Cancer Biology Commons^™

A Genomics Driven Induced Pluripotent Stem Cell Model Of Infant Acute Lymphoblastic Leukemia - Early Results, Meagan Vacek, Jacqelyn Nemechek, Irina Pushel, Bradley Thornton, Molly Leyda, Priyanka Prem Kumar, Midhat Farooqi, Jay L. Vivian, Erin M. Guest, John M. Perry

Research Days

While the cure rates for pediatric ALL have improved over the decades, infants with ALL (iALL) have not benefitted from these advances and continue to have a devastating prognosis. Unfortunately progress in treatment has also been slowed by inadequate research models. With this project, we address this unmet need by investigating a novel model to understand the cellular and molecular changes that occur during iALL onset and progression.

Optimizing Immunotherapies For Improved Cancer Treatment, Anne Talkington, Anthony Kearsley

Biology and Medicine Through Mathematics Conference

No abstract provided.

Unveiling The Nexus Of Cellular Quality Control: Exploring The Interplay Between Ribosome-Associated Protein Quality Control And Mitochondrial Quality Control Pathways, Foozhan Tahmasebinia

Biological Sciences Theses and Dissertations

In eukaryotic cells, the intricate interplay between cellular quality control mechanisms is crucial for maintaining homeostasis and safeguarding the integrity of vital processes, spanning from macromolecule synthesis to the renewal of entire cellular organelles.

Disruption of these networks can lead to severe diseases such as metabolic disorders, underscoring the interconnected nature and feedback control mechanisms inherent in biological systems, including cellular quality control systems. This interconnectedness extends to the intricate communication between organelles, enabling coordinated functioning and adaptation to changing cellular conditions, particularly in response to stressors.

While the exact mechanisms governing these communications within cellular quality control systems remain …

Identifying Novel Upstream Regulators Of The Hippo Pathway: Forward Genetic Screen In Drosophila Melanogaster, Akshara Iyer

Honors Scholar Theses

The Hippo pathway is an evolutionarily conserved developmental pathway that controls organ size and tissue homeostasis in all metazoan animals. Dysregulated Hippo pathway has been implicated in a wide range of human disorders, including cancer. The physiological function of the Hippo pathway is best understood in Drosophila, where inactivation of the Hippo pathway tumor suppressors, or overexpression of the Yorkie (Yki) oncoprotein, results in tissue overgrowth characterized by excessive cell proliferation and diminished apoptosis, and increased transcription of Hippo pathway target genes such as diap1 and expanded (ex). Despite the well-established Hippo pathway core signaling cascade, the upstream regulation of …

Homeobox A10: Regulator Of Pancreatic Cancer Progression And Survival, Sophia G. Kisling

Theses & Dissertations

Pancreatic ductal adenocarcinoma (PDAC) has one of the lowest incidence rates among all major cancers, yet it is disproportionally responsible for 8% of all cancer deaths. This high death rate is primarily attributed to the immunosuppressive tumor microenvironment and a lack of clinically relevant molecular targets. However, the underlying biology responsible for these poor outcomes remains obscure. To facilitate improved management of PDAC, an in-depth understanding of the molecular player(s) involved in PDAC aggressiveness is needed. Therefore, we analyzed the transcriptomic profiles of PDAC patients with long- and short-term survival and performed gene set enrichment analysis (GSEA), identifying a novel …

Novel Spirocyclic Dimer (Spid3) Displays Potent Preclinical Effects In Hematological Malignancies, Alexandria Eiken

Theses & Dissertations

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease characterized by the accumulation of mature CD5⁺ B-cells in the peripheral blood, bone marrow, and secondary lymphoid tissues (e.g., spleen and lymph nodes).Despite the efficacy of front-line therapies, CLL is still an incurable disease, highlighting the need for development of novel therapeutics and further study of resistance mechanisms. Within the lymph node CLL tumor microenvironment (TME), there is an upregulation of gene signatures associated with B-cell receptor (BCR) and downstream nuclear factor kappa B (NF-κB) signaling compared to CLL cells found within the blood or bone marrow niches. Additionally, BCR signaling …

Mucins: Drivers Of Cancer Cell And Microenvironment Crosstalk In Pancreatic Cancer, Xiaoqi Li

Theses & Dissertations

Mucins facilitate the pancreatic cancer (PC) initiation, progression, and metastasis. Among mucins, MUC4 has been reported to inhibit lymphokine-activated cell killing and induce the apoptosis of cytotoxic T-cells. Counterintuitively, MUC4 expression is upregulated by multiple T-cell-secreted cytokines, such as IFN-γ, IL-17, and stroma-secreted factors like retinoic acid. Previously, we have identified that nuclear receptor coactivator 3 (NCOA3) regulates the MUC1 and MUC4 expression by increasing chromatin accessibility and maintaining protein stability. However, the comprehensive crosstalk mediated by MUC4 in cancer cells and T-cells and how its upstream regulator, NCOA3, modifies the cancer cell-intrinsic behavior is still elusive. Here, we show …

Targeting Lifr/C-Myc/Ddx21 Axis To Overcome Docetaxel Resistance In Prostate Cancer, Sushanta Halder

Theses & Dissertations

Resistance to chemotherapy poses a significant challenge in the treatment of advanced-stage prostate cancer (PCa), specifically with chemotherapy drugs like docetaxel (Doce), which is often employed after the failure of hormone therapy. However, 50-90% of PCa patients develop resistance to docetaxel within three years of post-chemo treatment, compounded by serious adverse side effects necessitating dose reductions. Various strategies are being investigated to address this issue, including identifying new therapeutic targets or mechanisms, developing novel combination therapies, and optimizing dosing regimens. In particular, our research is focused on uncovering the underlying mechanisms of resistance to docetaxel, such as the activation of …

Identification Of Mitotic Phosphatases And Cyclin K As Novel Molecular Targets In Pancreatic Cancer, Yi Xiao

Theses & Dissertations

Pancreatic cancer is a highly lethal disease worldwide. Given the limited effectiveness of current regimens in restricting tumor progression, it is imperative that potential molecular targets be identified to offer valuable insights into alternative therapeutics. By using a phosphate-binding tag (Phos-tag) technique, previous studies have identified several Hippo pathway-related proteins and kinases required for cancer growth or paclitaxel resistance. This work has screened various phosphatases and cyclins/cyclin-dependent kinases (CDKs) as potential cancer targets, but specifically focuses on characterizing the roles of carboxy-terminal domain small phosphatase like 2 (CTDSPL2), apoptosis-stimulating protein of p53-2 (ASPP2), and Cyclin K in pancreatic cancer.

CTDSPL2 …

Therapeutic Effects Of Bet Protein Inhibition In B-Cell Malignancies And Beyond, Audrey L. Smith

Theses & Dissertations

Chronic lymphocytic leukemia (CLL) develops through a combination of intrinsic genetic defects, constitutively active survival/proliferation signaling pathways, and complex microenvironment interactions. Redundant tumor microenvironment (TME) immuno-suppressive mechanisms and epigenetic maintenance of terminal T-cell dysfunction also greatly hinder anti-tumor T-cell responses in CLL. Small-molecule agents targeting the B-cell receptor (BCR) pathway and anti-apoptotic proteins alone or in combination with chemo-immunotherapy have revolutionized the management of CLL, yet there is still a significant need for novel therapeutic strategies to yield durable tumor elimination. Bromodomain and extra-terminal domain (BET) proteins are epigenetic readers that bind to acetyl-lysine residues on histones to regulate gene …

Identifying The Molecular Determinants Of Lung Metastatic Adaptation In Prostate Cancer, Grace M. Waldron

Theses & Dissertations

Prostate cancer (PC) stands as the primary diagnosed cancer in men in the US at approximately 299,010 cases in 2024 and ranks second globally, posing a significant public health challenge. Clinical presentations vary widely, from indolent to aggressive forms, necessitating stage-specific treatment regimens. Understanding its metastatic nature is critical due to the impact of cancer cell dissemination on disease morbidity, with bone and visceral organs serving as key sites of metastasis. Despite bone metastasis being the most common site for metastasis, visceral metastases at sites such as the liver and lungs correlate with poorer survival, emphasizing the role of microenvironmental …

Investigating The Therapeutic Potential Of Soursop In Treating Hematologic Malignancies, Sabrina Marie Paparo, Rebeca Mendoza, Robert Chitren, Omar Al-Odat, Emily Nelson, Subash Jonnalagadda, Roger Strair, Manoj Pandey

Rowan-Virtua Research Day

Acute Myeloid Leukemia (AML) and Multiple Myeloma (MM) are hematologic malignancies that originate in the bone marrow and account for approximately 1.3% and 2% of cancer cases, respectively. AML is characterized by an accumulation of myeloblasts, or immature myeloid cells, that have the potential to spread to the peripheral blood. There is an uncontrolled proliferation of plasma cells in the bone marrow in MM. While the current treatment options for both AML and MM show promise in achieving initial remission, it is unfortunately common for patients to experience relapse and develop drug resistance. There is a theory that relapse and …

Investigating The Modulation Of Metastasis By Dax-1 In Adrenal Carcinoma Cells, Aarya Mishra

Undergraduate Honors Theses

The nuclear hormone receptor (NHR), DAX-1 (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1), is important in adrenal and gonadal development as well as steroidogenesis. It is encoded by the NR0B1 gene and functions mainly as a transcriptional repressor. Classified as an orphan receptor within the NHR superfamily, DAX-1 has been shown to inhibit other NHRs including estrogen receptor, androgen receptor and steroidogenic factor 1. DAX-1 is found to be underexpressed in breast and prostate cancers and, specifically in prostate cancer, is believed to be a transcriptional repressor of genes that are involved in epithelial-mesenchymal transition …

Sdf-1Α Mediates Primary Tumor Escape In Glioblastoma Through Activation Of Mesenchymal Transitions., Charles T. Froman-Glover

College of Arts & Sciences Senior Theses

Glioblastoma (GBM), a highly aggressive primary brain tumor originating in glial cells, poses a significant challenge due to its rapid growth and invasive nature within healthy brain tissue.

Current treatments involve surgical resection, chemotherapy, and radiation. These treatments alone are not enough to cure this disease, and a better understanding the mechanics of the tumor micro-environment is imperative to furthering the field of cancer research. This research focuses on understanding the tumor microenvironment's impact, specifically investigating the role of stromal cell-derived factor 1 (SDF-1) mechanics on GBM aggressiveness. SDF-1 is known to facilitate disease progression by facilitating chemotaxis toward the …

The Role Of Mettl21a In Kras-Driven Cancers, Xiaojie Yang

Dissertations and Theses (Open Access)

Abstract

More than 100 lysine methyltransferases (KMTs) were predicted to be present in the human proteome, and many were implicated in cancer etiology. However, the catalytic activity and substrate specificity for many of these enzymes remain unknown. Our work aimed to explore the role of Methyltransferase like 21A (METTL21A), amember of the little-studied seven β- strand family of candidate lysine methyltransferases (KMTs), and its role in regulating pancreatic ductal adenocarcinoma (PDAC) and lung adenocarcinoma (LUAC) tumorigenesis. Through the meta-analysis of publicly available gene expression datasets, I found that METTL21A is significantly downregulated in PDAC and LUAC versus normal tissue, and …

Oxidative Phosphorylation In Melanoma Brain Metastases: A Regulator Of The Tumor Immune Landscape, Renato A. Guerrieri

Dissertations and Theses (Open Access)

Previously, we demonstrated via RNA-sequencing analysis of murine intracranial melanoma tumors that pharmacologic inhibition of oxidative phosphorylation (OXPHOS) results in increased expression of genes consistent with activated anti-tumor immune responses. The central hypothesis of this dissertation is that OXPHOS plays a critical role in the pathogenesis and immune regulation of melanoma brain metastases (MBMs).

The functional significance of OXPHOS was assessed through genetic inhibition, involving knockout (KO) of key regulatory genes such as Ppargc1a (PGC1a) and Ndfus4 (NDUFS4), a component of mitochondrial complex I. PGC1a KO in an RCAS-TVA mouse model of autochthonous lung and brain tumors developing from primary …

Mast Cells In Mammary Carcinoma, Alexandria M. Ashbaugh

Undergraduate Honors Theses

Breast cancer (BC) is an aggressive disease that takes the lives of thousands of women every year. Although knowledge and treatment of this disease have improved over the years, much is still to be discovered about BC. One area of expertise that we are currently trying to learn more information about is the mast cell (MC) and its role in BC growth and development. The MC is an immune system component discovered in tumors' extracellular matrix (ECM). As a tumor grows within body tissues, the tumor recruits the MC from surrounding connective tissues to the tumor, using signaling cytokines such …

The Effect Of Yamanaka Factors On The Metastatic Potential Of Breast Cancer Cells, Riley Mendonca

Undergraduate Honors Theses

The mortality associated with cancer is most commonly a result of it spreading to other tissues and organs in a process known as metastasis. For carcinomas to do this they must first break through the basement membrane containing them to interact with the stroma. This is known as an epithelial-mesenchymal transition and occurs when carcinomas suppress their original epithelial qualities in order to adopt more mesenchymal ones. This involves cancers dedifferentiating from their original cell type to lose the specialized features that distinguished them and where they came from. As cancers become more invasive, this dedifferentiation becomes more pronounced. Recent …

Epigenetic Modification As A Therapeutic Target In Brafv600e-Mutated Metastatic Colorectal Cancer, Hey Min Lee

Dissertations and Theses (Open Access)

Patients with BRAF^V600E-mutated metastatic colorectal cancer (mCRC) experience a worse prognosis and demonstrate only a 5% response rate to BRAF inhibitor treatment. In this study, adaptive resistance, and a potential combination of standard therapies in BRAF^V600E CRC were unveiled. Intriguingly, a robust association of BRAF^V600E mutation and DNA hypermethylation suggests this is a unique subgroup harboring aberrant epigenetic phenotype. Firstly, DNA methyltransferase (DNMT) inhibitor treatment induced profound DNA hypomethylation in vivo, but minimal change in gene expression due to adaptive elevation of the repressive histone methylation, H3K27me3, leading to compensatory suppression of key tumor suppressor genes, …

Loss Of Ptdss1 In Tumor Cells Improves Anti-Pd-1 Therapy, Jielin Liu

Dissertations and Theses (Open Access)

PTDSS1 (Phosphatidylserine synthase 1) encodes an enzyme that facilitates production of phosphatidylserine (PS), which mediates a global immunosuppressive signal. Here, based on in vivo CRISPR screen, we identified PTDSS1 as a target to improve anti-PD-1 therapy. Depletion of PTDSS1 in tumor cells increased expression of IFNγ-regulated genes, including B2m, Cxcl9, Cxcl10, and Stat1. Loss of PTDSS1 in tumor cells also led to increased expression of MHC-I, which was associated with increased expression of cytolytic function related genes in CD8⁺ T cells and increased frequency of an iNOS⁺ myeloid subset. A gene signature derived from the iNOS⁺ myeloid …