Medical Biochemistry Commons^™

Analysis Of The Dna-Binding Properties Of Alx1, An Evolutionarily Conserved Regulator Of Skeletogenesis In Echinoderms, Jennifer Guerrero-Santoro, Jian Ming Khor, Ayşe Haruka Açıkbaş, James B. Jaynes, Charles A Ettensohn

Department of Biochemistry and Molecular Biology Faculty Papers

Alx1, a homeodomain-containing transcription factor, is a highly conserved regulator of skeletogenesis in echinoderms. In sea urchins, Alx1 plays a central role in the differentiation of embryonic primary mesenchyme cells (PMCs) and positively regulates the transcription of most biomineralization genes expressed by these cells. The alx1 gene arose via duplication and acquired a skeletogenic function distinct from its paralog (alx4) through the exonization of a 41-amino acid motif (the D2 domain). Alx1 and Alx4 contain glutamine-50 paired-type homeodomains, which interact preferentially with palindromic binding sites in vitro. Chromatin immunoprecipitation sequencing (ChIP-seq) studies have shown, however, that Alx1 binds both to …

Cd8+ T Cells Inhibit Metastasis And Cxcl4 Regulates Its Function, Robiya Joseph, Rama Soundararajan, Suhas Vasaikar, Fei Yang, Kendra L Allton, Lin Tian, Petra Den Hollander, Sevinj Isgandarova, Monika Haemmerle, Barbara Mino, Tieling Zhou, Crystal Shin, Melisa Martinez-Paniagua, Aysegul A Sahin, Jaime Rodriguez-Canales, Juri Gelovani, Jeffrey T Chang, Ghanashyam Acharya, Anil K Sood, Ignacio I Wistuba, Don L Gibbons, Luisa M Solis, Michelle C Barton, Navin Varadarajan, Jeffrey M Rosen, Xiang H Zhang, Sendurai A Mani

Faculty, Staff and Students Publications

Background

The mechanism by which immune cells regulate metastasis is unclear. Understanding the role of immune cells in metastasis will guide the development of treatments improving patient survival.

Methods

We used syngeneic orthotopic mouse tumour models (wild-type, NOD/scid and Nude), employed knockout (CD8 and CD4) models and administered CXCL4. Tumours and lungs were analysed for cancer cells by bioluminescence, and circulating tumour cells were isolated from blood. Immunohistochemistry on the mouse tumours was performed to confirm cell type, and on a tissue microarray with 180 TNBCs for human relevance. TCGA data from over 10,000 patients were analysed as …

The Effect Of Diazepam On Early Neural Stem Cells Proliferative Activity And Hippocampal-Dependent Memory After Traumatic Brain Injury, Van Khanh Doan

University Honors Theses

Traumatic brain injury (TBI) induces an upregulation of neurogenesis in the brain specifically in the hippocampus, an area pertaining to learning and memory formation. Although this upregulated response is intuitively thought to be restorative, previous studies show that the nascent neurons generated after TBI exhibit abnormalities, such as aberrant morphologies and early migrations, which could suggest to be maladaptive. The GABA-A agonist diazepam has been shown to inhibit this upregulation in neurogenesis and normalizes dendrites after TBI. To determine whether this modulation of neurogenesis is ultimately beneficial or detrimental to cognitive recovery, diazepam was administered to C57BI/6J wild-type mice following …

Diabetes Mellitus And Immunomodulation: A Double-Edged Sword., James Harte

International Undergraduate Journal of Health Sciences

Diabetes is an endocrinological disorder characterised by chronic hyperglycaemia due to abnormalities in insulin secretion, insulin action or a combination of both. According to the International Diabetes Federation, 463 million people worldwide are living with diabetes; 700 million people will be affected by 2045. The severity of the disease is dependent on the type and the stage of progression; when not correctly managed, diabetes can lead to potentially life-threatening micro- and macrovascular complications.

Prior to the discovery of insulin in 1922, the life expectancy of children with diabetes was short and the prognosis was very poor. The advocated treatment for …

Full Issue: The International Undergraduate Journal Of Health Sciences, Volume 1, Issue 1, June 2021, Iujhs Full Issue

International Undergraduate Journal of Health Sciences

The full June 2021 issue (Volume 1, Issue 1) of the International Undergraduate Journal of Health Sciences

The Roles Of Tumor-Derived Exosomes In Altered Differentiation, Maturation And Function Of Dendritic Cells, Reza Hosseini, Leila Asef-Kabiri, Hassan Yousefi, Hamzeh Sarvnaz, Majid Salehi, Mohammad Esmaeil Akbari, Nahid Eskandari

School of Graduate Studies Faculty Publications

Tumor-derived exosomes (TDEs) have been shown to impede anti-tumor immune responses via their immunosuppressive cargo. Since dendritic cells (DCs) are the key mediators of priming and maintenance of T cell-mediated responses; thus it is logical that the exosomes released by tumor cells can exert a dominant influence on DCs biology. This paper intends to provide a mechanistic insight into the TDEs-mediated DCs abnormalities in the tumor context. More importantly, we discuss extensively how tumor exosomes induce subversion of DCs differentiation, maturation and function in separate sections. We also briefly describe the importance of TDEs at therapeutic level to help guide …

The Synergy Of Bet Inhibitors With Aurora A Kinase Inhibitors In Mycn-Amplified Neuroblastoma Is Heightened With Functional Tp53, Joanna S Yi, Oscar Sias-Garcia, Nicole Nasholm, Xiaoyu Hu, Amanda Balboni Iniguez, Matthew D Hall, Mindy Davis, Rajarshi Guha, Myrthala Moreno-Smith, Eveline Barbieri, Kevin Duong, Jessica Koach, Jun Qi, James E Bradner, Kimberly Stegmaier, William A Weiss, W Clay Gustafson

Faculty, Staff and Students Publications

Amplification of MYCN is a poor prognostic feature in neuroblastoma (NBL) indicating aggressive disease. We and others have shown BET bromodomain inhibitors (BETi) target MYCN indirectly by downregulating its transcription. Here we sought to identify agents that synergize with BETi and to identify biomarkers of resistance. We previously performed a viability screen of ∼1,900 oncology-focused compounds combined with BET bromodomain inhibitors against MYCN-amplified NBL cell lines. Reanalysis of our screening results prominently identified inhibitors of aurora kinase A (AURKAi) to be highly synergistic with BETi. We confirmed the anti-proliferative effects of several BETi+AURKAi combinations in MYCN-amplified NBL cell lines. Compared …

Removing The Noise From X-Ray Image Using Image Processing Technology: A Bibliometric Survey And Future Research Directions, Ayushi Kamboj, Mrinal Bachute

Library Philosophy and Practice (e-journal)

The retrieval of superior-quality photographs with a minimal exposure is an interesting subject in radiography. Pre-processing is a key phase in signal and image processing such as healthcare, telecommunications, and satellite, and it focuses on reducing or eliminating the extent of noise in the image. Denoising aids in the recovery of finer data and relevant material. Medical images including ECG, Ultrasound, CT-scan, and X-ray provide incredibly fine data that has to be precise and noise-free in order for the knowledge and aspects of interest to be retained during diagnosis. Various noise reduction technologies for medical images, such as wavelet transform, …

Polymorphisms Of Vascular Endothelial Growth Factor -2578c/A Rs699947 Are Risk Factors For Diabetic Retinopathy In Type-2 Diabetes Mellitus Patients In Bali, Indonesia, Audrey Rachel Wijaya, I Wayan Surudarma, Desak Made Wihandani, I Wayan Ardyan Sudharta Putra

BioMedicine

Background: Diabetic retinopathy (DR) is one of the complications in diabetes mellitus (DM) which caused by microvascular damage in the retina due to long term metabolic changes in diabetes. To date, there has been much research targeted on the determinant of genetic identification in DR patients. In DR, Vascular Endothelial Growth Factor (VEGF) gene is accountable for breaking down the blood-retinal barrier and implicated in the role of neovascularization. It is thought that the polymorphism of VEGF -2578C/A (rs699947) contributed to the development of diabetic retinopathy in type 2 DM.

Aim: To determine whether the polymorphisms of VEGF-2578C/A are the …

Evaluation Of Liver Kinase B1 Downstream Signaling Expression In Various Breast Cancers And Relapse Free Survival After Systemic Chemotherapy Treatment, Khoa Nguyen, Andrew Rivera, Madlin Alzoubi, Henri Wathieu, Shengli Dong, Hassan Yousefi, Margarite Matossian, Suresh Alahari, David Drewry, Matthew Burow, Bridgette Collins-Burow

School of Medicine Faculty Publications

LKB1-signaling has prominent roles in cancer development and metastasis. This report evaluates LKB1-signaling pathway gene expression associations with patient survival in overall breast cancer, specific subtypes, as well as pre- and post-chemotherapy. Subtypes analyzed were based on intrinsic molecular subtyping and traditional biomarker classifications. Intrinsic molecular subtypes included were Luminal-A, Luminal-B, HER2-enriched, and Basal-like. The biomarker subtypes assessed were Estrogen-Receptor Positive (ER+) and Negative (ER-), Wild-Type TP53 (WT-TP53) & Mutant-TP53, and Triple-Negative Breast Cancer (TNBC). Additionally, comparisons were made between these subtypes and breast cancer overall, and analyses between LKB1 signaling to patient survival before and after chemotherapy were made. …

Androgen Receptor, Although Not A Specific Marker For, Is A Novel Target To Suppress Glioma Stem Cells As A Therapeutic Strategy For Glioblastoma, Nan Zhao, Fei Wang, Shaheen Ahmed, Kan Liu, Chi Zhang, Sahara J. Cathcart, Dominick J. Dimaio, Michael Punsoni, Bingjie Guan, Ping Zhou, Shuo Wang, Surinder K. Batra, Tatiana K. Bronich, Tom K. Hei, Chi Lin, Chi Zhang

Journal Articles: Biochemistry & Molecular Biology

Targeting androgen receptor (AR) has been shown to be promising in treating glioblastoma (GBM) in cell culture and flank implant models but the mechanisms remain unclear. AR antagonists including enzalutamide are available for treating prostate cancer patients in clinic and can pass the blood-brain barrier, thus are potentially good candidates for GBM treatment but have not been tested in GBM orthotopically. Our current studies confirmed that in patients, a majority of GBM tumors overexpress AR in both genders. Enzalutamide inhibited the proliferation of GBM cells both in vitro and in vivo. Although confocal microscopy demonstrated that AR is expressed …

Tumor- And Osteoclast-Derived Nrp2 In Prostate Cancer Bone Metastases, Navatha S. Polavaram, Samikshan Dutta, Ridwan Islam, Arup K. Bag, Sohini Roy, David Poitz, Jeffrey Karnes, Lorenz C. Hofbauer, Manish Kohli, Brian A. Costello, Raffael Jimenez, Surinder K. Batra, Benjamin A. Teply, Michael H. Muders, K Datta

Journal Articles: Biochemistry & Molecular Biology

Understanding the role of neuropilin 2 (NRP2) in prostate cancer cells as well as in the bone microenvironment is pivotal in the development of an effective targeted therapy for the treatment of prostate cancer bone metastasis. We observed a significant upregulation of NRP2 in prostate cancer cells metastasized to bone. Here, we report that targeting NRP2 in cancer cells can enhance taxane-based chemotherapy with a better therapeutic outcome in bone metastasis, implicating NRP2 as a promising therapeutic target. Since, osteoclasts present in the tumor microenvironment express NRP2, we have investigated the potential effect of targeting NRP2 in osteoclasts. Our results …

Untargeted Metabolomic Identification Of Diagnostic Biomarkers In Ectopic Pregnancy, Onur Turkoglu

Conference Presentation Abstracts

No abstract provided.

Myeloid Arginase 1 Insufficiency Exacerbates Amyloid-Β Associated Neurodegenerative Pathways And Glial Signatures In A Mouse Model Of Alzheimer’S Disease: A Targeted Transcriptome Analysis, Chao Ma, Jerry B. Hunt, Andrii Kovalenko, Huimin Liang, Maj-Linda B. Selenica, Michael B. Orr, Bei Zhang, John C. Gensel, David J. Feola, Marcia N. Gordon, Dave Morgan, Paula C. Bickford, Daniel C. Lee

Sanders-Brown Center on Aging Faculty Publications

Brain myeloid cells, include infiltrating macrophages and resident microglia, play an essential role in responding to and inducing neurodegenerative diseases, such as Alzheimer’s disease (AD). Genome-wide association studies (GWAS) implicate many AD casual and risk genes enriched in brain myeloid cells. Coordinated arginine metabolism through arginase 1 (Arg1) is critical for brain myeloid cells to perform biological functions, whereas dysregulated arginine metabolism disrupts them. Altered arginine metabolism is proposed as a new biomarker pathway for AD. We previously reported Arg1 deficiency in myeloid biased cells using lysozyme M (LysM) promoter-driven deletion worsened amyloidosis-related neuropathology and behavioral impairment. However, …

The Role Of Survivin Splice Variants In Pancreatic Ductal Adenocarcinoma Chemoresistance, Janviere Kabagwira

Loma Linda University Electronic Theses, Dissertations & Projects

Pancreatic cancer is currently one of the most difficult diseases to treat due to difficulty of detection and its aggressive nature. In addition, pancreatic cancer has the highest mortality rates compared to other cancer types. These mortality rates are attributable in part to increasing resistance to cancer therapy. Cancer therapy resistance is caused by adaptations that favor cancer cell survival. Some of these adaptations occur intrinsically before chemotherapy exposure (innate resistance) while others are a result of chemotherapy through selective and cellular adaptations (acquired chemoresistance). Important to pancreatic cancer diagnosis and management is to determine an optimal combination of clinical …

Biochemical Characterization Of Small Molecule Inhibitor Binding On A Ras Related Gtpase And Its Effector Interactions, Djamali Muhoza

Graduate Theses and Dissertations

The Ras superfamily of GTPases has 167 proteins that are involved in various cellular processes such as proliferation, transformation, migration, and inhibition of cell death. Mutations, abnormal expression, and function of these proteins are observed in many diseases, including several forms of cancer. Even though these GTPases were among the first discovered oncogenes, no successful Ras drug candidate has successfully passed clinical trials. Drugs targeting these proteins have failed mainly because of the complexity of their regulation, their high affinity to GTP, and their structure’s dynamic nature. Recently, novel promising targeting approaches have renewed interest in the Ras drug discovery …

Perivascular Adipose Tissue In Relation To Diet, Thermogenesis And Cardiovascular Health, Ginger Paquette, Caitlin Stieber, Ashely Soucy, Benjamin Tero, Lucy Liaw

Thinking Matters Symposium

Adipose tissue is a diverse and crucial component to vascular health due to its role in energy storage and heat production. The primary function of white adipose tissue (WAT) is energy storage while the function of mitochondria-rich brown adipose tissue (BAT) is heat production. Perivascular adipose tissue (PVAT), which surrounds blood vessels, contains both WAT and BAT adipocytes. Dietary calorie restriction is associated with increased lifespan with decreased adiposity. Increased prevalence of WAT-like PVAT, due to high-fat diets and obesity, leads to increased metabolic disfunction and cardiovascular-disease. We used a calorie-restriction model in C57BL6/J mice to test the hypothesis that …

An Insulator Blocks Access To Enhancers By An Illegitimate Promoter, Preventing Repression By Transcriptional Interference., Miki Fujioka, Anastasiya Nezdyur, James B. Jaynes

Department of Biochemistry and Molecular Biology Faculty Papers

Several distinct activities and functions have been described for chromatin insulators, which separate genes along chromosomes into functional units. Here, we describe a novel mechanism of functional separation whereby an insulator prevents gene repression. When the homie insulator is deleted from the end of a Drosophila even skipped (eve) locus, a flanking P-element promoter is activated in a partial eve pattern, causing expression driven by enhancers in the 3' region to be repressed. The mechanism involves transcriptional read-through from the flanking promoter. This conclusion is based on the following. Read-through driven by a heterologous enhancer is sufficient to repress, even …

Functional Interpretation Of Atad3a Variants In Neuro-Mitochondrial Phenotypes, Zheng Yie Yap, Yo Han Park, Saskia B Wortmann, Adam C Gunning, Shlomit Ezer, Sukyeong Lee, Lita Duraine, Ekkehard Wilichowski, Kate Wilson, Johannes A Mayr, Matias Wagner, Hong Li, Usha Kini, Emily Davis Black, Kristin G Monaghan, James R Lupski, Sian Ellard, Dominik S Westphal, Tamar Harel, Wan Hee Yoon

Faculty, Staff and Students Publications

BACKGROUND: ATPase family AAA-domain containing protein 3A (ATAD3A) is a nuclear-encoded mitochondrial membrane-anchored protein involved in diverse processes including mitochondrial dynamics, mitochondrial DNA organization, and cholesterol metabolism. Biallelic deletions (null), recessive missense variants (hypomorph), and heterozygous missense variants or duplications (antimorph) in ATAD3A lead to neurological syndromes in humans.

METHODS: To expand the mutational spectrum of ATAD3A variants and to provide functional interpretation of missense alleles in trans to deletion alleles, we performed exome sequencing for identification of single nucleotide variants (SNVs) and copy number variants (CNVs) in ATAD3A in individuals with neurological and mitochondrial phenotypes. A Drosophila Atad3a Gal4 …

The Crosstalk Between Insulin Resistance, Systemic Inflammation, Redox Imbalance And The Thyroid In Subjects With Obesity, Nicoleta Răcătăianu, Nicoleta Valentina Leach, Sorana D. Bolboacă, Maria Loredana Soran, Mirela Flonta, Ana Valea, Andrada-Luciana Lazăr, Cristina Ghervan

Journal of Mind and Medical Sciences

We aimed at assessing the interaction between visceral adipose tissue (VAT), insulin resistance (IR), circulating levels of monocyte chemoattractant protein-1 (MCP-1) and malondialdehyde (MDA) and the thyroid parameters in obese subjects. Methods. Obese subjects without thyroid pathologies or diseases associated with systemic inflammation and OS were recruited. Insulinemia, visceral fat thickness, metabolic and thyroid parameters were assayed. Circulating levels of MCP-1 and MDA were used to quantify inflammation and OS. Results. A number of 160 obese subjects were included. The MCP-1 level increased with the degree of obesity and HOMA-IR. MCP 1 was positively associated with antithyroperoxidase antibody (TPOab) levels …

A Stress-Free Strategy To Correct Point Mutations In Patient Ips Cells, Jingli Cai, Elizabeth Kropf, Ya-Ming Hou, Lorraine Iacovitti

Department of Biochemistry and Molecular Biology Faculty Papers

When studying patient specific induced pluripotent stem cells (iPS cells) as a disease model, the ideal control is an isogenic line that has corrected the point mutation, instead of iPS cells from siblings or other healthy subjects. However, repairing a point mutation in iPS cells even with the newly developed CRISPR-Cas9 technique remains difficult and time-consuming. Here we report a strategy that makes the Cas9 “knock-in” methodology both hassle-free and error-free. Instead of selecting a Cas9 recognition site close to the point mutation, we chose a site located in the nearest intron. We constructed a donor template with the fragment …

Ketogenic Diet As A Preventative Measure Or Treatment Option For Osteoarthritistargeting Nfl Athletes As A High-Risk Group, Kelsi J. Smith

Selected Honors Theses

Osteoarthritis (OA) is a prevalent joint disease that results from the degradation of articular cartilage, leading to inflammation, pain, and eventual joint failure. At one time, it was thought that OA was only the result of the natural decline experienced in old age; however, various risk factors have now been identified that may contribute to an increased risk for developing OA. Risk factors may include joint loading, altered biomechanics, obesity, and joint injury, to which athletes are exposed at a high rate. NFL athletes are one group of athletes that have continued to show a high prevalence of arthritis in …

Oxidative Stress And Dna Damage As Promoting Factors Of Hpv Integration, Meghri Katerji

Loma Linda University Electronic Theses, Dissertations & Projects

Human papillomaviruses (HPVs) cause virtually all cervical cancer cases and are also associated with other types of anogenital and oropharyngeal cancers. HPV-mediated carcinogenesis typically begins with the HPV episome integrating into the human genome. Unfortunately, the factors that promote this key process are not well defined. Since viral integration requires breaks in both viral and human genomes, DNA damage is likely a key determinant. The latter is primarily caused by an overproduction of reactive oxygen species (ROS). Therefore, high levels of background ROS in host cells, which may result from genetic/epigenetic factors together with exogenous influences, in principle, have the …

Global Sex Disparity Of Covid-19: A Descriptive Review Of Sex Hormones And Consideration For The Potential Therapeutic Use Of Hormone Replacement Therapy In Older Adults, Samuel C. Okpechi, Jordyn T. Fong, Shawn S. Gill, Jarrod C. Harman, Tina H. Nguyen, Queendaleen Chukwurah, Ifeanyichukwu O. Onor, Suresh K. Alahari

School of Graduate Studies Faculty Publications

The 2019-2020 SARS-related coronavirus-2 (SARS-CoV-2) pandemic has brought unprecedented challenges to healthcare sectors around the world. As of November 2020, there have been over 64 million confirmed cases and approaching 2 million deaths globally. Despite the large number of positive cases, there are very limited established standards of care and therapeutic options available. To date, there is still no Food and Drug Administration (FDA) approved vaccine for COVID-19, although there are several options in various clinical trial stages. Herein, we have performed a global review evaluating the roles of age and sex on COVID-19 hospitalizations, ICU admissions, deaths in hospitals, …

St6galnac-I Promotes Lung Cancer Metastasis By Altering Muc5ac Sialylation, Imayavaramban Lakshmanan, Sanjib Chaudhary, Raghupathy Vengoji, Parthasarathy Seshacharyulu, Satyanarayana Rachagani, Joseph Carmicheal, Rahat Jahan, Pranita Atri, Ramakanth C. Venkata, Rohitesh Gupta, Saravanakumar Marimuthu, Naveenkumar Perumal, Sanchita Rauth, Sukhwinder Kaur, Kavita Mallya, Lynette M. Smith, Subodh M. Lele, Moorthy P. Ponnusamy, Mohd W. Nasser, Ravi Salgia, Surinder K. Batra, Apar Kishor Ganti

Journal Articles: Biochemistry & Molecular Biology

Lung cancer (LC) is the leading cause of cancer-related mortality. However, the molecular mechanisms associated with the development of metastasis is poorly understood. Understanding the biology of LC metastasis is critical to unveil the molecular mechanisms for designing targeted therapies. We developed two genetically engineered LC mouse models- Kras^G12D ;Trp53^R172H/+ ;Ad-Cre (KPA) and Kras^G12D ; Ad-Cre (KA). Survival analysis showed significantly (P=0.0049) shorter survival in KPA tumor-bearing mice as compared to KA, suggesting the aggressiveness of the model. Our transcriptomic data showed high expression of St6galnac-I in KPA compared to KA tumors. ST6GalNAc-I is an O-glycosyltransferase, which …

Biological Activity And Solubility Of 5-Methoxy-1,4-Benzoquinone Having Bromoheptyl And Bromodecyl Substituents In The N-Octanol/Water System, Siti Mariyah Ulfa, Fath Dwisari, Laras Pangesti, Mohammad Farid Rahman

Makara Journal of Science

The biological activity and solubility of compounds are influenced by its chemical structure. These properties can be improved by substituting alkyl, alkoxy, and/or haloalkane in the parent skeleton. In this research, the synthesis of 3-(7-bromoheptyl)-2-methyl-5-methoxy-1,4-benzoquinone (3a) and 3-(10-bromodecyl)-2-methyl-5-methoxy-1,4-benzoquinone (3b) was achieved through the decarboxylation reaction. The solubility and biological activity of 3a and 3b were compared with that of thymoquinone (TQ), which acts as an anti-inflammatory agent. Compounds 3a and 3b were successfully synthesized and analyzed using Fourier Transform Infra-Red (FTIR) and Nuclear Magnetic Resonance (NMR). The FTIR spectrum showed the increasing intensity of …

Nmr Methods For Determining Lipid Turnover Via Stable Isotope Resolved Metabolomics, Penghui Lin, Li Dai, Daniel R. Crooks, Leonard M. Neckers, Richard M. Higashi, Teresa W.-M. Fan, Andrew N. Lane

Center for Environmental and Systems Biochemistry Faculty Publications

Lipids comprise diverse classes of compounds that are important for the structure and properties of membranes, as high-energy fuel sources and as signaling molecules. Therefore, the turnover rates of these varied classes of lipids are fundamental to cellular function. However, their enormous chemical diversity and dynamic range in cells makes detailed analysis very complex. Furthermore, although stable isotope tracers enable the determination of synthesis and degradation of complex lipids, the numbers of distinguishable molecules increase enormously, which exacerbates the problem. Although LC-MS-MS (Liquid Chromatography-Tandem Mass Spectrometry) is the standard for lipidomics, NMR can add value in global lipid analysis and …

Amyloid Precursor-Like Protein 2 Expression Increases During Pancreatic Cancer Development And Shortens The Survival Of A Spontaneous Mouse Model Of Pancreatic Cancer., Brittany J. Poelaert, Shelby M. Knoche, Alaina C. Larson, Poomy Pandey, Parthasarathy Seshacharyulu, Nuzhat Khan, H. Carlo Maurer, Kenneth P. Olive, Yuri Sheinin, Rizwan Ahmad, Amar B. Singh, Surinder K. Batra, Satyanarayana Rachagani, Joyce C. Solheim

Journal Articles: Biochemistry & Molecular Biology

In the United States, pancreatic cancer is a major cause of cancer-related deaths. Although substantial efforts have been made to understand pancreatic cancer biology and improve therapeutic efficacy, patients still face a bleak chance of survival. A greater understanding of pancreatic cancer development and the identification of novel treatment targets are desperately needed. Our analysis of gene expression data from patient samples showed an increase in amyloid precursor-like protein 2 (APLP2) expression within primary tumor epithelium relative to pancreatic intraepithelial neoplasia (PanIN) epithelial cells. Augmented expression of APLP2 in primary tumors compared to adjacent stroma was also observed. Genetically engineered …

Rna-Based Therapies: A Cog In The Wheel Of Lung Cancer Defense, Parvez Khan, Jawed A. Siddiqui, Imayavaramban Lakshmanan, Apar Kishor Ganti, Ravi Salgia, Maneesh Jain, Surinder K. Batra, Mohd W. Nasser

Journal Articles: Biochemistry & Molecular Biology

Lung cancer (LC) is a heterogeneous disease consisting mainly of two subtypes, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), and remains the leading cause of death worldwide. Despite recent advances in therapies, the overall 5-year survival rate of LC remains less than 20%. The efficacy of current therapeutic approaches is compromised by inherent or acquired drug-resistance and severe off-target effects. Therefore, the identification and development of innovative and effective therapeutic approaches are critically desired for LC. The development of RNA-mediated gene inhibition technologies was a turning point in the field of RNA biology. The critical regulatory …

Polθ Promotes The Repair Of 5'-Dna-Protein Crosslinks By Microhomology-Mediated End-Joining, Gurushankar Chandramouly, Shuren Liao, Timur Rusanov, Nikita Borisonnik, Marissa L Calbert, Tatiana Kent, Katherine Sullivan-Reed, Umeshkumar Vekariya, Ekaterina Kashkina, Tomasz Skorski, Hong Yan, Richard T Pomerantz

Department of Biochemistry and Molecular Biology Faculty Papers

DNA polymerase θ (Polθ) confers resistance to chemotherapy agents that cause DNA-protein crosslinks (DPCs) at double-strand breaks (DSBs), such as topoisomerase inhibitors. This suggests Polθ might facilitate DPC repair by microhomology-mediated end-joining (MMEJ). Here, we investigate Polθ repair of DSBs carrying DPCs by monitoring MMEJ in Xenopus egg extracts. MMEJ in extracts is dependent on Polθ, exhibits the MMEJ repair signature, and efficiently repairs 5' terminal DPCs independently of non-homologous end-joining and the replisome. We demonstrate that Polθ promotes the repair of 5' terminal DPCs in mammalian cells by using an MMEJ reporter and find that Polθ confers resistance to …