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Articles 1 - 30 of 640

Full-Text Articles in Medical Sciences

Synergistic Anti-Tumor Activity Of Ciclopirox Olamine And Metformin In Triple-Negative Breast Cancer, Yakun Wu, Hui Lyu, Congcong Tan, Margaret E. Larsen, Shou Ching Tang, Shile Huang, Bolin Liu Jan 2026

Synergistic Anti-Tumor Activity Of Ciclopirox Olamine And Metformin In Triple-Negative Breast Cancer, Yakun Wu, Hui Lyu, Congcong Tan, Margaret E. Larsen, Shou Ching Tang, Shile Huang, Bolin Liu

School of Graduate Studies Faculty Publications

No abstract provided.

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Zoliflodacin Versus Ceftriaxone Plus Azithromycin For Treatment Of Uncomplicated Urogenital Gonorrhoea: An International, Randomised, Controlled, Open-Label, Phase 3, Non-Inferiority Clinical Trial, Alison Luckey, Manica Balasegaram, Lindley A. Barbee, Teresa A. Batteiger, Helen Broadhurst, Stephanie E. Cohen, Sinead Delany-Moretlwe, Henry J.C. De Vries, Jodie A. Dionne, Katherine Gill, Chris Kenyon, Rossaphorn Kittiyaowamarn, Drew Lewis, John P. Mueller, Vimla Naicker, Seamus O'Brien, John P. O'Donnell, Nittaya Phanuphak, Elizabeth Spooner, Subasree Srinivasan, Stephanie N. Taylor, Magnus Unemo, Zinhle Zwane, Edward W. Hook, Zoliflodacin Phase 3 Study Group Jan 2026

Zoliflodacin Versus Ceftriaxone Plus Azithromycin For Treatment Of Uncomplicated Urogenital Gonorrhoea: An International, Randomised, Controlled, Open-Label, Phase 3, Non-Inferiority Clinical Trial, Alison Luckey, Manica Balasegaram, Lindley A. Barbee, Teresa A. Batteiger, Helen Broadhurst, Stephanie E. Cohen, Sinead Delany-Moretlwe, Henry J.C. De Vries, Jodie A. Dionne, Katherine Gill, Chris Kenyon, Rossaphorn Kittiyaowamarn, Drew Lewis, John P. Mueller, Vimla Naicker, Seamus O'Brien, John P. O'Donnell, Nittaya Phanuphak, Elizabeth Spooner, Subasree Srinivasan, Stephanie N. Taylor, Magnus Unemo, Zinhle Zwane, Edward W. Hook, Zoliflodacin Phase 3 Study Group

School of Medicine Faculty Publications

Background Development of new treatments for gonorrhoea is a global public health priority. We aimed to evaluate the efficacy and safety of zoliflodacin versus ceftriaxone plus azithromycin in patients with uncomplicated urogenital gonorrhoea. Methods In this phase 3, multinational, randomised, controlled, open-label, non-inferiority clinical trial, participants aged 12 years and older with clinical suspicion of uncomplicated urogenital gonorrhoea were eligible for inclusion. The trial was done in 17 outpatient clinics in Belgium, the Netherlands, South Africa, Thailand, and the USA. Participating countries with high disease prevalence were identified for participation in the study. Sites selected for participation were led by …

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The Vascular Density/Angiogenesis Marker Cd31/Pecam1 Does Not Correlate With Overall Survival In Neuroendocrine Tumors, Nicholas J. Skill, Kenneth Avanzino, Yvette Bren-Mattison, J. Philip Boudreaux, Ramcharan Thiagarajan, Mary Maluccio Jan 2026

The Vascular Density/Angiogenesis Marker Cd31/Pecam1 Does Not Correlate With Overall Survival In Neuroendocrine Tumors, Nicholas J. Skill, Kenneth Avanzino, Yvette Bren-Mattison, J. Philip Boudreaux, Ramcharan Thiagarajan, Mary Maluccio

School of Medicine Faculty Publications

Abstract: Neuroendocrine neoplasms (NENs) are rare cancers. CD31/PECAM1 is an adhesion molecule that modulates endothelial cell-to-cell contact. Increased CD31 expression is a marker for tumor growth, and cancer aggressiveness. The purpose of this study was to better understand the prognostic value of CD31 expression in primary and metastatic NEN tumors in terms of correlations with overall survival and pathological metrics, tumor grade, and tumor primary/metastatic location. As NENs are highly vascular tumors, the hypothesis is that CD31 staining is an important prognostic biomarker and target. This is based on prior correlations between CD31 staining and 3-year recurrence-free survival in pancreas …

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Inflammatory Co-Regulation Of Voltage-Gated Sodium Channels And Na,K-Atpase In Metastatic Breast Cancer, Steven D. Scahill, Kelly Jean Sherman, Dennis Paul Dec 2025

Inflammatory Co-Regulation Of Voltage-Gated Sodium Channels And Na,K-Atpase In Metastatic Breast Cancer, Steven D. Scahill, Kelly Jean Sherman, Dennis Paul

School of Graduate Studies Faculty Publications

Sodium regulation is a potentially major driver of cancer metastasis. Voltage-gated sodium channels (VGSCs) and Na,K-ATPase are sodium transporters that are upregulated in many advanced carcinomas and are implicated as metastatic drivers. However, little is known about what drives this overexpression, how these proteins influence metastatic behavior, or whether these complementary sodium transporters are co-regulated in cancer. Using sodium transporter regulation in healthy neurons as a model, the present study demonstrated that the inflammatory mediator tumor necrosis factor alpha (TNFα) affects the expression of VGSCs and Na,K-ATPase in an in vitro model of metastatic breast cancer. Acute TNFα challenge increased …

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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 Dec 2025

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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Role Of Gut Microbiome In Oncogenesis And Oncotherapies, Renuka Sri Sai Peddireddi, Sai Kiran Kuchana, Rohith Kode, Saketh Khammammettu, Aishwarya Koppanatham, Supriya Mattigiri, Harshavardhan Gobburi, Suresh K. Alahari Dec 2025

Role Of Gut Microbiome In Oncogenesis And Oncotherapies, Renuka Sri Sai Peddireddi, Sai Kiran Kuchana, Rohith Kode, Saketh Khammammettu, Aishwarya Koppanatham, Supriya Mattigiri, Harshavardhan Gobburi, Suresh K. Alahari

School of Graduate Studies Faculty Publications

The gut microbiome has emerged as a key regulator of human health, influencing not only metabolism and immunity but also the development and treatment of cancer. Mounting evidence suggests that microbial dysbiosis contributes to oncogenesis by driving chronic inflammation, producing genotoxic metabolites, altering bile acid metabolism, and disrupting epithelial barrier integrity. At the same time, the gut microbiome significantly modulates the host response to oncotherapies including chemotherapy, radiotherapy, and especially immunotherapy, where microbial diversity and specific taxa determine treatment efficacy and toxicity. This review synthesizes current evidence on the role of the gut microbiome in both oncogenesis and oncotherapies, focusing …

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Light-Induced Oslike1 Phosphorylation Enhances Rice Resistance Against Blast Disease, Jiangtao Liu, Lei Su, Wenya Wang, Jintao Wang, Weizhong Chen, Zhixiang Yang, Leiyun Yang, Gang Li, Xinyu Liu, Haifeng Zhang, Zhongqiang Qi, Yongfeng Liu, Yuqiang Liu, Ping Wang, Muxing Liu, Zhengguang Zhang Dec 2025

Light-Induced Oslike1 Phosphorylation Enhances Rice Resistance Against Blast Disease, Jiangtao Liu, Lei Su, Wenya Wang, Jintao Wang, Weizhong Chen, Zhixiang Yang, Leiyun Yang, Gang Li, Xinyu Liu, Haifeng Zhang, Zhongqiang Qi, Yongfeng Liu, Yuqiang Liu, Ping Wang, Muxing Liu, Zhengguang Zhang

School of Graduate Studies Faculty Publications

Rice blast caused by Magnaporthe oryzae poses a major threat to world food supply. Conditions conducive to the disease include insufficient light. Our previous studies found that light-dependent phosphorylation of light-harvesting complex II protein (LHCB5) mediates rice immunity; however, the underlying mechanisms, in particular, the upstream regulators of LHCB5 phosphorylation, remain unknown. Here, we show that OsLIKE1 functions as a lectin receptor-like kinase (LecRLK) to play a critical role in rice resistance against M. oryzae. OsLIKE1 interacts with and phosphorylates LHCB5. In addition, we find two phosphorylation sites in the kinase domain of OsLIKE1 important for its auto-phosphorylation and phosphorylation …

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Regulation Of Insm1 Gene Expression And Neuroendocrine Differentiation In High-Risk Neuroblastoma, Chiachen Chen, Siyuan Cheng, Xiuping Yu, Yisheng Lee, Michael S. Lan Dec 2025

Regulation Of Insm1 Gene Expression And Neuroendocrine Differentiation In High-Risk Neuroblastoma, Chiachen Chen, Siyuan Cheng, Xiuping Yu, Yisheng Lee, Michael S. Lan

School of Graduate Studies Faculty Publications

Neuroblastoma (NB), a pediatric cancer of sympatho-adrenal (SA) lineage, is marked by disrupted differentiation and cellular heterogeneity. INSM1, a zinc-finger transcription factor, is highly expressed in NB and developing SA tissues, where it regulates neuroendocrine differentiation, especially in chromaffin cells. We investigated INSM1's role in maintaining an undifferentiated, progenitor-like state in NB and its regulation via metabolic and epigenetic mechanisms. Transcriptomic profiling, promoter assays, and metabolic flux analysis revealed that INSM1 expression correlates with methionine cycle activity, particularly the S-adenosylmethionine (SAM)/S-adenosylhomocysteine (SAH) ratio. Disruption of SAM/SAH balance altered INSM1 promoter activity and histone methylation, implicating epigenetic control in NB cell …

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Long Covid Incidence Across Sars-Cov-2 Lineages And Identification Of Conserved Spike Targets For Multivalent Vaccines, Grace J. Kim, Md Ashad Alam, Judy S. Crabtree, Rebecca Rose, Susanna L. Lamers, San Chu, Ronald Horswell, Daniel Fort, Lucio Miele Dec 2025

Long Covid Incidence Across Sars-Cov-2 Lineages And Identification Of Conserved Spike Targets For Multivalent Vaccines, Grace J. Kim, Md Ashad Alam, Judy S. Crabtree, Rebecca Rose, Susanna L. Lamers, San Chu, Ronald Horswell, Daniel Fort, Lucio Miele

School of Graduate Studies Faculty Publications

Background: Long COVID remains poorly characterized at the genomic level. The primary aim of this study was to examine the relationship between viral sequences and the incidence of Long COVID at a tertiary care center in Louisiana between April 2020 and December 2022. A secondary aim was analysis of the Spike protein to identify conserved regions for multivalent vaccine targets. Method: To estimate Long COVID incidence across variants, we linked 4,789 SARS-CoV-2 sequences to 3,090 de-identified patient electronic health record information. The base population was defined as any patient with an International Classification of Diseases-10-Clinical Modification COVID-19 diagnosis code (U07.1) …

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Osteoprogenitor Cells From Non-Regenerative Bone Show Greater Resistance To Cellular Stress Than Those From Regenerative Bone, Joshua Broussard, Sylvia Culpepper, Tyrel Long, Alexander J. Trostle, Robert J. Tower, Mimi C. Sammarco, Jennifer Simkin Dec 2025

Osteoprogenitor Cells From Non-Regenerative Bone Show Greater Resistance To Cellular Stress Than Those From Regenerative Bone, Joshua Broussard, Sylvia Culpepper, Tyrel Long, Alexander J. Trostle, Robert J. Tower, Mimi C. Sammarco, Jennifer Simkin

School of Medicine Faculty Publications

INTRODUCTION: Bone regeneration following injury depends on osteoprogenitor cells derived predominantly from the periosteum. Incomplete regeneration has been attributed to both cell-extrinsic factors (e.g., environment, inflammation, mechanical instability) and cell-intrinsic factors (e.g., impaired proliferation or differentiation of stem cells). In the digit amputation mouse model, amputation through the third phalanx (P3) supports complete regeneration, while amputation through the second phalanx (P2) results in callus formation and scarring. Periosteal cells are known to be the major contributing cell source for repair and regeneration. Yet the healing outcomes of P2 and P3 amputations are significantly different. This study tests whether P2 and …

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Genomic Ascertainment Of Chek2 -Related Cancer Predisposition, Sunyoung Kim, Jung Kim, Mark Ramos, Jeremy Haley, Diane Smelser, H. Shanker Rao, Uyenlinh L. Mirshahi, Katherine L. Nathanson, Barry I. Graubard, Hormuzd A. Katki, David Carey, Douglas R. Stewart Dec 2025

Genomic Ascertainment Of Chek2 -Related Cancer Predisposition, Sunyoung Kim, Jung Kim, Mark Ramos, Jeremy Haley, Diane Smelser, H. Shanker Rao, Uyenlinh L. Mirshahi, Katherine L. Nathanson, Barry I. Graubard, Hormuzd A. Katki, David Carey, Douglas R. Stewart

School of Graduate Studies Faculty Publications

Importance: There is clear evidence that deleterious germline variants in CHEK2 increase risk for breast and prostate cancers; there is limited or conflicting evidence for other cancers. Objective: To quantify the prevalence of as well as cancer risk and survival associated with CHEK2 germline pathogenic and likely pathogenic variants using genomic ascertainment. Design, Setting, and Participants: This case-control study used 2 electronic health record-linked and exome-sequenced biobanks: UK Biobank (n = 469765) and Geisinger MyCode (adults only; n = 167050). Variants were classified according to American College of Medical Genetics and Genomics and the Association for Molecular Pathology criteria. Cases …

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Dermal Lymphatic Carcinomatosis As A Cutaneous Metastasis From Epidermal Growth Factor Receptor-Positive Lung Adenocarcinoma: A Case Report, Sarah A. Hemelt, Jonathan M. Joseph, Nicholas Culotta Dec 2025

Dermal Lymphatic Carcinomatosis As A Cutaneous Metastasis From Epidermal Growth Factor Receptor-Positive Lung Adenocarcinoma: A Case Report, Sarah A. Hemelt, Jonathan M. Joseph, Nicholas Culotta

School of Medicine Faculty Publications

Cutaneous metastases are an uncommon but clinically significant manifestation of internal malignancies. We present a rare case of dermal lymphatic carcinomatosis arising from epidermal growth factor receptor (EGFR)-positive lung adenocarcinoma, a presentation that may closely mimic inflammatory dermatoses and indicate therapeutic resistance or disease progression. We describe the clinical course of a 65-year-old woman who developed a violaceous cutaneous metastatic lesion beneath the left breast during treatment for metastatic lung adenocarcinoma. This case highlights the importance of recognizing cutaneous signs as indicators of disease progression and emphasizes the diagnostic challenges and prognostic implications of cutaneous metastases in lung cancer.

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Identification Of Predictive Pretreatment Biomarkers For Neoadjuvant Chemotherapy Response In Latino Invasive Breast Cancer Patients, Hedda Michelle Guevara-Nieto, Rafael Parra-Medina, Carlos A. Orozco, Sandra Diaz-Casas, Jone Garai, Jovanny Zabaleta, Liliana López-Kleine, Alba L. Combita Dec 2025

Identification Of Predictive Pretreatment Biomarkers For Neoadjuvant Chemotherapy Response In Latino Invasive Breast Cancer Patients, Hedda Michelle Guevara-Nieto, Rafael Parra-Medina, Carlos A. Orozco, Sandra Diaz-Casas, Jone Garai, Jovanny Zabaleta, Liliana López-Kleine, Alba L. Combita

School of Medicine Faculty Publications

Background: Breast cancer (BC) exhibits significant heterogeneity in incidence and mortality worldwide. Neoadjuvant chemotherapy (NAC) is the standard treatment for locally advanced BC; however, its efficacy varies by subtype. This study examined the gene expression profiles associated with NAC response in Colombian women with invasive BC. Methods: RNA sequencing of pre-treatment tissues from 58 patients (29 responders and 29 non-responders) identified differentially expressed genes (DEGs) for each molecular subtype, and prognostic performance was evaluated using risk scores. Results: Functional enrichment analysis highlighted the immune system pathways in non-responders. Changes in cytokine target activity and immune cell populations were analyzed to …

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The Need To Incorporate Polysubstance Use In Neuropsychopharmacology Research: Biological Lessons And New Opportunities, Max E. Joffe, Susan M. Ferguson, Nick W. Gilpin, Melissa A. Herman, Lori A. Knackstedt, Patrick A. Randall, Abigail G. Schindler, Mary M. Torregrossa, Jennifer A. Rinker Dec 2025

The Need To Incorporate Polysubstance Use In Neuropsychopharmacology Research: Biological Lessons And New Opportunities, Max E. Joffe, Susan M. Ferguson, Nick W. Gilpin, Melissa A. Herman, Lori A. Knackstedt, Patrick A. Randall, Abigail G. Schindler, Mary M. Torregrossa, Jennifer A. Rinker

School of Medicine Faculty Publications

Critical evaluation and refinement of animal models is essential for neuroscientists to understand complex physiological and pathological processes related to psychiatric diseases. In general, preclinical studies modeling drug dependence and problematic substance use have been limited to the administration of a single substance; however, there is a growing appreciation that this approach has failed to capture the complexities of humans and has stifled translational efforts. Polysubstance use represents the overwhelmingly common patterns of alcohol and drug use in humans. For example, epidemiological studies generally determine that between 70–95 % of individuals with alcohol use disorder use tobacco daily, and upwards …

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Are E-Cigarettes A Safer Alternative? Revisiting The Cardiovascular Cost Of Nicotine Delivery, Jason D. Gardner Dec 2025

Are E-Cigarettes A Safer Alternative? Revisiting The Cardiovascular Cost Of Nicotine Delivery, Jason D. Gardner

School of Graduate Studies Faculty Publications

No abstract provided.

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Endothelial-Derived Extracellular Vesicles During Exercise In Copd Patients, Samuel C Okpechi, Dorota Wyczechowska, Bennett Deboisblanc, Jessica L Johnson, Mohamed A Ghonim, Natalie Bauer, Hamid A Boulares, Matthew R Lammi Dec 2025

Endothelial-Derived Extracellular Vesicles During Exercise In Copd Patients, Samuel C Okpechi, Dorota Wyczechowska, Bennett Deboisblanc, Jessica L Johnson, Mohamed A Ghonim, Natalie Bauer, Hamid A Boulares, Matthew R Lammi

School of Medicine Faculty Publications

Introduction: There are no treatments directly targeting the pulmonary vasculature in chronic obstructive pulmonary disease (COPD), and further characterization of the underlying endothelial cell (EC) abnormalities could be helpful in drug development. Methods: We investigated the influence of exercise and the prostacyclin analog iloprost on extracellular vesicles derived from ECs (eEVs) in 15 moderate–severe COPD patients who were enrolled in a randomized, placebo-controlled crossover trial of iloprost. Results: Active smokers had a profile consistent with inflammatory-derived EVs, while exacerbation-prone COPD subjects had a profile consistent with apoptosis-derived eEVs. There were no significant effects of iloprost on eEV levels. However, there …

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Proteome-Wide Association Study Of Prostate Cancer Risk Across Populations, Hua Zhong, Jingjing Zhu, Shuai Liu, Chong Wu, Liang Wang, Seamus P. Whelton, Catherine H. Marshall, Michael J. Blaha, Peter Durda, Xiuqing Guo, Craig W. Johnson, Henry J. Lin, Kent D. Taylor, Russell P. Tracy, Ronit I. Yarden, Ani W. Manichaikul, Stephen S. Rich, Jerome I. Rotter, Rajat Deo, Ruth F. Dubin, Peter Ganz, Lang Wu Dec 2025

Proteome-Wide Association Study Of Prostate Cancer Risk Across Populations, Hua Zhong, Jingjing Zhu, Shuai Liu, Chong Wu, Liang Wang, Seamus P. Whelton, Catherine H. Marshall, Michael J. Blaha, Peter Durda, Xiuqing Guo, Craig W. Johnson, Henry J. Lin, Kent D. Taylor, Russell P. Tracy, Ronit I. Yarden, Ani W. Manichaikul, Stephen S. Rich, Jerome I. Rotter, Rajat Deo, Ruth F. Dubin, Peter Ganz, Lang Wu

School of Graduate Studies Faculty Publications

There is insufficient understanding of the molecular basis of prostate cancer (PCa) across different populations. We perform a large-scale proteome-wide association study (PWAS) to identify proteins with genetically regulated expression in plasma to be associated with PCa risk across populations. We develop genetic prediction models for expression of 1578, 1993, 1218, and 1390 proteins for African (n = 450), European (n = 758), Asian (n = 289), and Hispanic/Latino (n = 474) males, respectively, and evaluate associations of genetically regulated protein expression with PCa risk in 19,391 PCa cases and 61,608 controls of African population, 122,188 cases and 604,640 controls …

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Phosphorylation At S1288 Of Leukemia Associated Rhogef (Larg/Arhgef12) Induces Plasma Membrane Localization And Promotes Binding And Activation Of Rhoa, Won Seok Yang, Neda Z. Ghanem, Steven D. Scahill, Maisel J. Caliva, Hannah Röttig, Annika Fitz, Michelle L. Matter, Joe W. Ramos Dec 2025

Phosphorylation At S1288 Of Leukemia Associated Rhogef (Larg/Arhgef12) Induces Plasma Membrane Localization And Promotes Binding And Activation Of Rhoa, Won Seok Yang, Neda Z. Ghanem, Steven D. Scahill, Maisel J. Caliva, Hannah Röttig, Annika Fitz, Michelle L. Matter, Joe W. Ramos

School of Graduate Studies Faculty Publications

Leukemia-associated RhoGEF (LARG) is a guanine nucleotide exchange factor (GEF) known for its specificity toward Ras homolog family member A (RhoA). LARG plays a crucial regulatory role in various cellular processes such as migration, proliferation, invasion, and metastasis by facilitating the exchange of GDP to GTP on RhoA. Phosphorylation of LARG at S1288 by ribosomal S6 kinase 2 (RSK2) promotes RhoA activation. However, the precise mechanism remains unclear. Here, we demonstrate the essential role and mechanism by which S1288 phosphorylation facilitates LARG-mediated invasiveness in response to epidermal growth factor (EGF). Upon EGF stimulation, RSK2 phosphorylates LARG at S1288, thereby promoting …

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Overview Of Huntington's Disease And Emerging Treatment Strategies: A Narrative Review, Alexis J. Vega, Gabriel V. Hernandez, Pearse A. O'Malley, Connor J. Robin, Amanda N. Parra, Giustino Varrassi, Sahar Shekoohi, Alan D. Kaye Dec 2025

Overview Of Huntington's Disease And Emerging Treatment Strategies: A Narrative Review, Alexis J. Vega, Gabriel V. Hernandez, Pearse A. O'Malley, Connor J. Robin, Amanda N. Parra, Giustino Varrassi, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Huntington's disease (HD) is an autosomal dominant, progressive neurodegenerative disorder caused by a cytosine-adenine-guanine trinucleotide repeat expansion in the huntingtin (HTT) gene. The symptoms of HD include severe motor dysfunction, cognitive issues, and emotional dysregulation. These combined issues are not only debilitating but also lead to depression/anxiety, increased suicide rates, and caregiver burnout. Our narrative review summarizes several recent studies examining the efficacy and differences among emerging treatment strategies for HD. A systematic search of peer-reviewed literature was conducted, focusing on recent studies that describe molecular genetic manipulation of the HTT gene/huntingtin protein. The results of our narrative review reveal …

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Benchmarking Dna Foundation Models For Genomic And Genetic Tasks, Haonan Feng, Lang Wu, Bingxin Zhao, Chad Huff, Jianjun Zhang, Jia Wu, Lifeng Lin, Peng Wei, Chong Wu Nov 2025

Benchmarking Dna Foundation Models For Genomic And Genetic Tasks, Haonan Feng, Lang Wu, Bingxin Zhao, Chad Huff, Jianjun Zhang, Jia Wu, Lifeng Lin, Peng Wei, Chong Wu

School of Medicine Faculty Publications

The rapid evolution of DNA foundation models promises to revolutionize genomics, yet comprehensive evaluations are lacking. Here, we present a comprehensive, unbiased benchmark of five models (DNABERT-2, Nucleotide Transformer V2, HyenaDNA, Caduceus-Ph, and GROVER) across diverse genomic and genetic tasks including sequence classification, gene expression prediction, variant effect quantification, and topologically associating domain (TAD) region recognition, using zero-shot embeddings. Our analysis reveals that mean token embedding consistently and significantly improves sequence classification performance, outperforming other pooling strategies. Model performance varies among tasks and datasets; while general purpose DNA foundation models showed competitive performance in pathogenic variant identification, they were less …

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Mucosal Melanoma: Mechanisms Of Its Etiology, Progression, Resistance And Therapy, Sofie-Yasmin Hassan, Thomas W. Flanagan, Sarah-Lilly Hassan, Sybille Facca, Youssef Haikel, Mohamed Hassan Nov 2025

Mucosal Melanoma: Mechanisms Of Its Etiology, Progression, Resistance And Therapy, Sofie-Yasmin Hassan, Thomas W. Flanagan, Sarah-Lilly Hassan, Sybille Facca, Youssef Haikel, Mohamed Hassan

School of Graduate Studies Faculty Publications

Mucosal melanoma (MM) is a rare, aggressive cancer whose incidence has increased continuously over the years. This subtype of melanoma arises from melanocytes on hairless surfaces, typically in the respiratory tract, gastrointestinal (GI) tract, and urogenital tract. The most common sites of occurrence include the head and neck, the anorectal region, and the vulvovaginal region, while the rare sites of MM are the urinary tract and the upper and lower GI tract, including the esophagus, duodenum and the gallbladder. MM arises in melanocytes of the ectodermal mucosa that originate from neural crest cells and migrate through embryonic mesenchyme to their …

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Dietary Fiber Modulates Gut Microbiota And Lipid Metabolism Ameliorating Alzheimer's Pathology In 5xfad Mice, Yuhai Zhao, Christopher M. Taylor, Walter J. Lukiw, Nicolas G. Bazan Nov 2025

Dietary Fiber Modulates Gut Microbiota And Lipid Metabolism Ameliorating Alzheimer's Pathology In 5xfad Mice, Yuhai Zhao, Christopher M. Taylor, Walter J. Lukiw, Nicolas G. Bazan

School of Graduate Studies Faculty Publications

The gut-brain axis plays a critical role in maintaining neuronal integrity and influencing the progression of Alzheimer's disease (AD). Here, we investigated how commonly consumed dietary fibers modulate gut microbiota, lipid metabolism, and AD pathology in 5xFAD mice. Male mice were fed either fiber-free (FF) or fiber-plus (FP; 1% cellulose, 2% pectin, 2% inulin) diets for five months, followed by integrated analyses of gut microbiota (16 S rRNA sequencing), fecal lipid metabolites (LC-MS/MS), and neuropathological and behavioral outcomes. FP diets markedly altered microbial composition, characterized by increases in Muribaculaceae, Ileibacterium, and Lachnospiraceae NK4A136 group and reductions in Faecalibaculum and Coriobacteriaceae …

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Sulindac Sulfide Suppresses Oncogenic Transformation Through Let-7b-Mediated Repression Of K-Ras Signaling, Zhipin Liang, Ruixia Ma, Bin Yi, Adam I. Riker, Yaguang Xi Nov 2025

Sulindac Sulfide Suppresses Oncogenic Transformation Through Let-7b-Mediated Repression Of K-Ras Signaling, Zhipin Liang, Ruixia Ma, Bin Yi, Adam I. Riker, Yaguang Xi

School of Graduate Studies Faculty Publications

No abstract provided.

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Trypanosoma Cruzi Infection-Induced Changes In Cardiac Microvascular Endothelial Cell Morphology And Function, Lyndsey N. Gisclair, Douglas A. Johnston Nov 2025

Trypanosoma Cruzi Infection-Induced Changes In Cardiac Microvascular Endothelial Cell Morphology And Function, Lyndsey N. Gisclair, Douglas A. Johnston

School of Graduate Studies Faculty Publications

Introduction. Six to seven million individuals are infected with Trypanosoma cruzi, the causative agent of Chagas disease. With 12,000 deaths annually, chronic Chagas disease remains a significant global health challenge due to persistent vector transmission, increasing non-vector transmission and limited therapeutic options. Chronic Chagas cardiomyopathy is a leading cause of morbidity and mortality, yet the underlying mechanisms remain poorly understood.Gap Statement. Since its initial description more than 100 years ago, research efforts into the cardiomyopathy found in chronic Chagas disease have primarily focused on the contributions of immune cells, cardiomyocytes and cardiac fibroblasts, leaving a significant gap in understanding the …

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Immunogenomic Diversity Of Triple-Negative Breast Cancers In Obese And Non-Obese Black And White Women, Fokhrul Hossain, Denise Danos, Jovanny Zabaleta, Xiao-Cheng Wu, Luis Del Valle, Chindo Hicks, Jiande Wu, Jerneja Tomsic, Susan Neuhausen, Yuan Chun Ding, Kavitha Mukund, Zahra Mesrizadeh, Shankar Subramaniam, Augusto Ochoa, Victoria Seewaldt, Lucio Miele Nov 2025

Immunogenomic Diversity Of Triple-Negative Breast Cancers In Obese And Non-Obese Black And White Women, Fokhrul Hossain, Denise Danos, Jovanny Zabaleta, Xiao-Cheng Wu, Luis Del Valle, Chindo Hicks, Jiande Wu, Jerneja Tomsic, Susan Neuhausen, Yuan Chun Ding, Kavitha Mukund, Zahra Mesrizadeh, Shankar Subramaniam, Augusto Ochoa, Victoria Seewaldt, Lucio Miele

School of Medicine Faculty Publications

Racial disparities in incidence and outcomes of triple-negative breast cancer (TNBC) have been attributed to ancestry, socioeconomic factors and/or obesity. We studied 253 TNBCs from 128 Black and 125 White women. Arms were balanced for age, AJCC stage, histological grade and molecular subtypes, and differed significantly in BMI distribution, obesity, and Area Deprivation Index. We examined survival rates, whole-transcriptome RNASeq and genetic ancestry. In our sample, Black race or obesity were not intrinsically predictive of poor outcomes. TNBC molecular portraits varied with stage and biological aggressiveness, irrespective of race. We identified a novel group of TNBCs with a distinctive luminal-like …

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Her3 Promotes Triple-Negative Breast Cancer Progression By Upregulating Phf8 Via Mir-34b-5p-Dependent Mechanism, Hui Lyu, Cong Cong Tan, Yakun Wu, Margaret E. Larsen, Qingzhao Yu, Guobin Kang, Charles Wood, Shou Ching Tang, Bolin Liu Nov 2025

Her3 Promotes Triple-Negative Breast Cancer Progression By Upregulating Phf8 Via Mir-34b-5p-Dependent Mechanism, Hui Lyu, Cong Cong Tan, Yakun Wu, Margaret E. Larsen, Qingzhao Yu, Guobin Kang, Charles Wood, Shou Ching Tang, Bolin Liu

School of Graduate Studies Faculty Publications

Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer, with limited targeted treatment options and poor clinical outcomes. HER3 has recently emerged as a promising therapeutic target, with HER3-directed antibody–drug conjugates advancing to Phase III clinical trials for non-small cell lung cancer. However, the downstream molecular mechanisms by which HER3 promotes TNBC progression remain poorly defined. In this study, we uncovered a previously unrecognized HER3/miR-34b-5p/PHF8 signaling axis that drives TNBC cell proliferation and tumor growth. Mechanistically, HER3 activation suppresses the tumor-suppressive microRNA miR-34b-5p, resulting in the upregulation of the histone demethylase PHF8 (KDM7B), which in …

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Selective Depletion Of Gut Gram-Negative Bacteria Attenuates Alcohol Binge-Induced Cardiovascular Dysfunction By Lowering Cardiac Anandamide Levels, Sarah E. Cohen, Meagan E. Donovan, Davin J. Gardner, Danielle Sambo, Seray B. Karagoz, Resat Cinar, David Goldman, Jason D. Gardner, Pal Pacher, Janos Paloczi Nov 2025

Selective Depletion Of Gut Gram-Negative Bacteria Attenuates Alcohol Binge-Induced Cardiovascular Dysfunction By Lowering Cardiac Anandamide Levels, Sarah E. Cohen, Meagan E. Donovan, Davin J. Gardner, Danielle Sambo, Seray B. Karagoz, Resat Cinar, David Goldman, Jason D. Gardner, Pal Pacher, Janos Paloczi

School of Graduate Studies Faculty Publications

Binge drinking contributes to an increasing number of emergency department visits in the United States. Previous work demonstrated that an alcohol binge impairs cardiac performance and exerts complex hemodynamic effects through the activation of the endocannabinoid-mediated cannabinoid type 1 receptor (CB1R) signaling pathway. Anandamide (AEA), an endogenous CB1R agonist, is synthesized in response to various stressors and tissue injury. However, the role of binge drinking in increasing myocardial AEA levels, which leads to CB1R-dependent cardiodepression, remains unclear. This work studied how endotoxins from intestinal Gram-negative bacteria affect myocardial AEA levels, which further induce CB1R-dependent cardiac dysfunction following acute alcohol intoxication. …

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Alcohol And Metabolic Stress Synergize To Dysregulate Mitochondrial Health And Lipid Metabolism; Evidence From A Hepatocyte Spheroid Model, Eden M. Gallegos, Kaitlin Couvillion, Drake Darden, Keishla Rodriguez-Graciani, Patricia E. Molina, Liz Simon Nov 2025

Alcohol And Metabolic Stress Synergize To Dysregulate Mitochondrial Health And Lipid Metabolism; Evidence From A Hepatocyte Spheroid Model, Eden M. Gallegos, Kaitlin Couvillion, Drake Darden, Keishla Rodriguez-Graciani, Patricia E. Molina, Liz Simon

School of Graduate Studies Faculty Publications

Metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease frequently co-occur, manifesting as MetALD. Understanding the hepatocyte-specific effects of alcohol and metabolic stressors is critical to uncovering mechanisms of synergistic injury. This study evaluated the individual and combined effects of ethanol, sugars, and saturated/monounsaturated fats on hepatocyte lipid metabolism, oxidative stress, and mitochondrial function using a 3D human HepaRG spheroid model. HepaRG spheroids were treated with ethanol (50 mm), sugar (glucose and fructose), and fatty acids alone or in combination for 10 d. The combination of ethanol (E) and metabolic (sugar and fat, SF) stressors (ESF) synergistically increased triglyceride content …

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Assessing The Tumor Suppressive Impact And Regulatory Mechanisms Of Spdef Expression In Breast Cancer, Maansi Solanky, Maninder Khosla, Suresh K. Alahari Nov 2025

Assessing The Tumor Suppressive Impact And Regulatory Mechanisms Of Spdef Expression In Breast Cancer, Maansi Solanky, Maninder Khosla, Suresh K. Alahari

School of Graduate Studies Faculty Publications

Background/Objectives: Breast cancer is a heterogeneous disease, and the role of the transcription factor SPDEF remains controversial. We aimed to clarify the prognostic value of SPDEF, explore demographic and molecular correlates of its expression, and investigate potential regulatory mechanisms underlying its dysregulation. Methods: Genomic and clinical data for 1218 breast cancer tumors were obtained from The Cancer Genome Atlas (TCGA). SPDEF mRNA expression was compared across intrinsic subtypes, age, and race, and prognostic significance was evaluated by Kaplan–Meier analysis. Promoter methylation patterns and DNA methyltransferase (DNMT) expression were examined as potential regulatory drivers. Co-expression analysis was performed using gene panels …

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The Non-Coding Rna Journal Club: Highlights On Recent Papers-14, El Cheima Mhamedi, Florent Hubé, Suresh K. Alahari, Francisco J. Enguita, Barbara Pardini, Mark W. Feinberg, Laura Poliseno, Beshoy Armanios, Jing Jin, Xiao-Bo Zhong, Nikolaos Sideris, Salih Bayraktar, Leandro Castellano, Gaetano Santulli, Stanislovas S. Jankauskas, Will S. Plewa, Simon J. Conn, Ling Yang, Patrick K. Shiu, Abhishek Kaushik, Alexander Serganov, Gentile, Giuseppe Viglietto, Nicola Amodio, Tijana Mitić, Andrea Caporali Oct 2025

The Non-Coding Rna Journal Club: Highlights On Recent Papers-14, El Cheima Mhamedi, Florent Hubé, Suresh K. Alahari, Francisco J. Enguita, Barbara Pardini, Mark W. Feinberg, Laura Poliseno, Beshoy Armanios, Jing Jin, Xiao-Bo Zhong, Nikolaos Sideris, Salih Bayraktar, Leandro Castellano, Gaetano Santulli, Stanislovas S. Jankauskas, Will S. Plewa, Simon J. Conn, Ling Yang, Patrick K. Shiu, Abhishek Kaushik, Alexander Serganov, Gentile, Giuseppe Viglietto, Nicola Amodio, Tijana Mitić, Andrea Caporali

School of Graduate Studies Faculty Publications

The field of non-coding RNA research is advancing at a breathtaking pace, continually uncovering new layers of regulatory complexity and functional diversity [...].

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