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Immunology and Infectious Disease

USF Tampa Graduate Theses and Dissertations

Theses/Dissertations

Cereblon

Publication Year

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Full-Text Articles in Life Sciences

Understanding The Role Of Cereblon In Hematopoiesis Through Structural And Functional Analyses, Afua Adutwumwa Akuffo Apr 2020

Understanding The Role Of Cereblon In Hematopoiesis Through Structural And Functional Analyses, Afua Adutwumwa Akuffo

USF Tampa Graduate Theses and Dissertations

The discovery and implementation of immunomodulatory drugs (IMiD®s) has revolutionized the treatment of many hematological malignancies due to the plethora of IMiD®-induced clinical responses that include anti-angiogenesis, anti-inflammation, and anti-tumor effects, as well as enhanced erythropoiesis, immune modulation and improved metabolism. More ground-breaking was the identification of cereblon as the target of IMiD®s. Upon binding to thalidomide and other immunomodulatory drugs, the E3 ligase substrate receptor cereblon (CRBN) promotes proteosomal destruction of neo-substrates by engaging the DDB1-CUL4A-Roc1-RBX1 E3-ubiquitin ligase in human cells but not in mouse cells suggesting that sequence variations in CRBN may cause its inactivation. Therapeutically, CRBN engagers …


Understanding Immunometabolic And Suppressive Factors That Impact Cancer Development, Rebecca Swearingen Hesterberg Mar 2019

Understanding Immunometabolic And Suppressive Factors That Impact Cancer Development, Rebecca Swearingen Hesterberg

USF Tampa Graduate Theses and Dissertations

The immune system is responsible for surveillance against pathogens and malignancies and adoptive transfer of antigen-specific T is a powerful new cancer treatment option. There is a clinical need to understand more about the normal regulatory processes that prevent immunosurveillance and how to manipulate this for clinical benefit. This project aims to understand T cells from three different angles. First, the biological role of the negative regulator cereblon (CRBN) was investigated in CD8+ T cells and my studies showed that higher levels of specific derivatives downstream of the amino acid glutamine may be beneficial to T cells in the immune …