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Effect Of Vitamin D On Serum Markers Of Bone Turnover In Sle In A Randomised Controlled Trial, S. K. Tedeschi, C. Aranow, D. L. Kamen, M. Leboff, Diamond, H. Costenbader 2019 Zucker School of Medicine at Hofstra/Northwell

Effect Of Vitamin D On Serum Markers Of Bone Turnover In Sle In A Randomised Controlled Trial, S. K. Tedeschi, C. Aranow, D. L. Kamen, M. Leboff, Diamond, H. Costenbader

Journal Articles

© 2019 Author(s). Objective Bone health in SLE is adversely affected by vitamin D deficiency, inflammatory cytokines and glucocorticoid use. We hypothesised that vitamin D supplementation would increase markers of bone formation and decrease markers of bone resorption in SLE subjects. Methods We studied 43 vitamin D-deficient SLE subjects who participated in a 12-week randomised controlled trial of 2000-4000 IU/day vitamin D supplementation versus placebo. Subjects had inactive SLE (SLE Disease Activity Index ≤4) and were taking D, N-terminal propeptide of type 1 collagen (P1NP) and C-telopeptide (CTX). We tested the effect of vitamin D versus placebo on change ...


Clinically Significant Gains In Skillful Grasp Coordination By An Individual With Tetraplegia Using An Implanted Brain-Computer Interface With Forearm Transcutaneous Muscle Stimulation, M. Bockbrader, N. Annetta, D. Friedenberg, M. Schwemmer, Skomrock, Colachis, M. Zhang, C. Bouton, A. Rezai, W. J. Mysiw, +1 additional author 2019 Zucker School of Medicine at Hofstra/Northwell

Clinically Significant Gains In Skillful Grasp Coordination By An Individual With Tetraplegia Using An Implanted Brain-Computer Interface With Forearm Transcutaneous Muscle Stimulation, M. Bockbrader, N. Annetta, D. Friedenberg, M. Schwemmer, Skomrock, Colachis, M. Zhang, C. Bouton, A. Rezai, W. J. Mysiw, +1 Additional Author

Journal Articles

© 2019 American Congress of Rehabilitation Medicine Objective: To demonstrate naturalistic motor control speed, coordinated grasp, and carryover from trained to novel objects by an individual with tetraplegia using a brain-computer interface (BCI)-controlled neuroprosthetic. Design: Phase I trial for an intracortical BCI integrated with forearm functional electrical stimulation (FES). Data reported span postimplant days 137 to 1478. Setting: Tertiary care outpatient rehabilitation center. Participant: A 27-year-old man with C5 class A (on the American Spinal Injury Association Impairment Scale) traumatic spinal cord injury Interventions: After array implantation in his left (dominant) motor cortex, the participant trained with BCI-FES to control ...


Defining Inflammatory Cell States In Rheumatoid Arthritis Joint Synovial Tissues By Integrating Single-Cell Transcriptomics And Mass Cytometry, F. Zhang, K. Wei, K. Slowikowski, C. Y. Fonseka, A. Rao, Kelly, S. M. Goodman, D. Tabechian, P. K. Gregersen, S. Raychaudhuri, +55 additional authors 2019 Zucker School of Medicine at Hofstra/Northwell

Defining Inflammatory Cell States In Rheumatoid Arthritis Joint Synovial Tissues By Integrating Single-Cell Transcriptomics And Mass Cytometry, F. Zhang, K. Wei, K. Slowikowski, C. Y. Fonseka, A. Rao, Kelly, S. M. Goodman, D. Tabechian, P. K. Gregersen, S. Raychaudhuri, +55 Additional Authors

Journal Articles

© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc. To define the cell populations that drive joint inflammation in rheumatoid arthritis (RA), we applied single-cell RNA sequencing (scRNA-seq), mass cytometry, bulk RNA sequencing (RNA-seq) and flow cytometry to T cells, B cells, monocytes, and fibroblasts from 51 samples of synovial tissue from patients with RA or osteoarthritis (OA). Utilizing an integrated strategy based on canonical correlation analysis of 5,265 scRNA-seq profiles, we identified 18 unique cell populations. Combining mass cytometry and transcriptomics revealed cell states expanded in RA synovia: THY1(CD90) + HLA-DRA hi sublining fibroblasts, IL1B ...


Metabolic And Microstructural Alterations In The Sle Brain Correlate With Cognitive Impairment, M. Mackay, A. Vo, C. C. Tang, W. Anderson, N. J. Ploran, C. Aranow, P. Watson, B. T. Volpe, B. Diamond, D. Eidelberg, +5 additional authors 2019 Zucker School of Medicine at Hofstra/Northwell

Metabolic And Microstructural Alterations In The Sle Brain Correlate With Cognitive Impairment, M. Mackay, A. Vo, C. C. Tang, W. Anderson, N. J. Ploran, C. Aranow, P. Watson, B. T. Volpe, B. Diamond, D. Eidelberg, +5 Additional Authors

Journal Articles

No abstract provided.


Large-Scale Validation Of The Paddling Pool Task In The Clockmaze For Studying Hippocampus-Based Spatial Cognition In Mice, R. Sankowski, T. S. Huerta, R. Kalra, T. J. Klein, J. Strohl, A. Al-Abed, S. Robbiati, P. T. Huerta 2019 Zucker School of Medicine at Hofstra/Northwell

Large-Scale Validation Of The Paddling Pool Task In The Clockmaze For Studying Hippocampus-Based Spatial Cognition In Mice, R. Sankowski, T. S. Huerta, R. Kalra, T. J. Klein, J. Strohl, A. Al-Abed, S. Robbiati, P. T. Huerta

Journal Articles

No abstract provided.


Focused Hla Analysis In Caucasians With Myositis Identifies Significant Associations With Autoantibody Subgroups., S. Rothwell, H. Chinoy, J. A. Lamb, F. W. Miller, L. G. Rider, L. R. Wedderburn, N. J. McHugh, A. T. Lee, P. K. Gregersen, I. E. Lundberg, +23 additional authors 2019 Zucker School of Medicine at Hofstra/Northwell

Focused Hla Analysis In Caucasians With Myositis Identifies Significant Associations With Autoantibody Subgroups., S. Rothwell, H. Chinoy, J. A. Lamb, F. W. Miller, L. G. Rider, L. R. Wedderburn, N. J. Mchugh, A. T. Lee, P. K. Gregersen, I. E. Lundberg, +23 Additional Authors

Journal Articles

OBJECTIVES: Idiopathic inflammatory myopathies (IIM) are a spectrum of rare autoimmune diseases characterised clinically by muscle weakness and heterogeneous systemic organ involvement. The strongest genetic risk is within the major histocompatibility complex (MHC). Since autoantibody presence defines specific clinical subgroups of IIM, we aimed to correlate serotype and genotype, to identify novel risk variants in the MHC region that co-occur with IIM autoantibodies.

METHODS: We collected available autoantibody data in our cohort of 2582 Caucasian patients with IIM. High resolution human leucocyte antigen (HLA) alleles and corresponding amino acid sequences were imputed using SNP2HLA from existing genotyping data and tested ...


Environmental Regulation Of The Heart: The Role Of Non-Coding Rna And Epigenetics In Influencing Mitochondrial And Cellular Health, Quincy Alexander Hathaway 2019 West Virginia University

Environmental Regulation Of The Heart: The Role Of Non-Coding Rna And Epigenetics In Influencing Mitochondrial And Cellular Health, Quincy Alexander Hathaway

Graduate Theses, Dissertations, and Problem Reports

The mitochondrion, a small but ubiquitously distributed organelle in the cell, continues to be the focus of many disease pathogeneses, tissue and organ dysfunctions, and other morbidities that occur throughout the body. The purpose of this work was to understand how cardiac mitochondrion are altered in disease and pathological states, specifically in their adaptation to environmentally stimulated regulatory networks, such as epigenetic modifications and promotion/inhibition of non-coding RNAs. Acute stress to mitochondrial regulation (inhalation toxicology) as well as chronic (type 2 diabetes mellitus) was examined. Using a FVB transgenic microRNA-378a mouse knockout model, the cardiovascular impact derived from altering ...


Trefoil Factor(S) And Ca19.9: A Promising Panel For Early Detection Of Pancreatic Cancer, Rahat Jahan, Koelina Ganguly, Lynette M. Smith, Pranita Atri, Joseph Carmicheal, Yuri Sheinin, Satyanarayana Rachagani, Gopalakrishnan Natarajan, Randall E. Brand, Muzafar A. Macha, Paul M. Grandgenett, Sukhwinder Kaur, Surinder K. Batra 2019 University of Nebraska Medical Center

Trefoil Factor(S) And Ca19.9: A Promising Panel For Early Detection Of Pancreatic Cancer, Rahat Jahan, Koelina Ganguly, Lynette M. Smith, Pranita Atri, Joseph Carmicheal, Yuri Sheinin, Satyanarayana Rachagani, Gopalakrishnan Natarajan, Randall E. Brand, Muzafar A. Macha, Paul M. Grandgenett, Sukhwinder Kaur, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Trefoil factors (TFF1, TFF2, and TFF3) are small secretory molecules that recently have gained significant attention in multiple studies as an integral component of pancreatic cancer (PC) subtype-specific gene signature. Here, we comprehensively investigated the diagnostic potential of all the member of trefoil family, i.e., TFF1, TFF2, and TFF3 in combination with CA19.9 for detection of PC.

METHODS: Trefoil factors (TFFs) gene expression was analyzed in publicly available cancer genome datasets, followed by assessment of their expression in genetically engineered spontaneous mouse model (GEM) of PC (KrasG12D; Pdx1-Cre (KC)) and in human tissue microarray consisting of normal ...


Afatinib And Temozolomide Combination Inhibits Tumorigenesis By Targeting Egfrviii-Cmet Signaling In Glioblastoma Cells, Raghupathy Vengoji, Muzafar A. Macha, Rama Krishna Nimmakayala, Satyanarayana Rachagani, Jawed A. Siddiqui, Kavita Mallya, Santhi Gorantla, Maneesh Jain, Moorthy P. Ponnusamy, Surinder K. Batra, Nicole Shonka 2019 University of Nebraska Medical Center

Afatinib And Temozolomide Combination Inhibits Tumorigenesis By Targeting Egfrviii-Cmet Signaling In Glioblastoma Cells, Raghupathy Vengoji, Muzafar A. Macha, Rama Krishna Nimmakayala, Satyanarayana Rachagani, Jawed A. Siddiqui, Kavita Mallya, Santhi Gorantla, Maneesh Jain, Moorthy P. Ponnusamy, Surinder K. Batra, Nicole Shonka

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Glioblastoma (GBM) is an aggressive brain tumor with universal recurrence and poor prognosis. The recurrence is largely driven by chemoradiation resistant cancer stem cells (CSCs). Epidermal growth factor receptor (EGFR) and its mutant EGFRvIII are amplified in ~ 60% and ~ 30% of GBM patients, respectively; however, therapies targeting EGFR have failed to improve disease outcome. EGFRvIII-mediated cross-activation of tyrosine kinase receptor, cMET, regulates GBM CSC maintenance and promote tumor recurrence. Here, we evaluated the efficacy of pan-EGFR inhibitor afatinib and Temozolomide (TMZ) combination on GBM in vitro and in vivo.

METHODS: We analyzed the effect of afatinib and temozolomide (TMZ ...


Lactate-Mediated Epigenetic Reprogramming Regulates Formation Of Human Pancreatic Cancer-Associated Fibroblasts, Tushar D. Bhagat, Dagny Von Ahrens, Meelad Dawlaty, Yiyu Zou, Joelle Baddour, Abhinav Achreja, Hongyun Zhao, Lifeng Yang, Brijesh Patel, Changsoo Kwak, Gaurav S. Choudhary, Shanisha Gordon-Mitchell, Srinivas Aluri, Sanchari Bhattacharyya, Srabani Sahu, Yiting Yu, Matthias Bartenstein, Orsi Giricz, Masako Suzuki, Davendra Sohal, Sonal Gupta, Paola A. Guerrero, Surinder K. Batra, Michael Goggins, Ulrich Steidl, John Greally, Beamon Agarwal, Kith Pradhan, Debabrata Banerjee, Deepak Nagrath, Anirban Maitra, Amit Verma 2019 Albert Einstein College of Medicine

Lactate-Mediated Epigenetic Reprogramming Regulates Formation Of Human Pancreatic Cancer-Associated Fibroblasts, Tushar D. Bhagat, Dagny Von Ahrens, Meelad Dawlaty, Yiyu Zou, Joelle Baddour, Abhinav Achreja, Hongyun Zhao, Lifeng Yang, Brijesh Patel, Changsoo Kwak, Gaurav S. Choudhary, Shanisha Gordon-Mitchell, Srinivas Aluri, Sanchari Bhattacharyya, Srabani Sahu, Yiting Yu, Matthias Bartenstein, Orsi Giricz, Masako Suzuki, Davendra Sohal, Sonal Gupta, Paola A. Guerrero, Surinder K. Batra, Michael Goggins, Ulrich Steidl, John Greally, Beamon Agarwal, Kith Pradhan, Debabrata Banerjee, Deepak Nagrath, Anirban Maitra, Amit Verma

Journal Articles: Biochemistry & Molecular Biology

Even though pancreatic ductal adenocarcinoma (PDAC) is associated with fibrotic stroma, the molecular pathways regulating the formation of cancer associated fibroblasts (CAFs) are not well elucidated. An epigenomic analysis of patient-derived and de-novo generated CAFs demonstrated widespread loss of cytosine methylation that was associated with overexpression of various inflammatory transcripts including CXCR4. Co-culture of neoplastic cells with CAFs led to increased invasiveness that was abrogated by inhibition of CXCR4. Metabolite tracing revealed that lactate produced by neoplastic cells leads to increased production of alpha-ketoglutarate (aKG) within mesenchymal stem cells (MSCs). In turn, aKG mediated activation of the demethylase TET ...


Uncovering And Characterizing Splice Variants Associated With Survival In Lung Cancer Patients, Sean West, Sushil Kumar, Surinder K. Batra, Hesham Ali, Dario Ghersi 2019 University of Nebraska at Omaha

Uncovering And Characterizing Splice Variants Associated With Survival In Lung Cancer Patients, Sean West, Sushil Kumar, Surinder K. Batra, Hesham Ali, Dario Ghersi

Journal Articles: Biochemistry & Molecular Biology

Splice variants have been shown to play an important role in tumor initiation and progression and can serve as novel cancer biomarkers. However, the clinical importance of individual splice variants and the mechanisms by which they can perturb cellular functions are still poorly understood. To address these issues, we developed an efficient and robust computational method to: (1) identify splice variants that are associated with patient survival in a statistically significant manner; and (2) predict rewired protein-protein interactions that may result from altered patterns of expression of such variants. We applied our method to the lung adenocarcinoma dataset from TCGA ...


Vitamin E Δ-Tocotrienol Sensitizes Human Pancreatic Cancer Cells To Trail-Induced Apoptosis Through Proteasome-Mediated Down-Regulation Of C-Flip, Rony A. Francois, Anying Zhang, Kazim Husain, Chen Wang, Sean Hutchinson, Michael Kongnyuy, Surinder K. Batra, Domenico Coppola, Said M. Sebti, Mokenge P. Malafa 2019 H. Lee Moffitt Cancer Center and Research Institute

Vitamin E Δ-Tocotrienol Sensitizes Human Pancreatic Cancer Cells To Trail-Induced Apoptosis Through Proteasome-Mediated Down-Regulation Of C-Flip, Rony A. Francois, Anying Zhang, Kazim Husain, Chen Wang, Sean Hutchinson, Michael Kongnyuy, Surinder K. Batra, Domenico Coppola, Said M. Sebti, Mokenge P. Malafa

Journal Articles: Biochemistry & Molecular Biology

Background: Vitamin E δ-tocotrienol (VEDT), a vitamin E compound isolated from sources such as palm fruit and annatto beans, has been reported to have cancer chemopreventive and therapeutic effects.

Methods: We report a novel function of VEDT in augmenting tumor necrosis factor-related apoptosis-inducing ligand- (TRAIL-) induced apoptosis in pancreatic cancer cells. The effects of VEDT were shown by its ability to trigger caspase-8-dependent apoptosis in pancreatic cancer cells.

Results: When combined with TRAIL, VEDT significantly augmented TRAIL-induced apoptosis of pancreatic cancer cells. VEDT decreased cellular FLICE inhibitory protein (c-FLIP) levels without consistently modulating the expression of decoy death receptors 1 ...


Pr55Α Regulatory Subunit Of Pp2a Inhibits The Mob1/Lats Cascade And Activates Yap In Pancreatic Cancer Cells, Ashley L. Hein, Nichole D. Brandquist, Caroline Y. Ouellette, Parthasarathy Seshacharyulu, Charles A. Enke, Michel M. Ouellette, Surinder K. Batra, Ying Yan 2019 University of Nebraska Medical Center

Pr55Α Regulatory Subunit Of Pp2a Inhibits The Mob1/Lats Cascade And Activates Yap In Pancreatic Cancer Cells, Ashley L. Hein, Nichole D. Brandquist, Caroline Y. Ouellette, Parthasarathy Seshacharyulu, Charles A. Enke, Michel M. Ouellette, Surinder K. Batra, Ying Yan

Journal Articles: Biochemistry & Molecular Biology

PP2A holoenzyme complexes are responsible for the majority of Ser/Thr phosphatase activities in human cells. Each PP2A consists of a catalytic subunit (C), a scaffold subunit (A), and a regulatory subunit (B). While the A and C subunits each exists only in two highly conserved isoforms, a large number of B subunits share no homology, which determines PP2A substrate specificity and cellular localization. It is anticipated that different PP2A holoenzymes play distinct roles in cellular signaling networks, whereas PP2A has only generally been defined as a putative tumor suppressor, which is mostly based on the loss-of-function studies using pharmacological ...


Trypanosoma Brucei Prmt1 Is A Nucleic Acid Binding Protein With A Role In Energy Metabolism And The Starvation Stress Response., Lucie Kafková, Chengjian Tu, Kyle L. Pazzo, Kyle P. Smith, Erik W. Debler, Kimberly S. Paul, Jun Qu, Laurie K. Read 2018 University at Buffalo, State University of New York

Trypanosoma Brucei Prmt1 Is A Nucleic Acid Binding Protein With A Role In Energy Metabolism And The Starvation Stress Response., Lucie Kafková, Chengjian Tu, Kyle L. Pazzo, Kyle P. Smith, Erik W. Debler, Kimberly S. Paul, Jun Qu, Laurie K. Read

Department of Biochemistry and Molecular Biology Faculty Papers

In Trypanosoma brucei and related kinetoplastid parasites, transcription of protein coding genes is largely unregulated. Rather, mRNA binding proteins, which impact processes such as transcript stability and translation efficiency, are the predominant regulators of gene expression. Arginine methylation is a posttranslational modification that preferentially targets RNA binding proteins and is, therefore, likely to have a substantial impact on T. brucei biology. The data presented here demonstrate that cells depleted of T. brucei PRMT1 (TbPRMT1), a major type I protein arginine methyltransferase, exhibit decreased virulence in an animal model. To understand the basis of this phenotype, quantitative global proteomics was employed ...


The First In Vivo Human Methionine Sulfide Proteome And The Impact Of Smoking, Abdullah Qassab 2018 University of Arkansas, Fayetteville

The First In Vivo Human Methionine Sulfide Proteome And The Impact Of Smoking, Abdullah Qassab

Theses and Dissertations

Reactive oxygen species are naturally generated within the human body and they are known to modulate signaling pathway and mediate other physiological activities. However, excessive generation of ROS and the inability of body defense system in detoxifying them results in the so called “oxidative stress”. Methionine has powerful antioxidant properties due to the presence of electronegative sulfur in its structure. Therefore, Met is readily oxidized, and methionine sulfoxide has been linked to several pathological conditions.

The urinary proteome is an attractive candidate for the discovery of biomarkers to diagnose and classify health conditions because of the non-invasive collection procedure. However ...


The Role Of Bip Co-Chaperone Sil1 In Marinesco-Sjögren Syndrome Pathogenesis, Viraj Paresh Ichhaporia 2018 University of Tennessee Health Science Center

The Role Of Bip Co-Chaperone Sil1 In Marinesco-Sjögren Syndrome Pathogenesis, Viraj Paresh Ichhaporia

Theses and Dissertations (ETD)

Marinesco-Sjögren syndrome (MSS) is a rare, autosomal recessive, multisystem disorder, which is characterized by cerebellar ataxia, early-onset bilateral cataracts, and progressive myopathy amongst other symptoms. MSS has been attributed to mutations in the SIL1 gene, which encodes a nucleotide exchange factor for the endoplasmicreticulum- resident Hsp70 chaperone, BiP. To date, there are 46 MSS-associated mutations that have been reported in SIL1, which occur throughout this gene and are predicted to result in a loss of SIL1’s function. The large majority of these mutations cause deletions of large fractions of the SIL1 protein. Nine MSS-associated mutations are particularly interesting because ...


Sumo-Mediated Regulation Of Nlrp3 Modulates Inflammasome Activity., Rachael Barry, Sidonie Wicky John, Gianmaria Liccardi, Tencho Tenev, Isabel Jaco, Chih-Hong Chen, Justin Choi, Paulina Kasperkiewicz, Teresa Fernandes-Alnemri, Emad S Alnemri, Marcin Drag, Yuan Chen, Pascal Meier 2018 The Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research; Imperial College London

Sumo-Mediated Regulation Of Nlrp3 Modulates Inflammasome Activity., Rachael Barry, Sidonie Wicky John, Gianmaria Liccardi, Tencho Tenev, Isabel Jaco, Chih-Hong Chen, Justin Choi, Paulina Kasperkiewicz, Teresa Fernandes-Alnemri, Emad S Alnemri, Marcin Drag, Yuan Chen, Pascal Meier

Department of Biochemistry and Molecular Biology Faculty Papers

The NLRP3 inflammasome responds to infection and tissue damage, and rapidly escalates the intensity of inflammation by activating interleukin (IL)-1β, IL-18 and cell death by pyroptosis. How the NLRP3 inflammasome is negatively regulated is poorly understood. Here we show that NLRP3 inflammasome activation is suppressed by sumoylation. NLRP3 is sumoylated by the SUMO E3-ligase MAPL, and stimulation-dependent NLRP3 desumoylation by the SUMO-specific proteases SENP6 and SENP7 promotes NLRP3 activation. Defective NLRP3 sumoylation, either by NLRP3 mutation of SUMO acceptor lysines or depletion of MAPL, results in enhanced caspase-1 activation and IL-1β release. Conversely, depletion of SENP7 suppresses NLRP3-dependent ASC ...


Trna 3'-Amino-Tailing For Stable Amino Acid Attachment., Howard Gamper, Ya-Ming Hou 2018 Thomas Jefferson University

Trna 3'-Amino-Tailing For Stable Amino Acid Attachment., Howard Gamper, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

Amino acids are attached to the tRNA 3'-end as a prerequisite for entering the ribosome for protein synthesis. Amino acid attachment also gives tRNA access to nonribosomal cellular activities. However, the normal attachment is via an ester linkage between the carboxylic group of the amino acid and the 3'-hydroxyl of the terminal A76 ribose in tRNA. The instability of this ester linkage has severely hampered studies of aminoacyl-tRNAs. Although the use of 3'-amino-3'-deoxy A76 in a 3'-amino-tailed tRNA provides stable aminoacyl attachment via an amide linkage, there are multiple tailing protocols and the efficiency of ...


Parp-1 Regulates Dna Repair Factor Availability., M J Schiewer, Amy C. Mandigo, Nicolas Gordon, Fangjin Huang, Sanchaika Gaur, Renée de Leeuw, Shuang G Zhao, Joseph Evans, Sumin Han, Theodore Parsons, Ruth Birbe, Peter McCue, Christopher McNair, Saswati N. Chand, Ylenia Cendon-Florez, Peter Gallagher, Jennifer J McCann, Neermala Poudel Neupane, Ayesha A Shafi, Emanuela Dylgjeri, Lucas J Brand, Tapio Visakorpi, Ganesh V Raj, Costas D. Lallas, Edouard J Trabulsi, Leonard G Gomella, Adam Dicker MD, PhD, William Kevin Kelly, Benjamin E Leiby, Beatrice Knudsen, Felix Y Feng, Karen E Knudsen 2018 Department of Cancer Biology, Thomas Jefferson University; Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA

Parp-1 Regulates Dna Repair Factor Availability., M J Schiewer, Amy C. Mandigo, Nicolas Gordon, Fangjin Huang, Sanchaika Gaur, Renée De Leeuw, Shuang G Zhao, Joseph Evans, Sumin Han, Theodore Parsons, Ruth Birbe, Peter Mccue, Christopher Mcnair, Saswati N. Chand, Ylenia Cendon-Florez, Peter Gallagher, Jennifer J Mccann, Neermala Poudel Neupane, Ayesha A Shafi, Emanuela Dylgjeri, Lucas J Brand, Tapio Visakorpi, Ganesh V Raj, Costas D. Lallas, Edouard J Trabulsi, Leonard G Gomella, Adam Dicker Md, Phd, William Kevin Kelly, Benjamin E Leiby, Beatrice Knudsen, Felix Y Feng, Karen E Knudsen

Department of Cancer Biology Faculty Papers

PARP-1 holds major functions on chromatin, DNA damage repair and transcriptional regulation, both of which are relevant in the context of cancer. Here, unbiased transcriptional profiling revealed the downstream transcriptional profile of PARP-1 enzymatic activity. Further investigation of the PARP-1-regulated transcriptome and secondary strategies for assessing PARP-1 activity in patient tissues revealed that PARP-1 activity was unexpectedly enriched as a function of disease progression and was associated with poor outcome independent of DNA double-strand breaks, suggesting that enhanced PARP-1 activity may promote aggressive phenotypes. Mechanistic investigation revealed that active PARP-1 served to enhance E2F1 transcription factor activity, and specifically promoted ...


Cholesterol Metabolism And Statin Effects On An Fh Class Ii Ldl-Receptor Mutation., Linda Omer 2018 University of Louisville

Cholesterol Metabolism And Statin Effects On An Fh Class Ii Ldl-Receptor Mutation., Linda Omer

Electronic Theses and Dissertations

Familial hypercholesterolemia (FH) is a common genetic disease and has been studied with the aim of finding a curative measure for decades. FH is caused by mutations in the low-density lipoprotein receptor (LDLR) resulting in defects in LDL-cholesterol (LDL-C)-receptor mediated endocytosis and development of premature cardiovascular disease (CVD). Here I describe the use of a corrected and non-corrected LDLR FH cell model to investigate receptor-mediated endocytosis and statin effects. For these studies, we reprogrammed FH fibroblast cells to induced pluripotent stem cells (iPSC) and confirmed their pluripotency and ability to differentiate to hepatocyte-like cells (HLC). A clustered regularly interspaced ...


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