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Articles 1 - 26 of 26
Full-Text Articles in Cells
The Role Of Extracellular Vesicles As Diagnostic Tools In Gut-Brain Axis Disorders, Patricia Marçal Da Costa, Paulo Iury Gomes Nunes, Gabriella Cunha Vieira Ciurleo, José Wagner Leonel Tavares Junior, Pedro Braga Neto, Ludmila Belayev, Reinaldo Barreto Oriá
The Role Of Extracellular Vesicles As Diagnostic Tools In Gut-Brain Axis Disorders, Patricia Marçal Da Costa, Paulo Iury Gomes Nunes, Gabriella Cunha Vieira Ciurleo, José Wagner Leonel Tavares Junior, Pedro Braga Neto, Ludmila Belayev, Reinaldo Barreto Oriá
School of Graduate Studies Faculty Publications
The gut–brain axis represents a dynamic two-way signaling network whose dysregulation has been implicated in a wide range of neurogastrointestinal disorders. In this context, extracellular vesicles (EVs) have emerged as critical mediators of intercellular signaling and as promising non-invasive biomarkers. Derived from host and microbial cells, EVs carry bioactive cargo—including proteins, lipids, nucleic acids, and metabolites—that reflect the physiological or pathological state of their cells of origin. Their ability to cross biological barriers, such as the blood–brain barrier, underscores their potential for diagnosing and monitoring gut–brain axis dysfunctions. In this mini-review, we integrate microbial and brain-derived EVs within the framework …
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
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 …
Trypanosoma Cruzi Infection-Induced Changes In Cardiac Microvascular Endothelial Cell Morphology And Function, Lyndsey N. Gisclair, Douglas A. Johnston
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 …
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
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 …
Induction Of Myelopoiesis By Candida Dubliniensis Drives Protective Trained Immunity Against Sepsis In A Card9-Dependent Manner, Shannon Esher Righi, Elizabeth A. Lilly, Amanda J. Harriett, Patrick W. Daly, Maryjane Jones, Chad Steele, Mairi C. Noverr, Paul L. Fidel
Induction Of Myelopoiesis By Candida Dubliniensis Drives Protective Trained Immunity Against Sepsis In A Card9-Dependent Manner, Shannon Esher Righi, Elizabeth A. Lilly, Amanda J. Harriett, Patrick W. Daly, Maryjane Jones, Chad Steele, Mairi C. Noverr, Paul L. Fidel
School of Dentistry Faculty Publications
Trained immunity is a long-term functional reprogramming of innate cells that allows for the formation of immune memory akin to adaptive responses, but with a more rapid nonspecific response. We recently identified an anti-inflammatory trained immunity response, termed trained tolerogenic immunity (TTI), induced by low virulence Candida dubliniensis, that protects against acute lethal polymicrobial sepsis via myeloid-derived suppressor cells (MDSCs). Trained immunity and MDSCs arise following hematopoietic stem and progenitor cell (HSPC) expansion in the bone marrow. Here, we show that C. dubliniensis induces inoculum-dependent protection and HSPC expansion, whereas depletion of HSPCs following C. dubliniensis immunization abrogates protection. We …
Epdevatlas: Mapping Gabaergic Cells And Microglia In The Early Postnatal Mouse Brain, Josephine K. Liwang, Fae N. Kronman, Hyun-Jae Pi, Yuan-Ting Wu, Daniel J. Vanselow, Steffy B. Manjila, Deniz Parmaksiz, Donghui Shin, Yoav Ben-Simon, Michael Taormina, Sharon W. Way, Hongkui Zeng, Bosiljka Tasic, Lydia Ng, Yongsoo Kim
Epdevatlas: Mapping Gabaergic Cells And Microglia In The Early Postnatal Mouse Brain, Josephine K. Liwang, Fae N. Kronman, Hyun-Jae Pi, Yuan-Ting Wu, Daniel J. Vanselow, Steffy B. Manjila, Deniz Parmaksiz, Donghui Shin, Yoav Ben-Simon, Michael Taormina, Sharon W. Way, Hongkui Zeng, Bosiljka Tasic, Lydia Ng, Yongsoo Kim
School of Graduate Studies Faculty Publications
During development, brain regions follow encoded growth trajectories. Compared to classical brain growth charts, high-definition growth charts could quantify regional volumetric growth and constituent cell types, improving our understanding of typical and pathological brain development. Here, we create high-resolution 3D atlases of the early postnatal mouse brain, using Allen CCFv3 anatomical labels, at postnatal days (P) 4, 6, 8, 10, 12, and 14, and determine the volumetric growth of different brain regions. We utilize 11 different cell type-specific transgenic animals to validate and refine anatomical labels. Moreover, we reveal region-specific density changes in γ-aminobutyric acid-producing (GABAergic) neurons, cortical layer-specific cell …
Oncogenic Effects Of Ecm Remodeling In Obesity And Breast Cancer, Mackenzie L. Hawes, Marcus A. Moody, Caroline R. Mccauley, Abigail G. Huddleston, Maansi Solanky, Dara H. Khosravi, Ayushi R. Patel, Ronald M. Lynch, Suresh K. Alahari, Bruce A. Bunnell, Jorge A. Belgodere, Van T. Hoang, Matthew E. Burow, Elizabeth C. Martin
Oncogenic Effects Of Ecm Remodeling In Obesity And Breast Cancer, Mackenzie L. Hawes, Marcus A. Moody, Caroline R. Mccauley, Abigail G. Huddleston, Maansi Solanky, Dara H. Khosravi, Ayushi R. Patel, Ronald M. Lynch, Suresh K. Alahari, Bruce A. Bunnell, Jorge A. Belgodere, Van T. Hoang, Matthew E. Burow, Elizabeth C. Martin
School of Medicine Faculty Publications
Extracellular matrix (ECM) components are key regulators in breast cancer progression, as ECM remodeling is essential for breast cancer cells to invade into surrounding tissue. This process is characterized by the alignment of fibrillar collagens, breakdown of basement membrane components, and increased interstitial collagen stiffness. In patients with obesity, pre-existing ECM changes, including excessive collagen deposition and heightened matrix stiffness, mimic alterations detected in breast cancer. Given that obesity is a predictor of poor prognosis and resistance to treatment in breast cancer, it is crucial to understand how ECM conditioned by obesity affects disease outcomes. In this review, we highlight …
Exploring Hepatic Stellate Cell-Driven Fibrosis: Therapeutic Advances And Future Perspectives, Alka Singh, Ansab Akhtar, Prashant Shukla
Exploring Hepatic Stellate Cell-Driven Fibrosis: Therapeutic Advances And Future Perspectives, Alka Singh, Ansab Akhtar, Prashant Shukla
School of Medicine Faculty Publications
BACKGROUND AND PURPOSE: Liver fibrosis, a progressive liver disease arising from viral or metabolic causes, poses a major global health challenge due to its potential progression to cirrhosis and hepatocellular carcinoma. Due to the complex aetiology and epidemiology of liver fibrosis, most therapies fail in the clinic, and very few drugs have been approved by the US FDA. APPROACH: This review highlights the pathophysiological features of liver fibrosis, with a focus on novel targets in hepatic stellate cells (HSCs), key players in the fibrogenesis process, to develop successful therapeutic approaches using both pharmacological agents and active targeting strategies. The review …
Distinct Echinocandin Responses Of Candida Albicans And Candida Auris Cell Walls Revealed By Solid-State Nmr, Malitha C. Dickwella Widanage, Kalpana Singh, Jizhou Li, Jayasubba Reddy Yarava, Faith J. Scott, Yifan Xu, Neil A.R. Gow, Frederic Mentink-Vigier, Ping Wang, Frederic Lamoth, Tuo Wang
Distinct Echinocandin Responses Of Candida Albicans And Candida Auris Cell Walls Revealed By Solid-State Nmr, Malitha C. Dickwella Widanage, Kalpana Singh, Jizhou Li, Jayasubba Reddy Yarava, Faith J. Scott, Yifan Xu, Neil A.R. Gow, Frederic Mentink-Vigier, Ping Wang, Frederic Lamoth, Tuo Wang
School of Graduate Studies Faculty Publications
Invasive candidiasis affects 1.6 million people annually, with high mortality among immunocompromised and hospitalized patients. Echinocandins are frontline antifungals, but rising resistance limits their efficacy. Here, we show that Candida albicans and multidrug-resistant Candida auris share a conserved cell wall architecture yet differ markedly in their adaptive responses to echinocandins. Solid-state NMR reveals that both species possess a rigid inner layer of tightly associated chitin microfibrils and β−1,3-glucans, supported by a flexible matrix of β−1,6-glucans and additional β−1,3-glucans. Outer mannan fibrils rely on α−1,2-linked sidechains to maintain contact with the inner wall. In both species, caspofungin rigidifies β−1,6-glucans and mannan …
Soluble Cd13 Is A Potential Mediator Of Neutrophil-Induced Thrombogenic Inflammation In Sars-Cov-2 Infection, Pei-Suen Tsou, Ramadan A. Ali, Chenyang Lu, Gautam Sule, Carmelo Carmona-Rivera, Serena Lucotti, Yuzo Ikari, Qi Wu, Phillip L. Campbell, Mikel Gurrea-Rubio, Kohei Maeda, Sharon E. Fox, William D. Brodie, Megan N. Mattichak, Caroline Foster, Ajay Tambralli, Srilakshmi Yalavarthi, M Asif Amin, Katarina Kmetova, Bruna Mazetto Fonseca, Emily Chong, Yu Zuo, Michael D. Maile, Luisa Imberti, Arnaldo Caruso, Francesca Caccuri, Virginia Quaresima, Alessandra Sottini, Douglas B. Kuhns, Et Al
Soluble Cd13 Is A Potential Mediator Of Neutrophil-Induced Thrombogenic Inflammation In Sars-Cov-2 Infection, Pei-Suen Tsou, Ramadan A. Ali, Chenyang Lu, Gautam Sule, Carmelo Carmona-Rivera, Serena Lucotti, Yuzo Ikari, Qi Wu, Phillip L. Campbell, Mikel Gurrea-Rubio, Kohei Maeda, Sharon E. Fox, William D. Brodie, Megan N. Mattichak, Caroline Foster, Ajay Tambralli, Srilakshmi Yalavarthi, M Asif Amin, Katarina Kmetova, Bruna Mazetto Fonseca, Emily Chong, Yu Zuo, Michael D. Maile, Luisa Imberti, Arnaldo Caruso, Francesca Caccuri, Virginia Quaresima, Alessandra Sottini, Douglas B. Kuhns, Et Al
School of Medicine Faculty Publications
The soluble variant of the ectopeptidase CD13 (sCD13), released from the cell surface by matrix metalloproteinase 14 (MMP14), is a potent pro-inflammatory mediator, displaying chemotactic, angiogenic, and arthritogenic properties through bradykinin receptor B1 (B1R). We revealed a link between sCD13 and amplified neutrophil-mediated inflammatory responses in SARS-CoV-2 infection. sCD13 was markedly elevated in patients with COVID-19 and correlated with disease severity and variants, ethnicity, inflammation markers, and neutrophil extracellular trap formation (NETosis). Neutrophils treated with sCD13 showed heightened NETosis and chemotaxis, which were inhibited by sCD13 receptor blockade. Meanwhile sCD13 did not induce platelet aggregation. Single-cell analysis of COVID-19 lungs …
Mouse Adrenal Macrophages Are Associated With Pre- And Postsynaptic Neuronal Elements And Respond To Multiple Neuromodulators, Matthew D. Whim
Mouse Adrenal Macrophages Are Associated With Pre- And Postsynaptic Neuronal Elements And Respond To Multiple Neuromodulators, Matthew D. Whim
School of Medicine Faculty Publications
The adrenal medulla is packed with chromaffin cells, modified postganglionic sympathetic neurons that secrete the catecholamines, epinephrine and norepinephrine, during the fight-or-flight response. Sometimes overlooked is a population of immune cells that also resides within the gland but whose distribution and function are not clear. Here I examine the location of CD45+ hematopoietic cells in the mouse adrenal medulla and show the majority are F4/80+/Lyz2+ macrophages. These cells are present from early postnatal development and widely distributed. Anatomically they are associated with chromaffin cells, found aligned alongside synapsin-IR neuronal varicosities and juxtaposed to CD31-IR blood vessels. Using Lyz2cre-GCaMP6f mice to …
Molecular Architecture Of Chitin And Chitosan-Dominated Cell Walls In Zygomycetous Fungal Pathogens By Solid-State Nmr, Qinghui Cheng, Malitha C. Dickwella Widanage, Jayasubba Reddy Yarava, Ankur Ankur, Jean Paul Latgé, Ping Wang, Tuo Wang
Molecular Architecture Of Chitin And Chitosan-Dominated Cell Walls In Zygomycetous Fungal Pathogens By Solid-State Nmr, Qinghui Cheng, Malitha C. Dickwella Widanage, Jayasubba Reddy Yarava, Ankur Ankur, Jean Paul Latgé, Ping Wang, Tuo Wang
School of Medicine Faculty Publications
Zygomycetous fungal infections pose an emerging medical threat among individuals with compromised immunity and metabolic abnormalities. Our pathophysiological understanding of these infections, particularly the role of fungal cell walls in growth and immune response, remains limited. Here we conducted multidimensional solid-state NMR analysis to examine cell walls in five Mucorales species, including key mucormycosis causative agents like Rhizopus and Mucor species. We show that the rigid core of the cell wall primarily comprises highly polymorphic chitin and chitosan, with minimal quantities of β-glucans linked to a specific chitin subtype. Chitosan emerges as a pivotal molecule preserving hydration and dynamics. Some …
Loss Of Hormone Receptor Expression After Exposure To Fluid Shear Stress In Breast Cancer Cell Lines, Jonathan Cuccia, Braulio Andres Ortega Quesada, Ethan P. Littlefield, Alejandra M. Ham, Matthew E. Burow, Adam T. Melvin, Elizabeth C. Martin
Loss Of Hormone Receptor Expression After Exposure To Fluid Shear Stress In Breast Cancer Cell Lines, Jonathan Cuccia, Braulio Andres Ortega Quesada, Ethan P. Littlefield, Alejandra M. Ham, Matthew E. Burow, Adam T. Melvin, Elizabeth C. Martin
School of Medicine Faculty Publications
Following metastatic spread, many hormone receptor positive (HR(+)) patients develop a more aggressive phenotype with an observed loss of the HRs estrogen receptor (ER) and progesterone receptor (PR). During metastasis, breast cancer cells are exposed to high magnitudes of fluid shear stress (FSS). Unfortunately, the role for FSS on the regulation of HR expression and function during metastasis is not fully understood. This study was designed to elucidate the impact of FSS on HR(+) breast cancer. Utilizing a microfluidic platform capable of exposing breast cancer cells to FSS that mimics in situ conditions, we demonstrate the impact of FSS exposure …
Tumor Infiltrating Lymphocytes (Tils) Are A Prognosis Biomarker In Colombian Patients With Triple Negative Breast Cancer, Carlos A. Huertas-Caro, Mayra A. Ramírez, Laura Rey-Vargas, Lina María Bejarano-Rivera, Diego Felipe Ballen, Marcela Nuñez, Juan Carlos Mejía, Luz Fernanda Sua-Villegas, Alicia Cock-Rada, Jovanny Zabaleta, Laura Fejerman, María Carolina Sanabria-Salas, Silvia J. Serrano-Gomez
Tumor Infiltrating Lymphocytes (Tils) Are A Prognosis Biomarker In Colombian Patients With Triple Negative Breast Cancer, Carlos A. Huertas-Caro, Mayra A. Ramírez, Laura Rey-Vargas, Lina María Bejarano-Rivera, Diego Felipe Ballen, Marcela Nuñez, Juan Carlos Mejía, Luz Fernanda Sua-Villegas, Alicia Cock-Rada, Jovanny Zabaleta, Laura Fejerman, María Carolina Sanabria-Salas, Silvia J. Serrano-Gomez
School of Medicine Faculty Publications
Triple negative breast cancer (TNBC) is highly immunogenic and high levels of tumor infiltrating lymphocytes (TILs) have been associated with a better prognosis and higher probability to achieve pathological complete response. Here, we explore the potential role of stromal TILs level and composition as a prognostic and predictive biomarker in TNBC. 195 Tumor biospecimens from patients diagnosed with TNBC were included. Stromal TILs (sTILs), positive CD4/CD8 cells were evaluated. Differences in clinic-pathological characteristics according to immune infiltration were assessed. The predictive and prognostic value of immune infiltration was analyzed by multivariate models. Higher immune infiltration was observed in patients with …
Candida-Induced Granulocytic Myeloid-Derived Suppressor Cells Are Protective Against Polymicrobial Sepsis, Shannon Esher Righi, Amanda J. Harriett, Elizabeth A. Lilly, Paul L. Fidel Jr., Mairi C. Noverr
Candida-Induced Granulocytic Myeloid-Derived Suppressor Cells Are Protective Against Polymicrobial Sepsis, Shannon Esher Righi, Amanda J. Harriett, Elizabeth A. Lilly, Paul L. Fidel Jr., Mairi C. Noverr
School of Dentistry Faculty Publications
Polymicrobial intra-abdominal infections (IAI) can lead to life-threatening sepsis with significant morbidity and mortality, especially when pathogenic fungi are involved. We have employed an established clinically relevant mouse model of fungal/bacterial IAI and shown that immunization with low-virulence Candida species, that is, Candida dubliniensis, can induce responses that protect against sepsis via the suppression of lethal inflammation. This protection is dependent on long-lived Gr-1(+) polymorphonuclear leukocytes that display characteristics consistent with myeloid-derived suppressor cells (MDSCs) and trained innate immunity. Here we aimed to functionally and phenotypically characterize these protective Gr-1(+) leukocytes. Compared to nonimmunized control mice, we observed increased levels …
Targeting Cgas/Sting Signaling-Mediated Myeloid Immune Cell Dysfunction In Time, Vijay Kumar, Caitlin Bauer, John H. Stewart
Targeting Cgas/Sting Signaling-Mediated Myeloid Immune Cell Dysfunction In Time, Vijay Kumar, Caitlin Bauer, John H. Stewart
School of Graduate Studies Faculty Publications
Myeloid immune cells (MICs) are potent innate immune cells serving as first responders to invading pathogens and internal changes to cellular homeostasis. Cancer is a stage of altered cellular homeostasis that can originate in response to different pathogens, chemical carcinogens, and internal genetic/epigenetic changes. MICs express several pattern recognition receptors (PRRs) on their membranes, cytosol, and organelles, recognizing systemic, tissue, and organ-specific altered homeostasis. cGAS/STING signaling is a cytosolic PRR system for identifying cytosolic double-stranded DNA (dsDNA) in a sequence-independent but size-dependent manner. The longer the cytosolic dsDNA size, the stronger the cGAS/STING signaling activation with increased type 1 interferon …
Systemic Review Of Clot Retraction Modulators, Alaina Guilbeau, Rinku Majumder
Systemic Review Of Clot Retraction Modulators, Alaina Guilbeau, Rinku Majumder
School of Graduate Studies Faculty Publications
Through a process termed clot retraction, platelets cause thrombi to shrink and become more stable. After platelets are activated via inside-out signaling, glycoprotein αIIbβIII binds to fibrinogen and initiates a cascade of intracellular signaling that ends in actin remodeling, which causes the platelet to change its shape. Clot retraction is also important for wound healing. Although the detailed molecular biology of clot retraction is only partially understood, various substances and physiological conditions modulate clot retraction. In this review, we describe some of the current literature pertaining to clot retraction modulators. In addition, we discuss compounds from Cudrania trucuspidata, Arctium lappa, …
Incubation With Porcine Urinary Bladder Matrix Yields A Late-Stage Wound Transcriptome In Endothelial Cells And Keratinocytes Isolated From Both Diabetic And Non-Diabetic Subjects, John T. Paige, Daniel J. Lightell, Hunter F. Douglas, Natasha C. Klingenberg, Thaidan Pham, T. Cooper Woods
Incubation With Porcine Urinary Bladder Matrix Yields A Late-Stage Wound Transcriptome In Endothelial Cells And Keratinocytes Isolated From Both Diabetic And Non-Diabetic Subjects, John T. Paige, Daniel J. Lightell, Hunter F. Douglas, Natasha C. Klingenberg, Thaidan Pham, T. Cooper Woods
School of Medicine Faculty Publications
Proper wound closure requires the functional coordination of endothelial cells (ECs) and keratinocytes. In the late stages of wound healing, keratinocytes become activated and ECs promote the maturation of nascent blood vessels. In diabetes mellitus, decreased keratinocyte activation and impaired angiogenic action of ECs delay wound healing. Porcine urinary bladder matrix (UBM) improves the rate of wound healing, but the effect of exposure to UBM under diabetic conditions remains unclear. We hypothesized that keratinocytes and ECs isolated from both diabetic and non-diabetic donors would exhibit a similar transcriptome representative of the later stages of wound healing following incubation with UBM. …
Tumor Microenvironment As A Therapeutic Target In Melanoma Treatment, Naji Kharouf, Thomas W. Flanagan, Sofie Yasmin Hassan, Hosam Shalaby, Marla Khabaz, Sarah Lilly Hassan, Mosaad Megahed, Youssef Haikel, Simeon Santourlidis, Mohamed Hassan
Tumor Microenvironment As A Therapeutic Target In Melanoma Treatment, Naji Kharouf, Thomas W. Flanagan, Sofie Yasmin Hassan, Hosam Shalaby, Marla Khabaz, Sarah Lilly Hassan, Mosaad Megahed, Youssef Haikel, Simeon Santourlidis, Mohamed Hassan
School of Graduate Studies Faculty Publications
The role of the tumor microenvironment in tumor growth and therapy has recently attracted more attention in research and drug development. The ability of the microenvironment to trigger tumor maintenance, progression, and resistance is the main cause for treatment failure and tumor relapse. Accumulated evidence indicates that the maintenance and progression of tumor cells is determined by components of the microenvironment, which include stromal cells (endothelial cells, fibroblasts, mesenchymal stem cells, and immune cells), extracellular matrix (ECM), and soluble molecules (chemokines, cytokines, growth factors, and extracellular vesicles). As a solid tumor, melanoma is not only a tumor mass of monolithic …
Moerv14 Mediates The Intracellular Transport Of Cell Membrane Receptors To Govern The Appressorial Formation And Pathogenicity Of Magnaporthe Oryzae, Bin Qian, Xiaotong Su, Ziyuan Ye, Xinyu Liu, Muxing Liu, Haifeng Zhang, Ping Wang, Zhengguang Zhang
Moerv14 Mediates The Intracellular Transport Of Cell Membrane Receptors To Govern The Appressorial Formation And Pathogenicity Of Magnaporthe Oryzae, Bin Qian, Xiaotong Su, Ziyuan Ye, Xinyu Liu, Muxing Liu, Haifeng Zhang, Ping Wang, Zhengguang Zhang
School of Graduate Studies Faculty Publications
Magnaporthe oryzae causes rice blasts posing serious threats to food security worldwide. During infection, M. oryzae utilizes several transmembrane receptor proteins that sense cell surface cues to induce highly specialized infectious structures called appressoria. However, little is known about the mechanisms of intracellular receptor tracking and their function. Here, we described that disrupting the coat protein complex II (COPII) cargo protein MoErv14 severely affects appressorium formation and pathogenicity as the ΔMoerv14 mutant is defective not only in cAMP production but also in the phosphorylation of the mitogen-activated protein kinase (MAPK) MoPmk1. Studies also showed that either externally supplementing cAMP or …
Enhanced Ca2+-Channeling Complex Formation At The Er-Mitochondria Interface Underlies The Pathogenesis Of Alcohol-Associated Liver Disease, Themis Thoudam, Dipanjan Chanda, Jung Yi Lee, Min Kyo Jung, Ibotombi Singh Sinam, Byung Gyu Kim, Bo Yoon Park, Woong Hee Kwon, Hyo Jeong Kim, Myeongjin Kim, Chae Won Lim, Hoyul Lee, Yang Hoon Huh, Caroline A. Miller, Romil Saxena, Nicholas J. Skill, Nazmul Huda, Praveen Kusumanchi, Jing Ma, Zhihong Yang, Min Ji Kim, Ji Young Mun, Robert A. Harris, Jae Han Jeon, Suthat Liangpunsakul, In Kyu Lee
Enhanced Ca2+-Channeling Complex Formation At The Er-Mitochondria Interface Underlies The Pathogenesis Of Alcohol-Associated Liver Disease, Themis Thoudam, Dipanjan Chanda, Jung Yi Lee, Min Kyo Jung, Ibotombi Singh Sinam, Byung Gyu Kim, Bo Yoon Park, Woong Hee Kwon, Hyo Jeong Kim, Myeongjin Kim, Chae Won Lim, Hoyul Lee, Yang Hoon Huh, Caroline A. Miller, Romil Saxena, Nicholas J. Skill, Nazmul Huda, Praveen Kusumanchi, Jing Ma, Zhihong Yang, Min Ji Kim, Ji Young Mun, Robert A. Harris, Jae Han Jeon, Suthat Liangpunsakul, In Kyu Lee
School of Medicine Faculty Publications
Ca2+ overload-induced mitochondrial dysfunction is considered as a major contributing factor in the pathogenesis of alcohol-associated liver disease (ALD). However, the initiating factors that drive mitochondrial Ca2+ accumulation in ALD remain elusive. Here, we demonstrate that an aberrant increase in hepatic GRP75-mediated mitochondria-associated ER membrane (MAM) Ca2+-channeling (MCC) complex formation promotes mitochondrial dysfunction in vitro and in male mouse model of ALD. Unbiased transcriptomic analysis reveals PDK4 as a prominently inducible MAM kinase in ALD. Analysis of human ALD cohorts further corroborate these findings. Additional mass spectrometry analysis unveils GRP75 as a downstream phosphorylation target of PDK4. Conversely, non-phosphorylatable GRP75 …
H2s, Sg-1002, Protects Against Myocardial Oxidative Damage And Hypertrophy In Vitro Via Induction Of Cystathionine Β-Synthase And Antioxidant Proteins, Rahib K. Islam, Erinn Donnelly, Erminia Donnarumma, Fokhrul Hossain, Jason D. Gardner, Kazi N. Islam
H2s, Sg-1002, Protects Against Myocardial Oxidative Damage And Hypertrophy In Vitro Via Induction Of Cystathionine Β-Synthase And Antioxidant Proteins, Rahib K. Islam, Erinn Donnelly, Erminia Donnarumma, Fokhrul Hossain, Jason D. Gardner, Kazi N. Islam
School of Medicine Faculty Publications
Endogenously produced hydrogen sulfide (H2S) is critical for cardiovascular homeostasis. Therapeutic strategies aimed at increasing H2S levels have proven cardioprotective in models of acute myocardial infarction (MI) and heart failure (HF). The present study was undertaken to investigate the effects of a novel H2S prodrug, SG-1002, on stress induced hypertrophic signaling in murine HL-1 cardiac muscle cells. Treatment of HL-1 cells with SG-1002 under serum starvation without or with H2O2 increased the levels of H2S, H2S producing enzyme, and cystathionine β-synthase (CBS), as well as antioxidant protein levels, such as super oxide dismutase1 (SOD1) and catalase, and additionally decreased oxidative …
Quitting Smoking After A Cancer Diagnosis Is Associated With High-Risk Neutrophil-To-Lymphocyte Ratio Among Tobacco Use-Related Cancer Survivors, You Lu, Katherine Kwong, James Wells, Andrea Edwards, Zhong Chen, Tung-Sung Tseng, Kun Zhang
Quitting Smoking After A Cancer Diagnosis Is Associated With High-Risk Neutrophil-To-Lymphocyte Ratio Among Tobacco Use-Related Cancer Survivors, You Lu, Katherine Kwong, James Wells, Andrea Edwards, Zhong Chen, Tung-Sung Tseng, Kun Zhang
School of Public Health Faculty Publications
Quitting smoking could potentially minimize the risk of a high neutrophil-to-lymphocyte ratio (NLR) among tobacco use-related (TUR) cancer survivors. A total of 1263 TUR cancer survivors aged 20 to 85 years old were investigated using data from the National Health and Nutritional Examination Survey 1999-2018. The primary outcome was the NLR, which was defined as having two levels: high-risk (≥ 3) and low-risk (< 3). The association between smoking cessation time and a high-risk NLR level was analyzed using weighted logistic regression models. Overall, the current smoking rate of TUR cancer survivors was found to be 21.7%. Older age (75 years above), gender and respiratory-related cancers are covariables associated with high risk of NLR levels for individual who identified as Non-Hispanic White (NHW). Non-Hispanic Black (NHB) (n = 27) who quit smoking after a cancer diagnosis were associated with the highest risk of a high NLR (OR 4.83, 95% CI 1.40-16.61, p = 0.01) compared to NHB nonsmokers (n = 139). These findings suggest that the risk of a high NLR level is strongly associated with the time of smoking cessation in NHB TUR cancer survivors. As a result, NHB TUR cancer survivors should quit smoking as soon as possible because the benefits of quitting smoking were observed over the 5 year period following smoking cessation.
Inhibition Of Ribosome Assembly Factor Pno1 By Crispr/Cas9 Technique Suppresses Lung Adenocarcinoma And Notch Pathway: Clinical Application, Sanjit K. Roy, Shivam Srivastava, Andrew Hancock, Anju Shrivastava, Jason Morvant, Sharmila Shankar, Rakesh K. Srivastava
Inhibition Of Ribosome Assembly Factor Pno1 By Crispr/Cas9 Technique Suppresses Lung Adenocarcinoma And Notch Pathway: Clinical Application, Sanjit K. Roy, Shivam Srivastava, Andrew Hancock, Anju Shrivastava, Jason Morvant, Sharmila Shankar, Rakesh K. Srivastava
School of Medicine Faculty Publications
Growth is crucially controlled by the functional ribosomes available in cells. To meet the enhanced energy demand, cancer cells re-wire and increase their ribosome biogenesis. The RNA-binding protein PNO1, a ribosome assembly factor, plays an essential role in ribosome biogenesis. The purpose of this study was to examine whether PNO1 can be used as a biomarker for lung adenocarcinoma and also examine the molecular mechanisms by which PNO1 knockdown by CRISPR/Cas9 inhibited growth and epithelial–mesenchymal transition (EMT). The expression of PNO1 was significantly higher in lung adenocarcinoma compared to normal lung tissues. PNO1 expression in lung adenocarcinoma patients increased with …
Role Of Adenylyl Cyclase Type 7 In Functions Of Bv-2 Microglia, Yawen Hu, Rebecca A. Hill, Masami Yoshimura
Role Of Adenylyl Cyclase Type 7 In Functions Of Bv-2 Microglia, Yawen Hu, Rebecca A. Hill, Masami Yoshimura
School of Medicine Faculty Publications
To assess the role of adenylyl cyclase type 7 (AC7) in microglia’s immune function, we generated AC7 gene knockout (AC7 KO) clones from a mouse microglial cell line, BV-2, using the CRISPR-Cas9 gene editing system. The ability of BV-2 cells to generate cAMP and their innate immune functions were examined in the presence or absence of ethanol. The parental BV-2 cells showed robust cAMP production when stimulated with prostaglandin-E1 (PGE1) and ethanol increased cAMP production in a dose-dependent manner. AC7 KO clones of BV-2 cells showed diminished and ethanol-insensitive cAMP production. The phagocytic activity of the parental BV-2 cells was …
Efficacy Of Paracrine Factors From Mesenchymal Stem Cells For Treating Biofilm-Infected Wounds In A Murine Model, Alison A. Smith, Charles F. Bellows
Efficacy Of Paracrine Factors From Mesenchymal Stem Cells For Treating Biofilm-Infected Wounds In A Murine Model, Alison A. Smith, Charles F. Bellows
School of Medicine Faculty Publications
Background: Chronic wounds are a serious medical condition affecting over 6 million people in the United States. Biofilms, which alter the host immune response and establish a microenvironment that prevents wound healing, are intimately associated with the development of chronic wounds. Current treatment options do not specifically target the underlying molecular mechanisms of biofilm pathology. Paracrine factors secreted by mesenchymal stem cells (MSCs) have been demonstrated to play an important role in wound healing. The objective of this study was to examine the effects of the paracrine factors secreted from MSCs on reducing infection and accelerating wound closure in biofilm-infected …