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Articles 1 - 30 of 84

Full-Text Articles in Cancer Biology

Differential Roles Of Mammalian Target Of Rapamycin Complexes 1 And 2 In Migration Of Prostate Cancer Cells, Smrruthi Vaidegi Venugopal May 2019

Differential Roles Of Mammalian Target Of Rapamycin Complexes 1 And 2 In Migration Of Prostate Cancer Cells, Smrruthi Vaidegi Venugopal

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

In this study, we investigated differential activation and the role of two mTOR complexes in cell migration of prostate cancer cells. Specific knock-down of endogenous RAPTOR and RICTOR by siRNA resulted in decreased cell migration in LNCaP, DU145, and PC3 cells indicating that both mTORC1 and mTORC2 are required for cell migration. EGF treatment induced the activation of both mTORC1 and mTORC2 as determined by complex-specific phosphorylation of mTOR protein. Specific knock-down or inhibition of Rac1 activity in PC3 cells blocked EGF-induced activation of mTORC2, but had no effect on mTORC1 activation. Furthermore, the over-expression of constitutively active Rac1 (Rac1Q61L ...


Establishment Of Crispr/Cas-9 Aided Knockout Of The Zic2 Gene In The African-American Prostate Cancer Cell Line E006aa-Pr, Janelle Moore May 2019

Establishment Of Crispr/Cas-9 Aided Knockout Of The Zic2 Gene In The African-American Prostate Cancer Cell Line E006aa-Pr, Janelle Moore

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

The largest U.S. cancer health disparity exists in prostate cancer, with African American men having the highest incidence and mortality rates. The present study evaluated the effects of ZIC2 and the underlying mechanisms in the E006 parental African-American cell line that produces tumors at accelerated growth rates because of the increase of ZIC2 genes in African-American males. We analyzed the experimental research that the overexpression of ZIC2 contributes to progression of prostate cancer. E006AA cells with overexpressed or suppressed ZIC2 were analyzed to determine phenotypic differences, PCR, cell proliferation and immunoblot assays. The expression levels of ZIC2 were analyzed ...


Acute Promyelocytic Leukemia: A Case Study Correlating Cytogenetic Abnormality With Prognosis, Alyssa Lamond, Theresa Tellier-Castellone May 2019

Acute Promyelocytic Leukemia: A Case Study Correlating Cytogenetic Abnormality With Prognosis, Alyssa Lamond, Theresa Tellier-Castellone

Senior Honors Projects

Advancements in medical technology today have positively impacted the diagnosis, treatment, and prognosis of cancers. Particularly acute promyelocytic leukemia (APL) has completely improved from having the poorest prognosis to one of the best. Acute promyelocytic leukemia is a malignant disease of hematopoietic tissue classified by WHO as leukemia with >20% blasts from the myeloid lineage, specifically promyelocytes. Determined in 1976, FAB classified AML subtypes M1-M7, with APL being M3. Specific characteristics classify the subtype of AML, with each resulting from a different genetic abnormality. The focus of APL diagnosis, treatment, and prognosis occurs around the known PML-RARα fusion gene. Flow ...


Computational Analysis Of Genomic Variants Affecting Predicted Microrna:Target Interactions In Prostate Cancer., Angélica Paola Hernández Pérez Jul 2018

Computational Analysis Of Genomic Variants Affecting Predicted Microrna:Target Interactions In Prostate Cancer., Angélica Paola Hernández Pérez

KGI Theses and Dissertations

Prostate cancer (PCa) is the most common cancer of men in the United States and is third only to lung and colon as a cause of cancer death. Clinical behavior of the disease is variable and the combination of prostate-specific antigen (PSA) screening and Gleason score staging are currently the best available molecular and pathology tools to predict outcomes. Cancer biology research establishes microRNAs (miRNAs) as key molecular components in both normal and pathological states. Thus, elucidating miRNAs perturbed by genomic alterations will expand our understanding of the molecular taxonomy of PCa with the aim to complement current practices in ...


Identification And Utility Of Dna In Exosomes, Paul Kurywchak May 2018

Identification And Utility Of Dna In Exosomes, Paul Kurywchak

UT GSBS Dissertations and Theses (Open Access)

Cancer-associated mortality has been declining for two decades but remains a significant public health problem, especially when patients initially present with advanced disease. Early detection methods have improved survival rates but remain unavailable for a majority of cancers due to a lack of sensitive biomarkers or numerous limitations associated with current diagnosis strategies. Approaches to develop “liquid biopsies” by detecting tumor cells or DNA in the blood have led to several breakthroughs and create the potential for non-invasive, routine assessment of diseases status. However, these biomarkers are rare and currently difficult to isolate, especially in the early stages of disease ...


Characterization Of Notch1 And Pi3k-Pten-Akt/Mtor Pathway Interaction In Head And Neck Squamous Cell Carcinoma, Kyriante' Henry Dec 2017

Characterization Of Notch1 And Pi3k-Pten-Akt/Mtor Pathway Interaction In Head And Neck Squamous Cell Carcinoma, Kyriante' Henry

UT GSBS Dissertations and Theses (Open Access)

Head and neck squamous cell carcinoma (HNSCC) affects various mucosal sites of the upper aerodigestive tract, including the nasal and oral cavities, the nasopharynx, and the oropharynx. More than five hundred thousand new cases of HNSCC occurred in 2011 alone, with 50,000 reported cases in the United States. This trend made HNSCC the seventh most common non-skin cancer worldwide (Ferlay et al., 2015). Although significant epidemiological and pathological advancements have been made, survival rates have not improved much over the last 40 years, leaving a mortality rate that remains at approximately 50%. An unbiased drug screen demonstrated that HNSCC ...


Intracellular Signaling And Trafficking In Cancer: Role Of Rab5-Gtpase In Migration And Invasion Of Breast Cells, Nicole Porther Nov 2017

Intracellular Signaling And Trafficking In Cancer: Role Of Rab5-Gtpase In Migration And Invasion Of Breast Cells, Nicole Porther

Nicole Porther

Metastasis is characterized pathologically by uncontrolled cell invasion, proliferation, migration and angiogenesis. Steroid hormones, such as estrogen, and growth factors, which include insulin growth factor I/II (IGF-1/IGF-2) therapy has been associated with most if not all of the features of metastasis. It has been determined that IGF-1 increases cell survival of cancer cells and potentiate the effect of E2 and other ligand growth factors on breast cancer cells. However not much information is available that comprehensively expounds on the roles of insulin growth factor receptor (IGFR) and Rab GTPases may play in breast cancer. The latter, Rab GTPases ...


Preclinical Development Of Therapeutic Strategies Against Triple-Negative And Inflammatory Breast Cancer, Angie M. Torres-Adorno Aug 2017

Preclinical Development Of Therapeutic Strategies Against Triple-Negative And Inflammatory Breast Cancer, Angie M. Torres-Adorno

UT GSBS Dissertations and Theses (Open Access)

Triple-negative (TNBC) and inflammatory (IBC) breast cancer are the most aggressive forms of breast cancer, accounting for 20% and 10% of cancer-related deaths, respectively. Among IBC cases, 30% are additionally classified with TNBC molecular pathology, a diagnosis that significantly worsens patient’s prognosis. The current lack of TNBC and IBC molecular understanding prevents the development of effective therapeutic strategies. To identify effective treatments, we explored aberrant apoptosis pathways and cell membrane fluidity as novel therapeutic targets.

We first identified an effective therapeutic strategy against TNBC and IBC by pro-apoptotic protein NOXA-mediated inhibition of the anti-apoptotic protein MCL1 following inhibition of ...


The Role Of The Epithelial-To-Mesenchymal Transition (Emt) In Lung Cancer Progression, David H. Peng Aug 2017

The Role Of The Epithelial-To-Mesenchymal Transition (Emt) In Lung Cancer Progression, David H. Peng

UT GSBS Dissertations and Theses (Open Access)

Lung cancer is the leading cause of cancer-related deaths due to conventional therapy resistance and metastatic disease, therefore understanding the mechanisms governing these biological functions is vital for improving patient survival. Approximately 30% of patients with the adenocarcinoma histologic subset of lung cancer possess an activating KRAS mutation, characterized by a lack of response to chemotherapies with a poor overall 5-year survival rate. Despite the mutational frequency, KRAS remains a challenge to pharmacologically inhibit and current drugs undergoing clinical trials that target specific downstream effector proteins of KRAS, such as MEK inhibitors, have failed to produce significant clinical benefits. Previous ...


The Effect Of Target-Specific Biomolecules In Breast Cancer, Mohannad Garoub Jun 2017

The Effect Of Target-Specific Biomolecules In Breast Cancer, Mohannad Garoub

FIU Electronic Theses and Dissertations

Cancer is the second leading cause of mortality in the United States and the World, therefore, early effective prevention, diagnosis, and therapy is needed. Estrogens play a major role in the initiation and progression of breast cancer. Elevated lifetime exposure to estrogens is associated with an increased risk of developing breast cancer. Estrogens through influencing mitochondria contribute to estrogen induced breast carcinogenesis; however, the exact mitochondrial mechanisms underlying the estrogen carcinogenic effect in breast tissue are not clearly understood. For this dissertation, the mitotoxic and cytotoxic effects of triphenylphosphonium cation (TPP) and Origanum majorana organic extract (OME) as well as ...


Characterization Of Zic2 As An Oncoprotein In Prostate Cancer, Keira C. Davis May 2017

Characterization Of Zic2 As An Oncoprotein In Prostate Cancer, Keira C. Davis

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

The field of prostate cancer research is in need of biological markers that predict which cancers do not need treatment, those that can be treated successfully with a localized treatment and more specific cases in which patients are likely to have an aggressive form of cancer that will require more aggressive surgical and chemotherapeutic treatments. ZIC2 is one of five members of a family of proteins that play critical roles in neural crest and mesoderm growth in normal embryonic brain development and in the adult cerebellum of vertebrates. Found throughout the animal kingdom, ZIC1-5 genes encode five distinct ZIC proteins ...


The Role Of The Diras Family Members In Regulating Ras Function, Cancer Growth And Autophagy, Margie Nicole Sutton May 2017

The Role Of The Diras Family Members In Regulating Ras Function, Cancer Growth And Autophagy, Margie Nicole Sutton

UT GSBS Dissertations and Theses (Open Access)

DIRAS3 is a maternally imprinted tumor suppressor gene that is downregulated by multiple mechanisms across several tumor types. When re-expressed, DIRAS3 decreases proliferation, inhibits motility, and induces autophagy and tumor dormancy. DIRAS3 encodes a 26 kDa small GTPase with 60% homology to Ras and Rap, differing from oncogenic Ras family members by a 34-amino acid N-terminal extension that is required for its tumor suppressive function in ovarian cancer. By assessing the structure-function relationship, I found that DIRAS3 inhibits Ras-induced transformation and is a natural antagonist of Ras/MAPK signaling. DIRAS3 binds directly to Ras and disrupts cluster formation inhibiting the ...


Survival Model Of Intrahepatic Cholangiocarcinoma; Sex As A Biological Variable, Mary A. Phillippi, Justin L. Mott, Cody J. Wehrkamp, Ying Xie, David Oupicky, Ashley M. Mohr, Bailey A. Stringham Jan 2017

Survival Model Of Intrahepatic Cholangiocarcinoma; Sex As A Biological Variable, Mary A. Phillippi, Justin L. Mott, Cody J. Wehrkamp, Ying Xie, David Oupicky, Ashley M. Mohr, Bailey A. Stringham

Hepatobiliary Cancers: Pathobiology and Translational Advances

No abstract provided.


Mechanism Of Action Of Id4 As A Tumor Suppressor, Shravan Kumar Komaragiri Dec 2016

Mechanism Of Action Of Id4 As A Tumor Suppressor, Shravan Kumar Komaragiri

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

Initial studies demonstrated that Inhibitor of DNA binding/differentiation protein 4 (Id4) acts as a tumor suppressor in prostate cancer (PCa). To further confirm and investigate the mechanism by which ID4 acts as a tumor suppressor, herein we concentrated on two different approaches. In the first approach we investigated ID4 role as a tumor suppressor by regulating AKT/PI3K pathway. In the second approach, we examined the role of Id4 in blocking the tumorogenic properties of metastatic PC3 cells. Phosphoinositide 3-kinase/Protein kinase B (PI3/AKT) pathway regulates multiple biological processes leading to cell survival, proliferation and growth in cancerous ...


Id4 And Fkbp52 Interaction Regulates Androgen Receptor Activity: Mechanistic Insight, Jugal Bharat Joshi Dec 2016

Id4 And Fkbp52 Interaction Regulates Androgen Receptor Activity: Mechanistic Insight, Jugal Bharat Joshi

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

The inhibitor of DNA binding protein 4 (ID4) is a dominant negative regulator of basic helix loop helix (bHLH) family of transcription factors.1 Recently, Patel et al., demonstrated that inhibitor of differentiation 4 (ID4) acts as a tumor suppressor and its loss, frequently observed in prostate cancer, promotes castration-resistant prostate cancer (CRPC) through constitutive androgen receptor (AR) activation.2 However, the mechanism by which loss of ID4 promotes constitutively active AR signaling in the CRPC conditions is unknown. The rationale of the present study was to unravel the underlying molecular mechanisms through which loss of ID4 potentiates AR signaling ...


Regulation Of Breast Cancer Initiation And Progression By 14-3-3zeta, Chia-Chi Chang Aug 2016

Regulation Of Breast Cancer Initiation And Progression By 14-3-3zeta, Chia-Chi Chang

UT GSBS Dissertations and Theses (Open Access)

14-3-3ζ is a ubiquitously expressed family member of proteins that have been implicated to have oncogenic potential through its interactions and involvement in cancer initiation and progression. 14-3-3ζ belongs to the highly conserved 14-3-3ζ protein family and modulates numerous pathways in cancer. Overexpression of 14-3-3ζ is an early event, occurs in more than 40% of human breast cancer cases, and is associated with disease recurrence and poor prognosis. Metabolic reprogramming is a hallmark of cancer. Cancer cells elevate aerobic glycolysis to produce metabolic intermediates and reducing equivalents, thereby facilitating cellular adaptation to the adverse environment and sustaining fast proliferation. Interestingly ...


Influencing Pathways That Cause Metastasis And Stemness In Epithelial Ovarian Cancer, Alyse Lynn Huisken-Hill Jun 2016

Influencing Pathways That Cause Metastasis And Stemness In Epithelial Ovarian Cancer, Alyse Lynn Huisken-Hill

Electronic Theses, Projects, and Dissertations

Ovarian cancer is the fifth leading cause of cancer death in women between the ages of 35 and 74. With 22 thousand new cases and 15 thousand deaths annually ovarian cancer is among the most deadly cancers with a death to incidence ratio of 68%. With 70% of cases High Grade Serous Ovarian Carcinoma (HGSOC) is the most common type of ovarian cancer and causes 90% of ovarian cancer deaths. 80% of patients have reoccurrence within five years and only 15-30% of patients with recurrent metastatic ovarian cancer respond to current therapies, chemotherapy and surgery. One reason for the high ...


Normal Glycolytic Enzyme Activity Is Critical For Hypoxia Inducible Factor-1a Activity And Provides Novel Targets For Inhibiting Tumor Growth, Geoffrey Grandjean Phd Dec 2015

Normal Glycolytic Enzyme Activity Is Critical For Hypoxia Inducible Factor-1a Activity And Provides Novel Targets For Inhibiting Tumor Growth, Geoffrey Grandjean Phd

UT GSBS Dissertations and Theses (Open Access)

Normal Glycolytic Enzyme Activity is Critical for Hypoxia Inducible Factor-1α Activity and Provides Novel Targets for Inhibiting Tumor Growth

By Geoffrey Grandjean

Advisory Professor: Garth Powis, D. Phil

Unique to proliferating cancer cells is the observation that their increased need for energy is provided by a high rate of glycolysis followed by lactic acid fermentation in a process known as the Warburg Effect, a process many times less efficient than oxidative phosphorylation employed by normal cells to satisfy a similar energy demand [1]. This high rate of glycolysis occurs regardless of the concentration of oxygen in the cell and is ...


Clinical Significance Of The Integrin Α6Β4 In Human Malignancies, Rachel L Stewart, Kathleen L O'Connor Sep 2015

Clinical Significance Of The Integrin Α6Β4 In Human Malignancies, Rachel L Stewart, Kathleen L O'Connor

Pathology and Laboratory Medicine Faculty Publications

Integrin α6β4 is a cellular adhesion molecule that binds to laminins in the extracellular matrix and nucleates the formation of hemidesmosomes. During carcinoma progression, integrin α6β4 is released from hemidesmosomes, where it can then signal to facilitate multiple aspects of tumor progression including sustaining proliferative signaling, tumor invasion and metastasis, evasion of apoptosis, and stimulation of angiogenesis. The integrin achieves these ends by cooperating with growth factor receptors including EGFR, ErbB-2, and c-Met to amplify downstream pathways such as PI3K, AKT, MAPK, and the Rho family small GTPases. Furthermore, it dramatically alters the transcriptome ...


Intracellular Signaling And Trafficking In Cancer: Role Of Rab5-Gtpase In Migration And Invasion Of Breast Cells, Nicole Porther Mar 2015

Intracellular Signaling And Trafficking In Cancer: Role Of Rab5-Gtpase In Migration And Invasion Of Breast Cells, Nicole Porther

FIU Electronic Theses and Dissertations

Metastasis is characterized pathologically by uncontrolled cell invasion, proliferation, migration and angiogenesis. Steroid hormones, such as estrogen, and growth factors, which include insulin growth factor I/II (IGF-1/IGF-2) therapy has been associated with most if not all of the features of metastasis. It has been determined that IGF-1 increases cell survival of cancer cells and potentiate the effect of E2 and other ligand growth factors on breast cancer cells. However not much information is available that comprehensively expounds on the roles of insulin growth factor receptor (IGFR) and Rab GTPases may play in breast cancer. The latter, Rab GTPases ...


Mouse Polyomavirus T Antigens: Directors Of Cell Cycle Signaling, Catherine Nicholas Jan 2015

Mouse Polyomavirus T Antigens: Directors Of Cell Cycle Signaling, Catherine Nicholas

Undergraduate Honors Theses

Polyomaviruses (PyV) efficiently replicate by disrupting host cell signaling pathways. Disruption of the cell cycle is implicated in nearly all tumor formation. Studies of cellular transformation by primate PyV, SV40, and mouse polyomavirus (MPyV) have led to numerous findings concerning tumor suppressor proteins and cell cycle regulation pathways (Das D. and Imperiale 2009, Dahl et. al. 2005). Expression of PyV T Antigens (TAg) modifies signaling pathways and cell cycle checkpoints to the virus’ advantage. Expected modifications include inhibiting checkpoint proteins between G1 and S phases as well as promoting kinases with downstream signaling effects that result in progression to S ...


The Significance Of Crispr/Cas9-Directed Cul3 Knockout On Human Colorectal Cancer Cells, Zoe A. Lautz Jan 2015

The Significance Of Crispr/Cas9-Directed Cul3 Knockout On Human Colorectal Cancer Cells, Zoe A. Lautz

Departmental Honors Projects

Cancer, the second leading cause of death in the US, is caused by mutations in select genes that alter cellular function leading to uncontrolled proliferation. Understanding the specific genes that drive cancer can lead to the generation of novel cancer therapies. To identify novel genes that drive cancer in the colon (CRC), lungs, and ovaries in mice, Starr et al. employed a transposon-based insertional mutagenesis system. One of the genes identified, APC, is mutated in 70-80% of human CRCs. CUL3, suspected to be a general driver gene, was discovered in the lung cancer screen. CUL3 was analyzed for its role ...


Mdm2-Mediated Degradation Of Sirt6 Phosphorylated By Akt1 Promotes Tumorigenesis And Trastuzumab Resistance In Breast Cancer, Umadevi Thirumurthi Dec 2014

Mdm2-Mediated Degradation Of Sirt6 Phosphorylated By Akt1 Promotes Tumorigenesis And Trastuzumab Resistance In Breast Cancer, Umadevi Thirumurthi

UT GSBS Dissertations and Theses (Open Access)

Sirtuin6 (SIRT6) is one of the members of the Sirtuin family and functions as a longevity assurance gene by promoting genomic stability. It also regulates various cancer-associated pathways and was recently established as a bonafide tumor suppressor in colon cancer. This suggests that SIRT6 is an attractive target for pharmacological activation in cancer treatment, and hence, identification of potential regulators of SIRT6 would be an important and critical contribution towards cancer treatment. Here, we show that AKT1 phosphorylates SIRT6 at Ser338 and induces MDM2-SIRT6 interaction, priming SIRT6 for degradation via the MDM2-dependent ubiquitin-proteasome pathway. Blocking SIRT6 Ser338 phosphorylation ...


Targeting Cox-2 And Rank In Aggressive Breast Cancers: Inflammatory Breast Cancer And Triple-Negative Breast Cancer, Monica Elizabeth Reyes Dec 2014

Targeting Cox-2 And Rank In Aggressive Breast Cancers: Inflammatory Breast Cancer And Triple-Negative Breast Cancer, Monica Elizabeth Reyes

UT GSBS Dissertations and Theses (Open Access)

Inflammatory breast cancer (IBC) and triple-negative breast cancer (TNBC) are two highly aggressive breast cancer subtypes associated with a poor outcome. Despite sensitivity to current treatment, these breast cancers subtypes have a high recurrence rate and proclivity to metastasize early. The aggressiveness of IBC and TNBC have been linked to CSCs and epithelial to mesenchymal transition (EMT), which are critical features of breast cancer progression and metastasis. The clinical challenge faced in the treatment of IBC and TNBC is finding a treatment strategy to target the cancer stem-like (CSC) population to block metastasis. Cyclooxygenase-2 (COX-2) and receptor activator of nuclear ...


Novel Posttranslational Modification In Lkb1 Activation And Function, Szu-Wei Lee Dec 2014

Novel Posttranslational Modification In Lkb1 Activation And Function, Szu-Wei Lee

UT GSBS Dissertations and Theses (Open Access)

Cancer cells display dramatic alterations in cellular metabolism to meet their needs of increased growth and proliferation. In the last decade, cancer research has brought these pathways into focus, and one emerging issue that has come to attention is that many oncogenes and tumor-suppressors are intimately linked to metabolic regulation (Jones and Thompson, 2009). One of the key tumor-suppressors involved in metabolism is Liver Kinase B1 (LKB1). LKB1 is the major upstream kinase of the evolutionarily conserved metabolic sensor—AMP-activated protein kinase (AMPK). Activation of the LKB1/AMPK pathway provides a survival advantage for cells under energy stress. LKB1 forms ...


Sustained Adrenergic Signaling Promotes Cervical Cancer Progression, Nouara C. Sadaoui Dec 2014

Sustained Adrenergic Signaling Promotes Cervical Cancer Progression, Nouara C. Sadaoui

UT GSBS Dissertations and Theses (Open Access)

Background: Chronic stress and sustained adrenergic signaling are known to promote tumor progression. The underlying mechanisms behind this process are not well understood. We examined the effects of sustained adrenergic signaling on cervical cancer progression through increased expression of HPV oncogenes, E6 and E7.

Materials and Methods: ADRβ expression levels were examined in patient-derived cervical cancer samples. We used an orthotopic model of cervical cancer to investigate the effects of restraint stress on tumor growth and metastasis. We evaluated the in vivo effects of a β-blocker, propranolol, and HPV E6/E7 siRNA. In vitro, ADRβ positive cervical cancer cells were ...


Strategies To Sensitize Bladder Cancer Cells To Small Molecule Inhibitors Targeting The Pi3k Pathway, Giovanni Nitti Aug 2014

Strategies To Sensitize Bladder Cancer Cells To Small Molecule Inhibitors Targeting The Pi3k Pathway, Giovanni Nitti

UT GSBS Dissertations and Theses (Open Access)

After many years of cancer research, it is well accepted by the scientific community that the future cure for this disease lies in a personalized therapeutic approach. Anticipating therapeutic outcome based on the genetic signature of a tumor has become the new paradigm. The PI3K pathway represents an ideal target for bladder cancer, as many of the key proteins of this pathway are altered or mutated in this particular type of cancer. Several small molecule inhibitors have been developed to target this pathway, but their efficacy has been shown to be heterogeneous among different cell lines and mostly cytostatic but ...


Characterization Of The Anti-Apoptotic Function Of The Lysine Demethylase Plant Homeodomain Finger Protein 8 (Phf8), Kimberly Muranko Jun 2014

Characterization Of The Anti-Apoptotic Function Of The Lysine Demethylase Plant Homeodomain Finger Protein 8 (Phf8), Kimberly Muranko

Electronic Thesis and Dissertation Repository

Apoptosis is an essential process in development and tissue maintenance. The tumor suppressor protein p53 initiates apoptosis through transactivation of pro-apoptotic genes when cellular stress is detected. This study identifies a regulatory role for the lysine demethylase, PHF8, in the p53-mediated apoptosis pathway. We initially suspected PHF8 of demethylating the adaptor protein Numb, however found this to be untrue. PHF8 has been found to have oncogenic properties including an anti-apoptotic effect, however how PHF8 negatively affects apoptosis has not been previously investigated. We found PHF8 inhibits translation of the pro-apoptotic genes TP53, BAX and CASP3. Chromatin immunoprecipitation revealed PHF8 binding ...


Characterization Of Jak, Stat, And Src Interactions In Head And Neck Squamous Cell Carcinoma, Reshma Jaseja, Reshma Jaseja Aug 2013

Characterization Of Jak, Stat, And Src Interactions In Head And Neck Squamous Cell Carcinoma, Reshma Jaseja, Reshma Jaseja

UT GSBS Dissertations and Theses (Open Access)

Recurrence of Head and Neck Squamous Cell Carcinoma (HNSCC) is common; thus, it is essential to improve the effectiveness and reduce toxicity of current treatments. Proteins in the Src/Jak/STAT pathway represent potential therapeutic targets, as this pathway is hyperactive in HNSCC and it has roles in cell migration, metastasis, proliferation, survival, and angiogenesis. During short-term Src inhibition, Janus kinase (Jak) 2, and signal transducer and activator of transcription (STAT) 3 and STAT5 are dephosphorylated and inactivated. Following sustained Src inhibition, STAT5 remains inactive, but Jak2 and STAT3 are reactivated following their early inhibition. To further characterize the mechanism ...


Purification And Characterization Of Oxidation-Resistant Ribonuclease Inhibitor Variants, Alec W. Uebersohn May 2013

Purification And Characterization Of Oxidation-Resistant Ribonuclease Inhibitor Variants, Alec W. Uebersohn

Lawrence University Honors Projects

Ribonuclease inhibitor (RI) is an intracellular mammalian protein which binds vertebrate-specific ribonucleases; this interaction is one of the tightest non-covalent interactions yet discovered. The biological activity of RI is poorly understood, but it is thought to regulate the biological functions of ribonucleases, which include initiating blood vessel growth, maintaining neuron viability, attacking pathogens, and mediating cell stress responses. RI is also involved in pathways unrelated to ribonucleases, including interactions with Drosha and PTEN, an anti-tumor protein.

One of the defining characteristics of RI is its oxidation sensitivity, a result of its unusually high cysteine content. The oxidation of RI is ...