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Thomas Jefferson University

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

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Educational Case: An Invasive Salivary Gland Tumor: Adenoid Cystic Carcinoma Of The Parotid Gland, Jaime Eberle-Singh, Madalina Tuluc, Joanna Sue Yee Chan Nov 2023

Educational Case: An Invasive Salivary Gland Tumor: Adenoid Cystic Carcinoma Of The Parotid Gland, Jaime Eberle-Singh, Madalina Tuluc, Joanna Sue Yee Chan

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.


Increase In Hnrnpa1 Expression Suffices To Kill Motor Neurons In Transgenic Rats, Xionghao Liu, Tingting Zhang, Qinxue Wu, Cao Huang, Xu-Gang Xia, Hongxia Zhou, Bo Huang Nov 2023

Increase In Hnrnpa1 Expression Suffices To Kill Motor Neurons In Transgenic Rats, Xionghao Liu, Tingting Zhang, Qinxue Wu, Cao Huang, Xu-Gang Xia, Hongxia Zhou, Bo Huang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

A dominant mutation in hnRNPA1 causes amyotrophic lateral sclerosis (ALS), but it is not known whether this mutation leads to motor neuron death through increased or decreased function. To elucidate the relationship between pathogenic hnRNPA1 mutation and its native function, we created novel transgenic rats that overexpressed wildtype rat hnRNPA1 exclusively in motor neurons. This targeted expression of wildtype hnRNPA1 caused severe motor neuron loss and subsequent denervation muscle atrophy in transgenic rats that recapitulated the characteristics of ALS. These findings demonstrate that the augmentation of hnRNPA1 expression suffices to trigger motor neuron degeneration and the manifestation of ALS-like phenotypes. …


Immune Responses Induced At One Hour Post Cataract Surgery Wounding Of The Chick Lens, Jodirae Dedreu, Morgan Basta, Janice Walker, Sue Menko Nov 2023

Immune Responses Induced At One Hour Post Cataract Surgery Wounding Of The Chick Lens, Jodirae Dedreu, Morgan Basta, Janice Walker, Sue Menko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

While the lens is an avascular tissue with an immune-privileged status, studies have now revealed that there are immune responses specifically linked to the lens. The response to lens injury, such as following cataract surgery, has been shown to involve the activation of the resident immune cell population of the lens and the induction of immunomodulatory factors by the wounded epithelium. However, there has been limited investigation into the immediate response of the lens to wounding, particularly those induced factors that are intrinsic to the lens and its associated resident immune cells. Using an established chick embryo ex vivo cataract …


Identification Of Dual Strn-Ntrk2 Rearrangements In A High Grade Sarcoma, With Good Clinical Response To First-Line Larotrectinib Therapy, Ruihe Lin, Atrayee Basu Mallick, Zi-Xuan Wang, Phd, Scot Andrew Brown, Bo Lu, Md, Wei Jiang Oct 2023

Identification Of Dual Strn-Ntrk2 Rearrangements In A High Grade Sarcoma, With Good Clinical Response To First-Line Larotrectinib Therapy, Ruihe Lin, Atrayee Basu Mallick, Zi-Xuan Wang, Phd, Scot Andrew Brown, Bo Lu, Md, Wei Jiang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Among the three NTRK genes, NTRK2 possesses a tremendous structural complexity and involves tumorigenesis of several types of tumors. To date, only STRN and RBPMS are identified in the fusion with NTRK2 in adult soft tissue tumors. More recently, the highly selective Trk tyrosine kinases inhibitors, including larotrectinib and entrectinib, have shown significant efficacy for treating tumors harboring NTRK fusions and were approved by FDA.

CASE PRESENTATION: We report a case of sarcoma in a 35-year-old female harboring two STRN-NTRK2 gene fusions, with a good clinical response to first-line larotrectinib treatment. Core biopsy of the 16.5 cm gluteal mass …


Global Impact Of Proteoglycan Science On Human Diseases, Christopher Xie, Liliana Schaefer, Renato V. Iozzo Oct 2023

Global Impact Of Proteoglycan Science On Human Diseases, Christopher Xie, Liliana Schaefer, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

In this comprehensive review, we will dissect the impact of research on proteoglycans focusing on recent developments involved in their synthesis, degradation, and interactions, while critically assessing their usefulness in various biological processes. The emerging roles of proteoglycans in global infections, specifically the SARS-CoV-2 pandemic, and their rising functions in regenerative medicine and biomaterial science have significantly affected our current view of proteoglycans and related compounds. The roles of proteoglycans in cancer biology and their potential use as a next-generation protein-based adjuvant therapy to combat cancer is also emerging as a constructive and potentially beneficial therapeutic strategy. We will discuss …


Is Β-Lactamase Testing Acceptably Accurate For Predicting Haemophilus Influenzae Susceptibility To Β-Lactams? Epidemiological Data From Philadelphia, Usa, 2017–2023, Arianna B. Morton, Chairut Vareechon, Matthew A. Pettengill Sep 2023

Is Β-Lactamase Testing Acceptably Accurate For Predicting Haemophilus Influenzae Susceptibility To Β-Lactams? Epidemiological Data From Philadelphia, Usa, 2017–2023, Arianna B. Morton, Chairut Vareechon, Matthew A. Pettengill

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.


Neurotoxicity And Outcomes From Developmental Lead Exposure: Persistent Or Permanent?, Jay S. Schneider Aug 2023

Neurotoxicity And Outcomes From Developmental Lead Exposure: Persistent Or Permanent?, Jay S. Schneider

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background:

Childhood lead poisoning remains an important public health issue in the United States, as well as elsewhere in the world. Although primary prevention is a major goal and it is critically important to keep children from getting poisoned, it is also important to explore ways to reduce the neurotoxic effects of lead in those children already poisoned. Whether lead-induced neurotoxicity and its related adverse outcomes are viewed as “permanent” or “persistent” may influence the way in which potential remediation efforts are considered for improving outcomes from childhood lead poisoning.

Objectives:

The objective of this commentary was to discuss the …


Primary Adrenal Angiosarcoma: A Case Report And Review Of The Literature, Zunaira Naeem, Joon Yau Leong, Arianna Morton, Alaa Hrizat, Eric Shiffrin, Andrew Gomella, Peter Mccue, Mark Mann, Li Li Jul 2023

Primary Adrenal Angiosarcoma: A Case Report And Review Of The Literature, Zunaira Naeem, Joon Yau Leong, Arianna Morton, Alaa Hrizat, Eric Shiffrin, Andrew Gomella, Peter Mccue, Mark Mann, Li Li

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Primary adrenal angiosarcoma is an extremely rare malignant tumor with challenging diagnosis. A 66-year-old woman had a 4.3 cm right adrenal mass suspicious for adrenal cortical carcinoma. Pathological examination demonstrated a hemorrhagic adrenal cyst with numerous irregularly shaped anastomosing vascular channels lined by atypical endothelial cells that had frequent atypical mitotic figures (12/10 HPF, Ki67 10%). The tumor cells were positive for CD31, ERG, and FLI-1, but negative for adrenal and other tumor lineage markers by immunohistochemistry. NGS fusion gene testing ruled out epithelioid hemangioendothelioma. Accurate diagnosis and differential inclusion are important for appropriate treatment of this rare tumor.


Ifit2 Restricts Murine Coronavirus Spread To The Spinal Cord White Matter And Its Associated Myelin Pathology, Madhav Sharma, Debanjana Chakravarty, Afaq Hussain, Ajay Zalavadia, Amy Burrows, Patricia Rayman, Nikhil Sharma, Lawrence C. Kenyon, Cornelia Bergmann, Ganes C. Sen, Jayasri Das Sarma Jul 2023

Ifit2 Restricts Murine Coronavirus Spread To The Spinal Cord White Matter And Its Associated Myelin Pathology, Madhav Sharma, Debanjana Chakravarty, Afaq Hussain, Ajay Zalavadia, Amy Burrows, Patricia Rayman, Nikhil Sharma, Lawrence C. Kenyon, Cornelia Bergmann, Ganes C. Sen, Jayasri Das Sarma

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Interferon-induced protein with tetratricopeptide repeats 2, Ifit2, is critical in restricting neurotropic murine-β-coronavirus, RSA59 infection. RSA59 intracranial injection of Ifit2-deficient (-/-) compared to wild-type (WT) mice results in impaired acute microglial activation, reduced CX3CR1 expression, limited migration of peripheral lymphocytes into the brain, and impaired virus control followed by severe morbidity and mortality. While the protective role of Ifit2 is established for acute viral encephalitis, less is known about its influence during the chronic demyelinating phase of RSA59 infection. To understand this, RSA59 infected Ifit2-/- and Ifit2+/+ (WT) were observed for neuropathological outcomes at day 5 (acute phase) and 30 …


Editorial: Targeting Dna Damage Response To Enhance Antitumor Innate Immunity In Radiotherapy, Victoria Valvo, Emanuele Vitale, Marco Tigano, Rachel Evans, Meredith A. Morgan, Qiang Zhang Jul 2023

Editorial: Targeting Dna Damage Response To Enhance Antitumor Innate Immunity In Radiotherapy, Victoria Valvo, Emanuele Vitale, Marco Tigano, Rachel Evans, Meredith A. Morgan, Qiang Zhang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.


The Association Between Higher Expression Of Talin-1 And The Reduced Survival Rate In Ovarian Serous Carcinoma Patients, Mina Sharbatoghli, Leili Saeednejad Zanjani, Fahimeh Fattahi, Elham Kalantari, Zohre Habibi Shams, Mahshid Panahi, Medhi Totonchi, Mohsen Asadi-Lari, Zahra Madjd Jul 2023

The Association Between Higher Expression Of Talin-1 And The Reduced Survival Rate In Ovarian Serous Carcinoma Patients, Mina Sharbatoghli, Leili Saeednejad Zanjani, Fahimeh Fattahi, Elham Kalantari, Zohre Habibi Shams, Mahshid Panahi, Medhi Totonchi, Mohsen Asadi-Lari, Zahra Madjd

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background & Objective: Talin-1 is a constituent of the multiprotein adhesion complexes that play main role in the formation of tumors and migration in different types of malignancies. The present study aimed to assess expression and prognostic significance of the talin-1 protein in ovarian serous carcinoma (OSC) patients.

Methods: The expression of talin-1 in mRNA and its protein levels were investigated for ovarian cancer (OC) by using bioinformatics tools, including Gene Expression Profiling Interactive Analysis 2 (GEPIA2), Gene Expression Database of Normal and Tumor Tissue 2 (GENT2), and The University of ALabama at Birmingham CANcer data analysis Portal (UALCAN) databases. …


Using Individual Collector Blood Culture Volume Data To Improve Fill Volume, Richard S. Kirby, Jenna M. Meloni, Karishma B. Naik, Matthew D. Minnear, Matthew A. Pettengill Jul 2023

Using Individual Collector Blood Culture Volume Data To Improve Fill Volume, Richard S. Kirby, Jenna M. Meloni, Karishma B. Naik, Matthew D. Minnear, Matthew A. Pettengill

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.


Gm1 Ganglioside As A Disease-Modifying Therapeutic For Parkinson’S Disease: A Multi-Functional Glycosphingolipid That Targets Multiple Parkinson’S Disease-Relevant Pathogenic Mechanisms, Jay S. Schneider May 2023

Gm1 Ganglioside As A Disease-Modifying Therapeutic For Parkinson’S Disease: A Multi-Functional Glycosphingolipid That Targets Multiple Parkinson’S Disease-Relevant Pathogenic Mechanisms, Jay S. Schneider

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Parkinson’s disease (PD) is a progressive neurodegenerative disorder affecting millions of patients worldwide. Many therapeutics are available for treating PD symptoms but there is no disease-modifying therapeutic that has been unequivocally shown to slow or stop the progression of the disease. There are several factors contributing to the failure of many putative disease-modifying agents in clinical trials and these include the choice of patients and clinical trial designs for disease modification trials. Perhaps more important, however, is the choice of therapeutic, which for the most part, has not taken into account the multiple and complex pathogenic mechanisms and processes involved …


Species Delineation And Comparative Genomics Within The Campylobacter Ureolyticus Complex, Joel J Maki, Mondraya Howard, Sara Connelly, Matthew Pettengill, Dwight J Hardy, Andrew Cameron May 2023

Species Delineation And Comparative Genomics Within The Campylobacter Ureolyticus Complex, Joel J Maki, Mondraya Howard, Sara Connelly, Matthew Pettengill, Dwight J Hardy, Andrew Cameron

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Campylobacter ureolyticus is an emerging pathogen increasingly appreciated as a common cause of gastroenteritis and extra-intestinal infections in humans. Outside the setting of gastroenteritis, little work has been done to describe the genomic content and relatedness of the species, especially regarding clinical isolates. We reviewed the epidemiology of clinical C. ureolyticus cultured by our institution over the past 10 years. Fifty-one unique C. ureolyticus isolates were identified between January 2010 and August 2022, mostly originating from abscesses and blood cultures. To clarify the taxonomic relationships between isolates and to attribute specific genes with different clinical manifestations, we sequenced 19 available …


Zinc Treatment Reverses And Anti-Zn-Regulated Mirs Suppress Esophageal Carcinomas In Vivo, Louise Fong, Kay Huebner, Ruiyan Jing, Karl Smalley, Christopher R Brydges, Oliver Fiehn, John Farber, Carlo M Croce May 2023

Zinc Treatment Reverses And Anti-Zn-Regulated Mirs Suppress Esophageal Carcinomas In Vivo, Louise Fong, Kay Huebner, Ruiyan Jing, Karl Smalley, Christopher R Brydges, Oliver Fiehn, John Farber, Carlo M Croce

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Esophageal squamous cell carcinoma (ESCC) is a deadly disease with few prevention or treatment options. ESCC development in humans and rodents is associated with Zn deficiency (ZD), inflammation, and overexpression of oncogenic microRNAs: miR-31 and miR-21. In a ZD-promoted ESCC rat model with upregulation of these miRs, systemic antimiR-31 suppresses the miR-31-EGLN3/STK40-NF-κB-controlled inflammatory pathway and ESCC. In this model, systemic delivery of Zn-regulated antimiR-31, followed by antimiR-21, restored expression of tumor-suppressor proteins targeted by these specific miRs: STK40/EGLN3 (miR-31), PDCD4 (miR-21), suppressing inflammation, promoting apoptosis, and inhibiting ESCC development. Moreover, ESCC-bearing Zn-deficient (ZD) rats receiving Zn medication showed a 47% …


Sexual Dimorphism In Bidirectional Sr-Mitochondria Crosstalk In Ventricular Cardiomyocytes, Richard T Clements, Radmila Terentyeva, Shanna Hamilton, Paul M L Janssen, Karim Roder, Benjamin Y Martin, Fruzsina Perger, Timothy G Schneider, Zuzana Nichtova, Anindhya S Das, Roland Veress, Beth S Lee, Do-Gyoon Kim, Gideon Koren, Matthew S Stratton, György Csordás, Federica Accornero, Andriy E Belevych, Sandor Gyorke, Dmitry Terentyev May 2023

Sexual Dimorphism In Bidirectional Sr-Mitochondria Crosstalk In Ventricular Cardiomyocytes, Richard T Clements, Radmila Terentyeva, Shanna Hamilton, Paul M L Janssen, Karim Roder, Benjamin Y Martin, Fruzsina Perger, Timothy G Schneider, Zuzana Nichtova, Anindhya S Das, Roland Veress, Beth S Lee, Do-Gyoon Kim, Gideon Koren, Matthew S Stratton, György Csordás, Federica Accornero, Andriy E Belevych, Sandor Gyorke, Dmitry Terentyev

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Calcium transfer into the mitochondrial matrix during sarcoplasmic reticulum (SR) Ca2+ release is essential to boost energy production in ventricular cardiomyocytes (VCMs) and match increased metabolic demand. Mitochondria from female hearts exhibit lower mito-[Ca2+] and produce less reactive oxygen species (ROS) compared to males, without change in respiration capacity. We hypothesized that in female VCMs, more efficient electron transport chain (ETC) organization into supercomplexes offsets the deficit in mito-Ca2+ accumulation, thereby reducing ROS production and stress-induced intracellular Ca2+ mishandling. Experiments using mitochondria-targeted biosensors confirmed lower mito-ROS and mito-[Ca2+] in female rat VCMs challenged …


Micu1 Occludes The Mitochondrial Calcium Uniporter In Divalent-Free Conditions, Macarena Rodríguez-Prados, Elena Berezhnaya, Maria Teresa Castromonte, Sergio L. Menezes-Filho, Melanie Paillard, György Hajnóczky May 2023

Micu1 Occludes The Mitochondrial Calcium Uniporter In Divalent-Free Conditions, Macarena Rodríguez-Prados, Elena Berezhnaya, Maria Teresa Castromonte, Sergio L. Menezes-Filho, Melanie Paillard, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mitochondrial Ca2+ uptake is mediated by the mitochondrial uniporter complex (mtCU) that includes a tetramer of the pore-forming subunit, MCU, a scaffold protein, EMRE, and the EF-hand regulatory subunit, MICU1 either homodimerized or heterodimerized with MICU2/3. MICU1 has been proposed to regulate Ca2+ uptake via the mtCU by physically occluding the pore and preventing Ca2+ flux at resting cytoplasmic [Ca2+] (free calcium concentration) and to increase Ca2+ flux at high [Ca2+] due to cooperative activation of MICUs EF-hands. However, mtCU and MICU1 functioning when its EF-hands are unoccupied by Ca2+ is poorly studied due to technical limitations. To overcome this …


Educational Case: Ovarian Neoplasms: A Series Of Educational Cases To Review Malignancies Of Epithelial, Stromal, And Germ Cell Origin, Jordyn B. Tumas, Joanna Chan Apr 2023

Educational Case: Ovarian Neoplasms: A Series Of Educational Cases To Review Malignancies Of Epithelial, Stromal, And Germ Cell Origin, Jordyn B. Tumas, Joanna Chan

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.


Corneal Injury Is Associated With Stromal And Vascular Alterations Within Cranial Dura Mater, Olga V. Glinskii, Vladislav V. Glinsky, Leike Xie, Filiz Bunyak, Vladimir V. Glinskii, Sunilima Sinha, Suneel Gupta, Renato V. Iozzo, Rajiv R. Mohan Apr 2023

Corneal Injury Is Associated With Stromal And Vascular Alterations Within Cranial Dura Mater, Olga V. Glinskii, Vladislav V. Glinsky, Leike Xie, Filiz Bunyak, Vladimir V. Glinskii, Sunilima Sinha, Suneel Gupta, Renato V. Iozzo, Rajiv R. Mohan

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The cornea and cranial dura mater share sensory innervation. This link raises the possibility that pathological impulses mediated by corneal injury may be transmitted to the cranial dura, trigger dural perivascular/connective tissue nociceptor responses, and induce vascular and stromal alterations affecting dura mater blood and lymphatic vessel functionality. In this study, using a mouse model, we demonstrate for the first time that two weeks after the initial insult, alkaline injury to the cornea leads to remote pathological changes within the coronal suture area of the dura mater. Specifically, we detected significant pro-fibrotic changes in the dural stroma, as well as …


How Influential Are Medical School Curriculum And Other Medical School Characteristics In Students’ Selecting Pathology As A Specialty?, Cindy B. Mccloskey, Mark Brissette, John Michael Childs, Amanda Lofgreen, Kristen Johnson, Melissa R. George, Ashley M. Holloman, Bronwyn Bryant, Mary P. Berg, Lisa Ross Dixon, Julie Katz Karp, Barbara E.C. Knollmann-Ritschel, Victor Gerardo Prieto, Charles F. Timmons, Robert D. Hoffman Apr 2023

How Influential Are Medical School Curriculum And Other Medical School Characteristics In Students’ Selecting Pathology As A Specialty?, Cindy B. Mccloskey, Mark Brissette, John Michael Childs, Amanda Lofgreen, Kristen Johnson, Melissa R. George, Ashley M. Holloman, Bronwyn Bryant, Mary P. Berg, Lisa Ross Dixon, Julie Katz Karp, Barbara E.C. Knollmann-Ritschel, Victor Gerardo Prieto, Charles F. Timmons, Robert D. Hoffman

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

There has been a significant decline in the number of United States allopathic medical students matching to pathology residency programs. Data acquired from the American Association of Medical Colleges (AAMC) show sustained variation in the medical school production of students who go on to pathology residency. When divided into groups based on the medical school's historical volume of graduates entering pathology, the schools in groups labeled Group 1 and Group 2 produced significantly higher and lower proportions of pathology residents, respectively. This study aimed to identify what medical school curriculum elements and other medical school characteristics might explain the differences …


Experiential Exposure As The Key To Recruiting Medical Students Into Pathology, Ashley M. Holloman, Mary P. Berg, Bronwyn Bryant, Lisa Ross Dixson, Melissa R. George, Julie Katz Karp, Barbara E.C. Knollmann-Ritschel, Victor Gerardo Prieto, Charles F. Timmons, John Michael Childs, Amanda Lofgreen, Kristen Johnson, Cindy B. Mccloskey Apr 2023

Experiential Exposure As The Key To Recruiting Medical Students Into Pathology, Ashley M. Holloman, Mary P. Berg, Bronwyn Bryant, Lisa Ross Dixson, Melissa R. George, Julie Katz Karp, Barbara E.C. Knollmann-Ritschel, Victor Gerardo Prieto, Charles F. Timmons, John Michael Childs, Amanda Lofgreen, Kristen Johnson, Cindy B. Mccloskey

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Medical student interest and pursuit of a career in pathology have been steadily declining since 2015. We conducted three separate surveys of medical students to better understand these trends. In our first survey, we focused on assessing U.S. allopathic medical students understanding and perceptions of pathology. We later surveyed U.S. osteopathic medical students as a companion to the allopathic medical student survey, in which many similarities were discovered with some key differences. In our final survey, we specifically looked at curriculum differences between the U.S. allopathic medical schools that graduate the most students who enter pathology training programs (Group 1) …


Transcriptomic Changes Predict Metabolic Alterations In Lc3 Associated Phagocytosis In Aged Mice, Anuradha Dhingra, John W. Tobias, Nancy J. Philp, Kathleen Boesze-Battaglia Apr 2023

Transcriptomic Changes Predict Metabolic Alterations In Lc3 Associated Phagocytosis In Aged Mice, Anuradha Dhingra, John W. Tobias, Nancy J. Philp, Kathleen Boesze-Battaglia

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

LC3b (Map1lc3b) plays an essential role in canonical autophagy and is one of several components of the autophagy machinery that mediates non-canonical autophagic functions. Phagosomes are often associated with lipidated LC3b to promote phagosome maturation in a process called LC3-associated phagocytosis (LAP). Specialized phagocytes, such as mammary epithelial cells, retinal pigment epithelial (RPE) cells, and sertoli cells, utilize LAP for optimal degradation of phagocytosed material, including debris. In the visual system, LAP is critical to maintain retinal function, lipid homeostasis, and neuroprotection. In a mouse model of retinal lipid steatosis-mice lacking LC3b (LC3b−/−), we observed increased lipid deposition, metabolic dysregulation, …


High Expression Of Talin-1 Is Associated With Tumor Progression And Recurrence In Melanoma Skin Cancer Patients., Yasaman Rezaie, Fahimeh Fattahi, Baharnaz Mashinchi, Kambiz Kamyab Hesari, Sahar Montazeri, Elham Kalantari, Zahra Madjd, Leili Saeednejad Zanjani Apr 2023

High Expression Of Talin-1 Is Associated With Tumor Progression And Recurrence In Melanoma Skin Cancer Patients., Yasaman Rezaie, Fahimeh Fattahi, Baharnaz Mashinchi, Kambiz Kamyab Hesari, Sahar Montazeri, Elham Kalantari, Zahra Madjd, Leili Saeednejad Zanjani

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Talin-1 as a component of multi-protein adhesion complexes plays a role in tumor formation and migration in various malignancies. This study investigated Talin-1 in protein levels as a potential prognosis biomarker in skin tumors.

METHODS: Talin-1 was evaluated in 106 skin cancer (33 melanomas and 73 non-melanomas skin cancer (NMSC)) and 11 normal skin formalin-fixed paraffin-embedded (FFPE) tissue samples using immunohistochemical technique on tissue microarrays (TMAs). The association between the expression of Talin-1 and clinicopathological parameters, as well as survival outcomes, were assessed.

RESULTS: Our findings from data minings through bioinformatics tools indicated dysregulation of Talin-1 in mRNA levels …


Opa1 Disease-Causing Mutants Have Domain-Specific Effects On Mitochondrial Ultrastructure And Fusion, Benjamín Cartes-Saavedra, Daniel Lagos, Josefa Macuada, Duxan Arancibia, Florence Burté, Marcela K. Sjöberg-Herrera, María Estela Andrés, Rita Horvath, Patrick Yu-Wai-Man, György Hajnóczky, Verónica Eisner Mar 2023

Opa1 Disease-Causing Mutants Have Domain-Specific Effects On Mitochondrial Ultrastructure And Fusion, Benjamín Cartes-Saavedra, Daniel Lagos, Josefa Macuada, Duxan Arancibia, Florence Burté, Marcela K. Sjöberg-Herrera, María Estela Andrés, Rita Horvath, Patrick Yu-Wai-Man, György Hajnóczky, Verónica Eisner

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Inner mitochondrial membrane fusion and cristae shape depend on optic atrophy protein 1, OPA1. Mutations in OPA1 lead to autosomal dominant optic atrophy (ADOA), an important cause of inherited blindness. The Guanosin Triphosphatase (GTPase) and GTPase effector domains (GEDs) of OPA1 are essential for mitochondrial fusion; yet, their specific roles remain elusive. Intriguingly, patients carrying OPA1 GTPase mutations have a higher risk of developing more severe multisystemic symptoms in addition to optic atrophy, suggesting pathogenic contributions for the GTPase and GED domains, respectively. We studied OPA1 GTPase and GED mutations to understand their domain-specific contribution to protein function by analyzing …


Acute Acat1/Soat1 Blockade Increases Mam Cholesterol And Strengthens Er-Mitochondria Connectivity., Taylor C Harned, Radu V Stan, Ze Cao, Rajarshi Chakrabarti, Henry N Higgs, Catherine C Y Chang, Ta Yuan Chang Mar 2023

Acute Acat1/Soat1 Blockade Increases Mam Cholesterol And Strengthens Er-Mitochondria Connectivity., Taylor C Harned, Radu V Stan, Ze Cao, Rajarshi Chakrabarti, Henry N Higgs, Catherine C Y Chang, Ta Yuan Chang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Cholesterol is a key component of all mammalian cell membranes. Disruptions in cholesterol metabolism have been observed in the context of various diseases, including neurodegenerative disorders such as Alzheimer's disease (AD). The genetic and pharmacological blockade of acyl-CoA:cholesterol acyltransferase 1/sterol O-acyltransferase 1 (ACAT1/SOAT1), a cholesterol storage enzyme found on the endoplasmic reticulum (ER) and enriched at the mitochondria-associated ER membrane (MAM), has been shown to reduce amyloid pathology and rescue cognitive deficits in mouse models of AD. Additionally, blocking ACAT1/SOAT1 activity stimulates autophagy and lysosomal biogenesis; however, the exact molecular connection between the ACAT1/SOAT1 blockade and these observed benefits remain …


Progranulin Oncogenic Network In Solid Tumors, Elisa Ventura, Giacomo Ducci, Reyes Benot Dominguez, Valentina Ruggiero, Antonino Belfiore, Elena Sacco, Marco Vanoni, Renato V. Iozzo, Antonio Giordano, Andrea Morrione Mar 2023

Progranulin Oncogenic Network In Solid Tumors, Elisa Ventura, Giacomo Ducci, Reyes Benot Dominguez, Valentina Ruggiero, Antonino Belfiore, Elena Sacco, Marco Vanoni, Renato V. Iozzo, Antonio Giordano, Andrea Morrione

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Progranulin is a pleiotropic growth factor with important physiological roles in embryogenesis and maintenance of adult tissue homeostasis. While-progranulin deficiency is associated with a broad range of pathological conditions affecting the brain, such as frontotemporal dementia and neuronal ceroid lipofuscinosis, progranulin upregulation characterizes many tumors, including brain tumors, multiple myeloma, leiomyosarcoma, mesothelioma and epithelial cancers such as ovarian, liver, breast, bladder, adrenal, prostate and kidney carcinomas. The increase of progranulin levels in tumors might have diagnostic and prognostic significance. In cancer, progranulin has a pro-tumorigenic role by promoting cancer cell proliferation, migration, invasiveness, anchorage-independent growth and resistance to chemotherapy. In …


Longitudinal Ultrasound Imaging And Network Modeling In Rats Reveal Sex-Dependent Suppression Of Liver Regeneration After Resection In Alcoholic Liver Disease, Benjamin K. Barnhart, Toshiki Kan, Ankita Srivastava, Corinne E. Wessner, John Waters, Manju Ambelil, John R. Eisenbrey, Jan B. Hoek, Rajanikanth Vadigepalli Mar 2023

Longitudinal Ultrasound Imaging And Network Modeling In Rats Reveal Sex-Dependent Suppression Of Liver Regeneration After Resection In Alcoholic Liver Disease, Benjamin K. Barnhart, Toshiki Kan, Ankita Srivastava, Corinne E. Wessner, John Waters, Manju Ambelil, John R. Eisenbrey, Jan B. Hoek, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Liver resection is an important surgical technique in the treatment of cancers and transplantation. We used ultrasound imaging to study the dynamics of liver regeneration following two-thirds partial hepatectomy (PHx) in male and female rats fed via Lieber-deCarli liquid diet protocol of ethanol or isocaloric control or chow for 5–7 weeks. Ethanol-fed male rats did not recover liver volume to the pre-surgery levels over the course of 2 weeks after surgery. By contrast, ethanol-fed female rats as well as controls of both sexes showed normal volume recovery. Contrary to expectations, transient increases in both portal and hepatic artery blood flow …


Supporting A Culture Of Patient Safety: Resident-Led Patient Safety Event Reviews In A Pathology Residency Training Program, Catherine Tucker, Rebecca C. Jaffe,, Allison F Goldberg Feb 2023

Supporting A Culture Of Patient Safety: Resident-Led Patient Safety Event Reviews In A Pathology Residency Training Program, Catherine Tucker, Rebecca C. Jaffe,, Allison F Goldberg

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Patient safety is a critical component of quality patient care at any healthcare institution. In order to support a culture of patient safety, and in the context of a hospital-wide patient safety initiative at our institution, we have created and implemented a new patient safety curriculum within our training program. The curriculum is embedded in an introductory course for first-year residents, in which residents gain an understanding of the multifaceted role of the pathologist in patient care. The patient safety curriculum is a resident-centered event review process and includes 1) identification and reporting of a patient safety event, 2) event …


Estimated Impact Of Low Isolate Numbers On The Reliability Of Cumulative Antibiogram Data, Christian Tran, John Hargy, Bryan Hess, Matthew Pettengill Feb 2023

Estimated Impact Of Low Isolate Numbers On The Reliability Of Cumulative Antibiogram Data, Christian Tran, John Hargy, Bryan Hess, Matthew Pettengill

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Antibiograms are cumulative reports of antimicrobial susceptibility results that are used to guide the selection of empirical antibiotic therapy. Although Clinical and Laboratory Standards Institute (CLSI) guidelines recommend including only organisms that have at least 30 isolates in an antibiogram, previous studies demonstrated that adherence to this recommendation is highly variable. This paper aims to model the impact of small sample sizes on expected levels of error in cumulative antibiograms by comparing percent susceptibility results for random samples to those of the larger, entire data set. The results demonstrate relatively high error rates when utilizing low numbers of isolates in …


Modeling And Analysis Of The Intrinsic Cardiac Nervous System In Closed-Loop Cardiovascular Control, Michelle M. Gee, Abraham M. Lenhoff, James S. Schwaber, Babatunde A. Ogunnaike, Rajanikanth Vadigepalli Feb 2023

Modeling And Analysis Of The Intrinsic Cardiac Nervous System In Closed-Loop Cardiovascular Control, Michelle M. Gee, Abraham M. Lenhoff, James S. Schwaber, Babatunde A. Ogunnaike, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The baroreceptor reflex is a multi-input, multi-output physiological control system that regulates short-term blood pressure by modulating nerve activity between the brainstem and the heart. The computational model by Park et al. (2020) is the most recent iteration in our exploration of the system. However, the contributions of”the little brain of the heart”, the intrinsic cardiac nervous system (ICN), to local control of the heart and to the integration of sensory information is unknown and has been overlooked in previous models. We have incorporated a high-fidelity representation of the ICN into a model of the baroreceptor reflex based on anatomical, …