Molecular Biology Commons^™

Extracellular Matrix In Development And Disease, Julia Thom Oxford, Jonathon C. Reeck, Makenna J. Hardy

Biomolecular Research Center Publications and Presentations

The evolution of multicellular metazoan organisms was marked by the inclusion of an extracellular matrix (ECM), a multicomponent, proteinaceous network between cells that contributes to the spatial arrangement of cells and the resulting tissue organization. The development of an ECM that provides support in larger organisms may have represented an advantage in the face of selection pressure for the evolution of the ECM.

Ph-Induced Folding Of The Caspase-Cleaved Par-4 Tumor Suppressor: Evidence Of Structure Outside Of The Coiled Coil Domain, Andrea M. Clark, Komala Ponniah, Meghan S. Warden, Emily M. Raitt, Andrea C. Yawn, Stephen M. Pascal

Chemistry & Biochemistry Faculty Publications

Prostate apoptosis response-4 (Par-4) is a 38 kDa largely intrinsically disordered tumor suppressor protein that functions in cancer cell apoptosis. Par-4 down-regulation is often observed in cancer while up-regulation is characteristic of neurodegenerative conditions such as Alzheimer’s disease. Cleavage of Par-4 by caspase-3 activates tumor suppression via formation of an approximately 25 kDa fragment (cl-Par-4) that enters the nucleus and inhibits Bcl-2 and NF-ƙB, which function in pro-survival pathways. Here, we have investigated the structure of cl-Par-4 using biophysical techniques including circular dichroism (CD) spectroscopy, dynamic light scattering (DLS), and intrinsic tyrosine fluorescence. The results demonstrate pH-dependent folding of cl-Par-4, …

Genetic Testing And A Real World Case Of Lynch Syndrome, Paige Montanaro

Senior Honors Projects

In recent years, advancements in genetic testing methods have revolutionized the medical field by enhancing the ability to identify persons with an inherited predisposition to cancer. According to the American Society for Clinical Oncology, individuals should undergo genetic testing when he or she meets the following criteria: the individual demonstrates familial history that indicates a predisposition to certain cancers, the test can be adequately interpreted, and the results will aid in the diagnosis, treatment, or management of the patient or additional family members at risk. Genetic testing can be done on samples of hair, skin, blood, amniotic fluid, or other …

Investigating The Essential Roles Of Dprl-1 In Drosophila Melanogaster, Alex Lee

Summer Research

Phosphatase of Regenerating Liver (PRL) proteins regulate a number of important cellular processes, including cell growth and division. Humans have three PRL proteins: PRL-1, PRL-2, and PRL-3. An accumulation of evidence has shown that elevated levels of PRLs are strongly correlated with uncontrollable growth and metastasis of tumors. However, contradictory findings have arisen indicating that PRLs instead function to halt cell division thereby preventing uncontrollable tumor growth. In light of these results, the underlying mechanisms regarding how PRLs function within cellular processes remains unclear. To investigate the functions of PRLs, we will create transgenic fruit flies (Drosophila melanogaster) …

Ligands Of Therapeutic Utility For The Liver X Receptors., Rajesh Komati, Dominick Spadoni, Shilong Zheng, Jayalakshmi Sridhar

Faculty and Staff Publications

Liver X receptors (LXRs) have been increasingly recognized as a potential therapeutic target to treat pathological conditions ranging from vascular and metabolic diseases, neurological degeneration, to cancers that are driven by lipid metabolism. Amidst intensifying efforts to discover ligands that act through LXRs to achieve the sought-after pharmacological outcomes, several lead compounds are already being tested in clinical trials for a variety of disease interventions. While more potent and selective LXR ligands continue to emerge from screening of small molecule libraries, rational design, and empirical medicinal chemistry approaches, challenges remain in minimizing undesirable effects of LXR activation on lipid metabolism. …

Characterization And Target Identification Of Ak301: A Novel Mitotic Arrest Agent, Michael J. Bond, Avijeet S. Chopra, Marina Bleiler, Michelle Yeagley, Eric Scocchera

University Scholar Projects

The Giardina Laboratory has recently identified AK301 as a novel mitotic arrest agent. This work aimed to characterize the arrest state induced by AK301 (EC₅₀ ~ 150nM) and identify the cellar targets responsible for the arrest. It was found that AK301 arrest is readily reversible upon withdrawal of AK301. Cells that slip from mitosis after removal of AK301 are sensitized to apoptosis. This was found to be unique for AK301 when compared to other mitotic arrest agents like colchicine, vincristine, and BI2536. Arrested cells were found to have increased ATM activity as well as an upregulation of p53 and …

Non-Thermal Atmospheric Plasma Induces Ros-Independent Cell Death In U373mg Glioma Cells And Augments The Cytotoxicity Of Temozolomide, Gillian Conway, Alan Casey, Vladimir Milosavljevic, Yupeng Liu, Orla L. Howe, Patrick Cullen, James Curtin

Articles

Non-thermal atmospheric plasma (NTAP) is an ionised gas produced under high voltage that can generate short-lived chemically active species and induce a cytotoxic insult in cancer cells. Cell-specific resistance to NTAP-mediated cytotoxicity has been reported in the literature. The aim of this study was to determine whether resistance against NTAP could be overcome using the human glioma cell line U373MG.

Methods:

Non-thermal atmospheric plasma was generated using a Dielectric Barrier Device (DBD) system with a maximum voltage output of 120 kV at 50 Hz. The viability of U373MG GBM cells and HeLa cervical carcinoma cells was determined using morphology, flow …

Current Advances In The Application Of Raman Spectroscopy For Molecular Diagnosis Of Cervical Cancer, Ines Martins Ramos, Alison Malkin, Fiona Lyng

Articles

Raman spectroscopy provides a unique biochemical fingerprint capable of identifying and characterizing the structure of molecules, cells and tissues. In cervical cancer, it is acknowledged as a promising biochemical tool due to its ability to detect pre-malignancy and early malignancy stages. This review summarizes the key research in the area and the evidence compiled is very encouraging for ongoing and further research. In addition to the diagnostic potential, promising results for HPV detection and monitoring treatment response suggest more than just a diagnosis prospective. A greater body of evidence is however necessary before Raman spectroscopy is fully validated for clinical …

Mutagenesis Of 8-Oxoguanine Adjacent To An Abasic Site In Escherichia Coli Cells Proficient Or Deficient In Dna Polymerase Iv, Savas T. Tsikis

Honors Scholar Theses

It is well established that clustered DNA damages or multiply damaged sites (MDS) are the result of ionizing radiation and that they are characterized by an enhanced mutagenic potential. As a model MDS, we have evaluated the mutagenic and cytotoxic properties of the ubiquitous oxidative DNA damage 8-oxoguanine (G^8-oxo) adjacent to the abasic site lesion (Z) using a single stranded M13mp7L2 vector. The recombinant DNA was used to transform wild type E. coli strains and strains deficient in the translesion DNA polymerase of the Y-family, DNA polymerase IV, in the presence or absence of SOS induction. The percent …

The Role Of Formins In Human Disease, Aaron D. Deward, Kathryn M. Eisenmann, Stephen F. Matheson, Arthur S. Alberts

University Faculty Publications and Creative Works

Formins are a conserved family of proteins that play key roles in cytoskeletal remodeling. They nucleate and processively elongate non-branched actin filaments and also modulate microtubule dynamics. Despite their significant contributions to cell biology and development, few studies have directly implicated formins in disease pathogenesis. This review highlights the roles of formins in cell division, migration, immunity, and microvesicle formation in the context of human disease. In addition, we discuss the importance of controlling formin activity and protein expression to maintain cell homeostasis. © 2009 Elsevier B.V. All rights reserved.

Treg Depletion Inhibits Efficacy Of Cancer Immunotherapy: Implications For Clinical Trials., James Curtin, Marianela Candolfi, Tamer Fakhouri, Chunyan Liu, Anderson Alden, Matthew Edwards, Pedro Lowenstein, Maria Castro

Articles

BACKGROUND: Regulatory T lymphocytes (Treg) infiltrate human glioblastoma (GBM); are involved in tumor progression and correlate with tumor grade. Transient elimination of Tregs using CD25 depleting antibodies (PC61) has been found to mediate GBM regression in preclinical models of brain tumors. Clinical trials that combine Treg depletion with tumor vaccination are underway to determine whether transient Treg depletion can enhance anti-tumor immune responses and improve long term survival in cancer patients. FINDINGS: Using a syngeneic intracrabial glioblastoma (GBM) mouse model we show that systemic depletion of Tregs 15 days after tumor implantation using PC61 resulted in a decrease in Tregs …