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GSBS Dissertations and Theses

Cancer Biology

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Articles 1 - 12 of 12

Full-Text Articles in Cell Biology

Tumor-Stroma Interactions Differentially Alter Drug Sensitivity Based On The Origin Of Stromal Cells, Benjamin D. Landry Oct 2018

Tumor-Stroma Interactions Differentially Alter Drug Sensitivity Based On The Origin Of Stromal Cells, Benjamin D. Landry

GSBS Dissertations and Theses

Tumor heterogeneity observed between patients has made it challenging to develop universal or broadly effective cancer therapies. Therefore, an ever-growing movement within cancer research aims to tailor cancer therapies to individual patients or specific tumor subtypes. Tumor stratification is generally dictated by the genomic mutation status of the tumor cells themselves. Importantly, non-genetic influences – such as interactions between tumor cells and other components of the tumor microenvironment – have largely been ignored. Therefore, in an effort to increase treatment predictability and efficacy, we investigated how tumor-stroma interactions contribute to drug sensitivity and drug resistance.

I designed a high throughput co-culture screening ...


Runx1 Control Of Mammary Epithelial And Breast Cancer Cell Phenotypes, Deli Hong Dec 2017

Runx1 Control Of Mammary Epithelial And Breast Cancer Cell Phenotypes, Deli Hong

GSBS Dissertations and Theses

Breast cancer remains the most common malignant disease in women worldwide. Despite the advantages of early detection and improved treatments, studies into the mechanisms that initiate and drive breast cancer progression are still required. Recent studies have identified RUNX1, which is an essential transcription factor for hematopoiesis, is one of the most frequently mutated genes in breast cancer patients. However, the role of RUNX1 in the mammary gland is understudied.

In this dissertation, we examined the role of RUNX1 in both normal mammary epithelial and breast cancer cells. Our in vitro studies demonstrated that RUNX1 inhibits epithelial to mesenchymal transition ...


A Mechanistic Investigation Of Insulin Receptor Substrate 2 Function In Breast Cancer Progression, Jose R. Mercado-Matos Jun 2017

A Mechanistic Investigation Of Insulin Receptor Substrate 2 Function In Breast Cancer Progression, Jose R. Mercado-Matos

GSBS Dissertations and Theses

The advancement of cancer treatment depends on understanding the biological processes that contribute to disease progression. The spread of tumor cells from the primary site to distant organs is the biggest obstacle to efficacious treatment. The insulin receptor substrate (IRS) proteins IRS1 and IRS2 are cytoplasmic adaptor proteins that organize signaling events downstream of the Insulin receptor (IR) and the Insulin-like growth factor receptor 1 (IGF1R). Both of these receptors have been implicated in cancer progression. The IRS proteins share a significant level of homology and are both capable of recruiting and activating phosphatidylinositol-3 kinase (PI3K). Despite these similarities, signaling ...


Requirement And Function Of Hippo Pathway Signaling In The Mammalian Gastrointestinal Tract: A Dissertation, Jennifer L. Cotton Oct 2016

Requirement And Function Of Hippo Pathway Signaling In The Mammalian Gastrointestinal Tract: A Dissertation, Jennifer L. Cotton

GSBS Dissertations and Theses

In cancer, aberrant activation of developmental signaling pathways such as the Hippo Pathway has been shown to drive proliferation and invasion of cancer cells. Therefore, understanding the normal function of the Hippo Pathway during embryonic development can provide critical insight into how aberrant activity contributes to tumorigenesis. This dissertation explores the role of the Hippo Pathway members YAP and TAZ in gastrointestinal (GI) development and tumorigenesis. I use mouse genetics to systematically dissect the roles of YAP/TAZ in the endoderm-derived gastrointestinal epithelia and mesoderm-derived gastrointestinal mesenchyme during mammalian development. In the GI epithelium, I demonstrate that YAP/TAZ are ...


The Role Of Mdm2 Phosphorylation In P53 Responses To Dna Damage And Tumor Suppression: A Dissertation, Michael I. Carr Jul 2016

The Role Of Mdm2 Phosphorylation In P53 Responses To Dna Damage And Tumor Suppression: A Dissertation, Michael I. Carr

GSBS Dissertations and Theses

The p53 tumor suppressor protein is upregulated in response to DNA damage and other stress signals. The upregulation of p53 involves freeing it from negative regulation imposed by Mdm2 and MdmX (Mdm4). Accumulating evidence indicates that phosphorylation of Mdm proteins by different stress-activated kinases such as ATM or c-Abl significantly impacts p53 functions. We have previously shown that ATM phosphorylation of Mdm2 Ser394 is required for robust p53 stabilization and activation following DNA damage.

This dissertation describes in vivo examination of the mechanism by which Mdm2 Ser394 phosphorylation impacts p53 activities and its contribution to suppression of oncogene and DNA ...


The Smurf2-Yy1-C-Myc Axis In The Germinal Center Reaction And Diffuse Large B Cell Lymphoma: A Dissertation, Sally E. Trabucco Jun 2016

The Smurf2-Yy1-C-Myc Axis In The Germinal Center Reaction And Diffuse Large B Cell Lymphoma: A Dissertation, Sally E. Trabucco

GSBS Dissertations and Theses

Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin’s lymphoma. Patients who fail conventional therapy (~50%) have a poor prognosis and few treatment options. It is essential to understand the underlying biological processes, the progression of the disease, and utilize this information to develop new therapeutics.

DLBCL patients with high C-MYC expression have a poor prognosis and new therapeutics for these patients are needed. This thesis describes work testing the hypothesis that JQ1, which can indirectly inhibit C-MYC in some tumors, can be used as an effective treatment for DLBCL. Some tumors have an unknown mechanism causing ...


Characterization Of Higher-Order Chromatin Structure In Bone Differentiation And Breast Cancer: A Dissertation, Ahmet Rasim Barutcu Feb 2016

Characterization Of Higher-Order Chromatin Structure In Bone Differentiation And Breast Cancer: A Dissertation, Ahmet Rasim Barutcu

GSBS Dissertations and Theses

Higher-order genome organization is important for the regulation of gene expression by bringing different cis-regulatory elements and promoters in proximity. The establishment and maintenance of long-range chromatin interactions occur in response to cellular and environmental cues with the binding of transcription factors and chromatin modifiers. Understanding the organization of the nucleus in differentiation and cancer has been a long standing challenge and is still not well-understood. In this thesis, I explore the dynamic changes in the higher-order chromatin structure in bone differentiation and breast cancer. First, we show dynamic chromatin contact between a distal regulatory element and the promoter of ...


Insights Into Melanocyte Regeneration And Melanoma Initiation Using The Zebrafish Model System: A Dissertation, Sharanya Iyengar Oct 2015

Insights Into Melanocyte Regeneration And Melanoma Initiation Using The Zebrafish Model System: A Dissertation, Sharanya Iyengar

GSBS Dissertations and Theses

During regeneration, cells must coordinate proliferation and differentiation to rebuild tissues that are lost. Understanding how source cells execute the regeneration process has been a longstanding goal in regenerative biology with implications in wound healing and cell replacement therapies. Melanocytes are pigment-producing cells in the skin of vertebrates that can be lost during hair graying, injury and disease-related depigmentation. Melanoma is an aggressive skin cancer that develops from melanocytes, and it is hypothesized that melanoma cells have properties that are similar to melanocyte stem cells.

To gain insight into melanocyte regeneration we set out to identify the source of regeneration ...


Role And Regulation Of Autophagy During Developmental Cell Death In Drosophila Melanogaster: A Dissertation, Kirsten M. Tracy Apr 2015

Role And Regulation Of Autophagy During Developmental Cell Death In Drosophila Melanogaster: A Dissertation, Kirsten M. Tracy

GSBS Dissertations and Theses

Autophagy is a conserved catabolic process that traffics cellular components to the lysosome for degradation. Autophagy is required for cell survival during nutrient restriction, but it has also been implicated in programmed cell death. It is associated with several diseases, including cancer. Cancer is a disease characterized by aberrant cell growth and proliferation. To support this growth, the tumor cell often deregulates several metabolic processes, including autophagy. Interestingly, autophagy plays paradoxical roles in tumorigenesis. It has been shown to be both tumor suppressive through cell death mechanisms and tumor promoting through its cytoprotective properties. However, the mechanisms regulating the balance ...


Function And Regulation Of The Α6 Integrins In Mammary Epithelial Biology And Breast Cancer: A Dissertation, Cheng Chang Feb 2015

Function And Regulation Of The Α6 Integrins In Mammary Epithelial Biology And Breast Cancer: A Dissertation, Cheng Chang

GSBS Dissertations and Theses

Integrins have the ability to impact major aspects of epithelial biology including adhesion, migration, invasion, signaling and differentiation, as well as the formation and progression of cancer (Hynes 2002; Srichai and Zent 2010; Anderson et al. 2014). This thesis focuses on how integrins are regulated and function in the context of mammary epithelial biology and breast cancer with a specific focus on the α6 integrin heterodimers (α6β1 and α6β4). These integrins function primarily as receptors for the laminin family of extracellular matrix (ECM) proteins and they have been implicated in mammary gland biology and breast cancer (Friedrichs et al. 1995 ...


Autophagy-Independent Role For Beclin 1 In The Regulation Of Growth Factor Receptor Signaling: A Dissertation, Rasika Rohatgi Jan 2015

Autophagy-Independent Role For Beclin 1 In The Regulation Of Growth Factor Receptor Signaling: A Dissertation, Rasika Rohatgi

GSBS Dissertations and Theses

Beclin 1 is a haplo-insufficient tumor suppressor that is decreased in many human tumors. The function of Beclin 1 in cancer has been attributed primarily to its role in the degradative process of autophagy. However, the role of autophagy itself in tumorigenesis is context-dependent and can be both preventive and promoting. Due to its dual function in cancer a better understanding of this process is necessary to develop potential novel cancer therapies. To gain insight into the role of autophagy in breast carcinoma, I analyzed the autophagydependency of different subtypes of breast cancer. My results implicate that triple-negative breast carcinoma ...


A Novel Autophagy Regulatory Mechanism That Functions During Programmed Cell Death: A Dissertation, Tsun-Kai Chang Sep 2013

A Novel Autophagy Regulatory Mechanism That Functions During Programmed Cell Death: A Dissertation, Tsun-Kai Chang

GSBS Dissertations and Theses

Autophagy is a cellular process that delivers cytoplasmic materials for degradation by the lysosomes. Autophagy-related (Atg) genes were identified in yeast genetic screens for vehicle formation under stress conditions, and Atg genes are conserved from yeast to human. When cells or animals are under stress, autophagy is induced and Atg8 (LC3 in mammal) is activated by E1 activating enzyme Atg7. Atg8-containing membranes form and surround cargos, close and mature to become the autophagosomes. Autophagosomes fuse with lysosomes, and cargos are degraded by lysosomal enzymes to sustain cell viability. Therefore, autophagy is most frequently considered to function in cell survival. Whether ...