University of Illinois Urbana-Champaign

Deciphering the roles of scaffold proteins (IQGAP1 and IQGAP2) and xenosensor (CAR) in liver biology

Sen, Anushna

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https://hdl.handle.net/2142/121324

Description

Title
Deciphering the roles of scaffold proteins (IQGAP1 and IQGAP2) and xenosensor (CAR) in liver biology
Author(s)
Sen, Anushna
Issue Date
2023-07-05
Director of Research (if dissertation) or Advisor (if thesis)
Anakk, Sayeepriyadarshini
Doctoral Committee Chair(s)
Anakk, Sayeepriyadarshini
Committee Member(s)
  • Raetzman, Lori T
  • Tsai, Nien-Pei
  • 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)
  • liver
  • scaffold proteins
  • IQGAP1
  • IQGAP2
  • CAR
  • nuclear receptor
  • environmental toxicant
  • pesticide
  • metabolism
  • insulin signaling
  • cholestasis
  • liver injury
Abstract
The liver is essential for bile synthesis, coordinating intermediary metabolism, energy storage, and detoxification. Its many functions routinely expose it to a wide range of insults. The liver responds and adapts to these stressors using molecular regulators such as scaffold proteins and nuclear receptors. This dissertation examines the role of scaffold proteins (IQGAP1 and IQGAP2) and a nuclear receptor (CAR) in modulating the liver’s response to physiological and pathological stressors. Chapter 2 reviews the role of nuclear receptors in combating oxidative stress within the liver. Chapter 3 investigates the role of CAR during pesticide exposure within the liver. For instance, the absence of CAR led to imidacloprid pesticide accumulation in the liver and altered detoxification gene expression. Chapter 4 examines the role of scaffold protein IQGAP2 in maintaining liver metabolic homeostasis. Analysis of Iqgap2-/- mice and IQGAP2-depleted cells revealed IQGAP2’s mechanistic role in regulating AKT, GSK3, and FOXO3 phosphorylation and subsequent hepatic glycogen accumulation during fed-state response. Chapter 5 examines the role of IQGAP1 during cholestatic injury. The absence of IQGAP1 led to increased bile acid accumulation and liver injury. Overall, these results elucidate new roles of scaffold proteins, IQGAP1 and IQGAP2, and nuclear receptor CAR in contributing to liver function in health and disease states.
Graduation Semester
2023-08
Type of Resource
Thesis
Copyright and License Information
Copyright 2023 Anushna Sen

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