol Metab. 2021 Nov;53:101291. doi: 10.1016/j.molmet.2021.101291. Epub 2021 Jul 8. PMID: 34246806; PMCID: PMC8350412.*equal contribution.
- Price AJ, Manjegowda MC, Kain J, Anandh S, Bochkis IM. Hdac3, Setdb1, and Kap1 mark H3K9me3/H3K14ac bivalent regions in young and aged liver. Aging Cell. 2020 Feb;19(2):e13092. doi: 10.1111/acel.13092. Epub 2019 Dec 19. PMID: 31858687; PMCID: PMC6996956.
- Whitton, H., Singh, L.S., Patrick, M.A., Price, A.J., Osorio, F.G., Lopez-Otin, C., Bochkis, I.M. Changes at the nuclear lamina alter binding of pioneer factor Foxa2 in aged liver. Aging Cell 2018 Jun;17(3):e12742. PMCID: PMC5946061
- Bochkis, I.M.*, Przybylski, D., Chen, J., Regev, A. Changes in nucleosome occupancy associated with metabolic alterations in aged mammalian liver. Cell Reports 2014 Nov 9(3):996-1006 PMCID: PMC4250828 *corresponding author
- Bochkis, I.M., Shin, S., Kaestner, K. H. Bile acid-induced inflammatory signaling in Foxa2-deficient mice leads to activation of mTOR and age-onset obesity. Molecular Metabolism 2013 2(4):447-56. PMCID: PMC3855091
- Bochkis, I.M., Schug, J., Ye, D.Z., Stratton, S.A., Barton, M.C., Kaestner, K.H. Genome-wide location analysis reveals distinct transcriptional circuitry by paralogous regulators Foxa1 and Foxa2. 2012 PLoS Genet 8(6): e1002770. doi:10.1371/journal.pgen.1002770 PMCID: PMC3380847
- Bochkis, I.M., Schug, J., Rubins, N.E., Kaestner, K.H. Foxa2-dependent hepatic gene regulatory networks depend on physiological state. 2009 Physiol Genomics. Jul 9;38(2):186-95 PMCID: PMC2712224
- Bochkis, I.M., Rubins, N.E., White, P., Furth, E.E., Friedman, J.R., Kaestner, K.H. Hepatocyte-specific ablation of Foxa2 alters bile acid homeostasis and results in ER stress. 2008 Nature Medicine Aug;14(8):828-36. PMCID: PMC4095974