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Transatrial Balloon-Expandable Valve Implantation For Severe Mitral Annular Calcification With Native Leaflet Sealing, Omar Saleh, Rishab Agarwal, Israa Saleh, Nicholas Valle, Joshua Dolsen, Raymond L. Benza, Deepak R. Talreja, Clinton D. Kemp, Matthew R. Summers, Christopher M. Sciortino 2026 Macon & Joan Brock Virginia Health Sciences at Old Dominion University

Transatrial Balloon-Expandable Valve Implantation For Severe Mitral Annular Calcification With Native Leaflet Sealing, Omar Saleh, Rishab Agarwal, Israa Saleh, Nicholas Valle, Joshua Dolsen, Raymond L. Benza, Deepak R. Talreja, Clinton D. Kemp, Matthew R. Summers, Christopher M. Sciortino

Department of Medicine Faculty Publications

Background: Severe mitral annular calcification (MAC) limits mitral intervention options. Transseptal valve-in-MAC (ViMAC) transcatheter mitral valve replacement (TMVR) risks neo-left ventricular outflow tract (neo-LVOT) obstruction and paravalvular leak, while surgical replacement requires extensive annular reconstruction.

Case Summary: We report 3 high-risk patients with severe MAC (computed tomography [CT]-based MAC scores 7-10) who underwent open transatrial valve-in-MAC TMVR via a balloon-expandable valve after CT-based simulation and multidisciplinary heart review identified increased risk of valve malapposition or neo-LVOT obstruction precluding transseptal approach. Native anterior mitral leaflet tissue was preserved, everted, and fixed to the bioprosthetic valve cuff, creating a seal to address …


Balloon Aortic Valvuloplasty As A Bridge Therapy In Acute Valve Syndrome: A Narrative Review Of Evidence Gaps And Future Directions, Omar Saleh, Omar Jafar, Nicholas Valle, Shirish Yasa, Saleh Mostafa, Raymond L. Benza, Deepak R. Talreja, Benjamin D. Peterson, Matthew R. Summers 2026 Macon & Joan Brock Virginia Health Sciences at Old Dominion University

Balloon Aortic Valvuloplasty As A Bridge Therapy In Acute Valve Syndrome: A Narrative Review Of Evidence Gaps And Future Directions, Omar Saleh, Omar Jafar, Nicholas Valle, Shirish Yasa, Saleh Mostafa, Raymond L. Benza, Deepak R. Talreja, Benjamin D. Peterson, Matthew R. Summers

Department of Medicine Faculty Publications

Acute valve syndrome (AVS) represents a high-acuity, decompensated presentation of severe aortic stenosis (AS), often manifesting as acute heart failure, cardiogenic shock, or cardiac arrest. Transcatheter aortic valve replacement (TAVR) remains the only durable therapy for severe AS in patients with prohibitive surgical risk, yet AVS patients may be too unstable for standard preprocedural planning. Balloon aortic valvuloplasty (BAV) has re-emerged as a bridge strategy that can provide rapid hemodynamic stabilization and permit subsequent valve replacement. Registry analyses report lower mortality in emergent TAVR compared with BAV, but these comparisons are confounded by procedural indication and unmatched AS severity. Smaller …


An Analysis Of Heart Failure Among Cancer Patients In The United States Between 1999 And 2020, Abes A. Bautista Neughebauer, Deepak Talreja, Apostolos Gaitanidis 2026 Macon & Joan Brock Virginia Health Sciences at Old Dominion University

An Analysis Of Heart Failure Among Cancer Patients In The United States Between 1999 And 2020, Abes A. Bautista Neughebauer, Deepak Talreja, Apostolos Gaitanidis

Department of Medicine Faculty Publications

Background: Cancer and heart failure (HF) are highly prevalent in the population and can co-exist, due to shared risk factors and an aging population. The HF-related mortality burden in cancer patients across in the United States (US) remains poorly understood. The goal of this study is to evaluate the patterns of HF-related deaths among cancer patients in the United States.

Methods: A retrospective analysis was performed using the Centers for Disease Control and Prevention (CDC) WONDER Multiple Cause of Death database between years 1999 and 2020. HF-related deaths were defined as death certificates listing HF as a contributing cause of …


Redo Tavr With Asymmetric Coronary Risk: Interpreting Borderline Ct Findings, Connor J. McKechnie, Nicolas J. Valle, Omar A. Saleh, Matthew R. Summers, Deepak R. Talreja 2026 Macon & Joan Brock Virginia Health Sciences at Old Dominion University

Redo Tavr With Asymmetric Coronary Risk: Interpreting Borderline Ct Findings, Connor J. Mckechnie, Nicolas J. Valle, Omar A. Saleh, Matthew R. Summers, Deepak R. Talreja

Department of Medicine Faculty Publications

Image(s)

Computed tomography (CT) and computational modeling (DASI) in redo transcatheter aortic valve replacement (TAVR) planning.

Case Summary

A 77-year-old woman presented with severe symptomatic aortic stenosis due to degeneration of a prior transcatheter valve. CT demonstrated leaflet calcification with borderline left-sided valve-to-coronary distance (3.27 mm). Geometric assessment suggested low right coronary obstruction risk, but higher left main risk. Computational modeling demonstrated adequate leaflet-coronary clearance (distance from displaced leaflet cusp to coronary ostium normalized to coronary diameter >0.7). Redo TAVR with a 26-mm Evolut FX was performed without leaflet modification and no coronary obstruction.

Take-Home Message

Borderline CT findings in …


Microfluidic Encapsulation Of Sorafenib-Loaded Zif-8 Nanoparticles In Ph-Responsive Alginate Microparticles For Oral Chemotherapy Of Hepatocellular Carcinoma, Mojdeh Mirshafiei, Zahra Mahmoudi, Mehdi Mehrpouya, Mahdi Mahmoudi, Masoud Rezaeian, Mona Navaei-Nigjeh, Zahra Katoli, Lobat Tayebi 2026 University of Tehran

Microfluidic Encapsulation Of Sorafenib-Loaded Zif-8 Nanoparticles In Ph-Responsive Alginate Microparticles For Oral Chemotherapy Of Hepatocellular Carcinoma, Mojdeh Mirshafiei, Zahra Mahmoudi, Mehdi Mehrpouya, Mahdi Mahmoudi, Masoud Rezaeian, Mona Navaei-Nigjeh, Zahra Katoli, Lobat Tayebi

Electrical & Computer Engineering Faculty Publications

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality. Sorafenib is the current first-line oral therapy; however, its therapeutic efficacy is limited by poor aqueous solubility, low bioavailability, and gastrointestinal instability. This study aimed to develop a pH-responsive nano-in-microparticle delivery system using a single-step droplet-based microfluidic process to protect sorafenib in the gastric environment and achieve controlled release for enhanced oral chemotherapy. Sorafenib-loaded ZIF-8 nanoparticles (SZ NPs) were synthesized and characterized by scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, Energy-dispersive X-ray (EDX) spectroscopy, and X-ray diffraction (XRD), exhibiting a mean diameter of about 72 nm and …


Failure Rates And Patient-Reported Outcomes Are Similar Across 5 Arthroscopic, Suprapectoral Biceps Tenodesis Fixation Techniques, Senah E. Stephens, Samantha M. Strohm, Rachael M. Shaughnessy, Katherine S. Worcester, Kevin F. Bonner 2026 Macon & Joan Brock Virginia Health Sciences at Old Dominion University

Failure Rates And Patient-Reported Outcomes Are Similar Across 5 Arthroscopic, Suprapectoral Biceps Tenodesis Fixation Techniques, Senah E. Stephens, Samantha M. Strohm, Rachael M. Shaughnessy, Katherine S. Worcester, Kevin F. Bonner

Department Surgery Faculty Publications

Purpose

To compare failure rates and patient-reported outcome measures (PROMs) across 5 arthroscopic, suprapectoral biceps tenodesis fixation techniques: tenodesis screw, tenodesis anchor, expanding tenodesis anchor, onlay with single all-suture anchor, and soft tissue tenodesis in the bicipital groove with suture.

Methods

This was a retrospective cohort study approved by the Institutional Review Board, including patients age 18 years or older who underwent arthroscopic, suprapectoral biceps tenodesis between 2014 and 2024 with a minimum of 6 months of clinical follow-up. Exclusion criteria included cervical pathology, chronic pain syndromes, revisions, and workers' compensation cases. Patients completed PROMs including pain Visual Analog Scale …


Microarray Analysis Of Human Abdominal Aortic Aneurysm With Emphasis On Cardiovascular Genes Revealed Differentially Expressed Genes, Song Lu, Li Ping Li, John V. White, Xiaoying Zhang, Ifeyinwa Nwaneshiudu, Adaobi Nwaneshiudu, Nectaria Ntaoula, John Gaughan, Dimitri S. Monos, Wan-Lu Lin, Charalambos C. Solomides, Emilia L. Oleszak, Chris D. Platsoucas 2026 Temple University

Microarray Analysis Of Human Abdominal Aortic Aneurysm With Emphasis On Cardiovascular Genes Revealed Differentially Expressed Genes, Song Lu, Li Ping Li, John V. White, Xiaoying Zhang, Ifeyinwa Nwaneshiudu, Adaobi Nwaneshiudu, Nectaria Ntaoula, John Gaughan, Dimitri S. Monos, Wan-Lu Lin, Charalambos C. Solomides, Emilia L. Oleszak, Chris D. Platsoucas

Biological Sciences Faculty Publications

Background/Aim: We examined gene expression profiles in abdominal aortic aneurysm (AAA) lesions vs. normal aortas by cDNA microarray and real-time quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR).

Materials and Methods: Phosphorus (32P)-labeled cDNA from AAA specimens (mean AAA size 6.65 cm) and normal aortas were hybridized with a 588-gene microarray primarily of the cardiovascular system. The results were validated by qRT-PCR.

Results: A total of 35 out of the 588 genes were differentially expressed, with either log2 ratio of AAAs/controls ≥1 (upregulated; 20 genes) or ≤−1 (downregulated; 15 genes) in AAA lesions vs. normal aorta, and 25 of these were significantly …


Comparative Analysis Of Left Ventricular Sympathetic Axons In Shr And Wky Rats, Parker R. Tyson 2026 University of Central Florida

Comparative Analysis Of Left Ventricular Sympathetic Axons In Shr And Wky Rats, Parker R. Tyson

Honors Undergraduate Theses

Hypertension is a leading cause of cardiovascular morbidity and mortality and is strongly associated with dysregulation of the sympathetic nervous system, which plays a central role in controlling heart rate, vascular tone, and blood pressure. Although increased sympathetic activity has been widely documented in hypertensive disease, the precise structural organization of sympathetic innervation within the hypertensive heart remains incompletely characterized. This study investigates whether chronic hypertension is associated with structural remodeling of sympathetic axons in the left ventricle by comparing autonomic innervation patterns between spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Hearts were collected following transcardial perfusion …


Cervicovaginal Lavage Fluid Iron And Manganese Levels In Women With And Without Vaginitis, Barbara Kozma, David Ratonyi, Bence Kozma, Peter Takacs, Attila G. Sipos 2026 University of Debrecen

Cervicovaginal Lavage Fluid Iron And Manganese Levels In Women With And Without Vaginitis, Barbara Kozma, David Ratonyi, Bence Kozma, Peter Takacs, Attila G. Sipos

Department of Obstetrics & Gynecology Faculty Publications

Transition metals such as iron and manganese are critical for cellular metabolism, redox balance, and immune function, and they also influence host–pathogen interactions. Vaginitis is characterized by mucosal inflammation that may alter local trace-element homeostasis. We hypothesize that inflammatory conditions such as vaginitis may be associated with altered cervicovaginal iron and manganese levels. We performed a prospective, single-center cohort study at the University of Debrecen (Hungary) between April 2023 and April 2024, enrolling 80 women ≥ 18 years with vulvovaginal complaints. Participants were assessed at baseline and at weeks 4, 8, and 12 with clinical evaluation and cervicovaginal lavage (CVL) …


Assessment Of Major Adverse Cardiovascular Event Across Diverse Racial Groups Of Psoriasis Patients On Biologic Therapy: A Retrospective Cohort Study, Chunghwan Ro, Ana Ormaza Vera, Waleed Adawi, Clinton W. Enos 2026 Macon & Joan Brock Virginia Health Sciences at Old Dominion University

Assessment Of Major Adverse Cardiovascular Event Across Diverse Racial Groups Of Psoriasis Patients On Biologic Therapy: A Retrospective Cohort Study, Chunghwan Ro, Ana Ormaza Vera, Waleed Adawi, Clinton W. Enos

Department Dermatology Faculty Publications

Psoriasis is associated with an increased risk of major adverse cardiovascular events (MACE), and biologic therapy may reduce this risk by targeting systemic inflammation. However, limited data exist on whether long term MACE risk differs by biologic class or across racial groups. We conducted a retrospective cohort study to assess the risk of primary MACE in psoriasis patients receiving biological therapies, stratified by biological class, compared with biologic-naïve psoriasis patients. Whether MACE risk among biologic-treated patients varied by race was further examined. After 1:1 propensity score matching, 36 330 biologic-treated patients were compared with 36 330 non-biologic-treated patients. Incident MACE …


Homoplasy Of Maxillary Orthognathism In Derived Homo, Jared Jordan 2026 University of Central Florida

Homoplasy Of Maxillary Orthognathism In Derived Homo, Jared Jordan

Graduate Studies Theses and Dissertations 2026

The evolution of the orthognathic condition in the genus Homo represents a monumental transition toward the facial morphology of modern humans from that of earlier hominins, but the phylogenetic positioning of this transformation remains poorly understood. This study investigated temporal trends in maxillary and mandibular prognathism in the genus Homo, and whether maxillary and mandibular shortening in East Asian H. erectus and later East Asian Middle Pleistocene Homo (e.g., Homo longi) represent independent derivations of orthognathic morphology, thereby making orthognathism a homoplasy in the genus Homo. Using a sample of roughly 109 cranial and mandibular specimens spanning …


The Effects Of Abused Drugs On Ferroptosis Pathways: Potential Therapeutic Targets For Substance Use Disorders, Tamara Bouchard, Brooke Russell, Liam Liyang Guo, Tina Nguyen, Yan Cheng, Yan Y. Sanders, Ming-Lei Guo 2026 Macon & Joan Brock Virginia Health Sciences at Old Dominion University

The Effects Of Abused Drugs On Ferroptosis Pathways: Potential Therapeutic Targets For Substance Use Disorders, Tamara Bouchard, Brooke Russell, Liam Liyang Guo, Tina Nguyen, Yan Cheng, Yan Y. Sanders, Ming-Lei Guo

Department of Biomedical and Translational Sciences Faculty Publications

Substance use disorders (SUDs) remain major public health concerns worldwide, particularly in developed countries. SUDs are characterized by persistent neuroinflammation and synaptic dysfunction in the brain. Despite decades of extensive investigation, the detailed mechanisms underlying SUDs remain elusive. Ferroptosis is a highly regulated cell death process deeply affected by iron metabolism, lipid peroxidation, reactive oxygen species (ROS) production, and antioxidant systems. It has been implicated in multiple neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and ischemic stroke. Recently, emerging evidence has highlighted the role of ferroptosis in drug-induced pathological changes. Various types of abused substances including alcohol, cocaine, …


Senescent Fibroblasts In Aging And Pulmonary Fibrosis, Sara B. Palega, Aiwei Y. Borengasser, Yan Y. Sanders 2026 Macon & Joan Brock Virginia Health Sciences at Old Dominion University

Senescent Fibroblasts In Aging And Pulmonary Fibrosis, Sara B. Palega, Aiwei Y. Borengasser, Yan Y. Sanders

Microbiology & Molecular Cell Biology Faculty Publications

Aging is a major risk factor for many chronic lung diseases, including Idiopathic Pulmonary Fibrosis (IPF), a fatal and incurable disease characterized by progressive fibrotic remodeling. Age-associated structural alterations, impaired regenerative capacity, and dysregulated cellular signaling collectively create a pro-fibrotic microenvironment. A central driver of this pathological shift is the accumulation of senescent cells, which undergo irreversible growth arrest and develop a robust pro-inflammatory senescence-associated secretory phenotype (SASP). Emerging evidence identifies senescent lung fibroblasts as critical mediators of IPF pathogenesis. These cells promote excessive extracellular matrix deposition, myofibroblast differentiation, and tissue stiffening, while simultaneously impairing epithelial regeneration. Together, these effects …


Single-Cell Transciptomic Analysis Reveals Age-Related Remodeling Of Brain Endothelial Cells, Hai Duc Nguyen, Summer Siddiqui, Diana G. Bohannon, Robert V. Blair, Hong-Wen Deng, Alexandre Prat, Woong-Ki Kim 2026 Tulane University

Single-Cell Transciptomic Analysis Reveals Age-Related Remodeling Of Brain Endothelial Cells, Hai Duc Nguyen, Summer Siddiqui, Diana G. Bohannon, Robert V. Blair, Hong-Wen Deng, Alexandre Prat, Woong-Ki Kim

Microbiology & Molecular Cell Biology Faculty Publications

Blood–brain barrier (BBB) integrity naturally declines with age. Brain endothelial cells (ECs) and pericytes (PCs) form the BBB, and aging impairs tight junctions, likely via altered PC-to-EC signaling. However, the molecular mechanisms underlying this impairment remain unclear. Using single-cell RNA sequencing, we profiled 68,316 brain ECs expressing 15,564 genes from young and old mice. Unsupervised clustering and annotation revealed five distinct EC subtypes—Capillary EC1, Capillary EC2, Arterial EC, Venous EC1, and Venous EC2—defined by marker genes Mfsd2a, Plvap, Bmx, Nr2f2, and Vcam1, respectively. Aging shifted EC subtype distribution, with reduced Capillary EC1 (45% vs. 57%) and increased Arterial …


Chromnet: A Multi-Task Learning Framework For Cross-Cell Type Prediction Of 3d Chromatin Interactions Using Epigenetic Signals, Bin Wang, Shaokai Wang, Liqing Ding, Hongdong Li, Yaohang Li, Jianxin Wang 2026 Central South University

Chromnet: A Multi-Task Learning Framework For Cross-Cell Type Prediction Of 3d Chromatin Interactions Using Epigenetic Signals, Bin Wang, Shaokai Wang, Liqing Ding, Hongdong Li, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

The 3D organization of chromatin plays a fundamental role in gene regulation, cellular function, and disease mechanisms. However, current experimental techniques, such as Hi-C, remain costly and labor-intensive, limiting their application in large-scale and disease-related studies. To address this challenge, ChromNet is presented, a multi-task learning framework that integrates epigenetic signals across diverse cell types to enable high-precision prediction of chromatin architecture. By incorporating noise perturbation and auxiliary classification tasks, ChromNet improves the identification of topologically associating domains (TADs) and cell-type-specific chromatin structures, demonstrating superior generalization performance. Notably, ChromNet accurately predicts chromatin interactions in acute myeloid leukemia (AML) samples by …


Near Real-Time Adaptive Isotropic And Anisotropic Image-To-Mesh Conversion For Cerebral Aneurysm Simulations, Kevin Garner, Chander Sadasivan, Nikos Chrisochoides 2026 Old Dominion University

Near Real-Time Adaptive Isotropic And Anisotropic Image-To-Mesh Conversion For Cerebral Aneurysm Simulations, Kevin Garner, Chander Sadasivan, Nikos Chrisochoides

Computer Science Faculty Publications

This paper presents two performance optimization techniques for a mesh adaptation method that is designed to help streamline the discretization of complex vascular geometries within the numerical modeling process. This method is integrated into a pipeline with an image-to-mesh conversion tool to generate adaptive anisotropic meshes from segmented medical images. The pipeline is shown to satisfy quality, fidelity, smoothness, and robustness requirements while providing near real-time performance for medical image-to-mesh conversion. Tested with two brain aneurysm cases and utilizing up to 96 CPU cores within a single, multicore node on Purdue University’s Anvil supercomputer, the parallel adaptive anisotropic meshing method …


Sage: Spatially Aware Gene Selection And Dual-View Embedding Fusion For Domain Identification In Spatial Transcriptomics, Yi He, Yunpei Xu, Liqing Ding, Hong-Dong Li, Yaohang Li, Shaokai Wang 2026 Central South University

Sage: Spatially Aware Gene Selection And Dual-View Embedding Fusion For Domain Identification In Spatial Transcriptomics, Yi He, Yunpei Xu, Liqing Ding, Hong-Dong Li, Yaohang Li, Shaokai Wang

Computer Science Faculty Publications

Despite enabling high-resolution mapping of gene expression within tissues, spatial transcriptomics (ST) still faces challenges in accurately segmenting spatial domains due to complex tissue architecture and limitations of current methods. Most approaches rely on local spatial priors, lack gene-level interpretability, and fall short in capturing structure-discriminative genes or long-range functional relationships, limiting their ability to resolve biologically meaningful architectures. We present Spatially Aware Gene selection and dual-view Embedding fusion (SAGE), a unified and reproducible framework for domain identification in spatial transcriptomics that combines topic-driven gene selection with dual-view embedding fusion to address these gaps. SAGE integrates non-negative matrix factorization (NMF)-based …


The Effect Of Neoadjuvant Chemoradiotherapy On Perioperative Outcomes In Rectal Cancer Patients Following Stoma Reversal-A Retrospective Cohort Analysis, Mary Junak, Rosemarie Turk, Mohammad Afaque Alam, Eli Thompson, David Schaub, Joseph Gunderson, Anesu S. Masango, Srikar Kollipara, Andrea Moreno, Daniom Tecle, Valentine N. Nfonsam 2025 University of Wisconsin-Madison, Madison, WI

The Effect Of Neoadjuvant Chemoradiotherapy On Perioperative Outcomes In Rectal Cancer Patients Following Stoma Reversal-A Retrospective Cohort Analysis, Mary Junak, Rosemarie Turk, Mohammad Afaque Alam, Eli Thompson, David Schaub, Joseph Gunderson, Anesu S. Masango, Srikar Kollipara, Andrea Moreno, Daniom Tecle, Valentine N. Nfonsam

School of Medicine Faculty Publications

BACKGROUND: Anastomotic leak after reversal of an ostomy is a significant complication in rectal cancer patients. The effects of neoadjuvant chemoradiotherapy (NCRT) on outcomes following stoma reversal are not well established. The aim of our study was to evaluate the effect of NCRT on outcomes in rectal cancer patients following stoma reversal. METHODS: We performed a [2005-2012] retrospective cohort analysis of the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP), including adult (≥18 years) rectal cancer patients who had elective stoma reversal. Patients were stratified into those who received NCRT and those who did not. Primary outcomes were anastomotic …


Treatment Patterns For Genitourinary Syndrome Of Menopause: A Trinetx Analysis, Anushka Ghosh, Maria D'Amico, Yash B. Shah, Whitney R. Smith, Mihir S. Shah, Costas D. Lallas, Alana M. Murphy 2025 Thomas Jefferson University

Treatment Patterns For Genitourinary Syndrome Of Menopause: A Trinetx Analysis, Anushka Ghosh, Maria D'Amico, Yash B. Shah, Whitney R. Smith, Mihir S. Shah, Costas D. Lallas, Alana M. Murphy

Department of Urology Faculty Papers

BACKGROUND: Genitourinary syndrome of menopause (GSM) is a highly prevalent, underdiagnosed condition that can significantly impair quality of life (QoL). This study evaluates real-world treatment trends for GSM to better understand current management practices and highlight ongoing gaps in care. The background is in a different font than the rest of the abstract.

METHODS: We queried the TriNetX database for patients with a diagnosis of postmenopausal atrophic vaginitis (ICD N95.2) and treatment information from 2004-2024. A combination of RxNorm and International Classification of Diseases-10 (ICD) codes was used to classify disease and treatment type, including topical estrogen (RxNorm 4083, 4099), …


Isg15 Dysregulates Endoplasmic Reticulum-Mitochondrial Contacts And Calcium Homeostasis In Ataxia Telangiectasia, Oygul Mirzalieva, Ryan E. Reed, Arthur L. Haas, Meredith A. Juncker, Patrick Logarbo, Jennifer M. Klein, David Worthylake, Shyamal D. Desai 2025 LSU Health Sciences Center - New Orleans

Isg15 Dysregulates Endoplasmic Reticulum-Mitochondrial Contacts And Calcium Homeostasis In Ataxia Telangiectasia, Oygul Mirzalieva, Ryan E. Reed, Arthur L. Haas, Meredith A. Juncker, Patrick Logarbo, Jennifer M. Klein, David Worthylake, Shyamal D. Desai

School of Graduate Studies Faculty Publications

Dysregulation of endoplasmic reticulum and mitochondrial (ER:Mit) contacts and mitochondrial calcium (mitCa2+) homeostasis are found in several neurodegenerative disorders, including Ataxia Telangiectasia (A-T). However, the cellular basis of these defects remains unclear. Previously, we demonstrated that the aberrantly elevated Interferon-Stimulated Gene 15 (ISG15) pathway inhibits protein polyubiquitylation, its dependent protein turnover, and mitophagy pathways in A-T. Literature indicates that silencing of mitochondrial ubiquitin ligase 1 (MUL1) stabilizes mitofusin2 (MFN2) and attenuates mitCa2+ uptake from ER to Mit (mitCa2+influx) in primary neurons. We have replicated these findings in apparently healthy fibroblasts. We hypothesized that elevated ISG15 may inhibit ubiquitin-dependent MUL1-mediated degradation …


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