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Autocrine Epiregulin Activates Egfr Pathway For Lung Metastasis Via Emt In Salivary Adenoid Cystic Carcinoma, Shuli Liu, Dongxia Ye, Dongliang Xu, Yueling Liao, Ling Zhang, Liu Liu, Wenwen Yu, Yanan Wang, Yue He, Jingzhou Hu, Wenzheng Guo, Tong Wang, Beibei Sun, Hongyong Song, Huijing Yin, Jingyi Liu, Yadi Wu, Hanguang Zhu, Binhua P. Zhou, Jiong Deng, Zhiyuan Zhang

Markey Cancer Center Faculty Publications

Salivary adenoid cystic carcinoma (SACC) is characterized by invasive local growth and a high incidence of lung metastasis. Patients with lung metastasis have a poor prognosis. Treatment of metastatic SACC has been unsuccessful, largely due to a lack of specific targets for the metastatic cells. In this study, we showed that epidermal growth factor receptors (EGFR) were constitutively activated in metastatic lung subtypes of SACC cells, and that this activation was induced by autocrine expression of epiregulin (EREG), a ligand of EGFR. Autocrine EREG expression was increased in metastatic SACC-LM cells compared to that in non-metastatic parental SACC cells. Importantly, …

Anterior Cruciate Ligament Injuries In National Football League Athletes From 2010 To 2013: A Descriptive Epidemiology Study., Christopher C Dodson, Eric S Secrist, Suneel B Bhat, Daniel P Woods, Peter F Deluca

Rothman Institute Papers

BACKGROUND: There is a high incidence of anterior cruciate ligament (ACL) injuries among National Football League (NFL) athletes; however, the incidence of reinjury in this population is unknown.

PURPOSE: This retrospective epidemiological study analyzed all publicly disclosed ACL tears occurring in NFL players between 2010 and 2013 to characterize injury trends and determine the incidence of reinjury.

STUDY DESIGN: Descriptive epidemiological study.

METHODS: A comprehensive online search identified any NFL player who had suffered an ACL injury from 2010 to 2013. Position, playing surface, activity, and date were recorded. Each player was researched for any history of previous ACL injury. …

Establishment Of Prostate Cancer Spheres From A Prostate Cancer Cell Line After Phenethyl Isothiocyanate Treatment And Discovery Of Androgen-Dependent Reversible Differentiation Between Sphere And Neuroendocrine Cells, Yamei Chen, Shundong Cang, Liying Han, Christina Liu, Patrick Yang, Zeeshan Solangi, Quanyi Lu, Delong Liu, Jenwei Chiao

NYMC Faculty Publications

Prostate cancer can transform from androgen-responsive to an androgen-independent phenotype. The mechanism responsible for the transformation remains unclear. We studied the effects of an epigenetic modulator, phenethyl isothiocyanate (PEITC), on the androgen-responsive LNCaP cells. After treatment with PEITC, floating spheres were formed with characteristics of prostate cancer stem cells (PCSC). These spheres were capable of self-renewal in media with and without androgen. They have been maintained in both types of media as long term cultures. Upon androgen deprivation, the adherent spheres differentiated to neuroendocrine cells (NEC) with decreased proliferation, expression of androgen receptor, and PSA. NEC reverse differentiated to spheres …

Otolaryngology For Internal Medicine: Increasing Exposure To Otolaryngology Using Computer Assisted Instruction, Arielle Thal, Philip Zapanta

GW Research Days 2016 - 2020

It has been well identified in previous literature that there is a lack of otolaryngology teaching for general practitioners. There is not currently a standardized curriculum for otolaryngology in undergraduate medical education or during residency for those pursuing a general field such as Emergency Medicine, Internal Medicine, Pediatrics or Family Medicine. While the need for more exposure to otolaryngology within these fields has been well documented, as 25% of primary care complaints are otolaryngology related, little has been done to identify the best method for educational intervention. Important topics for inclusion in such a curriculum have been identified and methods …

Imparting Research Ethics In Emergency Medicine-A Perspective From The Developing World, Shahan Waheed, Muhammad Akbar Baig, Asad Mian

Department of Emergency Medicine

No abstract provided.

Effect Of The Time Of Day And Queue Position In The Endoscopic Schedule On The Performance Characteristics Of Endoscopic Ultrasound-Guided Fine-Needle Aspiration For Diagnosing Pancreatic Malignancies., Jason Korenblit, Danielle M Tholey, Joanna Tolin, David Loren, Thomas Kowalski, Douglas G. Adler, Julie Davolos, Ali A. Siddiqui

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND AND OBJECTIVES: Recent reports have indicated that the time of day may impact the detection rate of abnormal cytology on gynecologic cytology samples. The aim of this study was to determine if procedure time or queue position affected the performance characteristics of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for diagnosing solid pancreatic malignancies.

PATIENTS AND METHODS: We conducted a retrospective study evaluating patients with solid pancreatic lesions in whom EUS-FNA was performed. Three timing variables were evaluated as surrogate markers for endoscopist fatigue: Procedure start times, morning versus afternoon procedures, and endoscopy queue position. Statistical analyses were performed to determine …

Long Non-Coding Rnas As Prognostic Markers In Human Breast Cancer, Hairong Liu, Juan Li, Pratirodh Koirala, Xianfeng Ding, Binghai Chen, Yiheng Wang, Zheng Wang, Chuanxin Wang, Xu Zhang, Yin-Yuan Mo

Faculty Publications

Long non-coding RNAs (lncRNAs) have been recently shown to play an important role in gene regulation and normal cellular functions, and disease processes. However, despite the overwhelming number of lncRNAs identified to date, little is known about their role in cancer for vast majority of them. The present study aims to determine whether lncRNAs can serve as prognostic markers in human breast cancer. We interrogated the breast invasive carcinoma dataset of the Cancer Genome Atlas (TCGA) at the cBioPortal consisting of ~ 1,000 cases. Among 2,730 lncRNAs analyzed, 577 lncRNAs had alterations ranging from 1% to 32% frequency, which include …

Techniques And Approaches To Genetic Analyses In Nephrological Disorders., Laurel K. Willig

Manuscripts, Articles, Book Chapters and Other Papers

Inherited renal disease is a leading cause of morbidity and mortality in pediatric nephrology. High throughput advancements in genomics have led to greater understanding of the biologic underpinnings of these diseases. However, the underlying genetic changes explain only part of the molecular biology that contributes to disease manifestation and progression. Other omics technologies will provide a more complete picture of these cellular processes. This review discusses these omics technologies in the context of pediatric renal disease.

Alternative Regulation Of Myc In Lung Cancer, Patrick N. Backman

Open Access Theses

Lung cancer is the leading cause of cancer deaths in the United States, accounting for 27% of all cancer induced deaths1. In an attempt to create a effective targeted therapy for the treatment of lung cancer, a strategy used to treat an activated KrasG12D/+;p53 R172H/+ transgenic lung cancer mouse model was to deliver a known tumor suppressive microRNA (miRNA) to stop tumor growth. The tumor suppressive miRNA let-7 was lentivirally delivered in the form of its primary transcript, pri-let-7a-1, and resulted in increased lung size and inflammation compared to lungs exposed to a control lentivirus. It was identified …

Identification Of An Association Of Tnfaip3 Polymorphisms With Matrix Metalloproteinase Expression In Fibroblasts In An Integrative Study Of Systemic Sclerosis-Associated Genetic And Environmental Factors*, Peng Wei, Yang Yang, Xinjian Guo, Nainan Hei, Syeling Lai, Shervin Assassi, Mengyuan Liu, Filemon Tan, Xiaodong Zhou

Faculty, Staff and Students Publications

OBJECTIVE: Systemic sclerosis (SSc) is a fibrotic disease attributed to both genetic susceptibility and environmental factors. This study was undertaken to investigate the associations between SSc-associated genetic variants and the expression of extracellular matrix (ECM) genes in human fibroblasts stimulated with silica particles in time-course and dose-response experiments.

METHODS: A total of 200 fibroblast strains were examined for ECM gene expression after stimulation with silica particles. The fibroblasts were genetically profiled using Immunochip assays and then subjected to whole-genome genotype imputation. Associations of genotypes and gene expression were first analyzed in a Caucasian cohort and then validated in a meta-analysis …

Role Of Heme Oxygenase-1 In The Pathogenesis And Tumorigenicity Of Kaposi's Sarcoma-Associated Herpesvirus, Lu Dai, Jing Qiao, David Nguyen, Amanda P. Struckhoff, Lisa Doyle, Karlie Bonstaff, Luis Del Valle, Chris Parsons, Bryan P. Toole, Rolf Renne, Zhiqiang Qin

School of Medicine Faculty Publications

Kaposi's Sarcoma-associated Herpesvirus (KSHV) is the etiologic agent of several malignancies, including Kaposi's Sarcoma (KS), which preferentially arise in immunocompromised patients such as HIV+ subpopulation and lack effective therapeutic options. Heme oxygenase-1 (HO-1) has been reported as an important regulator of endothelial cell cycle control, proliferation and angiogenesis. HO-1 has also been found to be highly expressed in KSHV-infected endothelial cells and oral AIDS-KS lesions. We previously demonstrate that the multifunctional glycoprotein CD147 is required for KSHV/LANA-induced endothelial cell invasiveness. During the identification of CD147 controlled downstream genes by microarray analysis, we found that the expression of HO-1 is significantly …

Closed-Loop Cfd Analysis Of The Fontan Cardiovascular Circulation, Marwan Hameed

Doctoral Dissertations and Master's Theses

One out of 150 newborn babies born with congenital heart disease, approximately 7.5% of those infants have a single ventricle (SV). The Fontan operation, which is a procedure to create a harmonious circulation in SV patients, has been performed for a long time to save the newborn patients. In this procedure the superior vena cava and inferior vena cava, which carry the oxygen-poor blood from the upper and lower body back to the heart, are linked directly to the pulmonary arteries, bypassing the atrial connection. Even though this operation has been around for years, the patients who have undergone this …

A Call For The Structured Physicist Report, John M. Boone, Phd, Mahadevappa Mahesh, Ms, Phd, Eric L. Gingold, Phd, J. Anthony Seibert, Phd

Department of Radiology Faculty Papers

Introduction:

The field of diagnostic radiology continues to struggle with the clinical adoption of the structured interpretive report, with many radiologists preferring a semistructured, free-text dictation style to a more rigid, highly structured approach that some professional leaders have promoted [1]. Although structured reporting compliance in the radiologist community has been difficult to achieve, diagnostic radiologists have been thinking about and discussing this important issue for many years; it is also a part of the ACR’s Imaging 3.0_ campaign [2]. In the breast imaging community, the well-established BI-RADS_ recommendations produce a very structured report, with a discussion of interpretive findings …

Multi-Level Correlates Of Safer Conception Methods Awareness And Attitudes Among Ugandan Hiv Clients With Fertility Intentions., Glenn J. Wagner, Mahlet A. Woldetsadik, Jolly Beyeza-Kashesya, Kathy Goggin, Deborah Mindry, Sarah Finocchario-Kessler, Sarah Khanakwa, Rhoda K. Wanyenze

Manuscripts, Articles, Book Chapters and Other Papers

Many people living with HIV desire childbearing, but low cost safer conception methods (SCM) such as timed unprotected intercourse (TUI) and manual self-insemination (MSI) are rarely used. We examined awareness and attitudes towards SCM, and the correlates of these constructs among 400 HIV clients with fertility intentions in Uganda. Measures included awareness, self-efficacy, and motivation regarding SCM, as well as demographics, health management, partner and provider characteristics. Just over half knew that MSI (53%) and TUI (51%) reduced transmission risk during conception, and 15% knew of sperm washing and pre-exposure prophylaxis. In separate regression models for SCM awareness, motivation, and …

Safety Netting Through The Prevention And Detection Of Child Abuse In Low And Middle Income Countries: Lessons From Pakistan, Kanwal Nayani, Muhammad Akbar Baig, Nick Brown, Asad Mian

Department of Paediatrics and Child Health

No abstract provided.

Occupational Health Of Self-Employed Skilled Labourers And Daily-Wage Workers In Pakistan., Noor Ul-Ain Baloch, Abdul Rehman Alvi, Muhammad Awais

Department of Surgery Docs

No abstract provided.

Diagnostic Methods To Determine Microbiology Of Postpartum Endometritis In South Asia: Laboratory Methods Protocol Used In The Postpartum Sepsis Study: A Prospective Cohort Study, Sadia Shakoor, Megan E. Reller, Amnesty Lefevre, Aneeta Hotwani, Shahida M. Qureshi, Farheen Yousuf, Mohammad Shahidul Islam, Nicholas Connor, Iftekhar Rafiqullah, Fatima Mir

Department of Paediatrics and Child Health

Background: The South Asian region has the second highest risk of maternal death in the world. To prevent maternal deaths due to sepsis and to decrease the maternal mortality ratio as per the World Health Organization Millenium Development Goals, a better understanding of the etiology of endometritis and related sepsis is required. We describe microbiological laboratory methods used in the maternal Postpartum Sepsis Study, which was conducted in Bangladesh and Pakistan, two populous countries in South Asia.
Methods/Design: Postpartum maternal fever in the community was evaluated by a physician and blood and urine were collected for routine analysis and culture. …

Consecutive Bilateral Decompression Retinopathy After Mitomycin C Trabeculectomy: A Case Report., Ana Raquel Marcos Figueiredo, Isabel Coutinho Sampaio, Maria João Fernandes Dos Santos Menéres, George L. Spaeth

Wills Eye Hospital Papers

BACKGROUND: After a successful trabeculectomy, a sudden intraocular pressure decrease may alter the intracranial to intraocular pressure ratio and cause decompression retinopathy. Frequent Valsalva maneuvers may also play a role in its pathogenesis. This condition may manifest as multiple retinal hemorrhages, edema of the optic disc, macular edema, or a sudden decrease in visual acuity postoperatively. Outcomes for patients are usually good, with spontaneous resolution occurring within a matter of weeks. It has been rarely reported in the literature as a bilateral condition.

CASE PRESENTATION: We present a case of consecutive bilateral decompression retinopathy in a 54-year-old severely obese Caucasian …

Structural And Evolutionary Analyses Show Unique Stabilization Strategies In The Type Iv Pili Of Clostridium Difficile, Kurt H. Piepenbrink, Grace A. Maldarelli, Claudia F. Martinez De La Pena, Tanis C. Dingle, George L. Mulvey, Amanda Lee, Erik Von Rosenvinge, Glen D. Armstrong, Michael S. Donnenberg, Eric J. Sundberg

Food for Health: Publications

Type IV pili are produced by many pathogenic Gram-negative bacteria and are important for processes as diverse as twitching motility, biofilm formation, cellular adhesion and horizontal gene transfer. However, many Gram-positive species, including C. difficile, also produce Type IV pili. Here, we identify the major subunit of the Type IV pili of C. difficile, PilA1, and describe multiple three-dimensional structures of PilA1, demonstrating the diversity found in three strains of C. difficile. We also model the incorporation of both PilA1 and a minor pilin, PilJ, into the pilus fiber. Although PilA1 contains no cysteine residues, and therefore cannot form the …

Lambda Red-Mediated Recombineering In The Attaching And Effacing Pathogen Escherichia Albertii., Marisa Egan, Jasmine Ramirez, Christian Xander, Chirag Upreti, Shantanu Bhatt

Department of Medicine Faculty Papers

BACKGROUND: The ability to introduce site-specific mutations in bacterial pathogens is essential towards understanding their molecular mechanisms of pathogenicity. This has been greatly facilitated by the genetic engineering technique of recombineering. In recombineering, linear double- or single-stranded DNA molecules with two terminal homology arms are electroporated into hyperrecombinogenic bacteria that express a phage-encoded recombinase. The recombinase catalyzes the replacement of the endogenous allele with the exogenous allele to generate selectable or screenable recombinants. In particular, lambda red recombinase has been instrumental in engineering mutations to characterize the virulence arsenal of the attaching and effacing (A/E) pathogens enteropathogenic Escherichia coli (EPEC), …

Curcumin Nanoformulation For Cervical Cancer Treatment, Mohd S. Zaman, Neeraj Chauhan, Murali M. Yallapu, Rishi K. Gara, Diane M. Maher, Sonam Kumari, Mohammed Sikander, Sheema Khan, Nadeem Zafar, Meena Jaggi, Subhash C. Chauhan

School of Medicine Publications

Cervical cancer is one of the most common cancers among women worldwide. Current standards of care for cervical cancer includes surgery, radiation, and chemotherapy. Conventional chemotherapy fails to elicit therapeutic responses and causes severe systemic toxicity. Thus, developing a natural product based, safe treatment modality would be a highly viable option. Curcumin (CUR) is a well-known natural compound, which exhibits excellent anti-cancer potential by regulating many proliferative, oncogenic, and chemo-resistance associated genes/proteins. However, due to rapid degradation and poor bioavailability, its translational and clinical use has been limited. To improve these clinically relevant parameters, we report a poly(lactic-co-glycolic acid) based …

The Effects Of Acidified Pepsin On Porcine Vocal Fold Tissue: Developing A Porcine Model Of Laryngopharyngeal Reflux Disease, Abigail Cox Durkes

Open Access Dissertations

Approximately 7.5 million Americans are affected by a voice disorder. In the last year, 7.2% of people missed one or more days of work due to a voice problem. For professional voice users, such as teachers, the rate increases to 20% and an annual cost of $2.5 billion. Voice disorders are complex and multi-faceted, as well as difficult to diagnose and treat. Prospective animal studies are necessary to study the pathophysiology of voice disorders, optimize our understanding of laryngeal pathology, and improve treatment outcomes. The pig provides a unique opportunity to test hypotheses relating to laryngeal disease because porcine vocal …

Oncolog, Volume 61, Number 02, February 2016, Joe Munch, Bryan Tutt, C Graber

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Overcoming Challenges in Cutaneous T Cell Lymphomas: Cutaneous T Cell lymphomas (CTCLs) not only are largely incurable but also make patients miserable with itching, burning skin and unsightly lesions. Because CTCL can resemble various benign skin conditions, many patients are diagnosed at an advanced and difficult-to-treat stage. But ongoing clinical trials may offer patients with CTCL improved treatments and better quality of life.
• Swallowing Therapy Improves Function and Quality of Life for Patients with Head and Neck Cancer: In patients with head and neck cancer, loss of swallowing function may result from radiation therapy, surgery, or the cancer itself and …

Theory-Driven Longitudinal Study Exploring Indoor Tanning Initiation In Teens Using A Person-Centered Approach, Joel J. Hillhouse, Rob Turrisi, Michael J. Cleveland, Nichole M. Scaglione, Katie Baker, L. Carter Florence

ETSU Faculty Works

Background

Younger indoor tanning initiation leads to greater melanoma risk due to more frequent and persistent behavior. Despite this, there are no published studies exploring the predictors of indoor tanning initiation in teen populations.

Purpose

This longitudinal study uses latent profile analysis to examine indoor tanning initiation in indoor tanning risk subgroups from a national sample of female adolescents.

Methods

Latent profile analysis used indoor tanning beliefs and perceptions to identify indoor tanning initiation risk subgroups. The teens in each subgroup were reassessed on indoor tanning initiation after a year.

Results

Three subgroups were identified: a low risk, anti-tanning subgroup …

Differences And Similarities In The Clinicopathological Features Of Pancreatic Neuroendocrine Tumors In China And The United States: A Multicenter Study, Li-Ming Zhu, Laura Tang, Xin-Wei Qiao, Edward M. Wolin, Nicholas N. Nissen, Deepti Dhall, Jie Chen, Lin Shen, Yihebali Chi, Yao-Zong Yuan, Qi-Wen Ben, Bin Lv, Ya-Ru Zhou, Chun-Mei Bai, Jie Chen, Yu-Li Song, Tian-Tian Song, Chong-Mei Lu, Run Yu, Yuan-Jia Chen

Markey Cancer Center Faculty Publications

The presentation, pathology, and prognosis of pancreatic neuroendocrine tumors (PNETs) in Asian patients have not been studied in large cohorts. We hypothesized that the clinicopathological features of PNETs of Chinese patients might be different from those of US patients. The objectives of this study were to address whether PNETs in Chinese patients exhibit unique clinicopathological features and natural history, and can be graded and staged using the WHO/ENETS criteria.

This is a retrospective review of medical records of patients with PNETs in multiple academic medical centers in China (7) and the United States (2). Tumor grading and staging were based …

Safety And Efficacy Of Blood Exchange Transfusion For Priapism Complicating Sickle Cell Disease., Samir K. Ballas, David Lyon

Cardeza Foundation for Hematologic Research

BACKGROUND: Priapism is unwanted painful penile erection that affects about 36% of boys and men with sickle cell disease (SCD) most of whom have sickle cell anemia. Clinically, priapism could be stuttering, minor, or major. The first two types are mild, last < 4 h, are usually treated at home, have good prognosis with normal sexual function. The major type of priapism lasts >4 h, associated with severe pain, requires hospitalization; often does not respond to medical treatment and may require shunt surgery. Untreated major priapism and surgical intervention often cause impotence. In this study, we report our 15-year experience in treating adult patients with SCD and major priapism with blood exchange transfusion after being refractory to other medical therapies.

METHODS: …

Evaluation Of A Pacap Peptide Analogue Labeled With (68)Ga Using Two Different Chelating Agents., Pardeep Kumar, Sushil Kumar Tripathi, Chang-Po Chen, Neil Mehta, Bishnuhari Paudyal, Eric Wickstrom, Mathew L. Thakur

Department of Radiology Faculty Papers

OBJECTIVE: The authors have conjugated chelating agents (DOTA and NODAGA) with a peptide (pituitary adenylate cyclase-activating peptide [PACAP] analogue) that has a high affinity for VPAC1 receptors expressed on cancer cells. To determine a suitable chelating agent for labeling with (68)Ga, they have compared the labeling kinetics and stability of these peptide conjugates.

METHODS: For labeling, (68)GaCl3 was eluted in 0.1 M HCl from a [(68)Ge-(68)Ga] generator. The influences of peptide concentration, pH, and temperature on the radiolabeling efficiency were studied. The stability was evaluated in saline, human serum, DTPA, transferrin, and metallic ions (FeCl3, CaCl2, and ZnCl2). Cell binding …

Human Igg1 Antibodies Suppress Angiogenesis In A Target-Independent Manner, Sasha Bogdanovich, Younghee Kim, Takeshi Mizutani, Reo Yasuma, Laura Tudisco, Valeria Cicatiello, Ana Bastos-Carvalho, Nagaraj Kerur, Yoshio Hirano, Judit Z. Baffi, Valeria Tarallo, Shengjian Li, Tetsuhiro Yasuma, Parthasarathy Arpitha, Benjamin James Fowler, Charles B. Wright, Ivana Apicella, Adelaide Greco, Arturo Brunetti, Menotti Ruvo, Annamaria Sandomenico, Miho Nozaki, Ryo Ijima, Hiroki Kaneko, Yuichiro Ogura, Hiroko Terasaki, Balamurali K. Ambati, Jeanette H. W. Leusen, Wallace Y. Langdon, Michael R. Clark, Bradley D. Gelfand, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Publications

Aberrant angiogenesis is implicated in diseases affecting nearly 10% of the world’s population. The most widely used anti-angiogenic drug is bevacizumab, a humanized IgG1 monoclonal antibody that targets human VEGFA. Although bevacizumab does not recognize mouse Vegfa, it inhibits angiogenesis in mice. Here we show bevacizumab suppressed angiogenesis in three mouse models not via Vegfa blockade but rather Fc-mediated signaling through FcγRI (CD64) and c-Cbl, impairing macrophage migration. Other approved humanized or human IgG1 antibodies without mouse targets (adalimumab, alemtuzumab, ofatumumab, omalizumab, palivizumab and tocilizumab), mouse IgG2a, and overexpression of human IgG1-Fc or mouse IgG2a-Fc, also inhibited angiogenesis in wild-type …

Antimetabolite Ttl-315 Selectively Kills Glucose-Deprived Cancer Cells And Enhances Responses To Cytotoxic Chemotherapy In Preclinical Models Of Cancer., James Duhadaway, George C Prendergast

Kimmel Cancer Center Faculty Papers

Maintaining thiol homeostasis is an imperative for cancer cell survival in the nutrient-deprived microenvironment of solid tumors. Despite this metabolic vulnerability, a selective approach has yet to be developed to disrupt thiol homeostasis in solid tumors for therapeutic purposes. In this study, we report the identification of 2-mercaptopropionyl glycine disulfide (TTL-315) as a novel antimetabolite that blocks cell survival in a manner conditional on glucose deprivation. In the presence of glucose, TTL-315 lacks cytotoxic effects in normal cells where it is detoxified by reduction to 2-mercaptopropionyl glycine, a compound with known clinical pharmacologic and safety profiles. In several rodent models …

Pathological Tau Promotes Neuronal Damage By Impairing Ribosomal Function And Decreasing Protein Synthesis, Shelby Meier, Michelle Bell, Danielle N. Lyons, Jennifer Rodriguez-Rivera, Alexandria Ingram, Sarah N. Fontaine, Elizabeth Mechas, Jing Chen, Benjamin Wolozin, Harry Levine Iii, Haining Zhu, Jose F. Abisambra

Sanders-Brown Center on Aging Faculty Publications

One of the most common symptoms of Alzheimer's disease (AD) and related tauopathies is memory loss. The exact mechanisms leading to memory loss in tauopathies are not yet known; however, decreased translation due to ribosomal dysfunction has been implicated as a part of this process. Here we use a proteomics approach that incorporates subcellular fractionation and coimmunoprecipitation of tau from human AD and non-demented control brains to identify novel interactions between tau and the endoplasmic reticulum (ER). We show that ribosomes associate more closely with tau in AD than with tau in control brains, and that this abnormal association leads …