Uncovering a novel role for FXR-SHP axis in liver physiology, diseases and beyond

Mathur, Bhoomika

Permalink

https://hdl.handle.net/2142/105785 Copy

Description

Title

Uncovering a novel role for FXR-SHP axis in liver physiology, diseases and beyond

Author(s)

Mathur, Bhoomika

Issue Date

2019-07-09

Director of Research (if dissertation) or Advisor (if thesis)

Anakk, Sayeepriyadarshini

Doctoral Committee Chair(s)

Anakk, Sayeepriyadarshini

Committee Member(s)

• Bagchi, Milan K
• Kemper, Jongsook K
• Brieher, William M

Department of Study

Molecular & Integrative Physl

Discipline

Molecular & Integrative Physi

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Nuclear Receptors
• Bile Acid
• FXR
• SHP
• CAR
• Cholestasis
• Cardiomyopathy
• Golgi apparatus
• cholesterol
• glycosylation
• liver

Abstract

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.

Graduation Semester

2019-08

Type of Resource

text

Permalink

http://hdl.handle.net/2142/105785

Copyright and License Information

Copyright 2019 Bhoomika Mathur

Owning Collections