Targeting pro-tumorigenic signaling pathways in hematolymphoid malignancies

Hematolymphoid malignancies constitute diverse forms of cancers derived from hematopoietic and lymphoid tissues. Determining molecular alterations driving resistance to commonly used chemotherapies and defining disease mechanisms are of considerable relevance for understanding the pathogenesis of he...

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Main Author: Kizhakeyil Atish
Other Authors: Navin Kumar Verma
Format: Thesis-Doctor of Philosophy
Language:English
Published: Nanyang Technological University 2020
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Online Access:https://hdl.handle.net/10356/142248
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1422482020-11-01T05:34:08Z Targeting pro-tumorigenic signaling pathways in hematolymphoid malignancies Kizhakeyil Atish Navin Kumar Verma Lee Kong Chian School of Medicine (LKCMedicine) nkverma@ntu.edu.sg Science::Medicine Hematolymphoid malignancies constitute diverse forms of cancers derived from hematopoietic and lymphoid tissues. Determining molecular alterations driving resistance to commonly used chemotherapies and defining disease mechanisms are of considerable relevance for understanding the pathogenesis of hematolymphoid malignancies. Here, using RNA-seq and proteomics analyses we identified several pro-tumorigenic signaling, including STAT3 and ERK pathways, to be involved in drug resistance in hematolymphoid malignancies. We demonstrated that the X-linked DDX3X is a crucial determinant in NHL aggressiveness. We established that STAT3 activation upregulates PD-L1 expression in cells of hematolymphoid malignancies. We optimized the “GapmeR” technology and developed a novel gene silencer “epAON” that were effective in knocking down STAT3 in cells of hematolymphoid malignancies and successful in inducing apoptosis in these cells. epAON molecules can be exploited for therapeutic applications. Overall, the data presented in this thesis greatly enhances the understanding of fundamental intracellular mechanisms involved in hematolymphoid malignancies. Doctor of Philosophy 2020-06-17T12:31:31Z 2020-06-17T12:31:31Z 2020 Thesis-Doctor of Philosophy Kizhakeyil Atish. (2020). Targeting pro-tumorigenic signaling pathways in hematolymphoid malignancies. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/142248 10.32657/10356/142248 en This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). application/pdf Nanyang Technological University
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Medicine
spellingShingle Science::Medicine
Kizhakeyil Atish
Targeting pro-tumorigenic signaling pathways in hematolymphoid malignancies
description Hematolymphoid malignancies constitute diverse forms of cancers derived from hematopoietic and lymphoid tissues. Determining molecular alterations driving resistance to commonly used chemotherapies and defining disease mechanisms are of considerable relevance for understanding the pathogenesis of hematolymphoid malignancies. Here, using RNA-seq and proteomics analyses we identified several pro-tumorigenic signaling, including STAT3 and ERK pathways, to be involved in drug resistance in hematolymphoid malignancies. We demonstrated that the X-linked DDX3X is a crucial determinant in NHL aggressiveness. We established that STAT3 activation upregulates PD-L1 expression in cells of hematolymphoid malignancies. We optimized the “GapmeR” technology and developed a novel gene silencer “epAON” that were effective in knocking down STAT3 in cells of hematolymphoid malignancies and successful in inducing apoptosis in these cells. epAON molecules can be exploited for therapeutic applications. Overall, the data presented in this thesis greatly enhances the understanding of fundamental intracellular mechanisms involved in hematolymphoid malignancies.
author2 Navin Kumar Verma
author_facet Navin Kumar Verma
Kizhakeyil Atish
format Thesis-Doctor of Philosophy
author Kizhakeyil Atish
author_sort Kizhakeyil Atish
title Targeting pro-tumorigenic signaling pathways in hematolymphoid malignancies
title_short Targeting pro-tumorigenic signaling pathways in hematolymphoid malignancies
title_full Targeting pro-tumorigenic signaling pathways in hematolymphoid malignancies
title_fullStr Targeting pro-tumorigenic signaling pathways in hematolymphoid malignancies
title_full_unstemmed Targeting pro-tumorigenic signaling pathways in hematolymphoid malignancies
title_sort targeting pro-tumorigenic signaling pathways in hematolymphoid malignancies
publisher Nanyang Technological University
publishDate 2020
url https://hdl.handle.net/10356/142248
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