Cancer Biology Commons^™

Integrating Technologies For Synthetic, Systems, And Spatial Approaches In Cancer Research, Karmella A. Haynes, Kolade Adebowale, Belinda S. Akpa, Joel S. Bader, Trisha Bansal, Joshua Breunig, Ran Brosh, Lukasz J. Bugaj, George M. Burslem, Awalpreet Chadha, Moumita Das, Tara Deans, Cole A. Deforest, Lawrence J. Dooling, Zev Gartner, Laura M. Heiser, Alex Hughes, Melissa L. Kemp, Kirill S. Korolev, Chunru Lin, Timothee Lionnet, Xin Lu, Alison P. Mcguigan, Hamid Reza Mirzaei, Ajit J. Nirmal, Marina Pasca Di Magliano, Alexandros Poulopoulos, Kunal Rai, José Reyes, Dagan Segal, Mary Kathryn Sewell-Loftin, Evegeniya V. Shmeleva, Adam Stevens, Subbaya Subramanian, Thea Tlsty, Jennifer Totonchy, Alexander Vlahos, Pei Wang, Ioannis K. Zervantonakis, Yanding Zhao

Pharmacy Faculty Articles and Research

Emerging tools for spatial analysis, systems biology, and synthetic biology offer opportunities to observe, dissect, and perturb cancer mechanisms, to design strategies for the prevention of oncogenesis, and to identify therapies that lead to durable tumor control. Here, we summarize perspectives from the virtual Innovation Lab on “Synthetic and Systems Approaches to Interrogate Spatiotemporal Processes in Cancer” (S3) hosted by the National Institutes of Health (NIH), which assembled interdisciplinary experts to discuss cancer spatial organization and dynamic cellular interactions and how they can be addressed by leveraging novel synthetic and systems biology approaches. These discussions focused especially on cancer initiation, …

Pi3kδ Inhibition Alters Cd8 T Cell Differentiation And Reprograms The Tumor Microenvironment Following Adoptive Immunotherapy, Alexandrea Joy Turnquist

Dartmouth College Ph.D Dissertations

T cell exhaustion remains a significant barrier to effective adoptive cell therapy in solid tumors. Here, we demonstrate that in vitro treatment with the PI3Kδ inhibitor CAL-101 generates T cells with enhanced stemness and metabolic fitness, though the stemness of these cells is not dependent on HIF-1α -dependent mechanisms. These cells show increased mitochondrial dependence and spare respiratory capacity while maintaining normal basal metabolism. Under chronic antigen stimulation, CAL-101-treated T cells, including human T cells, resist terminal exhaustion and maintain stem-like properties. Using single-cell RNA sequencing and spatial transcriptomics of B16 melanoma tumors, we found that CAL-101-treated T cells preferentially …

Validation Of Next‑Generation Sequencing‑Derived Circulating Mrna Variants As Potential Diagnostic Tools In Hepatocellular Carcinoma And Cholangiocarcinoma, Daniel Zezulinski, Maarouf A. Hoteit, David E. Kaplan, Tingting Zhan, Cataldo Doria, Timothy M. Block, Aejaz Sayeed

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Liquid biopsy can transform oncology practice through early detection and real‑time monitoring of cancer progression and response to treatment. Circulating cell‑free tumor RNA offers promise as a novel and emerging alternative to circulating cell‑free tumor DNA for detecting the presence and understanding the biology of liver tumors. Both circulating DNA and RNA, which predominantly reside in extracellular vesicles, carry evidence of vital germline and somatic mutations. High impact single nucleotide changes, insertions and deletions in circulating RNA (ctRNA) serve a key role in cancer development and progression. Tumor cells exploit the RNA splicing machinery to induce structural and functional changes …

Charge Modulation Of Peptide/Nucleic Acid Complexes: An Anionic Additive Enhances Gene Silencing And Crispr/Cas9 Editing By Promoting Intracellular Nucleic Acid Release, Abdulelah Alhazza, Sorour Khayyatnejad Shoushtari, Hasan Uludag, Keykavous Parang, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Introduction: Small interfering RNA (siRNA) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated Protein 9 (Cas9) complexes are effective approaches to temporarily downregulate protein expression via post-transcription RNA interference or permanently altering protein expression via editing genomic DNA, respectively. However, the efficient delivery of these mediators to targeted cells has been challenging, largely due to their anionic and hydrophilic nature, which hinders their interaction with the cell membrane and cellular internalization. Cell-penetrating peptides (CPPs) exhibit dual characteristics as a carrier for nucleic acid delivery, where positively charged components bind to the negatively charged nucleic acid, and the hydrophobic components …

Urinary Collagen As An Indicator Of Prostate Fibrosis In Lower Urinary Tract Dysfunction, Claweens Quetant

Graduate Masters Theses

Lower urinary tract dysfunction (LUTD) is a progressive disorder that affects millions of men over the age of 50 years old. LUTD manifests as urgency, nocturia, urinary frequency, weak urinary stream, and incomplete bladder emptying (Egan, 2016). The current treatment for LUTD doesn’t always yield the desired results due to several issues. In this thesis, we aim to address the lack of suitable tools for detecting prostatic collagenization and to assess whether urine could serve as a substrate for detecting pro-fibrotic proteins associated with moderate-to-high AUASI scores. We used whole urine from 2 different cohorts, the Boston and the LURN …

Data Curation And Integration For Cancer Cell Line Pharmacogenomics Analysis, Meric Kinali

Graduate Masters Theses

Cancer cell lines are essential resources for connecting genomic and molecular features with drug response and identifying biomarkers. Therefore, large-scale cancer cell line resources have been growing, but this introduces challenges such as data standardization, consistent annotation, matching identifiers, cross-database integration, and a reproducible computational framework. CellMiner Cross Database (CellMinerCDB) integrates pharmacogenomic datasets from multiple resources and provides a standardized analysis of cell lines across datasets. This thesis examines cancer cell line cross-databases and their importance in pharmacogenomics, with a particular focus on CellMinerCDB. As part of this work, I developed an R package for the gCSI (Genentech Cell Line …

Apical-Out Lung Organoids: A Platform For Spaceflight And Cf Research, Valeria Jimenez, Ally Schwennesen

Discovery Day - Daytona Beach

A genetic condition known as cystic fibrosis (CF) is brought on by mutations in the CFTR gene, which results in chronic lung inflammation and impaired chloride ion transport. CF bronchial epithelial cells enable direct comparison of disease pathology, while normal human bronchial epithelial (NHBE) cells offer an essential model for researching airway physiology. Realistic modeling of respiratory tissue and its reaction to environmental stressors like microgravity is made possible by the creation of 3D lung organoids from these cells. In this project, we developed apical-out organoids, which expose the apical surface of epithelial cells to the external environment. These organoids …

Functional Characterization Of Fam120a As A Novel Effector In The Progranulin/Epha2 Oncogenic Axis In Bladder Cancer., Vrunda Satasiya, Canio Martinelli, Gabriel J. Pascal, Giacomo Ducci, Elisa Ventura, Stephen J. Williams, Sharon Raffaella Burk, Manuela Nana Tchamou, Shendi Shani, Michele Klain, Elena Sacco, Marco Vanoni, Antonino Belfiore, Renato V. Iozzo, Antonio Giordano, Andrea Morrione

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Bladder cancer (BC) is one of the most deadly diseases in the USA, with 84,530 new cases and 17,870 estimated deaths in 2026. The growth factor progranulin is involved in several human pathologies, including frontotemporal dementia (FTD), immune response, and cancer. We showed that in BC, progranulin and its signaling receptor, EphA2, drive tumor cell motility, invasion, and in vivo tumor formation, making it a critical pathway in tumor establishment. However, the molecular mechanisms of progranulin/EphA2 action are still poorly defined.

METHODS: Progranulin-dependent EphA2 interactome was explored by proteomic approaches. FAM120A or EphA2 protein levels in BC tissue microarrays …

Oxidative Stress Mediated Glutamate Release And Nmda Receptor-Dependent Synaptic Remodeling In Radiation-Induced Cognitive Dysfunction, Thanh Lam

Dissertations and Theses (Open Access)

In children younger than 14 years old, the brain and other parts of the central nervous system are the most common sites for solid tumors. Radiotherapy is an effective treatment for central nervous system (CNS) tumors. However, it often causes a progressive decline in cognitive functions, which is especially devastating for pediatric patients. Although post-mitotic neurons are generally considered resistant to radiation-induced immediate cell death, ionizing radiation causes complex neurochemical and structural changes that damage synaptic integrity. In this study, we examined the molecular cascades following a 10 Gy radiation dose applied to mouse cortical neurons. We found that radiation-induced …

Validating The Expression Of Genes Potentially Involved In The Development Of Aggressive Melanoma Tumor In The Zebrafish Melanoma Model, Mayra Matos Diaz

Theses, Dissertations and Culminating Projects

Melanoma is an aggressive form of skin cancer characterized by rapid progression, metastatic potential, and the frequent development of resistance to targeted therapies. Although the Inducible cAMP Early Repressor (ICER) has been identified as a potential tumor suppressor in melanoma, the molecular mechanisms underlying its role in tumor progression remain poorly understood. Building upon the transcriptomic findings of Wheelan et al. (2025), this study investigates the relationship between ICER and ten candidate genes (gdf6a, pdgfra, col4a4, fgfr2, pdgfrb, cdkn1a, fgf5, akt1, met, and notch3) associated with BMP signaling. Quantitative polymerase chain reaction (qPCR) was used to compare gene expression between …

Using Zebrafish To Investigate The Innate Immune Response To R132h Mutant Glioma, Mikaela L. Fairbanks

All NMU Master's Theses

Gliomas are the most commonly occurring brain tumor found in adults. The most dominant mutation found in glioma is in the isocitrate dehydrogenase 1 (IDH1) gene. IDH converts isocitrate into α-ketoglutarate (α-KG), but the mutated form of it will take α-KG and further convert it into D-2-hydroxyglutarate (D-2-HG). Mutated IDH1 glioma (mIDH1) produces a higher concentration of D-2-HG than the wild-type IDH1 glioblastoma (wtIDH1). These mIDH1 tumors tend to have a better prognosis, growing slower and having less inflammation than the wtIDH1 counterpart, potentially due to the increased D-2-HG. However, the effects of mIDH1 and D-2-HG on the innate immune …

Influence Of Smoking On Mlh1 Gene Polymorphism: Insights Into Colorectal Cancer Incidence, Ali Mohammed Al-Abedi, Rand Muhammed Abdul-Hussein Al-Husseini

Al-Bahir

Background: Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. The MutL Homolog 1 (MLH1) gene plays a critical role in DNA mismatch repair (MMR). Evidence suggests cigarette smoking increases CRC risk, potentially interacting with genetic factors.

Materials and Methods: This case-control study involved 50 Iraqi CRC patients and 50 age- and gender-matched healthy controls. The PCR-RFLP technique was employed for genotyping the -93G/A (rs1800734) polymorphism. Statistical analysis included Chi-square, Fisher's Exact Test, and logistic regression adjusted for confounders. Hardy-Weinberg Equilibrium (HWE) was assessed in controls.

Results: The frequency of the rs1800734 variant was significantly higher in CRC …

Uncovering Dkk1 As A Therapeutically Relevant Target In Aggressive Er+ Breast Cancer Using A Novel Antiestrogen, Kristen Young

Dissertations

Over 70 percent of breast cancers are estrogen receptor-positive (ERα+), meaning that the hormone estrogen drives tumor growth. Although first-line targeted therapies that directly block ERα from hormone-dependent pathologies are initially effective, almost half of patients ultimately progress. These patients show high mutational rates to the ESR1 gene that encodes for ERα. A hotspot missense tyrosine to serine mutation at position 537 (Y537S) initiates hormone-independent, allele-specific transcriptional programs that increase metastasis. While next-generation ERα-targeted therapies show promise, benefits are often limited compared to standard-of-care. Understanding the mechanisms of action used by the Y537S ESR1 breast cancer cells to evade therapeutic …

In Vitro Reversal Of Abc Transporter Mediated Multidrug Resistance In Human Ovarian And Non-Small Cell Lung Cancer Models, Alison K. Kellom, Pia D. Vogel

Biological Sciences Theses and Dissertations

One of the major causes of treatment failure in aggressive cancers is multidrug resistance (MDR), which is linked to the overexpression of membrane efflux proteins that export chemotherapeutics from cancer cells. This mechanism prevents chemotherapeutic drugs from reaching cytotoxic concentrations intracellularly, allowing the cancer to survive. Two primary mediators of this mechanism are P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP). P-gp and BCRP are transmembrane ATP-binding cassette (ABC) transporters that are frequently overexpressed in MDR cancers. They utilize the binding and hydrolysis of ATP to transport a diverse range of amphipathic molecules of varying size (Schinkel and Jonker, 2003), …

P300/Cbp Inhibition With Inobrodib In Combination With Gilteritinib And Venetoclax Targets Leukemia Stem Cells In Epigenetic Mutant Aml, Melanie L. Goetz, Jennifer S. Romer-Seibert, Amanda M. Versace, Scott Kogan, Chetan Jeurkar, Robert L. Bowman, Nigel Brooks, Kris Frese, Sara E. Meyer

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Acute myeloid leukemia (AML) is a fatal blood cancer with cytotoxic chemotherapy offering at best 25% 5-year survival. While targeted BCL2 and FLT3 inhibitors venetoclax and gilteritinib are used upfront in the treatment of a subset of adult patients with AML and help to extend the survival of some patients, a curative treatment combination with minimal side effects has yet to be discovered. We find that use of the dual histone acetyltransferase p300/CBP bromodomain inhibitor CCS1477 (inobrodib), together with venetoclax and gilteritinib, virtually eliminates leukemia stem cells in an aggressive preclinical model of DNMT3A/FLT3-mutant AML by impairing pro-oncogenic survival and …

Synthesis Of A Nicotine-Like Backbone Ligand For Binding Evaluation At Plk-1 Pbd, Carter Johnson

Undergraduate University Honors Capstones

Cancer is a significant problem and requires continued research, as it remains one of the leading causes of death worldwide (Ramos, 2021). This capstone explores the synthesis and preliminary evaluation of a nicotine-type compound as a potential cancer-curing agent targeting the PLK-1 PBD protein using fluorescence polarization. The hypothesis is that a specific ligand may contribute to cancer research. This project also reviews cancer management methods while illustrating the discovery of chemical drugs used in chemotherapy. The project involves synthesizing and testing 3-((1-methylpyrrolidin-2-yl)methoxy)-1-alkylpyridin-1-ium, known as Compound C, to determine whether it can function as a potential cancer management agent. The …

Cell Cycle Inhibition: Illudin S And Its Effects On Cdk2 In Ewing Sarcoma, Stephanie Diez, Natalie Flores, Alexandria Hernandez, Viviana Palacios, Terry Jo Shackleford

Cell and Molecular Methods

Ewing Sarcomas are aggressive round cell mesenchymal neoplasmas that have a high occurrence in children and young adults. CDK2 is a protein that is involved in the G1 phase of the cell cycle, which promotes the transition to the S phase. CDK2 kinase activation is mainly observed in the G1/S-phase transition.3 CDK2 binds to Cyclin proteins is responsible for entry and progression, thereby leading to maximal apoptosis activity in the S-phase. Illudin S is a drug that has been known to target cancer-specific cells, such as leukemia. Illudin S, in general are a cytotoxic metabolite that comes from plants, specifically …

Yap1 Knockdown And Panobinostat Treatment Increase Apoptotic Response And Decrease Gene Expression In Ewing Sarcoma Cells, Luna Collazo-Garcia, Alejandra Favela Santos, Madeline Torres-Salazar, Isabella Toscano, Terry Jo Shackleford

Cell and Molecular Methods

Ewing sarcoma (EWS) is considered to be one of the most aggressive pediatric malignancies, often characterized by its dysregulated gene expression driven by oncogenic fusion proteins. The Hippo signaling effector Yes-associated protein 1 (YAP1) has been known in promoting cell proliferation, survival, and therapeutic resistance in multiple cancers. However, its role in Ewing sarcoma response to treatment remains unclear. This study investigated whether YAP1 knockdown enhances the sensitivity of Ewing sarcoma cells to the histone deacetylase inhibitor Panobinostat. Ewing sarcoma, ES8, cells were transfected with a YAP1-targeting siRNA (siYAP1) or a non-targeting control (siControl) and treated with DMSO, 0.1 μM, …

Everolimus Treatment Combined With Akt1 Knockdown Increased Apoptosis And Decreased Cell Proliferation In Ewing Sarcoma Cells, Arisha Arif, Alfie Barcenez, Sophia Ruter, Nicole Vanegas-Riddick, Terry Jo Shackleford

Cell and Molecular Methods

The purpose of this study is to use the gene AKT1, due to the interest in AKT1’s role in cancer cell proliferation, and the drug Everolimus, to determine if combined targeted therapy works as a more efficient therapeutic approach. Ewing Sarcoma has been connected to chromosomal translocations and is most common in pediatric patients. It is most often treated with chemotherapy and local treatments. It may be connected to the gene AKT1 due to how it regulates cell metabolism, growth, and proliferation. The gene mTOR is similarly connected to cell metabolism and proliferation, and is inhibited by the drug Everolimus. …

Sirna Knockdown Of Rptor Reduces Rptor Expression, Increases Brd4 Expression, And Alters Proliferation And Apoptosis In Ewing's Sarcoma Cells, Sergio Cipriano, David Leavitt, Michael Olivia, Liam Valdez, Terry Jo Shackleford

Cell and Molecular Methods

Ewing sarcoma is a highly aggressive cancer that primarily affects children and young adults. Although treatment options exist, many patients do not respond effectively, showing the need for improved targeted therapies. RPTOR is a key in mTORC1 complex which regulates cell growth, proliferation, and survival. LY2874455 is a selective pan-FGFR inhibitor that targets growth factor signaling pathways involved in tumor progression, and FGFR signaling interacts with pathways such as mTOR, making it a potential target for combination therapies. We hypothesized that silencing RPTOR in Ewing sarcoma cells would disrupt mTOR signaling and alter expression of genes linked to cell survival …