Digital Commons Network^™

Characterization Of The Long Non-Coding Rna Proins In Human Pancreatic Β-Cell, Shareena Saeed Lootah

Dissertations

It is well established that the genome is pervasively transcribed. Only 2% of those transcripts are translated into proteins, and the remaining 98% are non-translated, generating the non-coding RNAs (ncRNAs) species. A close observation of these transcripts directed the scientific community to their increasing potential functional roles in the cells. Indeed, the literature exponentially unveils this notion, with many ncRNAs showing substantial and variable biological functions. The field is in its infancy; however, efforts are accelerating to discover and define this ocean of new species.

Long non-coding RNAs (lncRNAs) are sub-species of ncRNAs with an arbitrary size of more than …

Spatially Restricted Drivers And Transitional Cell Populations Cooperate With The Microenvironment In Untreated And Chemo-Resistant Pancreatic Cancer, Daniel Cui Zhou, Reyka G Jayasinghe, Siqi Chen, John M Herndon, Michael D Iglesia, Pooja Navale, Michael C Wendl, Wagma Caravan, Kazuhito Sato, Erik Storrs, Chia-Kuei Mo, Jingxian Liu, Austin N Southard-Smith, Yige Wu, Nataly Naser Al Deen, John M Baer, Robert S Fulton, Matthew A Wyczalkowski, Ruiyang Liu, Catrina C Fronick, Lucinda A Fulton, Andrew Shinkle, Lisa Thammavong, Houxiang Zhu, Hua Sun, Liang-Bo Wang, Yize Li, Chong Zuo, Joshua F Mcmichael, Sherri R Davies, Elizabeth L Appelbaum, Keenan J Robbins, Sara E Chasnoff, Xiaolu Yang, Ashley N Reeb, Clara Oh, Mamatha Serasanambati, Preet Lal, Rajees Varghese, Jay R Mashl, Jennifer Ponce, Nadezhda V Terekhanova, Lijun Yao, Fang Wang, Lijun Chen, Michael Schnaubelt, Rita Jui-Hsien Lu, Julie K Schwarz, Sidharth V Puram, Albert H Kim, Sheng-Kwei Song, Kooresh I Shoghi, Ken S Lau, Tao Ju, Ken Chen, Deyali Chatterjee, William G Hawkins, Hui Zhang, Samuel Achilefu, Milan G Chheda, Stephen T Oh, William E Gillanders, Feng Chen, David G Denardo, Ryan C Fields, Li Ding

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma is a lethal disease with limited treatment options and poor survival. We studied 83 spatial samples from 31 patients (11 treatment-naïve and 20 treated) using single-cell/nucleus RNA sequencing, bulk-proteogenomics, spatial transcriptomics and cellular imaging. Subpopulations of tumor cells exhibited signatures of proliferation, KRAS signaling, cell stress and epithelial-to-mesenchymal transition. Mapping mutations and copy number events distinguished tumor populations from normal and transitional cells, including acinar-to-ductal metaplasia and pancreatic intraepithelial neoplasia. Pathology-assisted deconvolution of spatial transcriptomic data identified tumor and transitional subpopulations with distinct histological features. We showed coordinated expression of TIGIT in exhausted and regulatory T cells …

Repurposing Epigenetic Inhibitors To Target The Clostridioides Difficile-Specific Dna Adenine Methyltransferase And Sporulation Regulator Cama, Jujun Zhou, John R Horton, Dan Yu, Ren Ren, Robert M Blumenthal, Xing Zhang, Xiaodong Cheng

Faculty, Staff and Student Publications

Epigenetically targeted therapeutic development, particularly for SAM-dependent methylations of DNA, mRNA and histones has been proceeding rapidly for cancer treatments over the past few years. However, this approach has barely begun to be exploited for developing new antibiotics, despite an overwhelming global need to counter antimicrobial resistance. Here, we explore whether SAM analogues, some of which are in (pre)clinical studies as inhibitors of human epigenetic enzymes, can also inhibit Clostridioides difficile-specific DNA adenine methyltransferase (CamA), a sporulation regulator present in all C. difficile genomes sequenced to date, but found in almost no other bacteria. We found that SGC0946 (an …

Hic2 Controls Developmental Hemoglobin Switching By Repressing Bcl11a Transcription, Peng Huang, Scott A Peslak, Ren Ren, Eugene Khandros, Kunhua Qin, Cheryl A Keller, Belinda Giardine, Henry W Bell, Xianjiang Lan, Malini Sharma, John R Horton, Osheiza Abdulmalik, Stella T Chou, Junwei Shi, Merlin Crossley, Ross C Hardison, Xiaodong Cheng, Gerd A Blobel

Faculty, Staff and Student Publications

The fetal-to-adult switch in hemoglobin production is a model of developmental gene control with relevance to the treatment of hemoglobinopathies. The expression of transcription factor BCL11A, which represses fetal β-type globin (HBG) genes in adult erythroid cells, is predominantly controlled at the transcriptional level but the underlying mechanism is unclear. We identify HIC2 as a repressor of BCL11A transcription. HIC2 and BCL11A are reciprocally expressed during development. Forced expression of HIC2 in adult erythroid cells inhibits BCL11A transcription and induces HBG expression. HIC2 binds to erythroid BCL11A enhancers to reduce chromatin accessibility and binding of transcription factor GATA1, …

Clinical Acceptability Of Fully Automated External Beam Radiotherapy For Cervical Cancer With Three Different Beam Delivery Techniques, Dong Joo Rhee, Anuja Jhingran, Kai Huang, Tucker J Netherton, Nazia Fakie, Ingrid White, Alicia Sherriff, Carlos E Cardenas, Lifei Zhang, Surendra Prajapati, Stephen F Kry, Beth M Beadle, William Shaw, Frederika O'Reilly, Jeannette Parkes, Hester Burger, Chris Trauernicht, Hannah Simonds, Laurence E Court

Faculty, Staff and Student Publications

Purpose: To fully automate CT-based cervical cancer radiotherapy by automating contouring and planning for three different treatment techniques.

Methods: We automated three different radiotherapy planning techniques for locally advanced cervical cancer: 2D 4-field-box (4-field-box), 3D conformal radiotherapy (3D-CRT), and volumetric modulated arc therapy (VMAT). These auto-planning algorithms were combined with a previously developed auto-contouring system. To improve the quality of the 4-field-box and 3D-CRT plans, we used an in-house, field-in-field (FIF) automation program. Thirty-five plans were generated for each technique on CT scans from multiple institutions and evaluated by five experienced radiation oncologists from three different countries. Every plan was …

Development And Validation Of A Checklist For Use With Automatically Generated Radiotherapy Plans, Kelly A Nealon, Laurence E Court, Raphael J Douglas, Lifei Zhang, Eun Young Han

Faculty, Staff and Student Publications

Purpose: To develop a checklist that improves the rate of error detection during the plan review of automatically generated radiotherapy plans.

Methods: A custom checklist was developed using guidance from American Association of Physicists in Medicine task groups 275 and 315 and the results of a failure modes and effects analysis of the Radiation Planning Assistant (RPA), an automated contouring and treatment planning tool. The preliminary checklist contained 90 review items for each automatically generated plan. In the first study, eight physicists were recruited from our institution who were familiar with the RPA. Each physicist reviewed 10 artificial intelligence-generated resident …

Multidimensional Single-Cell Analysis Identifies A Role For Cd2-Cd58 Interactions In Clinical Antitumor T Cell Responses, Gabrielle Romain, Paolo Strati, Ali Rezvan, Mohsen Fathi, Irfan N Bandey, Jay R T Adolacion, Darren Heeke, Ivan Liadi, Mario L Marques-Piubelli, Luisa M Solis, Ankit Mahendra, Francisco Vega, Laurence Jn Cooper, Harjeet Singh, Mike Mattie, Adrian Bot, Sattva S Neelapu, Navin Varadarajan

Faculty, Staff and Student Publications

The in vivo persistence of adoptively transferred T cells is predictive of antitumor response. Identifying functional properties of infused T cells that lead to in vivo persistence and tumor eradication has remained elusive. We profiled CD19-specific chimeric antigen receptor (CAR) T cells as the infusion products used to treat large B cell lymphomas using high-throughput single-cell technologies based on time-lapse imaging microscopy in nanowell grids (TIMING), which integrates killing, cytokine secretion, and transcriptional profiling. Our results show that the directional migration of CD19-specific CAR T cells is correlated with multifunctionality. We showed that CD2 on T cells is associated with …

Targeting The Dna Damage Response Beyond Poly(Adp-Ribose) Polymerase Inhibitors: Novel Agents And Rational Combinations, Natalie Y L Ngoi, Shannon N Westin, Timothy A Yap

Faculty, Staff and Student Publications

Purpose of review: Poly(ADP-ribose) polymerase (PARP) inhibitors have transformed treatment paradigms in multiple cancer types defined by homologous recombination deficiency (HRD) and have become the archetypal example of synthetic lethal targeting within the DNA damage response (DDR). Despite this success, primary and acquired resistance to PARP inhibition inevitability threaten the efficacy and durability of response to these drugs. Beyond PARP inhibitors, recent advances in large-scale functional genomic screens have led to the identification of a steadily growing list of genetic dependencies across the DDR landscape. This has led to a wide array of novel synthetic lethal targets and corresponding inhibitors, …

The Microbiome In Gastrointestinal Cancers, Michael G White, Jennifer A Wargo

Faculty, Staff and Student Publications

The human microbiome has been recognized as increasingly important to health and disease. This is especially prescient in the development of various cancers, their progression, and the microbiome's modulation of various anticancer therapeutics. Mechanisms behind these interactions have been increasingly well described through modulation of the host immune system as well as induction of genetic changes and local inactivation of cancer therapeutics. Here, we review these associations for a variety of gastrointestinal malignancies as well as contemporary strategies proposed to leverage these associations to improve cancer treatment outcomes.

Pharmacokinetic Evaluation Of Intravenous Vitamin C: A Classic Pharmacokinetic Study., Ping Chen, Greg Reed, Joyce Jiang, Yaohui Wang, Jean Sunega, Ruochen Dong, Yan Ma, Anna E. Esparham, Ryan Ferrell, Mark Levine, Jeanne Drisko, Qi Chen

Manuscripts, Articles, Book Chapters and Other Papers

Purpose: Intravenous vitamin C (IVC) is used in a variety of disorders with limited supporting pharmacokinetic data. Herein we report a pharmacokinetic study in healthy volunteers and cancer participants with IVC doses in the range of 1-100 g.

Methods: A pharmacokinetic study was conducted in 21 healthy volunteers and 12 oncology participants. Healthy participants received IVC infusions of 1-100 g; oncology participants received IVC infusions of 25-100 g. Serial blood and complete urine samples were collected pre-infusion and for 24 h post-infusion. Pharmacokinetic parameters were computed using noncompartmental methods. Adverse events were monitored during the study.

Results: In both cohorts, …

Game Of Clones: Battles In The Field Of Carcinogenesis, Zahraa Rahal, Ansam Sinjab, Ignacio I Wistuba, Humam Kadara

Faculty, Staff and Student Publications

Recent advances in bulk sequencing approaches as well as genomic decoding at the single-cell level have revealed surprisingly high somatic mutational burdens in normal tissues, as well as increased our understanding of the landscape of "field cancerization", that is, molecular and immune alterations in mutagen-exposed normal-appearing tissues that recapitulated those present in tumors. Charting the somatic mutational landscapes in normal tissues can have strong implications on our understanding of how tumors arise from mutagenized epithelium. Making sense of those mutations to understand the progression along the pathologic continuum of normal epithelia, preneoplasias, up to malignant tissues will help pave way …

Integrated Imaging And Molecular Analysis To Decipher Tumor Microenvironment In The Era Of Immunotherapy, Jia Wu, Aaron T Mayer, Ruijiang Li

Faculty, Staff and Student Publications

Radiological imaging is an integral component of cancer care, including diagnosis, staging, and treatment response monitoring. It contains rich information about tumor phenotypes that are governed not only by cancer cellintrinsic biological processes but also by the tumor microenvironment, such as the composition and function of tumor-infiltrating immune cells. By analyzing the radiological scans using a quantitative radiomics approach, robust relations between specific imaging and molecular phenotypes can be established. Indeed, a number of studies have demonstrated the feasibility of radiogenomics for predicting intrinsic molecular subtypes and gene expression signatures in breast cancer based on MRI. In parallel, promising results …

Imaging Characteristics Of 4th Ventricle Subependymoma, Ali S Haider, Tarek Y El Ahmadieh, Maryam Haider, Kimmo J Hatanpaa, Marco C Pinho, Bruce E Mickey, Raymond Sawaya, Gregory N Fuller, Donald F Schomer, Maria Gule-Monroe

Faculty, Staff and Student Publications

Purpose: Subependymomas located within the 4th ventricle are rare, and the literature describing imaging characteristics is sparse. Here, we describe the clinical and radiological characteristics of 29 patients with 4th ventricle subependymoma.

Methods: This is a retrospective multi-center study performed after Institutional Review Board (IRB) approval. Patients diagnosed with suspected 4th ventricle subependymoma were identified. A review of clinical, radiology, and pathology reports along with magnetic resonance imaging (MRI) images was performed.

Results: Twenty-nine patients, including 6 females, were identified. Eighteen patients underwent surgery with histopathological confirmation of subependymoma. The median age at diagnosis was 52 years. Median tumor volume …

Chth 414.00: Health And Culture - A Global Perspective, Gilbert A. Quintero

University of Montana Course Syllabi, 2021-2025

No abstract provided.

Chth 355.01: Theory And Practice Of Community Health Education, Ashley Glass

University of Montana Course Syllabi, 2021-2025

No abstract provided.

Csd 222.01: Introduction To Audiology, Kevin D. Duffy

University of Montana Course Syllabi, 2021-2025

No abstract provided.

Csd 320.50: Phonological Development & Phonetics, Amy M. Glaspey

University of Montana Course Syllabi, 2021-2025

No abstract provided.

Csd 320.01: Phonological Development & Phonetics, Amy M. Glaspey

University of Montana Course Syllabi, 2021-2025

No abstract provided.

Csd 330.01: Anatomy And Physiology Of The Speech And Swallowing Mechanism, Kimberly Ann Ramsey

University of Montana Course Syllabi, 2021-2025

No abstract provided.

Csd 396.01: Autism On Campus - Service Learning, Jennifer Katherine Schoffer-Closson

University of Montana Course Syllabi, 2021-2025

No abstract provided.

Csd 430.50: Senior Capstone, Sarah Jo Conkel

University of Montana Course Syllabi, 2021-2025

No abstract provided.

Edsp 456.01: Introduction To Methods For Low Incidence Disabilities, Jennifer Katherine Schoffer-Closson

University of Montana Course Syllabi, 2021-2025

No abstract provided.

Pubh 155.01: Reimagining Global Health - Biosocial Perspectives, Gilbert A. Quintero

University of Montana Course Syllabi, 2021-2025

No abstract provided.

Pubh 530.50: Public Health Administration And Management, Trisha N. Miller

University of Montana Course Syllabi, 2021-2025

No abstract provided.

Pubh 540.50: Social & Behavioral Science In Public Health, Jeffrey C. Peterson

University of Montana Course Syllabi, 2021-2025

No abstract provided.

Pubh 542.01: Applied Theoretical Foundations Of Community Health, James C. Caringi

University of Montana Course Syllabi, 2021-2025

No abstract provided.

Pubh 550.50: Program Evaluation & Research Methods, Kari J. Harris

University of Montana Course Syllabi, 2021-2025

No abstract provided.

Pubh 594.51: Integrated Learning Experience, Leigh A. Taggart

University of Montana Course Syllabi, 2021-2025

No abstract provided.

Pubh 595.51: Applied Practical Experience, Leigh A. Taggart

University of Montana Course Syllabi, 2021-2025

No abstract provided.

Pubh 615.50: Infectious Disease Epidemiology And Control, Sophia Raff Newcomer, Erin Landguth

University of Montana Course Syllabi, 2021-2025

No abstract provided.