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oai:www.ideals.illinois.edu:2142/121324 2023-12-13 col_2142_5131 col_2142_16508 com_2142_5130 com_2142_16507 com_2142_14793 com_2142_8903

Anakk, Sayeepriyadarshini Anakk, Sayeepriyadarshini Raetzman, Lori T Tsai, Nien-Pei Brieher, William M 2023-08 application/pdf en text Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2025-08-01 The student, Anushna Sen, accepted the attached license on 2023-06-29 at 10:19. The student, Anushna Sen, submitted this Dissertation for approval on 2023-06-29 at 10:44. This Dissertation was approved for publication on 2023-07-05 at 11:52. DSpace SAF Submission Ingestion Package generated from Vireo submission #19482 on 2023-12-04 at 17:18:09 Copyright 2023 Anushna Sen Deciphering the roles of scaffold proteins (IQGAP1 and IQGAP2) and xenosensor (CAR) in liver biology Sen, Anushna 2023-07-05 Liver Scaffold Proteins Iqgap1 Iqgap2 Car Nuclear Receptor Environmental Toxicant Pesticide Metabolism Insulin Signaling Cholestasis Liver Injury 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. Text eng https://hdl.handle.net/2142/121324 Ph.D. Dissertation Molecular & Integrative Physi University of Illinois at Urbana-Champaign Molecular & Integrative Physl