Medical Molecular Biology Commons^™

The Role Of Menin-Mll Interaction In The Dissociation Between Cholestatic Liver Diseases And Cholangiocarcinoma, Laurent Ehrlich 2085637, Chad Hall Dr., Tori Sheppard, Julie Venter, April O'Brien, Terry C. Lairmore Dr., Gianfranco Alpini Dr., Shannon Glaser Dr.

Hepatobiliary Cancers: Pathobiology and Translational Advances

No abstract provided.

Hepatocellular Cancer Genome And Transcriptome Analysis Validates Clinically Significant Mutational Signatures With The Tgf-𝛃 Pathway, Shuyun Rao, Jian Chen, Kazufumi Ohshiro, Shoujun Gu, Sobia Zaidi, Wilma S. Jogunoori, Jon White, Nagarajan Pattabiraman, Raja Mazumder, Anelia Horvath, Ray-Chang Wu, Shulin Li, Chuxia Deng, Bibhuti Mishra, Rehan Akbanni, The Tcga Cancer Network, Lopa Mishra

Hepatobiliary Cancers: Pathobiology and Translational Advances

No abstract provided.

Characterization, Regulation, And Targeting Of Erythroid Progenitors In Normal And Disordered Human Erythropoiesis, B. M. Dulmovits, J. Hom, A. Narla, N. Mohandas, L. Blanc

Journal Articles

No abstract provided.

Unraveling Macrophage Heterogeneity In Erythroblastic Islands, K. G. Seu, J. Papoin, R. Fessler, J. Hom, G. Huang, N. Mohandas, L. Blanc, T. A. Kalfa

Journal Articles

No abstract provided.

Levodopa-Induced Abnormal Involuntary Movements Correlate With Altered Permeability Of The Blood-Brain-Barrier In The Basal Ganglia, R. P. Lerner, V. Francardo, K. Fujita, Z. Bimpisidis, V. A. Jourdain, C. C. Tang, S. L. Dewey, T. Chaly, M. A. Cenci, D. Eidelberg

Journal Articles

© 2017 The Author(s). Chronic levodopa treatment leads to the appearance of dyskinesia in the majority of Parkinson's disease patients. Neurovascular dysregulation in putaminal and pallidal regions is thought to be an underlying feature of this complication of treatment. We used microPET to study unilaterally lesioned 6-hydroxydopamine rats that developed levodopa-induced abnormal involuntary movements (AIMs) after three weeks of drug treatment. Animals were scanned with [15O]-labeled water and [18F]-fluorodeoxyglucose, to map regional cerebral blood flow and glucose metabolism, and with [11C]-isoaminobutyric acid (AIB), to assess blood-brain-barrier (BBB) permeability, following separate injections of levodopa or saline. Multitracer scan data were acquired …

Nicotinic Acetylcholine Receptor-Mediated Protection Of The Rat Heart Exposed To Ischemia Reperfusion, S. A. Mavropoulos, N. S. Khan, A. C. J. Levy, B. T. Faliks, C. P. Sison, V. A. Pavlov, Y. Zhang, K. Ojamaa

Journal Articles

No abstract provided.

Characterization Of Malt1 Inhibitors And Their Effect On Leukemic Cell Growth Properties, Christina Snyder

Graduate School of Biomedical Sciences Theses and Dissertations

Leukemia is the most common childhood cancer, with a combined 40,000 predicted new cases in the United States in 2016 [8]. The two most common subtypes are acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) [9-11]. The commercially available inhibitor of Bruton’s tyrosine kinase (BTK) has shown promising results in clinical trials for CLL because of the importance of BCR signaling in CLL [12-15]. Recent studies suggest that the outgrowth of BTK inhibitor resistant clonal cells in some CLL patients results in a treatment-refractory phenotype [16-18]. MALT1, a protein involved in BCR activation of the NF-κB pathway that functions …

Targeting Hepatocellular Carcinoma Through Tgf-Β Pathway E3 Ligases, Kazufumi Ohshiro, Jian Chen, Shulin Li, Jon White, Asif Rashid, Lopa Mishra

Hepatobiliary Cancers: Pathobiology and Translational Advances

No abstract provided.

The Role Of Frabin (Fgd4) In Aggressive Prostate Cancer, Alexia M. Bossan

Honors Undergraduate Theses

A major problem in prostate cancer (PCa) management is the development of drug resistance. It is known that there are changes in PCa biology upon prolonged treatment with drugs, including anti-androgen drugs that alter cellular signaling processes leading to the development of castration resistant PCa. MicroRNAs (miRNAs) are regulatory molecules that modulate gene expression through inhibition of protein translation and modulate cellular functions. Altered expression of miRNAs is often noted in drug resistant cancer including PCa. Studies from our laboratory have identified a number of down-regulated miRNAs in PCa, including miR-l 7-92a miRNAs. Frabin (FGD4) is a target of the …

An Rnai Screen To Identify Components Of A Polyamine Transport System, Adam J. Foley

Honors Undergraduate Theses

Polyamines, specifically putrescine, spermidine, and spermine, are small cationic molecules found in all organisms. Cells can biosynthetically make these molecules, or alternatively, they can be transported from the extracellular environment. Malignant cells have been shown to require relatively high amounts of polyamines. There is a chemotherapeutic agent, DFMO, used to block the biosynthesis of polyamines. Many malignant cells can circumvent DFMO therapy by activating their transport system. A potential solution is to simultaneously block biosynthesis and transport of polyamines. However, little is known about the polyamine transport system in higher eukaryotes.

This thesis aims to add to the basic biological …

Validating Drug Targets Through Inhibition Of Protein-Protein Interactions In Mycobacterium Tuberculosis, Erin C. Driscoll

Honors Undergraduate Theses

Tuberculosis is the leading cause of death by single infectious disease worldwide; novel antibiotics are needed to continue to treat this disease. To goal of this project is to provide proof-of-principle support for the idea that targeting protein-protein interactions (PPI) is an appropriate course for the discovery of new drugs. This study optimized the M-PFC assay, which allows detection of PPI in Mycobacteria, through the use of stronger promoters and inducible expression of a peptide blocker by riboswitch. To accomplish this, promoter induction studies were used to find stronger promoters for the M-PFC, optimization of the riboswitch as a …

Factors Regulating Features Of Metabolic Syndrome, Sonja S. Pijut

Theses and Dissertations--Pharmacy

The collective presence of central obesity, low HDL-cholesterol, and elevated triglycerides, blood pressure, and fasting blood glucose constitutes Metabolic Syndrome (MetS), a disease state that increases the risk of cardiovascular disease (CVD) and Type 2 Diabetes Mellitus (T2DM). Nonalcoholic fatty liver disease (NAFLD), present in up to 90% of obese adults, is also linked to MetS. As in CVD, disruptions in cholesterol metabolism play a contributing role in the development of T2DM and NAFLD. Genes involved in cholesterol synthesis, secretion, and catabolism are diurnally regulated in the liver and adipose. Disruptions in the sleep-wake cycle are thought to potentiate metabolic …

Telomerase Reverse Transcriptase In Atherosclerosis, Hua Qing

Theses and Dissertations--Pharmacology and Nutritional Sciences

Telomerase reverse transcriptase (TERT) is the catalytic subunit of telomerase and the limiting factor for the enzyme activity. The expression of TERT and telomerase activity is increased in atherosclerotic plaques. However, the role of TERT dysregulation during atherosclerosis formation remains unknown.

The work herein first identified a multi-tiered regulation of TERT expression in smooth muscle cells (SMC) through histone deacetylase (HDAC) inhibition. HDAC inhibition induces TERT transcription and promoter activation. At the protein level in contrast, HDAC inhibition decreases TERT protein abundance through enhanced degradation, which decreases telomerase activity and induces senescence. Furthermore, during vascular remodeling in vivo, TERT protein …

Multifaceted Role Of Neuropilins In The Immune System: Potential Targets For Immunotherapy., Sohini Roy, Arup K. Bag, Rakesh Singh, James E. Talmadge, Surinder K. Batra, Kaustubh Datta

Journal Articles: Biochemistry & Molecular Biology

Neuropilins (NRPs) are non-tyrosine kinase cell surface glycoproteins expressed in all vertebrates and widely conserved across species. The two isoforms, such as neuropilin-1 (NRP1) and neuropilin-2 (NRP2), mainly act as coreceptors for class III Semaphorins and for members of the vascular endothelial growth factor family of molecules and are widely known for their role in a wide array of physiological processes, such as cardiovascular, neuronal development and patterning, angiogenesis, lymphangiogenesis, as well as various clinical disorders. Intriguingly, additional roles for NRPs occur with myeloid and lymphoid cells, in normal physiological as well as different pathological conditions, including cancer, immunological disorders, …

Initiator Trna Genes Template The 3' Cca End At High Frequencies In Bacteria., David H. Ardell, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

BACKGROUND: While the CCA sequence at the mature 3' end of tRNAs is conserved and critical for translational function, a genetic template for this sequence is not always contained in tRNA genes. In eukaryotes and Archaea, the CCA ends of tRNAs are synthesized post-transcriptionally by CCA-adding enzymes. In Bacteria, tRNA genes template CCA sporadically.

RESULTS: In order to understand the variation in how prokaryotic tRNA genes template CCA, we re-annotated tRNA genes in tRNAdb-CE database version 0.8. Among 132,129 prokaryotic tRNA genes, initiator tRNA genes template CCA at the highest average frequency (74.1%) over all functional classes except selenocysteine and …

A Biologically Active Tnf-Alpha Inhibitor Fails To Suppress Colitis In Balb/C Mice, Stephanie E. Biel

Graduate Theses/Dissertations

Tumor necrosis factor a (TNFα), a potent inflammatory cytokine, has long been established as a major driving force for pathologic inflammation. Currently, anti-TNFα therapies are the standard in Inflammatory Bowel Disease (IBD) management; however, one-third of IBD patients fail to respond to anti-TNFα therapies. Previous data from this lab indicate that TNFα Converting Enzyme (TACE) inhibition does not ameliorate colitis in BALB/C mice. Thus, we hypothesized that TNFα is not a critical component in the BALB/C model of colitis. To test this, acute colitis was induced in BALB/C mice by consumption of 5% dextran sulfate sodium (DSS) in drinking water …

Tgf-Β1 Increases Resistance Of Nih/3t3 Fibroblasts Toward Apoptosis Through Activation Of Smad2/3 And Erk1/2 Pathways, Ulugbek Negmadjanov, Alisher Holmuhamedov, Larisa Emelyanova, Hao Xu, Farhan Rizvi, Gracious R. Ross, A. Jamil Tajik, Yang Shi, Ekhson Holmuhamedov, Arshad Jahangir

Journal of Patient-Centered Research and Reviews

Purpose

Excessive fibrosis has been suggested to result from persistence of fibroblasts in injured tissue due to impaired apoptosis, but signaling pathways are not fully defined.

Methods

Suppression of apoptotic cell death following transforming growth factor-β1 (TGF-β1) exposure was studied using the culture of NIH/3T3 mouse embryonic fibroblasts. Caspase-3 activity, propidium iodide staining and annexin V binding induced by Fas-ligand (FasL) in NIH/3T3 fibroblasts in the absence and presence of TGF-β1 was determined, and relative contribution of signaling through Smad2/3 and noncanonical Erk1/2 and Akt pathways was dissected by assessing phosphorylation status of these kinases and caspase activity in the …

Functional Alterations Of Ion Channels From Cardiac Fibroblasts In Heart Diseases, Gracious R. Ross, Arshad Jahangir

Journal of Patient-Centered Research and Reviews

In an aged population, cardiovascular disease is the leading cause of fatality and morbidity. Age-related fibrotic remodeling of the heart contributes to progressive myocardial dysfunction. Cardiac fibroblasts (CF), responsible for the maintenance of extracellular matrix and fibrosis process, play an important role in cardiac health and disease. CFs influence myocardial function by their chemical, electrical and mechanical interactions with cardiomyocytes through extracellular matrix deposition or secretion of cytokines and growth factors. These, in turn, are modulated by ion channels, macromolecular pores in the plasma membrane that allow selective ionic fluxes of major ions like K⁺, Ca²⁺, …

Chromatin Proteins And Rna Are Associated With Dna During All Phases Of Mitosis., Kathryn L Black, Svetlana Petruk, Tyler K Fenstermaker, Jacob W Hodgson, Jeffrey L Caplan, Hugh W Brock, Alexander Mazo

Department of Biochemistry and Molecular Biology Faculty Papers

Mitosis brings about major changes to chromosome and nuclear structure. We used recently developed proximity ligation assay-based techniques to investigate the association with DNA of chromatin-associated proteins and RNAs in Drosophila embryos during mitosis. All groups of tested proteins, histone-modifying and chromatin-remodeling proteins and methylated histones remained in close proximity to DNA during all phases of mitosis. We also found that RNA transcripts are associated with DNA during all stages of mitosis. Reduction of H3K27me3 levels or elimination of RNAs had no effect on the association of the components of PcG and TrxG complexes to DNA. Using a combination of …

Changing Diagnostic Methods And Increased Detection Of Verotoxigenic Escherichia Coli, Ireland, Thomas Rice, Noreen Quinn, Roy D. Sleator, Brigid Lucey

Department of Biological Sciences Publications

The recent paradigm shift in infectious disease diagnosis from culture-based to molecular-based approaches is exemplified in the findings of a national study assessing the detection of verotoxigenic Escherichia coli infections in Ireland. The methodologic changes have been accompanied by a dramatic increase in detections of non-O157 verotoxigenic E. coli serotypes.