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Articles 61 - 90 of 496

Full-Text Articles in Cell and Developmental Biology

Regulation Of Icer Degradation And Its Role In Melanoma, Justin Wheelan Aug 2025

Regulation Of Icer Degradation And Its Role In Melanoma, Justin Wheelan

Theses, Dissertations and Culminating Projects

Melanoma is the deadliest form of skin cancer, with 100,640 new cases and 8,290 deaths estimated in the United States in 2024. While targeted therapies and immunotherapy have improved patient outcomes, resistance remains a major challenge, necessitating new therapeutic approaches. Approximately 50% of melanomas harbor BRAFⱽ⁶⁰⁰ᴱ mutations, leading to constitutive MAPK pathway activation. Targeted small molecule therapies such as BRAF and MEK inhibitors are available and initially reduce tumor burden, however resistance frequently occurs, likely through many pathways including compensatory activation of cAMP signaling. ICER (Inducible cAMP Early Repressor), a transcriptional repressor of CREB-mediated gene expression, is absent in melanoma …


Integrating Bulk And Single-Cell Transcriptomics To Investigate Intratumor Heterogeneity, Shuai Guo Aug 2025

Integrating Bulk And Single-Cell Transcriptomics To Investigate Intratumor Heterogeneity, Shuai Guo

Dissertations and Theses (Open Access)

Cancers are heterogeneous mixtures of tumor and surrounding cells, where each component comprises multiple distinct sub-types and/or states. Understanding the cell-type-specific contributions is critical for advancing cancer biology, yet high-throughput expression profiles from tumor tissues only represent combined signals from all diverse cellular sources. Bulk deconvolution with single-cell/nucleus (sc/sn) RNA-seq data has emerged as a powerful approach to dissect both cellular composition and cell-type-specific expression patterns, yet the technological discrepancy across sequencing platforms limits accuracy.

To systematically evaluate the impact of platform discrepancies on bulk deconvolution, we first generated a benchmark dataset of 24 healthy retinas with paired bulk and …


Metabolic Regulation Of Cardiac Fibroblast Phenotype And Function., Collin Kleis Wells Aug 2025

Metabolic Regulation Of Cardiac Fibroblast Phenotype And Function., Collin Kleis Wells

Electronic Theses and Dissertations

Cardiac fibroblasts are central effectors of cardiac repair after myocardial infarction (MI). In response to signaling cues, they differentiate to a range of phenotypes with robust capacities to synthesize and secrete extracellular matrix (ECM) and signaling molecules. Although activated fibroblast phenotypes are associated with pronounced changes in metabolism, it remains unclear how the metabolic network upholds the effector functions of fibroblasts in the post-infarcted heart. Here, we identified that critical enzymes in the phosphoenolpyruvate (PEP) cycle, i.e. pyruvate kinase muscle-2 (PKM2) and phosphoenolpyruvate carboxykinase-2 (PCK2), are elevated in the heart after MI and examined their role in regulating post-MI remodeling …


Combination Of Irreversible Electroporation And Clostridium Novyi-Nt Bacterial Therapy For Colorectal Liver Metastasis, Zigeng Zhang, Guangbo Yu, Qiaoming Hou, Farideh Amirrad, Sha Webster, Surya M. Nauli, Jianhua Yu, Vahid Yaghmai, Aydin Eresen, Zhuoli Zhang Jul 2025

Combination Of Irreversible Electroporation And Clostridium Novyi-Nt Bacterial Therapy For Colorectal Liver Metastasis, Zigeng Zhang, Guangbo Yu, Qiaoming Hou, Farideh Amirrad, Sha Webster, Surya M. Nauli, Jianhua Yu, Vahid Yaghmai, Aydin Eresen, Zhuoli Zhang

Pharmacy Faculty Articles and Research

Colorectal liver metastasis (CRLM) poses a significant challenge in oncology due to its high incidence and poor prognosis in unresectable cases. Current treatments, including surgical resection, systemic chemotherapy, and liver-directed therapies, often fail to effectively target hypoxic tumor regions, which are inherently more resistant to these interventions. This review examines the potential of a novel therapeutic strategy combining irreversible electroporation (IRE) ablation and Clostridium novyi-nontoxic (C. novyi-NT) bacterial therapy. IRE is a non-thermal tumor ablation technique that uses high-voltage electric pulses to create permanent nanopores in cell membranes, leading to cell death while preserving surrounding structures, and …


A Cancer Education Needs Assessment: Informing Middle-Aged Female Patients About The Relationships Between Obesity And Women’S Health Concerns In The Reproductive System, Breast, And Endometrial Health, Batul Mirza Jul 2025

A Cancer Education Needs Assessment: Informing Middle-Aged Female Patients About The Relationships Between Obesity And Women’S Health Concerns In The Reproductive System, Breast, And Endometrial Health, Batul Mirza

MUSC Theses and Dissertations

Obesity significantly impacts women’s health, particularly among middle-aged women, by increasing the risk of hormone-sensitive cancers such as breast, endometrial, and reproductive system cancers. This study examines the educational needs of this demographic group regarding obesity-related cancer risks and explores effective intervention strategies. Obesity-induced mechanisms – hormonal imbalances, chronic inflammation, and insulin resistance – drive cancer susceptibility, emphasizing the need for targeted health education. The study employs a qualitative design, which includes interviews with subject matter experts (SMEs) and surveys of middle-aged women. The goal is to assess awareness, perceived barriers, and preferred learning methods. Findings suggest that with many …


Modulation Of Redox-Sensitive Cardiac Ion Channels, Rawan S. Orfali, Al Hassan Gamal El-Din, Varnika Karthik, Elisanjer Lamis, Vanna Xiao, Alena Ramanishka, Abdullah Alwatban, Osama Alkhamees, Ali Alaseem, Young-Woo Nam, Miao Zhang Jul 2025

Modulation Of Redox-Sensitive Cardiac Ion Channels, Rawan S. Orfali, Al Hassan Gamal El-Din, Varnika Karthik, Elisanjer Lamis, Vanna Xiao, Alena Ramanishka, Abdullah Alwatban, Osama Alkhamees, Ali Alaseem, Young-Woo Nam, Miao Zhang

Pharmacy Faculty Articles and Research

Redox regulation is crucial for the cardiac action potential, coordinating the sodium-driven depolarization, calcium-mediated plateau formation, and potassium-dependent repolarization processes required for proper heart function. Under physiological conditions, low-level reactive oxygen species (ROS), generated by mitochondria and membrane oxidases, adjust ion channel function and support excitation–contraction coupling. However, when ROS accumulate, they modify a variety of important channel proteins in cardiomyocytes, which commonly results in reducing potassium currents, enhancing sodium and calcium influx, and enhancing intracellular calcium release. These redox-driven alterations disrupt the cardiac rhythm, promote after-depolarizations, impair contractile force, and accelerate the development of heart diseases. Experimental models demonstrate …


Irradiation Of Prostate Cancer Alters Circulating Small Extracellular Vesicle Functions, Aejaz Sayeed, Vaughn Garcia, Cecilia E. Verrillo, Rachel M. Derita, Md Niamat Hossain, Shiv R. Krishn, Samuel Sey, Christopher D. Shields, Adrian D. Altieri, Qin Liu, Khalid Sossey-Alaoui, William K. Kelly, Lucia R. Languino Jul 2025

Irradiation Of Prostate Cancer Alters Circulating Small Extracellular Vesicle Functions, Aejaz Sayeed, Vaughn Garcia, Cecilia E. Verrillo, Rachel M. Derita, Md Niamat Hossain, Shiv R. Krishn, Samuel Sey, Christopher D. Shields, Adrian D. Altieri, Qin Liu, Khalid Sossey-Alaoui, William K. Kelly, Lucia R. Languino

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

It is known that β1 integrins and a downstream signaling molecule c-Src are upregulated in prostate cancer (PrCa) tissues, are co-expressed in circulating small extracellular vesicles (sEVs) and contribute to cancer progression. Here, we demonstrate that sEVs from PrCa patients show robust expression of both β1 integrins and c-Src. The impact of irradiation, a widely used therapy for the treatment of PrCa, on circulating sEVs is however not fully understood. We show that sEVs isolated from the plasma of transgenic adenocarcinoma of mouse prostate (TRAMP) mice, stimulate migration and anchorage-independent growth of recipient cancer cells, but sEVs are not active …


Neovascular Pruning By Ido1 Inhibitors Can Potentiate Immunogenic Cytotoxicity Of Ischemia-Targeted Agents To Synergistically Enhance Anti-Pd-1 Responsiveness, Shih-Chun Shen, Souvik Dey, James B. Duhadaway, Erika Sutanto-Ward, Maurice T. Hampton, Serguei V. Kozlov, George C. Prendergast, Alexander J. Muller May 2025

Neovascular Pruning By Ido1 Inhibitors Can Potentiate Immunogenic Cytotoxicity Of Ischemia-Targeted Agents To Synergistically Enhance Anti-Pd-1 Responsiveness, Shih-Chun Shen, Souvik Dey, James B. Duhadaway, Erika Sutanto-Ward, Maurice T. Hampton, Serguei V. Kozlov, George C. Prendergast, Alexander J. Muller

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Strategies for deploying indoleamine 2,3-dioxygenase 1 (IDO1)-targeted therapies for use against cancer have focused on IDO1's role in promoting peripheral immune tolerance that shields tumors from effector T cells. However, preclinical investigation of both primary and metastatic tumor development in the lungs has uncovered a previously unappreciated role for IDO1 in directing a counterregulatory response to interferon (IFN)-γ that realigns the local inflammatory environment to promote tumor neovascularization. Understanding how to therapeutically leverage the ability of IDO1 inhibitors to subvert inflammatory neovascularization within the tumor microenvironment has potential ramifications for future clinical development of these compounds.

METHODS: Pulmonary metastases …


Myocardin Effector Proteins Affect Tgf-Beta-Induced Myofibroblast Differentiation In Ipf Cells, Allison Gonzalez May 2025

Myocardin Effector Proteins Affect Tgf-Beta-Induced Myofibroblast Differentiation In Ipf Cells, Allison Gonzalez

Biotechnology Theses

Idiopathic pulmonary fibrosis (IPF) is an incurable interstitial lung disease defined by the progressive, irreversible scarring of the tissues between the lung’s alveoli. To date, only two drugs have received approval for treatment. However, these medications are not considered cures since they do not stop the progression of the disease. A deeper understanding of the mechanisms underlying IPF could aid in discovering a cure. We recently found that myocardin (MyoCD) regulates SMAD2/3 transcription factors in the TGF-β signaling pathway and governs the genes involved in pleural fibrosis. However, it is unclear whether MyoCD plays a critical role in IPF by …


Ks151 Synergizes With Venetoclax And Abt-737 In Aml: Efficacy In Both Flt3-Wildtype And Flt3-Mutant Models, Sahil Jethi, Arnold Rojas, Omar S. Al-Odat, Krishne Gowda, Subash C. Jonnalagadda, Manoj Pandey May 2025

Ks151 Synergizes With Venetoclax And Abt-737 In Aml: Efficacy In Both Flt3-Wildtype And Flt3-Mutant Models, Sahil Jethi, Arnold Rojas, Omar S. Al-Odat, Krishne Gowda, Subash C. Jonnalagadda, Manoj Pandey

Rowan-Virtua Research Day

Acute myeloid leukemia (AML) is the most common leukemia in adult patients, with a 5-year survival rate of less than 30 percent. Therefore, more effective therapeutic strategies are required to prolong the survival of AML patients. Importantly, anti-apoptotic proteins, especially B-cell lymphoma 2 (Bcl-2), overexpression in AML is associated with uncontrolled growth as well as chemoresistance. Unsurprisingly, Bruton’s tyrosine kinase (BTK) overexpresses in AML and associated with poor prognosis and chemoresistance. The FDA-approved BTK inhibitor, ibrutinib, has been successful in treating other hematologic malignancies, but a proportion of patients relapse mainly because of acquired mutations at Cys481Ser (C481S) in the …


Identifying Novel Molecular Targets To Induce Ferroptosis In Drug-Tolerant Cancer Cells Through Computational Modeling, Haris J. Rana May 2025

Identifying Novel Molecular Targets To Induce Ferroptosis In Drug-Tolerant Cancer Cells Through Computational Modeling, Haris J. Rana

Biological Sciences Undergraduate Honors Theses

Ferroptosis is an iron-dependent, reactive oxygen species (ROS)-driven form of regulated cell death in which the cell membrane is degraded by lipid peroxidation. It is regulated by multiple enzymes, such as glutathione peroxidase 4 (GPX4), which prevents membrane degradation by reducing lipid peroxides and protecting cells from oxidative damage. When inhibitors like RSL3 target GPX4, lipid peroxides build up, and toxic ROS compromises membrane integrity. Traditional anticancer treatments, such as most chemotherapies, aim to eliminate tumor cells by damaging DNA and triggering apoptosis. However, resistance to apoptosis is a “hallmark of cancer,” often resulting in treatment failure. As a distinct …


Exploring Intracellular Signaling Responses To Ks18, A Potent Mcl-1 Inhibitor, In Multiple Myeloma, Emily Nelson, Omar S Al-Odat, Dhruti A. Brahmbhatt, Tulin Budak-Alpdogan, Subash Jonnalagadda, Manoj Kumar Pandey May 2025

Exploring Intracellular Signaling Responses To Ks18, A Potent Mcl-1 Inhibitor, In Multiple Myeloma, Emily Nelson, Omar S Al-Odat, Dhruti A. Brahmbhatt, Tulin Budak-Alpdogan, Subash Jonnalagadda, Manoj Kumar Pandey

Rowan-Virtua Research Day

Multiple myeloma (MM), a cancer of plasma B cells, is a hematological malignancy in which patients inevitably relapse and develop drug resistance. Mcl-1, a member of the anti-apoptotic subgroup of Bcl-2 family proteins, plays a critical role in the progression of multiple myeloma and contributes significantly to drug resistance. Elevated Mcl-1 expression is observed in approximately 52% of MM patients at diagnosis, increasing to 81% at relapse. Given its driving role in disease progression and therapy resistance, Mcl-1 inhibition has emerged as a promising therapeutic target, prompting ongoing research into the development and clinical evaluation of Mcl-1 inhibitors, particularly for …


Accelerated Tumor Growth And Lymphatic Spread Of Transplantable Melanomas In Tumor Necrosis Factor(Tnf)-Transgenic Mice, Catherine F. Alapatt, Robert Hughes, Roger Sheffmaker, Gillian Mcguire, Daniel Deegan, Igor Kuzin, Andrea Bottaro May 2025

Accelerated Tumor Growth And Lymphatic Spread Of Transplantable Melanomas In Tumor Necrosis Factor(Tnf)-Transgenic Mice, Catherine F. Alapatt, Robert Hughes, Roger Sheffmaker, Gillian Mcguire, Daniel Deegan, Igor Kuzin, Andrea Bottaro

Rowan-Virtua Research Day

Melanoma is the fifth most common cancer among American adults, with significant morbidity and mortality at 5 years remaining >60% for patients with stage IV disease. The malignancy is due to the transformation of melanocytes, with one of the major risk factors being ultraviolet light exposure. Although as many as one in five human cancers have been linked to chronic inflammation, the role of inflammatory signals in melanoma growth and metastasis remains poorly understood.

Tumor necrosis factor (TNF)-transgenic (TNFtg) mice are a well-established model of chronic systemic inflammation, with involvement of joints and other organ systems. To assess the effect …


The Role Of Myosin L In The Survival Of Toxoplasma Gondii And The Importance Of Mlc1 For In Vitro And In Vivo Myosin F Motility, Victoria K. Yi May 2025

The Role Of Myosin L In The Survival Of Toxoplasma Gondii And The Importance Of Mlc1 For In Vitro And In Vivo Myosin F Motility, Victoria K. Yi

Honors Scholar Theses

My thesis discusses the work that I have conducted on two myosins in Toxoplasma gondii, which is an obligate intracellular parasite that has chronically infected around 10% of the American population. It causes toxoplasmosis and severe health consequences for individuals with compromised immune systems or when infections occur in utero. However, immunocompetent individuals are asymptomatic or present with subclinical symptoms. In the Heaslip lab, I investigated two myosins in the parasite: Myosin L and Myosin F. MyoL is an uncharacterized motor that localizes at the apical end of the parasite. It was shown to be important for parasite …


Investigating The Effects Of Prenatal E-Cigarette Exposure On Postnatal Liver Histology, Emma Mcclellan May 2025

Investigating The Effects Of Prenatal E-Cigarette Exposure On Postnatal Liver Histology, Emma Mcclellan

College of Arts & Sciences Senior Theses

The electronic cigarette (e-cigarette) entered the American market in the mid-2000s and quickly became popular. This product poses a significant threat to youth with 1.63 million students reporting use in 2024. Adverse health effects to different organs are well known. The liver is less studied, and despite its role in detoxification of e-cigarette chemicals, is a target of injury. Unlike the known effects of cigarettes and nicotine on the liver from adult or prenatal exposure, effects of prenatal exposure to e-cigarettes on liver remain to be defined. The current study investigated the effects of prenatal exposure of e-cigarettes on liver …


Targeting Bard1 Suppresses A Myc-Dependent Transcriptional Program And Tumor Growth In Pancreatic Ductal Adenocarcinoma, Sohum Patel, Eleanor Jenkins, Rutuj P. Kusurkar, Sherry Lee, Wei Jiang, Avinoam Nevler, Matthew Mccoy, Michael J. Pishvaian, Rosalie C. Sears, Jonathan R. Brody, Charles J. Yeo, Aditi Jain May 2025

Targeting Bard1 Suppresses A Myc-Dependent Transcriptional Program And Tumor Growth In Pancreatic Ductal Adenocarcinoma, Sohum Patel, Eleanor Jenkins, Rutuj P. Kusurkar, Sherry Lee, Wei Jiang, Avinoam Nevler, Matthew Mccoy, Michael J. Pishvaian, Rosalie C. Sears, Jonathan R. Brody, Charles J. Yeo, Aditi Jain

Department of Surgery Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers demanding better and more effective therapies. BARD1 or BRCA1-Associated -Ring Domain-1 plays a pivotal role in homologous recombination repair (HRR). However, its function and the underlying molecular mechanisms in PDAC are still not fully elucidated. Here, we demonstrate that BARD1 is overexpressed in PDAC and its genetic inhibition suppresses c-Myc and disrupts c-Myc dependent transcriptional program. Mechanistically, BARD1 stabilizes c-Myc through ubiquitin-proteasome system by regulating FBXW7. Importantly, targeting BARD1 using either siRNAs or CRISPR/Cas9 deletion blocks PDAC growth in vitro and in vivo, without any signs of toxicity to mice. …


The Role Of Ucp2 In Pancreatic Cancer Metabolism And Its Potential As A Radiosensitizer, Emily Rieff May 2025

The Role Of Ucp2 In Pancreatic Cancer Metabolism And Its Potential As A Radiosensitizer, Emily Rieff

Dissertations and Theses (Open Access)

Uncoupling protein 2 (UCP2) is a mitochondrial protein that regulates the flow of protons down the gradient established by the electron transport chain (ETC) without generating ATP, thus uncoupling the proton gradient from ATP generation. In tumors, specifically pancreatic cancer (PDAC), the ETC is highly stimulated to generate the copious ATP needed by the tumor to grow. However, extended ETC use increases reactive oxygen species (ROS), and if left unchecked, results in cell death. To evade this, PDAC employs antioxidant strategies, including upregulating UCP2 in tumor cells. In addition to its uncoupling function, UCP2 indirectly controls ROS levels by maintaining …


Thymosin Beta-4: A Novel Treatment For Acanthamoeba Keratitis, Victoria A. Murphey May 2025

Thymosin Beta-4: A Novel Treatment For Acanthamoeba Keratitis, Victoria A. Murphey

All Theses

Acanthamoeba keratitis (AK) is a severe corneal infection caused by the free-living amoeba, Acanthamoeba. Both stages of its life cycle (trophozoite and cyst) cause infection, primarily in contact lens wearers. It is often misdiagnosed, leading to delayed treatment and poor clinical outcomes. Current treatment options for AK rely on anti-amoebic agents that are toxic to corneal epithelial cells. Further, no single drug can eliminate both forms of the amoeba. Approximately 30% of all AK infections require a corneal transplant.

Thymosin beta-4 (Tβ4) is a G-actin binding protein synthesized in almost all human cells, including corneal epithelial cells. Tβ4 exhibits …


Rod Photoreceptor Regeneration In A Zebrafish Model With Retinitis Pigmentosa, Eyad Shihabeddin May 2025

Rod Photoreceptor Regeneration In A Zebrafish Model With Retinitis Pigmentosa, Eyad Shihabeddin

Dissertations and Theses (Open Access)

A cellular hallmark of inherited retinal degenerative diseases is progressive loss of photoreceptors until one is completely blind. Unlike mammalian models, Zebrafish have the ability to naturally regenerate their neurons after injury or disease is detected. We have generated a zebrafish model with the most common autosomal dominant form of the inherited retinal degenerative disease known as Retinitis Pigmentosa. We utilize immunohistochemistry, single-cell RNA sequencing, several analysis tools, behavioral assays and oligonucleotides to characterize our zebrafish model and identify the transcription factors necessary for rod photoreceptor regeneration. We show that our zebrafish model has continuous degeneration and regeneration of rod …


Uncovering A Fundamental Mechanism Underlying Female Oocyte Quality And Rasopathies Using C. Elegans As A Model System, Han Bit Baek May 2025

Uncovering A Fundamental Mechanism Underlying Female Oocyte Quality And Rasopathies Using C. Elegans As A Model System, Han Bit Baek

Dissertations and Theses (Open Access)

Signaling pathways are molecular networks that allow cells to communicate between and within themselves. They are crucial for the coordination of diverse cellular processes and are the molecular mechanism in which cells sense and respond to their environment. RAS (Rat Sarcoma) is a small GTPase that transmits extracellular growth factor signals through a downstream kinase cascade and ERK (Extracellular-signal regulated kinase) is the terminal kinase, and it controls cellular processes such as proliferation, differentiation, and survival by phosphorylating its downstream effectors. This post translational modification regulates the effector by modulating its activity, levels, and/or interaction with other molecules. Given the …


Exploring The Immunologic Consequences Of Atrx Deficiency In Glioma, Benjamin Whitfield May 2025

Exploring The Immunologic Consequences Of Atrx Deficiency In Glioma, Benjamin Whitfield

Dissertations and Theses (Open Access)

ATRX is a key chromatin regulator that is frequently mutated across multiple cancer types. One of the most common ATRX-mutated tumor types is the adult-type glioma, IDH-mutant, Astrocytoma. It is known that ATRX mutation leads to increases in DNA damage, replication stress, and global epigenetic regulation at a cell level; however, less is known about the impact of ATRX mutation on immune signaling. Furthermore, little is known about the interaction of ATRX loss with gain-of-function mutations in IDH. In this paper we set out to explore the impact of ATRX loss on immune signaling in gliomas, both in the context …


Characterizing Kmt2d In Endometrial Cancer, Katherine R. Davanzo Apr 2025

Characterizing Kmt2d In Endometrial Cancer, Katherine R. Davanzo

Medical Student Research Symposium

Endometrial cancer is rising in incidence in the United States, notably among premenopausal women. This increase and the trend of delayed childbearing warrant the need for further advancement in fertility-sparing treatment for endometrial cancer. A gene left widely unexplored in its possible clinical utility as a target for fertility-sparing treatment is KMT2D, a lysine-specific methyltransferase and tumor suppressor. Preliminary gene set enrichment analysis on a 12Z endometriotic epithelial cell line identified TIMP3 as a gene that is possibly regulated by KMT2D expression. TIMP3 encodes an irreversible inhibitor of matrix metalloproteinases (MMPs), a well-recognized class of proteins as contributing to the …


Hiv Associated Epigenetic Trends And Chronic Diseases: Insights Into The Hidden Burden Of Chronic Infection, Courtney G. Wallace, Zachary Capriotti, Zachary Klase Jan 2025

Hiv Associated Epigenetic Trends And Chronic Diseases: Insights Into The Hidden Burden Of Chronic Infection, Courtney G. Wallace, Zachary Capriotti, Zachary Klase

Kimmel Cancer Center Faculty Papers

Human Immunodeficiency Virus (HIV) remains a major health challenge despite dramatic advances in treatment and prevention. People living with HIV (PLWH) continue to experience high rates of non-AIDS comorbidities, including cardiovascular, renal, pulmonary, oncologic, and neurocognitive disorders. These conditions persist under viral suppression, underscoring the lasting biological impact of infection. Epigenetic dysregulation has emerged as a key driver of these outcomes. HIV integration, viral proteins, chronic inflammation, and ART exposure have all been reported to alter DNA methylation, histone modifications, transcription factor networks, and noncoding RNA regulation. These changes extend beyond infected cells, reprogramming uninfected immune and tissue compartments. Long-lived …


Tdp43 Autoregulation Gives Rise To Dominant Negative Isoforms That Are Tightly Controlled By Transcriptional And Post-Translational Mechanisms, Megan M. Dykstra, Kaitlin Weskamp, Nicolás B. Gómez, Jacob Waksmacki, Elizabeth Tank, M. Rebecca Glineburg, Allison Snyder, Emile Pinarbasi, Michael Bekier, Xingli Li, Morgan R. Miller, Jen Bai, Shameena Shahzad, Neha Nedumaran, Clare Wieland, Corey Stewart, Sydney Willey, Nikolas Grotewold, Jonathon Mcbride, John J. Moran, Aditya V. Suryakumar, Michael Lucas, Peter M. Tessier, Michael Ward, Peter K. Todd, Sami J. Barmada Jan 2025

Tdp43 Autoregulation Gives Rise To Dominant Negative Isoforms That Are Tightly Controlled By Transcriptional And Post-Translational Mechanisms, Megan M. Dykstra, Kaitlin Weskamp, Nicolás B. Gómez, Jacob Waksmacki, Elizabeth Tank, M. Rebecca Glineburg, Allison Snyder, Emile Pinarbasi, Michael Bekier, Xingli Li, Morgan R. Miller, Jen Bai, Shameena Shahzad, Neha Nedumaran, Clare Wieland, Corey Stewart, Sydney Willey, Nikolas Grotewold, Jonathon Mcbride, John J. Moran, Aditya V. Suryakumar, Michael Lucas, Peter M. Tessier, Michael Ward, Peter K. Todd, Sami J. Barmada

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The nuclear RNA-binding protein TDP43 is integrally involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Previous studies uncovered N-terminal TDP43 isoforms that are predominantly cytosolic in localization, prone to aggregation, and enriched in susceptible spinal motor neurons. In healthy cells, however, these shortened (s)TDP43 isoforms are difficult to detect in comparison to full-length (fl)TDP43, raising questions regarding their origin and selective regulation. Here, we show that sTDP43 is created as a by-product of TDP43 autoregulation and cleared by nonsense-mediated RNA decay (NMD). sTDP43-encoding transcripts that escape NMD are rapidly degraded post-translationally via the proteasome …


The C-Terminal Phdvc5hch Tandem Domain Of Nsd2 Is A Combinatorial Reader Of Modified H3k4 And Tri-Methylated H3k27 That Regulates Transcription Of Cell Adhesion Genes In Multiple Myeloma, Andrea Berardi, Charlotte Leonie Kaestner, Michela Ghitti, Giacomo Quilici, Paolo Cocomazzi, Jianping Li, Federico Ballabio, Chiara Zucchelli, Stefan Knapp, Jonathan Licht, Giovanna Musco Jan 2025

The C-Terminal Phdvc5hch Tandem Domain Of Nsd2 Is A Combinatorial Reader Of Modified H3k4 And Tri-Methylated H3k27 That Regulates Transcription Of Cell Adhesion Genes In Multiple Myeloma, Andrea Berardi, Charlotte Leonie Kaestner, Michela Ghitti, Giacomo Quilici, Paolo Cocomazzi, Jianping Li, Federico Ballabio, Chiara Zucchelli, Stefan Knapp, Jonathan Licht, Giovanna Musco

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Histone methyltransferase NSD2 (MMSET) overexpression in multiple myeloma (MM) patients plays an important role in the development of this disease subtype. Through the expansion of transcriptional activating H3K36me2 and the suppression of repressive H3K27me3 marks, NSD2 activates an aberrant set of genes that contribute to myeloma growth, adhesive and invasive activities. NSD2 transcriptional activity also depends on its non-catalytic domains, which facilitate its recruitment to chromatin through histone binding. In this study, using NMR, ITC and molecular dynamics simulations, we show that the tandem PHD domain of NSD2 (PHDVC5HCHNSD2) is a combinatorial reader of unmodified histone H3K4 and tri-methylated H3K27 …


An In Vivo Study Of Lns8801, A Gper Agonist, In A Spontaneous Melanoma-Prone Mouse Model, Tgs., Christina Marinaro, John Sauer, Christopher A Natale, Todd Ridky, Suzie Chen Jan 2025

An In Vivo Study Of Lns8801, A Gper Agonist, In A Spontaneous Melanoma-Prone Mouse Model, Tgs., Christina Marinaro, John Sauer, Christopher A Natale, Todd Ridky, Suzie Chen

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Melanoma is the most aggressive and deadly form of skin cancer that arises from the transformation of melanocytes, the pigment producing cells of the skin. In the year 2024 there will be approximately 10,000 new cases of melanoma diagnosed and approximately 8,000 deaths attributed to melanoma in the United States. In this study we treated a group of male and female transgenic mice that spontaneously develop metastatic melanoma, TGS, with a G-protein-coupled estrogen receptor agonist LNS8801 to assess the efficacy on disease progression. A second group of male and female TGS mice was also exposed to UVB irradiation to mimic …


Impact Of Hiv-2 Rod9 Vpx Mutations On Samhd1 Degradation And Vpx Nuclear Trafficking, Tolulope R. Oladimeji Jan 2025

Impact Of Hiv-2 Rod9 Vpx Mutations On Samhd1 Degradation And Vpx Nuclear Trafficking, Tolulope R. Oladimeji

All Graduate Theses, Dissertations, and Other Capstone Projects

Human Immunodeficiency Virus (HIV) is a leading cause of death in many parts of the world. HIV-2, endemic to West Africa, has infected over 2 million people globally. A key difference between HIV-2 and the more widespread HIV-1 is the HIV-2 protein Vpx, which facilitates infection in non-dividing cells by targeting SAMHD1, a host innate immune protein, for proteasomal degradation. This research aims to identify specific amino acid residues in HIV-2 ROD9 Vpx that are essential for mediating SAMHD1 degradation by the proteosome. I hypothesize that amino acid residues located in the C-terminal region of Vpx play a critical role …


Effects Of Round-Up On The Environment, Sandra J. Marcu Jan 2025

Effects Of Round-Up On The Environment, Sandra J. Marcu

Journal of Earth and Life Science

Many people around the world have used and still currently use Roundup but are unaware of the effects it has on the environment. Roundup is a spray on application weedkiller that is widely used around the world today both residentially and commercially. It enables its user to grow a garden or a field of crops with a no-tilling approach to eliminate weeds. It is a well-known and popular choice for killing weeds that has been around since the mid 1970’s (Oca, 2017). John Franz, a Monsanto scientist discovered that glyphosate (main ingredient in Roundup) was an herbicide or weedkiller, and …


Characterizing A Rad23 Dependent Ultraviolet Radiation Resistance In Tetrahymena Thermophila, Emma June Liimatta Jan 2025

Characterizing A Rad23 Dependent Ultraviolet Radiation Resistance In Tetrahymena Thermophila, Emma June Liimatta

Graduate Theses/Dissertations

In 2020, 10 million deaths were attributed to cancer, with multidrug resistance being responsible for over 90% of deaths in cancer patients receiving treatment. This study utilized the model organism Tetrahymena thermophila to study how cells become resistant to Ultraviolet Radiation (UV) radiation, a process similar to multidrug resistance, specifically focusing on the nucleotide excision repair and ubiquitin shuttle protein Rad23. The National Cancer Institute documented 30-60% of cancers tested had a mutation in RAD23. Knockdown of RAD23 in Tetrahymena thermophila demonstrated a UV resistance phenotype with decreased nucleotide excision repair and differential expression of proteins active within caspase-independent …


The Role Of Host Factor Sptbn1 In Hiv-1 Capsid Uncoating In Human Microglial Cells, Callie Marie Fry Jan 2025

The Role Of Host Factor Sptbn1 In Hiv-1 Capsid Uncoating In Human Microglial Cells, Callie Marie Fry

Graduate Theses/Dissertations

HIV-1 is the virus that causes acquired immunodeficiency syndrome (AIDS), and currently, there is no cure once an individual is infected. The development of new drugs targeting HIV-1 replication steps is essential for keeping viral loads low or undetectable to prevent further transmission. An attractive replication step for new drug targets is viral capsid uncoating, where the virus loses the protein structure encapsulating the genome. The exact mechanism of capsid uncoating is unknown; however, several host-factors may be involved including protein SPTBN1. Recent studies have shown a significant decrease in viral infectivity when SPTBN1 is knocked down, yet its role …