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Full-Text Articles in Cancer Biology

The Development Of A Crispr-Based Calibrated Functional Assay For Classifying Pathogenicity Of Msh2 And Msh6 Variants In Lynch Syndrome, Olivia N. Amodeo May 2026

The Development Of A Crispr-Based Calibrated Functional Assay For Classifying Pathogenicity Of Msh2 And Msh6 Variants In Lynch Syndrome, Olivia N. Amodeo

Honors Scholar Theses

Lynch syndrome is a hereditary disease caused by the inheritance of a mismatch repair gene variant. Individuals with this condition are predisposed to cancer development, most commonly colorectal cancer. Current guidelines for variant classification are based on numerous evidence categories, including functional evidence. However, many novel clinical variants are not well characterized, and evidence is difficult to obtain if functional assays are not calibrated.

To address this, our lab created a calibrated functional assay that calculates an odds of pathogenicity score for MSH2 and MSH6 gene variants that can be used as evidence for classifying variants of uncertain significance. This …


Comparative Spatial Biology: A Cross-Species Analysis Of Canine Oral Cancers As Models For Human Disease, Ram Pradhyumnan Jan 2026

Comparative Spatial Biology: A Cross-Species Analysis Of Canine Oral Cancers As Models For Human Disease, Ram Pradhyumnan

Honors Undergraduate Theses

Oral squamous cell carcinoma (OSCC), one of the most common malignancies of the oral cavity, remains a clinically challenging disease due to its aggressive behavior, late-stage diagnosis, and limited improvements in therapeutic outcomes over recent decades. A significant barrier to progress in OSCC research and treatment is the lack of suitable preclinical models that recapitulate the complexity and natural progression of the disease. Most current models—including cell lines, xenografts, and genetically engineered mice—fail to capture key features such as the spatial organization of tumor epithelium, interactions with an intact immune system, and the stepwise evolution from normal mucosa to invasive …


Synthesis And Characterization Of Succinate Dehydrogenase Inhibitors H2/Z14 And C6/Z96 In Order To Combat Small Cell Lung Cancer, Lauren M. Graves Jan 2026

Synthesis And Characterization Of Succinate Dehydrogenase Inhibitors H2/Z14 And C6/Z96 In Order To Combat Small Cell Lung Cancer, Lauren M. Graves

Honors Undergraduate Theses

The use of ubiquinone inhibitors to combat cancer is a recent development in medicinal science and procedures to efficiently synthesize these drugs remain limited. C6/Z96 and H2/Z14, two succinate dehydrogenase inhibitors, have been previously tested in vitro against NSCLC with positive results. Their similarity to ubiquinone is what makes them a strong candidate for a succinate dehydrogenase inhibitor at the ubiquinone binding site. The heterocyclic scaffolds and substituents are proposed to bind strongly through a combination of electronics, hydrogen-bonding, and fit, allowing them to bind well and prove to be more favorable than ubiquinone when competing for the Q-site. By …


Runx2 Cooperates With Srebp1 To Rewire Cancer Metabolism And Promote Aggressiveness, Emanuele Vitale, Mila Gugnoni, Veronica Manicardi, Silvia Muccioli, Federica Torricelli, Benedetta Donati, Simonetta Piana, Gloria Manzotti, Elisa Salviato, Francesca Reggiani, Cristian Ascione, Rebecca Vezzani, Moira Ragazzi, Mattia Forcato, Oriana Romano, Silvio Bicciato, Aaron Goldman, Marco Tigano, Alessia Ciarrocchi Oct 2025

Runx2 Cooperates With Srebp1 To Rewire Cancer Metabolism And Promote Aggressiveness, Emanuele Vitale, Mila Gugnoni, Veronica Manicardi, Silvia Muccioli, Federica Torricelli, Benedetta Donati, Simonetta Piana, Gloria Manzotti, Elisa Salviato, Francesca Reggiani, Cristian Ascione, Rebecca Vezzani, Moira Ragazzi, Mattia Forcato, Oriana Romano, Silvio Bicciato, Aaron Goldman, Marco Tigano, Alessia Ciarrocchi

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Embryonic Transcription Factors (TFs) are often reactivated in cancer, driving developmental gene programs that support phenotypic plasticity. Metabolic adaptation fuels this plasticity by supplying energy and molecular building blocks for growth. RUNX2, the master regulator of bone morphogenesis, is ectopically expressed in epithelial cancer, promoting metastasis through trans-differentiation processes like Epithelial-to-Mesenchymal Transition (EMT) and osteomimicry. By combining omics data with functional validation, we demonstrated that RUNX2 drives cancer cell metabolic rewiring by repressing mitochondrial respiration while promoting anabolic processes. We showed that RUNX2 upregulates key genes of lipid biosynthesis by regulating and cooperating with SREBP1. In vivo expression analysis in …


Setdb1 Is Critically Required For Uveal Melanoma Growth And Represents A Promising Therapeutic Target, Imène Krossa, Céline Pisibon, Yann Cheli, Karine Bille, Mélanie Dalmasso, Sabah Hamadat, Chrystel Husser, Marie Irondelle, Julien Cherfils-Vicini, Frédéric Soysouvanh, Sacha Nahon-Esteve, Arnaud Martel, Sandra Lassalle, Jean-Pierre Caujolle, Célia Maschi, Stéphanie Baillif, Dan Hasson, Saul Carcamo, Andrerw E. Aplin, Irwin Davidson, Emily Bernstein, Valeria Naim, Robert Ballotti, Corine Bertolotto, Thomas Strub Oct 2025

Setdb1 Is Critically Required For Uveal Melanoma Growth And Represents A Promising Therapeutic Target, Imène Krossa, Céline Pisibon, Yann Cheli, Karine Bille, Mélanie Dalmasso, Sabah Hamadat, Chrystel Husser, Marie Irondelle, Julien Cherfils-Vicini, Frédéric Soysouvanh, Sacha Nahon-Esteve, Arnaud Martel, Sandra Lassalle, Jean-Pierre Caujolle, Célia Maschi, Stéphanie Baillif, Dan Hasson, Saul Carcamo, Andrerw E. Aplin, Irwin Davidson, Emily Bernstein, Valeria Naim, Robert Ballotti, Corine Bertolotto, Thomas Strub

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Metastatic uveal melanomas are highly resistant to all existing treatments. To identify actionable vulnerabilities, we conducted a CRISPR-Cas9 knockout screen using a library composed of chromatin regulators. We revealed that the lysine methyltransferase, SETDB1, plays a critical role in metastatic uveal melanoma cell proliferation and survival. Functionally, SETDB1 deficiency induces a DNA damage response, senescence-like state and growth arrest. Knockdown of SETDB1 is associated with a decreased expression of genes related to replication and cell cycle. Moreover, deficiency in CDC6, an essential regulator of DNA replication, phenocopies SETDB1 inhibition. Using a pre-clinical model, we further demonstrated that anti-SETDB1 therapy impairs …


Molecular Determinants Of Neoadjuvant Chemotherapy Resistance In Breast Cancer: An Analysis Of Gene Expression And Tumor Microenvironment, Hedda Michelle Guevara-Nieto, Carlos A. Orozco-Castaño, Rafael Parra-Medina, Jenny Nathaly Poveda-Garavito, Jone Garai, Jovanny Zabaleta, Liliana López-Kleine, Alba Lucia Combita Oct 2025

Molecular Determinants Of Neoadjuvant Chemotherapy Resistance In Breast Cancer: An Analysis Of Gene Expression And Tumor Microenvironment, Hedda Michelle Guevara-Nieto, Carlos A. Orozco-Castaño, Rafael Parra-Medina, Jenny Nathaly Poveda-Garavito, Jone Garai, Jovanny Zabaleta, Liliana López-Kleine, Alba Lucia Combita

School of Graduate Studies Faculty Publications

Neoadjuvant chemotherapy (NAC) is a critical component of breast cancer treatment, but the molecular mechanisms underlying resistance remain poorly understood. This study aimed to identify transcriptomic changes associated with NAC resistance across four breast cancer subtypes: Luminal A, Luminal B/HER2-positive, Luminal B/HER2-negative, and Triple-Negative Breast Cancer (TNBC). RNA-seq analysis was performed on paired pre- and post-NAC breast cancer samples from 32 nonresponders. Differentially expressed genes (DEGs) were identified, and functional enrichment analyses were conducted. Protein-protein interaction (PPI) networks were constructed to identify hub genes. Tumor microenvironment (TME) infiltration was estimated using deconvolution algorithms. The results revealed distinct gene expression profiles …


A Novel Sialylation Pathway Mediated By Extracellular Vesicles In Aggressive Prostate Cancer, Camila A. Bach, Md Niamat Hossain, Ishan J. Chaudhari, Cecilia E. Verrillo, Nicole M. Naranjo, Isabella Amoroso, Anna Testa, Samuel Sey, W. Kevin Kelly, Susan L. Bellis, Aurelio Lorico, Ada G. Blidner, Gabriel A. Rabinovich, Lucia R. Languino Sep 2025

A Novel Sialylation Pathway Mediated By Extracellular Vesicles In Aggressive Prostate Cancer, Camila A. Bach, Md Niamat Hossain, Ishan J. Chaudhari, Cecilia E. Verrillo, Nicole M. Naranjo, Isabella Amoroso, Anna Testa, Samuel Sey, W. Kevin Kelly, Susan L. Bellis, Aurelio Lorico, Ada G. Blidner, Gabriel A. Rabinovich, Lucia R. Languino

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Altered cell surface glycosylation is a hallmark of cancer; among aberrant glycan structures, hypersialylated proteins contribute to disease progression. The enzyme ST6 β-galactoside α2,6-sialyltransferase 1 (ST6GAL1) mediates α2,6-linked sialylation of N-glycosylated proteins and is upregulated in many cancers, including prostate cancer (PrCa). We propose that ST6GAL1 may be released by cancer cells in small extracellular vesicles (sEVs) in the PrCa tumor microenvironment to potentially modulate cell surface sialylation in recipient cells. We isolated sEVs from PrCa cells by density gradient separation and characterized them by nanoparticle tracking analysis using ZetaView and immunoblotting analysis. We identified ST6GAL1 in both its membrane-bound …


Subtype-Specific Her3 Enrichment In Basal-Like Breast Cancer Is Regulated Via The Gata2/Gata3–Foxa1 Axis, Congcong Tan, Hui Lyu, Sanbao Ruan, Yakun Wu, Margaret E. Larsen, Shou Ching Tang, Bolin Liu Sep 2025

Subtype-Specific Her3 Enrichment In Basal-Like Breast Cancer Is Regulated Via The Gata2/Gata3–Foxa1 Axis, Congcong Tan, Hui Lyu, Sanbao Ruan, Yakun Wu, Margaret E. Larsen, Shou Ching Tang, Bolin Liu

School of Medicine Faculty Publications

Basal-like breast cancer (BLBC) is a major subtype of triple-negative breast cancer (TNBC), characterized by aggressive behavior, limited treatment options, and poor prognosis. While HER3 overexpression is frequently observed in TNBC and associated with poor outcomes, its subtype-specific expression and therapeutic potential remain unclear. Here, we demonstrated that HER3 signaling is selectively hyperactivated in BLBC compared to claudin-low breast cancer (CLBC) using transcriptomic profiling. Histone deacetylase inhibitors (HDACi), Romidepsin and Panobinostat, exerted potent antitumor effects on BLBC by selectively downregulating HER3 expression. HER3 levels were positively correlated with FOXA1, a key transcriptional activator. Mechanistically, we identified GATA2 and GATA3 as …


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 …


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 …


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 …


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 …


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 …


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 …


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 …


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 …


Gain-Of-Function Tp53 Mutations Induce Non-Canonical Nf-Κb Transcriptional Targets To Promote Tumor Development, Kelsey A. Yutan Jan 2025

Gain-Of-Function Tp53 Mutations Induce Non-Canonical Nf-Κb Transcriptional Targets To Promote Tumor Development, Kelsey A. Yutan

Scripps Senior Theses

Background: Gain-of-function TP53 mutations have previously been shown to induce chromosomal instability (CIN) in cancer cells, triggering the cGAS-STING innate immune response and subsequently activating the non-canonical NF-κB (NC-NF-κB) signaling pathway. This signaling cascade promotes cancer cell metastasis and an immunosuppressive tumor microenvironment (TME), significantly impacting tumor development and progression. However, the precise downstream mechanisms by which the mutp53-CIN-cGAS-STING-NC-NF-κB signaling pathway facilitates tumor development and progression remain poorly understood. Here, our objective was to identify direct downstream targets of mutp53-CIN-cGAS-STING-induced NC-NF-κB signaling that potentially impact the TME to promote the development and progression of oral squamous cell carcinoma.

Methods …


Repositioning Antimalarial Drugs As Anticancer Agents: Focus On Tafenoquine, Chris Barton Jan 2025

Repositioning Antimalarial Drugs As Anticancer Agents: Focus On Tafenoquine, Chris Barton

Funded Scholarship

Due to the expensive and lengthy process of drug design and approval, drug repurposing (or repositioning) has become another option for identifying preexisting molecules that may be used for alternative purposes. Recently, some antimalarial compounds have been shown to display efficacy against cancer cell proliferation. In this study, we provide evidence to suggest that multiple preexisting antimalarial drugs can reduce the viability of human cancer cells in culture. Furthermore, we provide the first evidence that one antimalarial, Tafenoquine (LD50 = 9.6 μM in HCT116 cells), is capable of decreasing viability with an efficacy comparable to Etoposide (LD50 = 15.2 μM …


Investigating Tumor Growth And Regulation In Supratentorial Ependymomas; The Impact Of Dlk1 And Egr1 Knockout, Om Sinojia Dec 2024

Investigating Tumor Growth And Regulation In Supratentorial Ependymomas; The Impact Of Dlk1 And Egr1 Knockout, Om Sinojia

Honors Scholar Theses

Ependymomas (EPNs) are primary brain tumors that often arise from radial glial cells lining the ventricular system. Supratentorial ependymomas (ST-EPNs) are particularly aggressive, and understanding the molecular factors driving their growth is critical for developing targeted therapies. This study investigates the roles of DLK1 and EGR1, key regulators in cellular differentiation and tumorigenesis, in the development of ST-EPNs. We utilized genetically engineered mouse models to induce postnatal knockouts of DLK1 and EGR1 and evaluated tumor growth using histological and imaging techniques. Tumor area was quantified across multiple brain sections from both male and female mice. DLK1 knockout brains exhibited consistent …


Adiposity Throughout Adulthood And Risk Of Young-Onset Breast Cancer Tumor Subtypes In The Young Women's Health History Study, Lydia Marcus Post, Dorothy R. Pathak, Ann S. Hamilton, Kelly A. Hirko, Richard T. Houang, Emily H. Guseman, Dan Sanfelippo, Nicole Bohme Carnegie, L. Karl Olson, Hallgeir Rui, Ann G. Schwartz, Ellen M. Velie Dec 2024

Adiposity Throughout Adulthood And Risk Of Young-Onset Breast Cancer Tumor Subtypes In The Young Women's Health History Study, Lydia Marcus Post, Dorothy R. Pathak, Ann S. Hamilton, Kelly A. Hirko, Richard T. Houang, Emily H. Guseman, Dan Sanfelippo, Nicole Bohme Carnegie, L. Karl Olson, Hallgeir Rui, Ann G. Schwartz, Ellen M. Velie

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

BACKGROUND: The role of adult adiposity in young-onset breast cancer (YOBC) subtype risk is not well understood.

METHODS: In this population-based case (n = 1812)-control (n = 1,381) study of invasive YOBC (ages <50 >years), cases were identified from the Los Angeles County and Metropolitan Detroit Surveillance, Epidemiology, and End Results registries, 2010 to 2015. Area-based, frequency-matched controls were sampled from the 2010 Census. General adiposity [body mass index (BMI)] and central adiposity (waist circumference and waist-to-height ratio) across adulthood and covariates were collected from in-person interviews and measurements. ORs and 95% confidence intervals (CI) for adiposity and YOBC tumor subtypes …


Early Ctdna Kinetics As A Dynamic Biomarker Of Cancer Treatment Response, Aaron Li, Emil Lou, Kevin Leder, Jasmine Foo Nov 2024

Early Ctdna Kinetics As A Dynamic Biomarker Of Cancer Treatment Response, Aaron Li, Emil Lou, Kevin Leder, Jasmine Foo

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.


Predicting And Monitoring Immune Checkpoint Inhibitor Therapy Using Artificial Intelligence In Pancreatic Cancer, Guangbo Yu, Zigeng Zhang, Aydin Eresen, Qiaoming Hou, Farideh Amirrad, Sha Webster, Surya M. Nauli, Vahid Yaghmai, Zhuoli Zhang Nov 2024

Predicting And Monitoring Immune Checkpoint Inhibitor Therapy Using Artificial Intelligence In Pancreatic Cancer, Guangbo Yu, Zigeng Zhang, Aydin Eresen, Qiaoming Hou, Farideh Amirrad, Sha Webster, Surya M. Nauli, Vahid Yaghmai, Zhuoli Zhang

Pharmacy Faculty Articles and Research

Pancreatic cancer remains one of the most lethal cancers, primarily due to its late diagnosis and limited treatment options. This review examines the challenges and potential of using immunotherapy to treat pancreatic cancer, highlighting the role of artificial intelligence (AI) as a promising tool to enhance early detection and monitor the effectiveness of these therapies. By synthesizing recent advancements and identifying gaps in the current research, this review aims to provide a comprehensive overview of how AI and immunotherapy can be integrated to develop more personalized and effective treatment strategies. The insights from this review may guide future research efforts …