Genetics Commons^™

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 …

Associations Of Variation In Mtdna With Feed Efficiency In Beef Cattle And The Evaluation Of Transcriptomic Changes In Fetal Kidney Due To Hydrallantois, Lauren Elizabeth Seier

Department of Animal Science: Dissertations, Theses, and Student Research

Project 1 focused on the central role that mitochondria play in ATP production, highlighting that variation within the mtDNA may influence feed efficiency. Variation in the mitochondrial genome was uncovered, and associations with feed efficiency in beef cattle were identified. Growth and feed intake phenotypes, as well as low-pass sequencing, were collected on beef steers across two populations. Protein coding variants were identified and used to classify animals into mitochondrial haplotypes. A linear mixed model was employed, which detected a significant association between mitochondrial haplotype and DMI. A significant haplotype with a variant in Complex I was associated with reduced …

Meta-Analysis Of Uveal Melanoma Genome-Wide Association Studies Identifies Novel Risk Loci And Population Effect Size Heterogeneity., Georgia Mies, Noah L. Tsao, Alexandre Houy, Sarah E. Coupland, Helen Kalirai, Asta Försti, Kari Hemminki, Hauke Thomsen, Marc-Henri Stern, Carol L. Shields, Scott M. Damrauer, Katheryn G. Ewens, Arupa Ganguly, Iain Mathieson

Wills Eye Hospital Papers

Uveal melanoma (UM) is a rare but frequently metastasizing cancer. Genome-wide association studies have identified three common genome-wide significant germline risk loci. Here, we perform a genome-wide association study on 401 new cases and conduct a meta-analysis with three independent previously published cohorts for a total sample size of 2,426 cases. We confirm the three previously identified risk loci and identify four additional genome-wide significant loci. We find that eye pigmentation-decreasing variants are systematically associated with increased UM risk and that selection for lighter pigmentation in the past 5,000 years explains about 73% of the difference in UM incidence between …

Investigating The Regulation Of The Hypothalamic-Pituitary-Interrenal Axis In Atlantic Sturgeon (Acipenser Oxyrinchus) Following An Acute Stressor, Liam Doherty, Ciarán A. Shaughnessy, Robert M. Dores

DU Undergraduate Research Journal Archive

This study investigated the response to acute stress in Atlantic sturgeon (Acipenser oxyrinchus) and HPI axis regulation of glucocorticoid production during stress by examining the expression of key genes―corticotropin-releasing hormone (crh), corticotropin-releasing hormone receptor (crhr), proopiomelanocortin (pomca/pomcb), melanocortin 2 receptor (mc2r), and steroidogenic acute regulatory protein (star)―that are associated with hypothalamus/pituitary/interrenal (HPI) axis of bony fishes. Additionally, tyrosine hydrogenase (th1 and th2) and phosphoenolpyruvate carboxykinase (pepck), found in catecholamine-producing cells in the head kidney of the sturgeon, were investigated as …

Du Undergraduate Showcase Abstracts: Research, Scholarship, And Creative Works, Kabe Aberle, Nadia Kako, Kateri Mcrae, Brooke Agulnek, Sky Palmon, Yasmine Ramirez, Francisca Aguirre Beltran, Ashley Juarez, Bridget Kim, Tessa Appel, Sterling Kerr, Spencer Ingley, Gabe Meyer, Robin Tinghitella, Dale Broder, Lily Baeza, Chloe Beers, Julia Coakley, Whitney Kelsey, Sydney Gainforth, Gabi Wing, Audrey Martin, Aaliyah Amore Berry, Brooke Watley, Kiruthika Venkatesan, Rachel Bienstock, Annabella Brotherston, Madison Bryant, Mia Burgener, Emma P. Lieb, Rachel A. Johnson, Jennifer L. Hoffman, Kania Campbell, Kiena Campbell, Courtney Cassidy, Sage Krzyzkowski, Maddox Jones, Skylar Abookire, Luke Hawkins, Sunnah Yoon, Andrea Chu, Yan Qin, Nyah Cubbison, Brian Gearity, Daniel Mcintosh, Mariely Cruz, Edward Garrido, Grady Dionne, Nicole Doris, Lyndsie Salvagio, Ann-Charlotte Granholm-Bentley, Anna Dymov, Hannah Eckert, Gabrielle Welsh, Erica Larson, Charlie Ernst, Anna Zhou, Sarah Watamura, Larissa Fedorovich-Klein, Georgie Fields, Kimberly A. Guevara, Aven Mccall, Ben Peltier, Feruz Yahia, Patrick Flores, Jadyn Floyd, Sophia Forcier, J. Von R. Monteza, Peter Sokol-Hessner, Gwendolyn Geiger, Scott Nichols, Camryn Gunter, Kendal Hengst, Charlie Bednarz, Issy Garside, Addison Baker, Rachel Mina, Brooke Hermanson, Amanda Klingler, William Highfill, Sydney Jaques, Kerstin Lewey, Allison Grossery, Daniel Linseman, Ethan Lim, Jagger Livengood, Owen Mantelli, Gabby Pappas, Abby Mcdonald, Madeleine Dierking, Eve Miller, Emma Loeber, Anna Marlow, Michael Kerwin, Ella Mathews, Hillary Hamann, Khadija Mohamed, Vivian Nguyen, Gabri Notov, Ifunayachi Ogbonna-Ukuku, Sunil Kumar, Charles Baysah, Sarah Olson, Don Sullivan, Anna Paradiso, Jay Parrish, Mira Pronobis, Alisha Pravasi, Kerstin Haring, Diego Ramirez, Christopher Reardon, Juliana Ramirez, Casey Doherty, Ella Kestner, Teagan Weindel, Cate Billings, Pablo Torre-Walter, Lucy Rand, Samantha Reynolds, Mark Siemens, Khadeeja Rashid, Laine Satterlee, Piper Heilbronner, Lily Pound, Ben Whitehurst, Anna Respet, Lizzie Lesoing, Sydney Hertel, Aya Saad-Masri, Brooke Ballenger, Max Proske, Hannah Rosenberg, Ellia Nakahara, Sophia Espinoza, Ivan Woolhouse, Simon Ruland, Gorkem Er, Timothy Sweeny, Melaku Saketa, Michela Schenk, Maren Lynch, Madi Hamm, Grace Schroeder, Michelle Rozenman, Rana Seif, Jackson Hall, Marisela Simental, Daniel Paredes, Aaron Mena, Preston Spaan, Evelyn Stovin, David Andrew Swartz, Anh Tran, Daniel Pittman, Luke Farchione, Emily Boyer, Ukari Verner, Lacey Conrad, Jonathan Velotta, James Weiner, Jagger Gossett, Noah Sherry, Sam Proud, Ben Block, Avi Narayana, Zoey Weiss, Alyssa Wilson, Gabrielle Walsh, David Zonana, Keely Wright, Kena Riveria, Lillybelle Deer, Jena Doom, Elysia Davis, Isabelle Yaremenko, Caitlyn Young

DU Undergraduate Research Journal Archive

Abstracts from the DU Undergraduate Research Showcase.

Alpha-Synuclein Null Mutation Exacerbates The Phenotype Of A Model Of Menkes Disease In Female Mice, Meganne Casey, Dan Zou, Renee Reijo Pera Phd, Tiffany Hensley-Mcbain, Deborah E. Cabin

Touro College of Osteopathic Medicine (Great Falls) Publications and Research

Human SNCA, which encodes a-synuclein protein (SNCA), was the first gene linked to familial Parkinson's disease (PD). Since the discovery of the genetic link of SNCA to Parkinson's nearly three decades ago, many studies have investigated the normal function of SNCA protein. However, understanding of the normal function of SNCA is complicated by the lack of a reliable mammalian model of PD; indeed, mice with homozygous null mutations in the Snca gene live a normal lifespan and have only subtle synaptic deficits. Here, we report the first genetic modifier (a sensitized mutation) of a murine Snca null …

Foxo Factors’ Ability In Binding To And Inducing Tcf7 In Glioblastoma Cells, Stephanie Oyervides

Theses and Dissertations

Glioblastoma Multiforme (GBM) is an aggressive astrocytoma tumor type with a poor prognosis and limited immunotherapeutic options for those inflicted. Stem gene expression of this cancer indicates a direct relationship with the transcription factors, Forkhead box subfamily O (FOXO-1, -3 and - 4). These transcription factors are evolutionarily conserved, partially redundant. They are involved in diverse and fundamental biological processes such as cell survival, stem cell homeostasis, cell fate determination, cell cycle maintenance, metabolism, and apoptosis. Increasing evidence suggests interconnectivity between the WNT Pathway and FOXO transcription factors; however, the mechanism and full extent to which these interactions play a …

Changes In Immune-Regulated Gene Methylation Over Time In Women Who Do And Do Not Develop Breast Cancer, Kyle Laney

USF Tampa Graduate Theses and Dissertations

Breast cancer survivors face elevated risks of chronic inflammatory conditions and immunedysfunction compared to the general population. These elevated health risks in survivors are well-documented but mechanistically poorly understood. This study aimed to characterize longitudinal changes in DNA methylation patterns of immune-regulatory genes in women who developed breast cancer compared to cancer-free controls. We conducted an EWAS using Sister Study cohort data, analyzing longitudinal changes in DNA methylation by comparing the difference in beta values between pre- and post-diagnosis time points in breast cancer cases versus changes over the same period in cancer-free controls. The analysis included 414 participants: 189 …

Selecting For Less: How Much Methane Can We Truly Breed Away?, Sean B. Crowley

ORBioM (Open Research BioSciences Meeting)

Background

Genetic selection has potential to reduce enteric methane emissions from cattle, but a key challenge is determining how much of the genetic variation in methane traits is independent of traits already targeted in breeding programs, such as feed intake and growth.

Methods

Methane and carbon dioxide emissions were recorded in 1,700 crossbred, indoor-fed beef cattle using Greenfeed systems. Performance data included feed intake, metabolic liveweight, average daily gain, carcass weight, and ultrasound and skeletal traits. Genetic parameters and correlations among traits were estimated using animal linear mixed models to quantify the independence of methane-related genetic variation.

Results

Daily methane …

A Review On The Cytogenetic Integrity Of Micropropagated Plants [Review Paper], Eliaza Alumbro Peniton Jr

The Philippine Agricultural Scientist

Cytogenetic stability is essential for the survival of micropropagated plants. While micropropagation allows rapid propagation of plants with desirable phenotypes, it may also produce genetic variations that are, at times, cytogenetically observable. Factors affecting these variations are not fully understood, and micropropagation protocols are optimized to produce genetically stable regenerants. The genetic stability of micropropagated plants is traditionally assessed by comparing the phenomorphological traits of the regenerants to the mother plant. However, genetic variation does not often result in obvious morphological changes. Therefore, molecular and cytogenetic markers are typically used to evaluate the genetic variations of regenerants. Moreover, analyzing plant …

Individual, Social, And Environmental Factors Associated With Patterns Of Parasitic Infection In Capuchin Monkeys (Cebus Imitator), Megan C. Henriquez

Dissertations, Theses, and Capstone Projects

Parasites, and the infectious diseases they carry, are thought to have significantly impacted our evolutionary trajectory for millennia. Exploring how parasites are acquired and transmitted by their hosts in wild, natural populations is integral to understanding how similar processes may have shaped host-parasite co-evolutionary relationships over time. However, parasitological studies in humans and in non-human primates have produced inconsistent results, highlighting the dynamic, nuanced, and unique relationships individual parasites have with their hosts. These relationships are largely regulated by variation in factors at host, social, and environmental levels. Characteristics unique to the host (e.g., age and sex), factors pertaining to …

Investigating A Link Between Dna Repair And Dna Replication In Escherichia Coli Using A Bacterial Two-Hybrid System, Lo Cooper

University Honors Theses

Cells rely on nucleotide excision repair (NER) to remove bulky DNA lesions, such as those caused by UV light. In Escherichia coli, NER involves the UvrABC complex, and includes two main pathways, global genomic repair and transcription-coupled repair (TCR). While TCR, which preferentially removes lesions that block RNA polymerase on the transcribed strand of active genes, is well studied, less is known about whether a similar coupling between repair proteins and replisomes blocked by damaged DNA exists. Such a process has been suggested by a high throughput interactome study, using the replisome subunit HolC as bait and the damage …

Network Analysis Of Antimicrobial Resistance In Staphylococcus Aureus: Characterization Of Hub Genes And Their Functional Implications, Md Imran Hasan, Davida Smyth, Jeong Yang, Ashley Teufel

Masters Theses (Archived)

Antimicrobial resistance is a major cause of morbidity and mortality in patients with S. aureus infections. In this study, we analyzed genes, molecular mechanisms, and pathways driving drug resistance in S. aureus using network analysis. Using whole-genome sequencing (WGS) data and systems biology approaches, we identified 229 AMR-associated genes and constructed a protein-protein interaction network among these genes. Through network topology and functional enrichment analyses, we not only confirmed their association with resistance, but also highlighted the central roles of these genes in resistance pathways, such as efflux, target replacement, and target protection, which are directly linked to multiple drug …

Sex, Skulls, And Selection: An Exploration Of Blakely Island's Deer Population And Their Ecology Through Genetic Sex Differentiation Of Juvenile Crania, Blair P. Graves

Honors Projects

As an isolated landmass with no natural predators, Blakely Island serves as an effective study site for the study of evolutionary factors relating to insular populations of large mammals. A disparity in the adult sex ratio of local deer has been observed, but the demographics of juveniles must still be ascertained through genetic methods. This study aims to further research concerning the development of a replicable and non-toxic procedure through which undergraduate students can identify the sex of numerous juvenile deer crania. Specifically, differing decalcification lengths, DNA extraction kit methods, and amelogenin primer sets were evaluated for relative success in …

Diagnostic And Clinical Utility Of Oncoscan Microarray And Ngs-Based Sequencing In Pediatric Solid Tumors: Children’S Mercy Hospital’S Experience, Aravindh Nagarajan, Lisa Lansdon, Midhat Farooqi, Lei Zhang, Elena Repnikova

Research Days

This papers attempts to evaluate the diagnostic and clinical utility of microarray-based OS+ in detecting clinically relevant genetic alterations in FFPE solid tumor samples and to compare the yield of somatic mutation detection by WGS/WES in pediatric solid tumors at Children’s Mercy Hospital - Kansas City.

Generation Of A Transgenic Vector For The Purpose Of Transforming Charcoal Rot Resistance Into Soybeans (Glycine Max), John M. Bear Jr

Electronic Theses & Dissertations

Charcoal rot, caused by Macrophomina phaseolina, is among the most devastating fungal pathogens affecting G. max, particularly in drought-susceptible regions such as the midwestern United States. Traditional agricultural practices have included crop rotation and irrigation, which have proved ineffective or economically unfeasible. Charcoal rot infects over 500 other species of plants and can overwinter as dormant sclerotia which can germinate once soybeans are re-planted and infect young plants. As a result, transgenic solutions have offered a promising alternative for the development of disease-resistant soybeans. This thesis documents the construction of a transgenic vector to express BOZO, a …

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 …

Investigating The Influence Of Environmental Stressors To Exopolysaccharide Production In Soil Cyanobacteria: Genomic And Physiological Perspectives, Benjy Sedano-Herrera

UNLV Theses, Dissertations, Professional Papers, and Capstones

Cyanobacteria are photosynthetic microbes with essential roles in Earth’s ecosystems. The secretion of long–chain polysaccharides, known as exopolysaccharides (EPS), is a key trait facilitating cyanobacterial adaptation to diverse ecosystems. Genomics studies have shown that aquatic cyanobacteria harbor multiple gene copies encoding EPS export proteins, likely conferring a selective advantage in lakes or oceans. In addition, physiological experiments showed that nutrient limitation in aquatic habitats influences EPS production, affecting cyanobacterial fitness. However, whether terrestrial cyanobacteria also harbor multiple EPS-related genes and how nutrient limitation impacts their EPS production is not well understood.In the first chapter of my thesis, we investigated the …

Investigating The Effects Of Transcription Factor Binding And Genetic Variants In The Striatum Of Post-Mortem Cohorts With Opioid Use Disorder, Rajashree Chakraborty

Theses & Dissertations

The opioid crisis has emerged as one of the most pressing public health challenges of our time, with Opioid Use Disorder (OUD) affecting millions of lives across the globe. Studying OUD is not merely an academic pursuit but a critical necessity in addressing this multifaceted epidemic. The urgency of this research is underscored by the staggering prevalence of OUD, with an estimated 3.7% of U.S. adults requiring treatment in 2022 alone. Despite the availability of effective medications for OUD, a significant treatment gap persists, with only a quarter of those in need receiving these life-saving interventions. The far-reaching consequences of …

Genomic Structure Among Populations Of A Regionally Rare Perennial Plant Indicates The Need For Reevaluation Of Management Units, Cheyenne Moore, Angela J. Mcdonnell, Scott Schuette, Christopher T. Martine

Faculty Journal Articles

Conservation of rare species often relies on the delineation of management units and genomic tools can now be applied for this purpose. However, this is not as common on a local scale, where populations are often small and fragmented, despite the utility of informing conservation and management practice at the regional level. We use a genotyping by sequencing (GBS) approach to assess the perennial riparian plant species Baptisia australis (Fabaceae) in Pennsylvania, where the taxon is at the edge of its natural distribution and considered threatened. In this system, we investigate whether sampled subpopulations exhibit genetic structure. We find that …

Examining Loss Of Imprint In F1 Hybrid Female Mice Due To X Chromosome Epimutation And The Implications For Autism, Arianna H. Roach

Honors Scholar Theses

Sex biases are prevalent among various neurodevelopmental disorders, with males experiencing them at higher frequencies or severities than females. This male bias is poorly understood, and our lab aims to elucidate this mechanism using our model of transgenerational epigenetic inheritance. Our lab identified the cluster of genes Xlr3b/4b/4c on the X chromosome that are imprinted in the female brain. Preliminary studies suggest that Xlr3 acts as a mediator molecule in our model. Xlr3 knockdown male mice exhibited significant meiocyte loss that can be attributed to Meiotic Sex Chromosome Inactivation. Their female offspring also displayed loss of imprinting of Xlr3 and …

The Role Of Elongin B In Drosophila Melanogaster Muscle Development, Madelyne Dayan

Student Theses and Dissertations

Muscle atrophy is a result of a number of muscle diseases, as well as aging, disuse, and infections. Muscles weakened in these ways exhibit a characteristic decrease in size, strength, and mobility. The similarities between muscle in humans and Drosophila allow for direct comparisons to be made in vertebrates from studying muscle in Drosophila. Differential gene expression has been shown to play an important role in embryonic muscle development in Drosophila melanogaster. A previous study identified Elongin B (EloB) to be involved in somatic muscle morphogenesis in Drosophila, with mutant embryos displaying severe muscle defects, including thin, mis-attached, and missing …

Rnai Pathway Homeostasis Is Essential For Longevity In C. Elegans., Sejal Dulal

2025 Spring Honors Capstone Projects - Archive

RNA interference (RNAi) is a gene regulatory mechanism that is conserved across all animal species, including humans and the microscopic nematode, Caenorhabditis elegans. Many studies have identified the RNAi pathway factors and dissected the regulatory mechanisms of RNAi pathways, but there is little understanding of how the RNAi pathways themselves are regulated. Previously, Rogers and Phillips identified a feedback loop mediated by a pair of small RNA sensors, Sensor of siRNAs-1 (sosi-1) and eri-6[e-f], embedded within the genomic locus of a small RNA biogenesis factor, ERI-6/7. In this feedback motif, loss of small RNA-mediated silencing of …

A Review On Treatment, Prevention, And Research Of Worldwide Parasitic Disease: Toxoplasmosis, Hannah Skinner

All Theses

Toxoplasmosis is a worldwide, yet often overlooked, parasitic disease caused by the protozoan parasite, Toxoplasma gondii. The parasite is capable of infecting humans and almost all warm-blooded vertebrates. Over a million people are infected in the United States with toxoplasmosis each year. Most infections are asymptomatic but severe cases can lead to vision impairment, neurological disorders, and congenital birth defects. T. gondii is transmitted through undercooked meat, infected feline feces, or contaminated water and soil. The burden of T. gondii infection is most notable in livestock, felines, and immunocompromised humans. Despite being a widespread disease, toxoplasmosis is neglected in …

Life History Inhibits Deleterious Effects Of Dams On Genetic Health And Structure Of A Headwater Stream Fish, Riley Phelps

Electronic Theses and Dissertations

Habitat loss, fragmentation, and land use changes in river networks are common globally. The resulting fragmentation of landscapes and riverscapes threatens biodiversity and can affect dispersal and subsequently, gene flow and genetic health of species. Headwater streams are an integral part of river networks and contribute to biodiversity by providing habitat for temporary and permanent residents, yet they are easily altered and fragmented. The sandhills chub (Semotilus lumbee) is an endemic headwater leuciscid that lives in highly fragmented streams of the sandhills ecoregion in North and South Carolina, USA. New knowledge on the population genetics of the sandhills chub is …

A Genetic And Spatial Analysis Of The Last Megafaunal Species (Tapirus Terrestris) In The Paraguayan Dry Chaco Forest, Emily Bowers

LSU New Orleans Theses and Dissertations

No abstract provided.

Investigating The Effects Of Sod1 Knockout On Oxidative Stress And Stress Coping Styles In Zebrafish Using Crispr Technology, Tai Prauner, Ryan Wong

Theses/Capstones/Creative Projects

Reactive oxygen species are byproducts of cellular metabolism that, when not efficiently neutralized, can damage DNA, proteins, and lipids. Superoxide dismutase 1 (SOD1) is an antioxidant enzyme that converts superoxide radicals into less harmful molecules. While its molecular function is well documented, the role of SOD1 in shaping stress-related behavior remains underexplored. This project aimed to establish foundational tools for studying the behavioral impact of SOD1 knockout across proactive and reactive stress-coping styles in zebrafish.

To support future gene-editing experiments, microinjection and breeding protocols were refined across wildtype AB, proactive, and reactive zebrafish lines. No embryos were injected with CRISPR-Cas9 …

Sibship Analysis Of Fall And Spring Spawn Gulf Sturgeon Eggs In The Choctawhatchee River, Florida, Lyric Mccullouch

Honors Theses

The Gulf sturgeon (Acipenser oxyrinchus desotoi) is an anadromous species that inhabits rivers along the northern Gulf of Mexico. Facing challenges from overfishing and habitat alteration, the Gulf sturgeon is listed as threatened under the Endangered Species Act. This study investigated the genetic distinctiveness of fall and spring spawning groups of Gulf sturgeon in the Choctawhatchee River, a critical habitat for the species. In this study, I used microsatellite loci to analyze Gulf sturgeon eggs previously collected in the fall and spring of 2019 and 2020. The goals of this study were to verify the genetic identity of …

Developing A Small Molecule To Inhibit Hsf1 Expression In Cancer And Evaluating Natural Genetic Variation In Small Molecule Toxicity., Michaela Kendal Foley

Theses and Dissertations

Each year cancer affects nearly 20 million people worldwide and genetic differences across populations can impact cancer onset and progression. Specifically, tumors with high levels of HSF1, the master regulator of the cytoprotective heat shock response (HSR), are correlated with poor patient outcomes in multiple cancers such as prostate, breast, and melanoma. Subsequently, the development of pharmacological inhibitors of HSF1 represents a promising strategy for anticancer therapeutics. Using a luciferase-based transcriptional reporter, two small molecule libraries were screened for inhibitors of HSF1 expression in human embryonic kidney cells, yielding ten compounds that decrease HSF1 expression. To identify if cancer lines …

Therapeutic Applications Of A Novel Humanized Monoclonal Antibody Targeting Chemokine Receptor Ccr9 In Pancreatic Cancer, Hannah G. Mcdonald, Anna M. Reagan, Charles J. Bailey, Mei Gao, Muqiang Gao, Angelica L. Solomon, Michael J. Cavnar, Prakash Pandalai, Mautin Barry-Hundeyin, Megan Harper, Justin A. Rueckert, Ángela Turrero, Araceli Tobio, Anxo Vidal, Daniel Roca-Lema, Elia Álvarez-Coiradas, Pablo Garrido, Laureano Simón, Joseph Kim

Markey Cancer Center Faculty Publications

The relative failure of immune checkpoint inhibitors in pancreatic ductal adenocarcinoma (PDAC) despite having a dense, immunosuppressive tumor microenvironment highlights the need to target alternate/escape pathways. We have previously examined C–C chemokine receptor type 9 (CCR9) as a candidate immune checkpoint and developed a targeted, humanized monoclonal antibody (SRB2). Cytotoxicity of SRB2 was evaluated in vitro and in vivo. CCR9 expression on PDAC cells/tissues, immune components of patient-derived organoids (PDOs), and antibody-dependent cell-mediated cytotoxicity were examined. In PANC-1 and MIA PaCa-2 cell lines, we demonstrated highest CCR9 expression; however, no direct cytotoxic effect was observed with SRB2 treatment. In PANC-1 …