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Anakk, Sayeepriyadarshini Anakk, Sayeepriyadarshini Bagchi, Milan K Kemper, Jongsook K Brieher, William M Mathur, Bhoomika 2019-11-26T20:49:21Z 2019-11-26T20:49:21Z 2021-11-27T10:15:09Z 2019-07-09 2019-08 Liver performs a multitude of functions ranging from detoxification, metabolism and digestion. To execute these tasks, one of the mechanisms that the liver utilizes is nuclear receptor signaling, which in turn can transcriptionally regulate gene networks. My doctoral thesis focuses on studying the role of two nuclear receptors, FXR and SHP in maintaining liver function. Farnesoid X Receptor (FXR) and Small Heterodimer Partner (SHP) are well-known regulators of glucose, fat and bile acid homeostasis. Here, I uncover novel roles for FXR-SHP axis not only in the liver but also in extrahepatic organs, like heart. In Chapter 2, I discuss how hepatic loss of FXR and SHP results in increased glycosylation of liver proteins and structural defects in Golgi apparatus, and ultimately liver cancer. Chapter 3 focuses on comprehending how FXR-SHP ablation results in increased drug metabolic capacity of the liver. Finally, chapter 4 discusses how liver dysfunction, caused by loss of FXR and SHP, can induce metabolic and functional defects in heart. Taken together, these projects will help understand some of the FXR and SHP transcriptional networks under different physiological and pathological contexts and may open avenues for pharmacological manipulation to treat various diseases. Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2021-08-01 The student, Bhoomika Mathur, accepted the attached license on 2019-07-04 at 01:18. The student, Bhoomika Mathur, submitted this Dissertation for approval on 2019-07-04 at 01:31. This Dissertation was approved for publication on 2019-07-09 at 15:41. DSpace SAF Submission Ingestion Package generated from Vireo submission #14170 on 2019-11-26 at 13:04:27 Made available in DSpace on 2019-11-26T20:49:21Z (GMT). No. of bitstreams: 3 MATHUR-DISSERTATION-2019.pdf: 4474420 bytes, checksum: 0728cd0303f8ab823c20e40908832fc6 (MD5) LICENSE.txt: 4212 bytes, checksum: c236fb3ffdc64338bde4c118696e9cf1 (MD5) RightsLink Printable License_Copyright letter_Bhoomika.pdf: 202690 bytes, checksum: 3eb71388cf9fd446d7a972db6b8c76f4 (MD5) Previous issue date: 2019-07-09 Embargo set by: Seth Robbins for item 112930 Lift date: 2021-11-26T20:49:41Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system U of I Only Restriction Lifted for Item 112930 on 2021-11-27T10:15:09Z. application/pdf http://hdl.handle.net/2142/105785 en Copyright 2019 Bhoomika Mathur Nuclear Receptors Bile Acid FXR SHP CAR Cholestasis Cardiomyopathy Golgi apparatus cholesterol glycosylation liver Uncovering a novel role for FXR-SHP axis in liver physiology, diseases and beyond text text Molecular & Integrative Physl Molecular & Integrative Physi University of Illinois at Urbana-Champaign Dissertation Ph.D.