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Friend Or Foe? The Role Of Transforming Growth Factor-Β (Tgfβ) Signaling In Calcineurin Inhibitor-Induced Renal Damage, Adaku Ume Jan 2023

Friend Or Foe? The Role Of Transforming Growth Factor-Β (Tgfβ) Signaling In Calcineurin Inhibitor-Induced Renal Damage, Adaku Ume

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With its incorporation into clinical practice in the early 1980s, the class of pharmacological agents known as calcineurin inhibitors (CNIs) quickly became the cornerstone of immunosuppressive therapy post-organ transplantation. However, its use is limited by irreversible kidney damage in the form of renal fibrosis. The molecular mechanism by which CNIs induce renal fibrosis remains to be better understood, and to date, there are no specific therapeutic strategies to mitigate this damage. This dilemma presents a critical need to explain mechanisms by which CNIs cause renal damage. Kidneys of patients on chronic CNI therapy show increased expression of the proinflammatory cytokine …


Identifying A Novel Ferrocene Derivative As A K-Ras Inhibitor, Kristen Marie Rehl Jan 2023

Identifying A Novel Ferrocene Derivative As A K-Ras Inhibitor, Kristen Marie Rehl

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Ras proteins are small GTPases that regulate cell proliferation, differentiation and survival at the plasma membrane (PM). There are three Ras isoforms ubiquitously expressed in mammalian cells: H-, N- and K-Ras. Constitutively active Ras mutations are found in ~19% of all human cancers, with ~75% of those being in K-Ras. There are K-Ras inhibitors in clinic but they only target the oncogenic K-RasG12C mutant, which only makes up a small sub-set of K-Ras-driven cancers. Thus, there still exists a need for a pan anti-K-Ras drug. Ferrocene derivatives are a class of compounds that have been shown to inhibit the growth …


Brain Morphometry From Neuroimaging As A Biomarker For Alzheimer's Disease, Nonyelum Benedicta Aniebo Jan 2023

Brain Morphometry From Neuroimaging As A Biomarker For Alzheimer's Disease, Nonyelum Benedicta Aniebo

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Alzheimer’s disease (AD) is the seventh leading cause of death globally with an estimated 6.5 million Americans aged 65 and above living with Alzheimer’s dementia in 2022 and at a projected national cost of $321 billion. AD is characterized by a progressive and irreversible neurodegenerative dysfunction with clinical symptoms such as deterioration in cognition and memory loss. The Alzheimer’s Disease Neuroimaging Initiative (ADNI) is a multi-site, public-private global research initiative that supports both investigation and development of treatments that slow or terminate AD progression. The study included 60 participants, comprising 30 AD and 30 control cohorts respectively. All participants were …


Friend Or Foe? The Role Of Transforming Growth Factor-Β (Tgfβ) Signaling In Calcineurin Inhibitor-Induced Renal Damage, Adaku Uwe Jan 2023

Friend Or Foe? The Role Of Transforming Growth Factor-Β (Tgfβ) Signaling In Calcineurin Inhibitor-Induced Renal Damage, Adaku Uwe

Browse all Theses and Dissertations

With its incorporation into clinical practice in the early 1980s, the class of pharmacological agents known as calcineurin inhibitors (CNIs) quickly became the cornerstone of immunosuppressive therapy post-organ transplantation. However, its use is limited by irreversible kidney damage in the form of renal fibrosis. The molecular mechanism by which CNIs induce renal fibrosis remains to be better understood, and to date, there are no specific therapeutic strategies to mitigate this damage. This dilemma presents a critical need to explain mechanisms by which CNIs cause renal damage. Kidneys of patients on chronic CNI therapy show increased expression of the proinflammatory cytokine …