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2025

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Articles 31 - 60 of 143

Full-Text Articles in Cancer Biology

Co-Culture 3d Model For Breast Cancer, Anh Duc Nguyen Aug 2025

Co-Culture 3d Model For Breast Cancer, Anh Duc Nguyen

Research from the Berry Summer Thesis Institute, 2025

The ability to replicate the tumor microenvironment using 3D models have allowed researchers to study the tumors in vitro closer to their in vivo counterparts without the drawbacks of those models. The 3D co-culture model is an improved version of the 3D monoculture model, capable of replicating the tumor microenvironment, letting researchers study cancer response mechanism, tumor metastases, drug resistance, simulate cell-cell interactions, etc., in breast cancer. The models can be classified into four classes based on their formation method and content, all of which have different advantages and disadvantages.


Heterogeneity Of Molecular Subtypes In Multifocal And Multicentric Breast Cancer, Anna M. Schmitz Aug 2025

Heterogeneity Of Molecular Subtypes In Multifocal And Multicentric Breast Cancer, Anna M. Schmitz

Research from the Berry Summer Thesis Institute, 2025

Multifocal and multicentric breast cancers (MMBC), commonly referred to as multiple synchronous ipsilateral breast cancers, are heterogeneous diseases. There is a high degree of diversity between and within the tumors of a MMBC-bearing patient. Tumor heterogeneity can describe multiple features, such as morphological and molecular profiles. Knowledge about a patient's tumor heterogeneity can be used to determine a prognosis and treatment plan. However, transferring our growing knowledge of heterogeneity in MMBC into a clinical setting remains a challenge due to the large degree of diversity between tumor microenvironments and the cancer cells that tumors are composed of. This review article …


Role Of Stabilin-1 Expressing Macrophages In Colorectal Liver Metastasis, Jampa L. Gurung Aug 2025

Role Of Stabilin-1 Expressing Macrophages In Colorectal Liver Metastasis, Jampa L. Gurung

Theses & Dissertations

Colorectal cancer (CRC) is the 2nd most common cause of cancer-related mortality, primarily due to its spread to distant organs. Colorectal liver metastasis (CRLM) is the foremost form of CRC spread due to the anatomical link between the liver and intestine. Despite advancements in diagnostic tools and adjuvant therapies, the survival rate of CRLM remains low, indicating the significant need to identify targetable mechanisms. Stabilin-1 (STAB1), a scavenger receptor expressed on tumor-associated macrophages, has been linked to tumorigenesis and poor outcomes in various cancers. However, the role of STAB1 in CRLM is not known. Here, we investigated the role of …


Claudin-1-Mediated Signaling And Therapy Resistance In Colorectal Cancer: From Mechanism To Translation, Mark W. Primeaux Aug 2025

Claudin-1-Mediated Signaling And Therapy Resistance In Colorectal Cancer: From Mechanism To Translation, Mark W. Primeaux

Theses & Dissertations

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality, with metastatic cases showing poor response to chemotherapy due to both intrinsic and acquired therapy resistance. Claudin-1 (CLDN1), a tight junction protein, is overexpressed and mislocalized outside of tight junctions in CRC, where it contributes to an aggressive, metastatic phenotype. Although this causal relationship has been well established, the mechanisms by which CLDN1 promotes tumor progression were unclear due to its lack of intrinsic enzymatic activity. This dissertation investigates the molecular mechanisms through which CLDN1 drives oncogenic signaling, its role in therapy resistance, and its translational potential as both a …


Global Erk/Mapk Activation Determines Oncogenic Fitness In Kras-Mutant Pancreatic Ductal Adenocarcinoma, Rachel A. Burge Aug 2025

Global Erk/Mapk Activation Determines Oncogenic Fitness In Kras-Mutant Pancreatic Ductal Adenocarcinoma, Rachel A. Burge

MUSC Theses and Dissertations

In pancreatic ductal adenocarcinoma (PDAC), ~95% of cases harbor an activating KRAS mutation. The most common KRAS mutations in PDAC are KRASG12D (42%), KRASG12V (31%), and KRASG12R (15%). Patients harboring KRASG12R mutations have increased overall survival compared to those with KRASG12D/V-mutations. While KRASG12D/Vare common in all KRAS-mutant cancers, KRASG12Ris only common in PDAC.

KRASG12R is unable to activate the lipid kinase PIK3CA, a KRAS effector that is important for tumorigenesis in murine models. To investigate the tumorigenic potential of KRASG12R and the mechanisms that enable this mutation …


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 …


Clonal Phenotype Mapping Reveals Genomic Alterations Underlying Tumor Immunosuppression During Immunotherapy, Er-Yen Yen Aug 2025

Clonal Phenotype Mapping Reveals Genomic Alterations Underlying Tumor Immunosuppression During Immunotherapy, Er-Yen Yen

Dissertations and Theses (Open Access)

Tumors are dynamic ecosystems that evolve under selective pressures, shaping their ability to either elicit or evade immune responses. In pancreatic ductal adenocarcinoma (PDAC), where immunotherapy has yet to become an effective treatment option, we investigated the role of intratumoral heterogeneity in influencing immune interactions. Using orthotopic clonal replica tumors, we tracked clonal dynamics in response to anti-PD1 therapy and found that while treatment had limited impact on overall tumor volume, it induced profound shifts in clonal composition. Spatial lineage analysis of treatment-naïve tumors revealed that clones with distinct immunotherapy sensitivities occupy unique tumor microenvironments, a pattern that remained stable …


Impact Of S-Phase Kinase Protien 2 Blockades On Hematopoetic Stem Cell Metabolism, Nicole Elmaraghy Aug 2025

Impact Of S-Phase Kinase Protien 2 Blockades On Hematopoetic Stem Cell Metabolism, Nicole Elmaraghy

Electronic Theses, Projects, and Dissertations

Hematopoietic stem and progenitor cells (HSPCs) quiescence is vital for the success of bone marrow transplantation, as it preserves long term self- renewal and prevents premature exhaustion (Takubo et al., 2013; Wilson et al., 2008). However, bone marrow transplant (BMT) failure remains a clinical challenge, often due to lack of long-term engraftment and insufficient stress reliance. Both of these characteristics are tightly linked to disrupted stem cell quiescence and metabolic imbalance (Anso et al., 2017; Vannini et al., 2016). One key player is S-phase kinase protein (SKP2), an E3 ubiquitin ligase that targets cell cycle inhibitors, like p27, for proteosome …


Investigating The Role Of The Lysine-Specific Demethylase 4c In Pancreatic Ductal Adenocarcinoma, Mennatallah Shaheen Aug 2025

Investigating The Role Of The Lysine-Specific Demethylase 4c In Pancreatic Ductal Adenocarcinoma, Mennatallah Shaheen

Dissertations and Theses (Open Access)

Deregulation of proteins involved in chromatin regulation is common in pancreatic ductal adenocarcinoma (PDAC). Lysine demethylase 4C (KDM4C) is one of the chromatin modifying proteins frequently overexpressed across multiple solid cancers and is linked to chromatin instability, increased cell proliferation, and enhanced stem cell-like behavior. We observed upregulation of KDM4C protein in a panel of human PDAC cell lines and patient samples compared to non-neoplastic controls. CRISPR/Cas9-mediated deletion of KDM4C in human and murine PDAC cells reduced proliferation, clonogenicity, and increased survival of orthotopically implanted murine PDAC allografts. Transcriptomic and proteomics analyses revealed that loss of KDM4C in both human …


Bifunctional Fusion Protein Pdl1sfv/Micae For Cancer Immunothearpy, Junyi Li Aug 2025

Bifunctional Fusion Protein Pdl1sfv/Micae For Cancer Immunothearpy, Junyi Li

All Dissertations

Cancer immunotherapy has highlighted the importance of immune checkpoint blockade and innate immune cell engagement in battling tumor-mediated immune suppression in the past few decades. However, with cancer development, advanced tumors are often found to develop resistance towards single-target immunotherapy due to the complexity of the immunosuppressive mechanisms within the tumor microenvironment (TME). To address this, we developed a novel bifunctional fusion protein, PDL1sFv/MICAe, which combines the tumor-targeting capability of an anti-PDL1 single-chain variable fragment (sFv) with the NK cells immunostimulatory properties of the MICA extracellular domain.

In vitro functional assays revealed that PDL1sFv/MICAe significantly enhanced cytotoxicity towards natural killer …


Elevated Nr2f1 Underlies The Persistence Of Invasive Disease After Treatment Of Braf-Mutant Melanoma, Manoela Tiago, Timothy J. Purwin, Casey D. Stefanski, Renaira Oliveira Da Silva, Mitchell E. Fane, Yash Chhabra, Jelan I. Haj, Jessica L. F. Teh, Rama Kadamb, Weijia Cai, Sheera Rosenbaum, Vivian Chua, Nir Hacohen, Michael A. Davies, Jessie Villanueva, Inna Chervoneva, Ashani T. Weeraratna, Dan A. Erkes, Claudia Capparelli, Julio A. Aguirre-Ghiso, Andrew E. Aplin Jul 2025

Elevated Nr2f1 Underlies The Persistence Of Invasive Disease After Treatment Of Braf-Mutant Melanoma, Manoela Tiago, Timothy J. Purwin, Casey D. Stefanski, Renaira Oliveira Da Silva, Mitchell E. Fane, Yash Chhabra, Jelan I. Haj, Jessica L. F. Teh, Rama Kadamb, Weijia Cai, Sheera Rosenbaum, Vivian Chua, Nir Hacohen, Michael A. Davies, Jessie Villanueva, Inna Chervoneva, Ashani T. Weeraratna, Dan A. Erkes, Claudia Capparelli, Julio A. Aguirre-Ghiso, Andrew E. Aplin

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Despite the success of targeted inhibitors in cutaneous melanoma, therapeutic responses are limited by the aged tumor microenvironment and drug-tolerant residual cells. Given the similarities between drug tolerance and cellular dormancy, we studied the dormancy marker, nuclear receptor subfamily 2 group F member 1 (NR2F1), in response to BRAF-V600E inhibitors (BRAFi) plus MEK inhibitors (MEKi) in BRAF-mutant melanoma models. Transcriptomic analysis of melanoma patient samples treated with BRAFi + MEKi showed increased NR2F1. NR2F1 was highly expressed in the drug-tolerant invasive cell state of minimal residual disease in patient-derived and mouse-derived xenografts on BRAFi + MEKi. NR2F1 over-expression was sufficient …


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 …


Utilizing The Combinatory Power Of Chemotherapeutic Compounds In Triple Negative Breast Cancer Cells, Matthew I. Hyder Jul 2025

Utilizing The Combinatory Power Of Chemotherapeutic Compounds In Triple Negative Breast Cancer Cells, Matthew I. Hyder

Biology Summer Fellows

Breast cancer is the leading cause of cancer-related deaths among women worldwide and the second most common cause of cancer deaths in women in the United States. Genetic variants that increase the risk of breast cancer include mutations in the breast cancer susceptibility genes 1 and 2 (BRCA1 and BRCA2). Apoptosis, or programmed cell death, is a natural process that helps the body remove aged cells. However, in cancer, deregulated apoptotic signaling—especially the activation of anti-apoptotic mechanisms—enables cancer cells to evade this process, leading to uncontrolled proliferation, tumor survival, therapeutic resistance, and cancer recurrence. Most anti-cancer drugs function as chemotherapeutic …


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 …


Surface Keratin 1, A Tumor-Selective Peptide Target In Human Triple-Negative Breast Cancer, Shih-Jing Yao, Farideh Amirrad, Elmira Ziaei, Azam Saghaeidehkordi, Moom R. Roosan, Kiumars Shamloo, Ajay Sharma, Rachita K. Sumbria, Surya M. Nauli, Christopher G. Bunick, Kamaljit Kaur Jul 2025

Surface Keratin 1, A Tumor-Selective Peptide Target In Human Triple-Negative Breast Cancer, Shih-Jing Yao, Farideh Amirrad, Elmira Ziaei, Azam Saghaeidehkordi, Moom R. Roosan, Kiumars Shamloo, Ajay Sharma, Rachita K. Sumbria, Surya M. Nauli, Christopher G. Bunick, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Targeting drugs to cancer cells via overexpressed cell-surface receptors has emerged as an effective therapeutic strategy for several cancers. However, identifying cell-surface receptors that allow selective uptake of targeting ligands by cancer cells—while sparing normal cells—remains a challenge, especially for triple-negative breast cancer (TNBC), which lacks a well-defined receptor for targeted delivery. In this study, immunohistochemical (IHC) analysis revealed that human TNBC patient tissues have significantly higher levels of keratin 1 (K1) compared to normal breast tissues. Among TNBC tissues, grade 3 tumors showed significantly higher (threefold) K1 expression compared to grade 2 tumors. We analyzed human TNBC and normal …


Microscopic Nucleic Acid-To-Protein Ratio: A Label-Free Approach For Pancreatic Cancer Detection, Sky Gao, Keerthi Priya Jangili, Alfred Akinlalu, Emmanuel Ogberefor, Tommy Gao, Kalpana Devaraj, Dali Sun Jun 2025

Microscopic Nucleic Acid-To-Protein Ratio: A Label-Free Approach For Pancreatic Cancer Detection, Sky Gao, Keerthi Priya Jangili, Alfred Akinlalu, Emmanuel Ogberefor, Tommy Gao, Kalpana Devaraj, Dali Sun

Electrical and Computer Engineering: Faculty Scholarship

Accurate and timely diagnosis remains a major clinical challenge, hindered by the limitations of conventional histopathological methods, which often rely on labor-intensive staining protocols and subjective interpretation by specialized pathologists. These methods can fail to capture the full molecular and phenotypic heterogeneity of tumors, leading to increased diagnostic time, cost, and variability. To overcome these challenges, we developed a novel label-free ultraviolet (UV) microscopic imaging technique that exploits the intrinsic optical absorption properties of cellular nucleic acids and proteins. By modifying standard brightfield microscopes, our approach quantitatively measures the nucleic acid-to-protein ratio (NPr), enabling high-resolution visualization and discrimination between malignant …


Murine Tbk1 Regulates Mpp3-Type Hspcs And Circulating Leukocytes In Normal Hematopoiesis And Flt3+ Lscs In Mll-Af9-Driven Leukemia, Austin P. Runde, Joseph Cannova, Ryan Mack, Kanak Joshi, Mark Sellin, Rohit Thalla, Allan Youmaran, Mattias Lenz, Peter Breslin, Wei Wei, Jiwang Zhang Jun 2025

Murine Tbk1 Regulates Mpp3-Type Hspcs And Circulating Leukocytes In Normal Hematopoiesis And Flt3+ Lscs In Mll-Af9-Driven Leukemia, Austin P. Runde, Joseph Cannova, Ryan Mack, Kanak Joshi, Mark Sellin, Rohit Thalla, Allan Youmaran, Mattias Lenz, Peter Breslin, Wei Wei, Jiwang Zhang

School of Medicine

BACKGROUND: Acute myeloid leukemia (AML) is an aggressive hematologic cancer with a notoriously bleak prognosis; for non-M3 AML, the overall 5-year survival rate is ∼30%. While 60-70% of newly diagnosed AML patients will achieve complete remission (CR), half of these patients will experience relapse (secondary resistance) by three years from their diagnosis. Moreover, 30-40% of AML patients present with refractory disease (primary resistance) and cannot respond to frontline treatments. Leukemia stem cells (LSCs) are implicated in both primary and secondary resistance, and their eradication is necessary to maintain CR. LSCs have unique transcriptomes and immunophenotypes, thus can be identified relatively …


Abstract 2853 Prmt7 Negatively Regulates The Expression P53 In Response To Dna Damage, Molly Niswender, Lorenzo Pessi, Cecilia Lopez, Marco Bisoffi Jun 2025

Abstract 2853 Prmt7 Negatively Regulates The Expression P53 In Response To Dna Damage, Molly Niswender, Lorenzo Pessi, Cecilia Lopez, Marco Bisoffi

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Protein Arginine Methyltransferase 7 (PRMT7) is the only member of the protein arginine methyltransferase protein family that monomethylates its protein substrates. PRMT7 is found in both the nucleus and cytoplasm of breast cells and is believed to play a robust role in the tumorigenesis and metastasis of breast cancer. The goal of this project is to uncover possible pathways for PRMT7 to promote cancer progression. A preliminary antibody array was performed to determine the regulation of known cancer-related proteins by PRMT7. An early-stage human breast cancer cell line, MCF-7, was transfected with plasmid pCDH1-hPRMT7-GFP to over-express PRMT7. Qualitative and quantitative …


Elucidating The Roles Of Eukaryotic Initiation Factors Involved In Dap5 Mediated Translation, Jacob Nk Quartey Jun 2025

Elucidating The Roles Of Eukaryotic Initiation Factors Involved In Dap5 Mediated Translation, Jacob Nk Quartey

Dissertations, Theses, and Capstone Projects

Translation initiation in eukaryotes is a highly regulated process essential for accurate protein synthesis. It is a dynamic process that involves a complex interplay between messenger RNAs (mRNAs), ribosomal subunits, and a host of initiation factors, ensuring precise start codon selection and the subsequent assembly of the translation machinery. This process has well been known to be mediated by the eukaryotic Initiation Factor (eIF4F), which consists of the cap binding protein eIF4E, the scaffolding protein eIF4GI, and the helicase factor eIF4A.The recognition and binding of eIF4E to the m7G cap structure of the mRNA is essential for the …


Understanding How Genetic Mutations Induce Oligodendrocyte Progenitors To Become Cancer Cells, Dennis Huang Jun 2025

Understanding How Genetic Mutations Induce Oligodendrocyte Progenitors To Become Cancer Cells, Dennis Huang

Dissertations, Theses, and Capstone Projects

Gliomas are the most devastating adult brain tumors characterized by poor survival rate and limited options for treatment. Previous studies have shown that they are very heterogeneous and can be further sub-classified based on their transcriptional signature and the presence of specific mutations. One such subtype, is the “proneural glioma”, which is characterized by the enrichment in oligodendrocyte progenitor cell (OPC) transcripts and mutations in genes encoding for the tumor suppressor P53 (Trp53) and for Platelet Derived Grow Factor (PDGF) signaling. Since OPCs are the most abundant proliferative population in the adult brain, in this …


Investigating Genes Associated With Oncogenic Pka Activity In Fibrolamellar Carcinoma, Ananya Singh May 2025

Investigating Genes Associated With Oncogenic Pka Activity In Fibrolamellar Carcinoma, Ananya Singh

Undergraduate Honors Theses

Fibrolamellar Carcinoma (FLC) is a rare liver cancer, predominantly affecting younger individuals with no history of primary liver disease. As FLC comprises only < 1% of all liver tumors, our understanding of its development and treatment are extremely limited. All clinical cases of FLC contain a specific DNAJB1-PRKACA fusion. The mutation produces an oncogenic form of Protein Kinase A (PKA), known as DNAJ-PKAc, with enhanced binding activity compared to wild-type PKA. Specifically, DNAJ-PKAc interacts with different substrates than wild type PKA, affecting downstream signaling pathways to promote cancer development. However, the genetic dependencies that result from oncogenic DNAJ-PKAc signaling are not known. In this paper, I will show the process of performing a genome-wide CRISPRi screen in AML12DNAJ-PKAc cells to identify genes associated with oncogenic DNAJ-PKAc signaling. I will detail the preliminary benchmarking experiments, the screening process, the preparation of genomic DNA for sequencing, and the ongoing validation of screen results. I anticipate that this project will discover genes whose knockdown inhibits oncogenic DNAJ-PKAc signaling and reduces cell growth exclusively in the presence of PKA. The identified genes could represent potential therapeutic targets for cancer drugs that inhibit FLC progression. However, additional research is necessary to characterize their interactions with DNAJ-PKAc and their specific role in FLC development.


Targeting Neuronal Nitric Oxide Synthase (Nnos) As A Novel Approach To Enhancing The Anti-Melanoma Activity Of Immune Checkpoint Inhibitors, Anika R. Patel, Shirley Tong, Kate Alison Lozada, Amardeep Awasthi, Richard B. Silverman, Jennifer Totonchy, Sun Yang May 2025

Targeting Neuronal Nitric Oxide Synthase (Nnos) As A Novel Approach To Enhancing The Anti-Melanoma Activity Of Immune Checkpoint Inhibitors, Anika R. Patel, Shirley Tong, Kate Alison Lozada, Amardeep Awasthi, Richard B. Silverman, Jennifer Totonchy, Sun Yang

Pharmacy Faculty Articles and Research

Background and Objectives: Neuronal nitric oxide synthase (nNOS) overexpressed in melanoma plays a critical role in disease progression. Our previous studies demonstrated that nNOS inhibitors exhibited potent anti-melanoma activity and regulated PD-L1 expressions in the presence of interferon-gamma (IFN-γ). However, the role of nNOS in the melanoma immune response has not been well defined. Methods: Changes in gene expression profiles after nNOS inhibitor treatment were determined by transcriptomic analysis. A melanoma mouse model was used to determine the effects of nNOS inhibition on peripheral T cells and the in vivo anti-tumor activity of combining nNOS inhibitors with immune …


Assessing The Efficiency Of Methotrexate (Mtx) As An Antiviral Drug Against Gammaherpes Virus Replication, Yennifer A. Gaspar Garcia May 2025

Assessing The Efficiency Of Methotrexate (Mtx) As An Antiviral Drug Against Gammaherpes Virus Replication, Yennifer A. Gaspar Garcia

Honors Projects

It is estimated that ~15% of all cancers are caused by oncogenic virus infections. Two of the top seven cancer-causing human viruses are members of the gammaherpesvirus family: Epstein Barr Virus (EBV) and Kaposi’s Sarcoma Herpesvirus (KSHV). Our lab uses Murine Herpesvirus 68 (MHV-68), a mouse gammaherpesvirus with shares significant genetic homology to KSHV and EBV, as a model system to understand how gammaherpesviruses alter the metabolism of their host during lytic infection to promote their replication. We recently metabolically profiled MHV-68 infected host cells at various time points during the lytic infectious cycle. Our data showed nucleotide metabolism is …


Identification Of Methylation Patterns, Associated Dna Methylating Proteins, And Methyltransferase Inhibitors On The Promoter Regions Of Dax-1, Brandon Tyler Toy May 2025

Identification Of Methylation Patterns, Associated Dna Methylating Proteins, And Methyltransferase Inhibitors On The Promoter Regions Of Dax-1, Brandon Tyler Toy

Master's Theses

The DAX-1 gene (Dosage-Sensitive Sex Reversal, Adrenal Hypoplasia Congenita, Critical Region on the X chromosome, gene 1) encodes for an orphan nuclear hormone receptor and its mutation is implicated in multiple diseases including congenital adrenal hypoplasia, adrenal cancer, and breast cancer. Previous research has linked DAX-1 downregulation to tumor initiation in breast tissue, suggesting the gene acts as a tumor suppressor with respect to breast cancer. Additional studies completed by the Tzagarakis-Foster laboratory have shown that methylation of the DAX-1 promoter region is heavily influential in breast cancer development, with release of epigenetic repression resulting in slowing of cellular proliferation …


A Bitter Brew For Cancer: Egcg’S Impact On Ewing Sarcoma Cells, Lizzeth Holguin, Mary-Esther Leblanc, Mariana Reyes, Terry Jo Shackleford May 2025

A Bitter Brew For Cancer: Egcg’S Impact On Ewing Sarcoma Cells, Lizzeth Holguin, Mary-Esther Leblanc, Mariana Reyes, Terry Jo Shackleford

Cell and Molecular Methods

Epigallocatechin Gallate (EGCG), a powerful antioxidant found in green tea, is an abundant treatment to treat Ewing Sarcoma cells, a pediatric cancer affecting the skeletal system. Given EGCG’s known role in other cancer treatments, these tests aim to investigate its effects as a standalone natural compound on Ewing Sarcoma cells. Focusing on the PI3K/AKT pathway, if the PI3K/AKT pathway is inhibited by EGCG, then it will lead to reduced cell survival and proliferation of EW8 cells. Using cell culture techniques, IncuCyte-based IC50 analysis, caspase 3/7, RNA purification, cDNA synthesis, and qRT-PCR, EGCG’s impact was assessed on cell apoptosis and gene …


The Effect Of Epigallocatechin Gallate (Egcg) And Alpha L-Mangostin On Tp53, Bax, And Vim Gene Expression And Apoptosis In Ewing Sarcoma Cells, Victoria Valdez, Terry Jo Shackleford May 2025

The Effect Of Epigallocatechin Gallate (Egcg) And Alpha L-Mangostin On Tp53, Bax, And Vim Gene Expression And Apoptosis In Ewing Sarcoma Cells, Victoria Valdez, Terry Jo Shackleford

Cell and Molecular Methods

Ewing Sarcoma (ES) is a malignant pediatric bone tumor driven by chromosomal translocations and fusion oncogenes with limited targeted treatment options. This study investigated the chemopreventive potential of two natural compounds, Epigallocatechin Gallate (EGCG) found in green tea, and Alpha L-Mangostin from mangosteen, on apoptosis and gene expression in ES cells. We hypothesized that EGCG and Alpha L-Mangostin treatment would induce apoptosis and downregulate cancer-promoting genes. To test this, we performed tissue culture, IC50 assays, caspase-based apoptosis detection, RNA purification, cDNA synthesis, and qRT-PCR on ES cell lines treated with a high and low concentration of the two compounds. Our …


Early Hematopoietic Differentiation Of An Inducible Pluripotent Stem Cell Model Of Infant Lymphoblastic Leukemia, Meagan Vacek, Jacqelyn Nemechek, Irina Pushel, Bradley Thornton, Priyanka Kumar, Jay L. Vivian, John M. Perry May 2025

Early Hematopoietic Differentiation Of An Inducible Pluripotent Stem Cell Model Of Infant Lymphoblastic Leukemia, Meagan Vacek, Jacqelyn Nemechek, Irina Pushel, Bradley Thornton, Priyanka Kumar, Jay L. Vivian, John M. Perry

Research Days

This abstract describes our work regarding the differentiation of human inducible pluripotent stem cells into hematopoietic stem and progenitor cells as the groundwork for the development of a genomics driven inducible pluripotent stem cell model of KMT2A rearranged infant acute lymphoblastic leukemia.


Minimal Anti-Cancer Effects Of Mushroom-Derived Compounds Hispidin And Chaga Extract On Ewing Sarcoma Cells, Jordan Cosgrove, Fiona Coulbourne, Iris Reyna, Giselle Serna-Flores, Terry Jo Shackleford May 2025

Minimal Anti-Cancer Effects Of Mushroom-Derived Compounds Hispidin And Chaga Extract On Ewing Sarcoma Cells, Jordan Cosgrove, Fiona Coulbourne, Iris Reyna, Giselle Serna-Flores, Terry Jo Shackleford

Cell and Molecular Methods

Ewing sarcoma is a rare and aggressive cancer of adolescents and young adults driven by the EWSR1–FLI1 gene fusion. Standard treatments include chemotherapy, surgery, and radiation, though survival rates remain low. Natural compounds such as hispidin, derived from fungi, and Chaga mushroom extract have shown potential anti-cancer effects by disrupting cell cycle progression and promoting apoptosis in other cancer models. In this study, we tested the effects of hispidin and Chaga extract on Ewing sarcoma cells to evaluate their ability to suppress cell growth and identify potential therapeutic benefits.