Medicine and Health Sciences Commons^™

Identification Of Colorectal Cancer Cell Stemness From Single-Cell Rna Sequencing, Kangyu Lin, Saikat Chowdhury, Mohammad A Zeineddine, Fadl A Zeineddine, Nicholas J Hornstein, Oscar E Villarreal, Dipen M Maru, Cara L Haymaker, Jean-Nicolas Vauthey, George J Chang, Elena Bogatenkova, David Menter, Scott Kopetz, John Paul Shen

Faculty, Staff and Student Publications

UNLABELLED: Cancer stem cells (CSC) play a critical role in metastasis, relapse, and therapy resistance in colorectal cancer. While characterization of the normal lineage of cell development in the intestine has led to the identification of many genes involved in the induction and maintenance of pluripotency, recent studies suggest significant heterogeneity in CSC populations. Moreover, while many canonical colorectal cancer CSC marker genes have been identified, the ability to use these classical markers to annotate stemness at the single-cell level is limited. In this study, we performed single-cell RNA sequencing on a cohort of 6 primary colon, 9 liver metastatic …

Peritoneal Microenvironment Promotes Appendiceal Adenocarcinoma Growth: A Multi-Omics Approach Using Patient-Derived Xenografts, Vinay K Pattalachinti, Ichiaki Ito, Saikat Chowdhury, Abdelrahman Yousef, Yue Gu, Betul Beyza Gunes, Emma R Salle, Melissa W Taggart, Keith Fournier, Natalie W Fowlkes, John Paul Shen

Faculty, Staff and Student Publications

Appendiceal adenocarcinoma (AA) is unique from other gastrointestinal malignancies in that it almost exclusively metastasizes to the peritoneal cavity. However, few studies have investigated the molecular interaction of the peritoneal microenvironment and AA. Here, we use a multi-omics approach with orthotopic and flank-implanted patient-derived xenografts (PDX) to study the effect of the peritoneal microenvironment on AA. AA tumors implanted in the peritoneal microenvironment tended to grow faster and displayed greater nuclear expression of Ki-67 relative to the same tumors implanted in the flank. Comparing the tumor-specific transcriptome (excluding stromal transcription), the peritoneal microenvironment relatively upregulated genes related to proliferation, including …

Neutrophil Elastase Remodels Mammary Tumors To Facilitate Lung Metastasis, Amriti R Lulla, Said Akli, Cansu Karakas, Joseph A Caruso, Lucas D Warma, Natalie W Fowlkes, Xiayu Rao, Jing Wang, Kelly K Hunt, Stephanie S Watowich, Khandan Keyomarsi

Faculty, Staff and Student Publications

Metastatic disease remains the leading cause of death due to cancer, yet the mechanism(s) of metastasis and its timely detection remain to be elucidated. Neutrophil elastase (NE), a serine protease secreted by neutrophils, is a crucial mediator of chronic inflammation and tumor progression. In this study, we used the PyMT model (NE+/+ and NE-/-) of breast cancer to interrogate the tumor-intrinsic and -extrinsic mechanisms by which NE can promote metastasis. Our results showed that genetic ablation of NE significantly reduced lung metastasis and improved metastasis-free survival. RNA-sequencing analysis of primary tumors indicated differential regulation of tumor-intrinsic actin cytoskeleton signaling pathways …

Author Correction: Automating Data Analysis For Hydrogen/Deuterium Exchange Mass Spectrometry Using Data-Independent Acquisition Methodology, Frantisek Filandr, Vladimir Sarpe, Shaunak Raval, D Alex Crowder, Morgan F Khan, Pauline Douglas, Stephen Coales, Rosa Viner, Aleem Syed, John A Tainer, Susan P Lees-Miller, David C Schriemer

Faculty, Staff and Student Publications

No abstract provided.

Antigen-Clustered Nanovaccine Achieves Long-Term Tumor Remission By Promoting B/Cd 4 T Cell Crosstalk, Chengyi Li, Ryan Clauson, Luke F Bugada, Fang Ke, Bing He, Zhixin Yu, Hongwei Chen, Binyamin Jacobovitz, Hongxiang Hu, Polina Chuikov, Brett Dallas Hill, Syed M Rizvi, Yudong Song, Kai Sun, Pasieka Axenov, Daniel Huynh, Xinyi Wang, Lana Garmire, Yu Leo Lei, Irina Grigorova, Fei Wen, Marilia Cascalho, Wei Gao, Duxin Sun

Faculty, Staff and Student Publications

Current cancer vaccines using T cell epitopes activate antitumor T cell immunity through dendritic cell/macrophage-mediated antigen presentation, but they lack the ability to promote B/CD4 T cell crosstalk, limiting their anticancer efficacy. We developed antigen-clustered nanovaccine (ACNVax) to achieve long-term tumor remission by promoting B/CD4 T cell crosstalk. The topographic features of ACNVax were achieved using an iron nanoparticle core attached with an optimal number of gold nanoparticles, where the clusters of HER2 B/CD4 T cell epitopes were conjugated on the gold surface with an optimal intercluster distance of 5-10 nm. ACNVax effectively trafficked to lymph nodes and cross-linked with …

Targeting Branched N-Glycans And Fucosylation Sensitizes Ovarian Tumors To Immune Checkpoint Blockade, Hao Nie, Pratima Saini, Taito Miyamoto, Liping Liao, Rafal J Zielinski, Heng Liu, Wei Zhou, Chen Wang, Brennah Murphy, Martina Towers, Tyler Yang, Yuan Qi, Toshitha Kannan, Andrew Kossenkov, Hiroaki Tateno, Daniel T Claiborne, Nan Zhang, Mohamed Abdel-Mohsen, Rugang Zhang

Faculty, Staff and Student Publications

Aberrant glycosylation is a crucial strategy employed by cancer cells to evade cellular immunity. However, it's unclear whether homologous recombination (HR) status-dependent glycosylation can be therapeutically explored. Here, we show that the inhibition of branched N-glycans sensitizes HR-proficient, but not HR-deficient, epithelial ovarian cancers (EOCs) to immune checkpoint blockade (ICB). In contrast to fucosylation whose inhibition sensitizes EOCs to anti-PD-L1 immunotherapy regardless of HR-status, we observe an enrichment of branched N-glycans on HR-proficient compared to HR-deficient EOCs. Mechanistically, BRCA1/2 transcriptionally promotes the expression of MGAT5, the enzyme responsible for catalyzing branched N-glycans. The branched N-glycans on HR-proficient tumors augment their …

Alterations In Serum Thiol-Disulfide Homeostasis And Ischemia-Modified Albumin Concentrations In Clinical Canine Parvoviral Enteritis, Yasi̇n Şenel, Osman Safa Terzi̇, Erdal Kara, Özcan Erel, Sali̇m Neşeli̇oğlu, Ebubeki̇r Ceylan

Turkish Journal of Veterinary & Animal Sciences

Monitoring biomarkers related to inflammation and oxidative stress is critical in dogs because parvovirus causes both inflammatory and antioxidant alterations. The aim of this study was to investigate inflammatory and antioxidant changes caused by canine parvoviral enteritis to better understand the oxidative stress process related to this disease. Thus, the total thiol, native thiol, disulfide, and ischemia-modified albumin levels of Canine parvovirus infected symptomatic puppies and healthy puppies were examined. Using the results of complete blood counts, the blood serum thiol-disulfide homeostasis and ischemia modified albumin levels of the puppies with Canine parvoviral enteritis (n = 65) and the healthy …

Ai Is A Viable Alternative To High Throughput Screening: A 318-Target Study, The Atomwise Aims Program

Faculty, Staff and Student Publications

High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, …

Early Screening Of Colorectal Cancer Using Feature Engineering With Artificial Intelligence-Enhanced Analysis Of Nanoscale Chromatin Modifications, Andrew Chang, Sravya Prabhala, Ali Daneshkhah, Jianan Lin, Hariharan Subramanian, Hemant Kumar Roy, Vadim Backman

Faculty, Staff and Students Publications

Colonoscopy is accurate but inefficient for colorectal cancer (CRC) prevention due to the low (~ 7 to 8%) prevalence of target lesions, advanced adenomas. We leveraged rectal mucosa to identify patients who harbor CRC field carcinogenesis by evaluating chromatin 3D architecture. Supranucleosomal disordered chromatin chains (~ 5 to 20 nm, ~1 kbp) fold into chromatin packing domains (~ 100 to 200 nm, ~ 100 to 1000 kbp). In turn, the fractal-like conformation of DNA within chromatin domains and the folding of the genome into packing domains has been shown to influence multiple facets of gene transcription, including the transcriptional plasticity …

In Silico Identification Of Small Molecule Agonist Binding Sites On Kcc2, Kenyon Mitchell, Alfred Amendolara, Ruth Hunter, Jaden Miner, Andrew Payne

Annual Research Symposium

Purpose: Potassium-Chloride Cotransporter 2 (KCC2) is a neuronal membrane protein specific to the central nervous system. It is responsible for removing Cl- ions from the intracellular space, maintaining a normal Cl- gradient essential for proper function at inhibitory synapses. Dysregulation causes an upward shift in the Cl- reversal potential resulting in a hyperexcitable state of the postsynaptic neuron. Existing literature indicates that KCC2 may be involved in the addiction pathway of a variety of drugs of abuse, including opioids and alcohol. This makes KCC2 an attractive potential drug target when treating substance use disorders. A novel direct KCC2 agonist, VU0500469, …

Hedgehog Signaling And Congenital Disorders; The Case Of Anencephaly And Polydactyly, Joshua Towery

First-Year Research Immersion (FRI) Scholarship

The Hedgehog pathway is a fundamental signaling pathway in the human body; involved in carcinogenesis, stem cell maintenance, as well as limb patterning in embryonic development. Originally discovered in drosophila, their initial discovery, and subsequent analysis revealed many novel pieces of information about the mechanisms inside the human body, as many core components of the signaling pathway are carried over from fruit flies to humans. Because of the key roles hedgehog signaling plays in human development, dysfunction and mutations in the pathway can be detrimental. This review will focus on two congenital birth defects thought to be caused by hedgehog …

Search, The Jackson Laboratory

Search Magazine

No abstract provided.

Santa Clara Magazine, Volume 65 Number 1, Spring 2024, Santa Clara University

Santa Clara Magazine

14 - A CAMPUS ON THE RISE Six new buildings on campus aren’t the only changes brought by a successful $1 billion fundraising campaign. Lauren Loftus & Leslie Griffy

20 - HUMAN AT HEART How Santa Clara University is distinguishing itself as a leader in human-focused health care innovation. Lauren Loftus

26 - SHEPHERDING INNOVATION How wonder, and God, can make us better scientists. Brother Guy Consolmagno, S.J.

30 - THE CO-OP Santa Clara University has long been a bastion of interdisciplinary learning. A new fund is taking cross-collaboration to new heights. SCM Staff

34 - MAKE AI THE BEST …

2024- The Twenty-Eighth Annual Symposium Of Student Scholars

Symposium of Student Scholars Program Books

The full program book from the 28th Annual Symposium of Student Scholars, held on April 17-19, 2024. Includes abstracts from the presentations and posters.

Cortisol Production In Female Soccer Players, Katelyn Seagraves

Honors Projects

Cortisol is released from the adrenal glands when there is an apparent stressor. Exercise, while beneficial, is seen as stress to the body and incites increased cortisol release. Cortisol is known to increase with exercise, and higher-intensity exercise tends to raise cortisol more compared to lower intensities. However, less is known about interval training and cortisol concentrations.

This review of literature dives into the background of cortisol: how it's produced, what systems it regulates, and differences in production based on gender, stressors, exercise intensity, and duration. This paper identifies some knowledge gaps and links training intensities in soccer to cortisol …

Cortisol Production In Female Soccer Players, Katelyn Seagraves

ASPIRE 2024

Cortisol is released from the adrenal glands when there is an apparent stressor. Exercise, while beneficial, is seen as stress to the body and incites increased cortisol release. Cortisol is known to increase with exercise, and higher-intensity exercise tends to raise cortisol more compared to lower intensities. However, less is known about interval training and cortisol concentrations.

This review of literature dives into the background of cortisol: how it's produced, what systems it regulates, and differences in production based on gender, stressors, exercise intensity, and duration. This paper identifies some knowledge gaps and links training intensities in soccer to cortisol …

Neurotensin Modulates Ovarian Vascular Permeability Via Adherens Junctions, Andrew Pearson, Ketan Shrestha, Thomas E. Curry, Diane M. Duffy

UK CARES Faculty Publications

Neurotensin (NTS) is a 13-amino acid peptide which is highly expressed in the mammalian ovary in response to the luteinizing hormone surge. Antibody neutralization of NTS in the ovulatory follicle of the cynomolgus macaque impairs ovulation and induces follicular vascular dysregulation, with excessive pooling of red blood cells in the follicle antrum. We hypothesize that NTS is an essential intrafollicular regulator of vascular permeability. In the present study, follicle injection of the NTS receptor antagonist SR142948 also resulted in vascular dysregulation. To measure vascular permeability changes in vitro, primary macaque ovarian microvascular endothelial cells (mOMECs) were enriched from follicle aspirates …

Short-Term Larval Surveys Reveal Rainy Season Breeding Site Preferences Of Malaria Vector Anopheles Spp. In Zanzibar City, Kaeden K. Hill

Independent Study Project (ISP) Collection

Malaria is a serious illness that causes over 500,000 deaths annually worldwide, with Tanzania alone contributing to approximately 4% of those deaths. Malaria is caused by Plasmodium spp. parasites, and it is vectored by mosquitoes in the Anopheles genus. In Zanzibar City, the incidence of malaria has decreased over the past few decades due to standardized treatment protocols and public health interventions targeting adult mosquitoes. However, the incidence remains between 1-2%, with an increasing trend observed over the past few years likely stemming from continued exchange of Plasmodium spp. from other malaria-endemic areas. Because larvicidal strategies can be useful in …

Exploring The Use Of Trauma-Informed Care Practices In Extension, Caitlin O'Brien, Martie Gillen

Journal of Human Sciences and Extension

A content analysis of 63 land-grant Extension university websites was conducted to examine the promotion of trauma-informed care (TIC) through the sharing of resources, providing instructive webinars and/or in-person events, and offering comprehensive programs. While many Extension universities are sharing resources, only nine universities (14%) featured robust TIC Extension programs, and 40% shared no TIC information. Additionally, we found no indication of internal education programs across the universities on adverse childhood experiences (ACEs) and TIC practices for Extension faculty and staff. These findings highlight opportunities to increase efforts with the public as well as internally within Extension.

Winners And Losers: Emotional Shifts Across Elections Are Conveyed By A Politician’S Smile, Carl Senior, Patrick A. Stewart, Erik Bucy, Nick Lee

Political Science Faculty Publications and Presentations

The human smile can convey both rewarding and affiliative social intent and thus has significant utility in politics, where the ability to bond with and reassure voters is vital to electoral success. We examine experimental evidence from the 2019 UK general election to investigate the influence of a politician’s reward or affiliative smile on voter emotions. It was hypothesised that the winner’s affiliative smile would engender positive affect across all partisan groups compared to the winner’s reward smile display. Participants from a nationally representative sample were shown campaign footage containing both types of smiles from the leaders of the main …

Decoding Disease Mechanisms: Unraveling Large-Scale Biological Data For Novel Therapeutic Target Discovery, Yuntao Yang

Dissertations and Theses (Open Access)

This dissertation leverages large biological datasets and data-driven research to enhance our understanding of complex human diseases, deploying a unified narrative across three interconnected bioinformatics studies. Each study targets a different biological level, including genes, proteins, cells, and tissues, to uncover disease mechanisms and speed up the discovery of potential therapeutic targets.

The first study addresses gene-level analysis in the context of bladder cancer. It integrates gene expression data from lab models with clinical survival data to identify new therapeutic targets. This research pinpoints the IL6/JAK/STAT3 signaling pathway as a promising target for treating SMARCB1-deficient bladder cancer, demonstrating how combining …

Intercellular Communication Via Gap Junctions Influences Stem Cell Therapy, Madison Bohatuk, Megan Bohatuk, Lauren Harmon

Honors Projects

Adult somatic stem cell therapy can be beneficial for cardiac muscle recovery following injury to the heart. However, a common problem with various approaches to this therapy has been the early (< 24 hrs) loss of a large percentage of the implanted stem cells, which decreases their therapeutic potential. We have demonstrated that cell coupling occurs between stem and cardiac cells through Cx43 gap junctions.Thus, we hypothesize that gap junctions may act as conduits for molecular apoptotic signals from injured cardiac muscle cells that impair the viability of implanted stem cells ('Bystander Effect' ). In our initial experiments, we will use a fluorescently-tagged RNAi control oligo to transfect mouse bone marrow-derived mesenchymal stem cells (mBM- MSCs) and measure transfection efficiency with fluorescence-activated cell sorting (FACS). Additional studies will determine mBM-MSC Cx43 protein expression and the level of Cx43 protein down-regulation in the mBM-MSCs.

Introduction To The Special Centennial Issue, Woodward S. Bousquet, Christopher Osgood

Virginia Journal of Science

This special issue of the Virginia Journal of Science (VJS) is dedicated to the 2023 Centennial of the Virginia Academy of Science (VAS). It includes congratulations from Commonwealth leaders, a proclamation by the Virginia General Assembly Senate, Academy members’ personal reflections, several historical papers and summaries, and portions of the program for the May 25-26, 2023 Annual Meeting in Williamsburg on the William & Mary campus.

Reflections About The Academy And Its Centennial, Marco Aldi, Woodward S. Bousquet

Virginia Journal of Science

Brief reflective essays from members of the Virginia Academy of Science were solicited as part of the Academy's centennial commemoration in 2023. The essays received demonstrate the many and varied ways in which the Academy has fostered collegiality, encouraged research, supported science education, and shaped the course of science in Virginia during the organization's 100-year history.

Transcriptional Signature Of Durable Effector T Cells Elicited By A Replication Defective Hcmv Vaccine, Xiaohua Ye, David J H Shih, Zhiqiang Ku, Junping Hong, Diane F Barrett, Richard E Rupp, Ningyan Zhang, Tong-Ming Fu, W Jim Zheng, Zhiqiang An

Faculty, Staff and Student Publications

Human cytomegalovirus (HCMV) is a leading infectious cause of birth defects and the most common opportunistic infection that causes life-threatening diseases post-transplantation; however, an effective vaccine remains elusive. V160 is a live-attenuated replication defective HCMV vaccine that showed a 42.4% efficacy against primary HCMV infection among seronegative women in a phase 2b clinical trial. Here, we integrated the multicolor flow cytometry, longitudinal T cell receptor (TCR) sequencing, and single-cell RNA/TCR sequencing approaches to characterize the magnitude, phenotype, and functional quality of human T cell responses to V160. We demonstrated that V160 de novo induces IE-1 and pp65 specific durable polyfunctional …

04.01.2024 Orsp Connect, Liz Williamson

ORED Newsletter

NSF Conference, Jennifer Baumbaugh, Sustainable Food Packaging research, Export Control Policy Update

The Influence Of Cards Toxin In Abetting The Virulence Of Mycoplasma Pneumoniae, Layla Abdulbaki

Posters - 2024

Mycoplasma pneumonia is a human bacterial pathogen known to induce chronic upper and lower respiratory infections. This bacterium commonly causes acute, chronic infections, such as atypical pneumonia, and spreads through droplet transmission (> 5 microns). M. pneumoniae damages cells by attacking the epithelium of the respiratory tract, resulting in epithelium shedding. Infection of the airway tract by M. pneumoniae will usually express itself in people with chronic symptoms such as coughing, dyspnea, diarrhea, and epiphora. With this being said, this bacterium is ambit, meaning that it is versatile in who it affects (children to adults), how it manifests (pneumonia, tracheobronchitis, …

Mycoplasma Pneumoniae: Long-Term Effects On The Lungs, Alyssa David

Posters - 2024

Mycoplasma pneumoniae is a bacterium responsible for causing pneumonia in the lungs. M. pneumoniae is responsible for an average of 2 million cases of bacterial pneumonia in the United States each year (ASM Journal). When M. pneumonia infects the lungs, it releases community-acquired respiratory distress syndrome (CARDS toxin), which is capable of two enzymatic functions, vacuolization and ADP-ribosylation. ADPribosylation is found in the N-terminal domain of the protein, and the glutamic acid at amino acid residue 132 is critical for enzymatic function. There is evidence that the vacuolization function is encoded by the C-terminal of the protein. Preliminary findings in …

An Investigation On The Intricacies Of Epigenetic Modulations In The Pathogenesis Of Human Papillomavirus-Associated Cervical Cancer: A Comprehensive Meta-Narrative Synthesis, Jade Carolina Cabello, Marcella Victoria Ras, Katelyn Thy Nhung Tran, Athit Voytas

Research Methods Poster Session 2024

Abstract

Objective: To conduct a meta-analysis of the available and relevant literature on E1/E2 genes and their affect on the epigenetics of Human Papillomavirus caused uterine cervical cancer.

Background/Significance: Human Papillomavirus is strongly linked to cervical cancer, and cervical cancer is the fourth most common type of cancer in women. 99.7% of patients with cervical cancer have a “high risk HPV genotype” which factors greatly into the causation if their diagnosis. The HPV vaccine that came out in 2006 has greatly decreased cervical cancer in the population as well as increased the preventative chances of highly susceptible individuals.

Methods: To …

Occupational Engagement In Recreational Sports For The Deaf And Hard Of Hearing: An Employee Guidebook, Colleen Mcerlean, Mary Ann Smith, Christopher Ebner

Spring 2024 Virtual OTD Capstone Symposium

An employee guidebook to help increase occupational engagement within recreational sports for the Deaf and Hard of Hearing population in the Austin, TX area.