Digital Commons Network^™

Clinical Interrogation Of Tp53 Aberrations And Its Impact On Survival In Patients With Myeloid Neoplasms, Jayastu Senapati, Sanam Loghavi, Guillermo Garcia-Manero, Guillin Tang, Tapan Kadia, Nicholas J Short, Hussein A Abbas, Naszrin Arani, Courtney D Dinardo, Gautam Borthakur, Naveen Pemmaraju, Betul Oran, Elizabeth Shpall, Uday Popat, Richard Champlin, Sherry Pierce, Sankalp Arora, Ghayas Issa, Musa Yilmaz, Keyur Patel, Koichi Takahashi, Guillermo Montalban-Bravo, Danielle Hammond, Fadi G Haddad, Farhad Ravandi, Hagop M Kantarjian, Naval G Daver

Faculty, Staff and Student Publications

In myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with TP53 aberrations, dissecting the interaction amongst patient, disease and treatment factors are important for therapeutic decisions and prognostication. This retrospective analysis included patients with newly diagnosed MDS (>5% blasts) and AML with TP53 mutation(s) treated at MD Anderson Cancer Center. We factored patient age, TP53 aberration burden, therapy intensity and use of venetoclax in the AML subgroup, and allogeneic hematopoietic stem cell transplantation (HSCT) to interrogate outcomes. TP53 was annotated as high-risk (TP53HR) if >1 mutation, one mutation plus allelic deletion or a single mutation with variant allele frequency …

An Enzyme-Linked Immunosorbent Assay (Elisa)-Based Activity Assay For Amp-Activated Protein Kinase (Ampk), Trezze P Nguyen, Shangze Lyu, Yang Liu

Faculty, Staff and Student Publications

AMP-activated protein kinase (AMPK) is the master regulator of cellular and organismal energy homeostasis, playing an essential role in modulating metabolism and other cellular processes. Substantial efforts have been made to develop pharmacological modulators of AMPK activity due to their therapeutic potential against various diseases. Measuring AMPK activity in vitro is a fundamental step for testing AMPK activators and inhibitors. Here, we report an enzyme-linked immunosorbent assay (ELISA)-based AMPK activity assay with simple steps and high sensitivity. This assay offers a robust, in-house alternative to the traditional radioactive methods and other approaches that rely on specialized reagents or commercial kits.

Targeted Sting Activation Using Modified Ultrasound-Responsive Microbubbles Enhances Immune Checkpoint Blockade Against Melanoma, Sina Khorsandi, Kristin Huntoon, Yifan Wang, Adam Woodward, Abin Antony, Connor Endsley, Nazia Hafeez, Jared L Edwards, Nicole Mccuen, Prasanna G Alluri, Betty Y S Kim, Wen Jiang, Jacques Lux

Faculty, Staff and Student Publications

Despite the recent successes of immune checkpoint inhibitors (ICIs) in treating advanced melanoma, durable clinical responses still remain limited. To boost immune responses, agents that target immune regulators, such as the Stimulator of Interferon Genes (STING) agonist cyclic GMP-AMP (cGAMP), are being investigated. However, their clinical translation is impeded by poor serum stability, rapid tissue clearance, and T-cell death due to off-target activation. Recently, a novel strategy termed Microbubble-assisted UltraSound-guided Immunotherapy of Cancer (MUSIC) has been reported to selectively deliver cGAMP directly into the cytosol of antigen-presenting cells with spatiotemporal control. The resulting activation of STING and downstream proinflammatory pathways …

Gsk-3484862, A Dnmt1 Degrader, Promotes Dnmt3b Expression In Lung Cancer Cells, Qin Chen, Swanand Hardikar, Kimie Kondo, Nan Dai, Ivan R Corrêa Jr, Meigen Yu, Marcos R Estecio, Xing Zhang, Taiping Chen, Xiaodong Cheng

Faculty, Staff and Student Publications

DNA methylation alterations, including hypermethylation and silencing of tumor suppressor genes, contribute to cancer formation and progression. The FDA-approved nucleoside analogs azacytidine and decitabine are effective demethylating agents for hematologic malignancies but their general use has been limited by their toxicity and ineffectiveness against solid tumors. GSK-3484862, a dicyanopyridine-containing, DNMT1-selective inhibitor and degrader, offers a promising lead for developing novel demethylating therapeutics. Here, we demonstrate that GSK-3484862 treatment upregulates DNMT3B expression in lung cancer cell lines (A549 and NCI-H1299). Disrupting DNMT3B in NCI-H1299 sensitizes these cells to GSK-3484862, enhancing its inhibitory effects on cell viability and growth. GSK-3484862 treatment induces …

Nlrp3 Inflammasome Activation Expands The Immunosuppressive Myeloid Stroma And Antagonizes The Therapeutic Benefit Of Sting Activation In Glioblastoma, Spencer T Lea, Chao-Hsien Chen, Jun Wei, Ivana William, Inés Lopez Del Castillo, Michael A Curran

Faculty, Staff and Student Publications

Glioblastoma (GBM) is the most common and deadly primary brain malignancy and is clinically refractory to immunotherapy. Active NLRP3 inflammasome signaling and IL-1β secretion have been observed in GBM, and NLRP3-driven myeloid-derived suppressor cell (MDSC) recruitment can mediate cancer immune evasion. Agonists of the cytosolic double-stranded DNA-sensing stimulator of IFN gene (STING) pathway can mediate proinflammatory conversion of cancer MDSCs; however, secretion of the NLRP3 products IL-1β and IL-18 has also been observed in certain myeloid populations following STING activation. In this study, we aimed to determine both the potential mechanistic synergy between STING and NLRP3 agonists, and the effects …

A Plain Language Summary Of Polaris: A Study To Look At Different Doses Of Encorafenib Plus Binimetinib For People With Braf V600-Mutant Melanoma With Brain Metastasis, Alexander M Menzies, Georgina V Long, Amiee Kohn, Hussein Tawbi, Jeffrey Webe, Keith Flaherty, Grant A Mcarthur, Paolo A Ascierto, Yanina Pfluger, Karl Lewis, Katy K Tsai, Omid Hamid, Hans Prenen, Luis Fein, Erjian Wang, Carolin Guenzel, Fan Zhang, Joseph F Kleh, Alessandra Di Pietro, Michael A Davies

Faculty, Staff and Student Publications

What is this summary about?People with a type of melanoma called advanced or metastatic BRAF V600- mutant melanoma, with a change in the BRAF gene, that has spread to the brain have poor outcomes.Current treatments include encorafenib (BRAFTOVI®) and binimetinib (MEKTOVI®). The POLARIS clinical study looked at whether increasing the encorafenib dose would make treatment more effective, with similar side effects, in these patients.The first part of the study, known as the safety lead-in, looked at the side effects of a high dose of encorafenib together with binimetinib. This was followed by a phase 2 part to …

Advancing The Development Of Trip13 Inhibitors: A High-Throughput Screening Approach, Rae M Sammons, Soma Ghosh, Lacin Yapindi, Eun Jeong Cho, Faye M Johnson, Kevin N Dalby

Faculty, Staff and Student Publications

TRIP13, a promising target for cancer therapy, has been identified as a key regulator of the mitotic checkpoint. Overexpression of TRIP13 is associated with poor clinical outcomes in various cancers. Inhibition of TRIP13 has the potential to address therapeutic challenges in cancer, particularly in therapy-resistant and Rb-deficient cancers. Despite the potential therapeutic benefits of TRIP13 inhibition, the development of TRIP13 inhibitors has been hindered by the lack of a robust high-throughput screening (HTS) assay. We developed a luminescence-based biochemical assay for TRIP13 activity to address this challenge using the ADP-Glo detection system. This assay offers high sensitivity, low background signal, …

Summaries Of Arkansas Cotton Research 2024, Fred M. Bourland

Arkansas Agricultural Experiment Station Research Series

Planted cotton acreage in Arkansas increased in 2024 to 670,000 planted acres, which was 160,000 acres more than in 2023 when Arkansas producers planted approximately 510,000 acres of cotton. A wet spring, and two hurricanes in three weeks in late summer/early fall led to a slight decrease in harvested acres that culminated in a final number of 640,000 (https://www.nass.usda.gov/Quick_Stats/Ag_Overview/stateOverview.php?state=ARKANSAS). Producers harvested 640,00 acres of cotton, which ranked third nationally, behind Texas and Georgia (https://downloads.usda.library.cornell.edu/usda-esmis/files/k3569432s/nk324887m/qn59s0097/cropan25.pdf). The total harvested acreage is the greatest amount since 680,000 acres in 2011. The average cotton yield in Arkansas in 2024 was …

Does Pollination By Non-Flying Mammals Contribute Substantially To Fruit Set Of Banksia (Proteaceae)? A Test In Four Species With Contrasting Floral Traits, Stanislaw K. Wawrzyczek, Robert A. Davis, Siegfried L. Krauss, Susan E. Hoebee, Ryan D. Phillips

Research outputs 2022 to 2026

Pollination by non-flying mammals (NFMs) is thought to be associated with cryptic, dull coloured, strongly scented flowers. In Western Australia, various Banksia species exhibit these traits, suggesting adaptation to primary pollination by NFMs, particularly the marsupial honey possum (Tarsipes rostratus). Here, we compare floral visitation rates and assess contribution to fruit set of NFMs and other pollinators in four species of Banksia with contrasting floral traits. Camera trap-based surveys revealed that honeyeater birds visited all species equally and were more frequent visitors than NFMs to the brightly coloured, unscented flowers of B. sessilis and B. splendida. By contrast, NFMs were …

International Expert-Based Consensus Definition, Classification Criteria, And Minimum Data Elements For Osteoradionecrosis Of The Jaw: An Interdisciplinary Modified Delphi Study, Amy C Moreno, Erin E Watson, Laia Humbert-Vidan, Douglas E Peterson, Lisanne V Van Dijk, Teresa Guerrero Urbano, Lisa Van Den Bosch, Andrew J Hope, Matthew S Katz, Frank J P Hoebers, Ruth A Aponte Wesson, James E Bates, Paolo Bossi, Adeyinka F Dayo, Mélanie Doré, Eduardo Rodrigues Fregnani, Thomas J Galloway, Daphna Y Gelblum, Issa A Hanna, Christina E Henson, Sudarat Kiat-Amnuay, Anke Korfage, Nancy Y Lee, Carol M Lewis, Charlotte Duch Lynggaard, Antti A Mäkitie, Marco Magalhaes, Yvonne M Mowery, Carles Muñoz-Montplet, Jeffrey N Myers, Ester Orlandi, Jaymit Patel, Jillian M Rigert, Deborah Saunders, Jonathan D Schoenfeld, Ugur Selek, Efsun Somay, Vinita Takiar, Juliette Thariat, Gerda M Verduijn, Alessandro Villa, Nicholas S West, Max J H Witjes, Alex M Won, Mark E Wong, Christopher M K L Yao, Simon W Young, Kamal Al-Eryani, Carly E A Barbon, Doke J M Buurman, François J Dieleman, Theresa M Hofstede, Abdul Ahad Khan, Adegbenga O Otun, John C Robinson, Lauren Hum, Jorgen Johansen, Rajesh Lalla, Alexander Lin, Vinod Patel, Richard J Shaw, Mark S Chambers, Daniel Ma, Mabi Singh, Noam Yarom, Abdallah Sherif Radwan Mohamed, Katherine A Hutcheson, Stephen Y Lai, Clifton David Fuller

Faculty, Staff and Student Publications

Purpose: Osteoradionecrosis of the jaw (ORNJ) is a severe iatrogenic disease characterized by bone death after radiation therapy to the head and neck. With >9 published definitions and at least 16 classification systems, the true incidence and severity of ORNJ are obscured by lack of a standard for disease definition and severity assessment, leading to inaccurate estimation of incidence, reporting ambiguity, and likely underdiagnosis worldwide. This study aimed to achieve consensus on an explicit definition and phenotype of ORNJ and related precursor states through data standardization to facilitate effective diagnosis, monitoring, and multidisciplinary management of ORNJ.

Methods and materials: The …

Implications Of Omitting Sentinel Lymph Node Biopsy On Adjuvant Decision Making For Patients With Small Breast Cancers, Kerollos Nashat Wanis, Melissa P Mitchell, Sharon H Giordano, Jennifer Keating Litton, Simona F Shaitelman, Nina Tamirisa, Isabelle Bedrosian, Wenli Dong, Yu Shen, Kelly K Hunt, Puneet Singh, Susie X Sun, Abigail S Caudle, Henry M Kuerer, Funda Meric-Bernstam, Rosa F Hwang, Taiwo Adesoye

Faculty, Staff and Student Publications

Background: Selective omission of sentinel lymph node biopsy (SLNB) in patients with early breast cancer limits surgical morbidity. Adoption of this strategy relies on multidisciplinary consensus. Understanding how SLNB omission influences guideline-based adjuvant treatment decisions, and the proportion of patients impacted, can help guide decision-making.

Patients and methods: Data from the National Cancer Database (2018-2020) was used to estimate the proportions of patients with cT1N0 hormone receptor-positive breast cancer for whom adjuvant chemotherapy, CDK4/6 inhibitor therapy, and regional nodal irradiation decisions would be impacted by the absence of lymph node pathology if national treatment guidelines were followed. Because OncotypeDX score …

Therapeutic Hurdles In Acute Myeloid Leukemia: Leukemic Stem Cells, Inflammation And Immune Dysfunction, Bofei Wang, Patrick K Reville, Hussein A Abbas

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) is an aggressive and highly heterogeneous hematological malignancy characterized by clonal expansion and differentiation arrest in myeloid progenitor cells. Despite advancements in chemotherapy, allogeneic hematopoietic stem cell transplantation, and post-remission maintenance therapies, the long-term survival remains unsatisfactory with high rates of relapse and refractory. These therapeutic challenges are mediated by multiple factors, including the complexity of the cellular hierarchies in AML, the interaction of leukemic stem cells (LSCs) with the bone marrow niche, inflammation, and immune evasion mechanisms. Further, the absence of specific surface markers that distinguish LSCs from normal hematopoietic stem cells, together with LSCs' …

Trem2 Depletion In Pancreatic Cancer Elicits Pathogenic Inflammation And Accelerates Tumor Progression Via Enriching Il-1Β+ Macrophages, Daowei Yang, Xinlei Sun, Hua Wang, Ignacio I Wistuba, Huamin Wang, Anirban Maitra, Yang Chen

Faculty, Staff and Student Publications

Background & aims: Pancreatic ductal adenocarcinoma (PDAC) has a complex tumor microenvironment enriched with tumor-associated macrophages. Triggering receptor expressed on myeloid cells 2 (TREM2) is highly expressed by a subset of macrophages in PDAC. However, the functional role of TREM2 in PDAC progression remains elusive.

Methods: We generated a novel transgenic mouse model (KPPC;Trem2-/-) that enables the genetic depletion of TREM2 in the context of spontaneous PDAC development. Single-cell RNA-sequencing analysis was used to identify changes in the tumor immune microenvironment on TREM2 depletion. We evaluated the impacts of TREM2 depletion on the tumor immune microenvironment to elucidate the functions …

Gut Microbiota In Immuno-Oncology: A Practical Guide For Medical Oncologists With A Focus On Antibiotics Stewardship, Arielle Elkrief, Bertrand Routy, Lisa Derosa, Laura Bolte, Jennifer A Wargo, Jennifer L Mcquade, Laurence Zitvogel

Faculty, Staff and Student Publications

The gut microbiota has emerged as a critical determinant of immune checkpoint inhibitor (ICI) efficacy, resistance, and toxicity. Retrospective and prospective studies profiling the taxonomic composition of intestinal microbes of patients treated with ICI have revealed specific gut microbial signatures associated with response. By contrast, dysbiosis, which can be caused by chronic inflammatory processes (such as cancer) or comedications, is a risk factor of resistance to ICI. Recent large-scale meta-analyses have confirmed that antibiotic (ATB) use before or during ICI therapy alters the microbiota repertoire and significantly shortens overall survival, even after adjusting for prognostic factors. These results underscore the …

A Gut-On-A-Chip Incorporating Human Faecal Samples And Peristalsis Predicts Responses To Immune Checkpoint Inhibitors For Melanoma, Mattia Ballerini, Serena Galiè, Punit Tyagi, Carlotta Catozzi, Hariam Raji, Amir Nabinejad, Angeli D G Macandog, Alessandro Cordiale, Bianca Ionela Slivinschi, Karol K Kugiejko, Martina Freisa, Paola Occhetta, Jennifer A Wargo, Pier F Ferrucci, Emilia Cocorocchio, Nicola Segata, Andrea Vignati, Andrey Morgun, Michela Deleidi, Teresa Manzo, Marco Rasponi, Luigi Nezi

Faculty, Staff and Student Publications

Patient responses to immune checkpoint inhibitors can be influenced by the gastrointestinal microbiome. Mouse models can be used to study microbiome-host crosstalk, yet their utility is constrained by substantial anatomical, functional, immunological and microbial differences between mice and humans. Here we show that a gut-on-a-chip system mimicking the architecture and functionality of the human intestine by including faecal microbiome and peristaltic-like movements recapitulates microbiome-host interactions and predicts responses to immune checkpoint inhibitors in patients with melanoma. The system is composed of a vascular channel seeded with human microvascular endothelial cells and an intestinal channel with intestinal organoids derived from human …

Bispecific Antibodies In Hematologic And Solid Tumors: Current Landscape And Therapeutic Advances, Lorenzo Guidi, Julian Etessami, Carmine Valenza, Augusto Valdivia, Funda Meric-Bernstam, Enriqueta Felip, Giuseppe Curigliano

Faculty, Staff and Student Publications

Bispecific antibodies (bsAbs) have emerged as a novel class of therapeutics, offering a dual-targeting strategy to enhance the therapeutic efficacy of monoclonal antibodies, which is often limited by tumor heterogeneity and the occurrence of resistance mechanisms. By simultaneously engaging two distinct antigens or pathways, bsAbs disrupt multiple signaling cascades simultaneously, preventing escape mechanisms and offering a more durable response. Furthermore, they can optimize immune activation, improving immune cell recruitment strategies. In particular, T-cell engager bsAbs facilitate immune cell-mediated tumor destruction by linking T cells to tumor antigens. Instead, dual immune checkpoint inhibitors (CPIs) enhance immune activation by blocking inhibitory signals. …

Cll Cell-Derived Exosomes Alter The Immune And Hematopoietic Systems, Ivo Veletic, David M Harris, Uri Rozovski, Maria Teresa S Bertilaccio, George A Calin, Koichi Takahashi, Ping Li, Zhiming Liu, Taghi Manshouri, Rares-Constantin Drula, Ken Furudate, Muharrem Muftuoglu, Anwar Hossain, William G Wierda, Michael J Keating, Zeev Estrov

Faculty, Staff and Student Publications

The origins of immunosuppression, neutropenia, and anemia in patients with chronic lymphocytic leukemia (CLL) are not fully understood. Because in patients with CLL, circulating exosomes, which participate in cell-to-cell interactions, are CLL cell-derived, we examined whether those exosomes contribute to abnormal features of this disease. Our data revealed that CLL cell-derived exosomes engulfed by healthy donors’ monocytes, fibrocytes, and lymphocytes altered target-cell gene and protein expression and suppressed normal hematopoiesis. CLL cell-derived exosomes increased normal monocytes’ CD14 and CD16 expression such that it mimicked the accessory cell profile and upregulated T cells’ checkpoint PD-1 and CD160 protein levels, potentially reducing …

Genetic Analysis Of Psychosis Biotypes: Shared Ancestry-Adjusted Polygenic Risk And Unique Genomic Associations, Cuihua Xia, Ney Alliey Rodriguez, Carol A. Tamminga, Matcheri S. Keshavan, Godfrey Pearlson

School of Medicine Publications

The Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) created psychosis Biotypes based on neurobiological measurements in a multi-ancestry sample. These Biotypes cut across DSM diagnoses of schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis. Two recently developed post hoc ancestry adjustment methods of Polygenic Risk Scores (PRSs) generate Ancestry-Adjusted PRSs (AAPRSs), which allow for PRS analysis of multi-ancestry samples. Applied to schizophrenia PRS, we found the Khera AAPRS method to show superior portability and comparable prediction accuracy as compared with the Ge method. The three Biotypes of psychosis disorders had similar AAPRSs across ancestries. In genomic analysis of Biotypes, 12 genes, …

Insights Into Prey Handling And Feeding Strategies By Ghost Crabs On Sea Turtle Eggs And Hatchlings, Casper Avenant

Research outputs 2022 to 2026

The feeding behaviour on sea turtle eggs and hatchlings by the golden ghost crab Ocypode convexa, a species endemic to the west coast of Australia, was observed in field and laboratory settings using infrared videography. On beaches where ghost crab densities are high, multiple crabs can feed on nests over several nights, often resulting in destruction of clutches. Crabs appear to anticipate the emergence of hatchlings, often congregating near nests in the moments prior to emergence. When feeding on eggs crabs rupture eggshells using the sharp tips of their claws, with tissue subsequently moved to the mouthparts for ingestion using …

Exposure To Metoprolol And Propranolol Mixtures On Biochemical, Immunohistochemical, And Molecular Alterations In The American Oyster, Crassostrea Virginica, Andrew Salinas, Md Saydur Rahman

School of Earth, Environmental, & Marine Sciences Faculty Publications

Pharmaceutical drugs, particularly beta-blockers (e.g., metoprolol, propranolol, etc.), are extensively used to treat human cardiovascular conditions, yet pose significant risks to non-target aquatic organisms when introduced into coastal and marine environments via wastewater effluent. This study aimed to investigate the effects of short-term exposure (one week) to environmentally relevant concentrations of metoprolol and propranolol (MP) mixtures (low-dose: 50 ng/L propranolol and 250 ng/L metoprolol, and high-dose: 250 ng/L propranolol and 650 ng/L metoprolol) in the American oyster (Crassostrea virginica, a commercially and ecologically important marine bivalve mollusk) under controlled laboratory conditions. Histopathological assessments revealed structural damage to gills, …

Impact Of Seed Moisture And Temperature On Hemp Seed Germination, Paul Cockson, Andrea Webb, Natalia Martinez-Ochoa, Lindsey Moffitt, Robert Pearce, Manohar Chakrabarti

School of Integrative Biological & Chemical Sciences Faculty Publications

Germination rates of commercial lots of hemp have been highly variable, resulting in poor stand establishment. Germination rates in some seed lots have decreased by 50% after only 1 year of storage. The objective of this trial was to investigate the impact of seed storage conditions on seed germination over time. Industrial hemp (IH) seeds (cv. NWG2730) were harvested from the field. The seeds were cleaned, sorted, and dried to specific moisture contents (MC) 6%, 8%, 10%, and 14%. Seeds were subdivided, placed in hermetically sealed packets, and stored at temperatures of −20°C, 4°C, 10°C, or 21°C for 3, 6, …

Dynamic Environments Generate Geographic Fluctuations In Population Structure Of An Inland Shorebird, Andrea Contina, Scott W. Yanco, Allison K. Pierce, Hannah B. Vander Zanden, Craig A. Stricker, Gabriel J. Bowen, Michael B. Wunder

School of Integrative Biological & Chemical Sciences Faculty Publications

Species distributions depend on fine-scale ecological processes and population growth trajectories and are influenced by climate and weather changes. However, the characterization of inter-population dynamics underlying the geographic distributions of migratory organisms remains challenging. We adopted a stable isotope approach to investigate the dynamic population geography of a terrestrial migratory bird across multiple generations. We found that the age-specific geographic source of Mountain Plovers sampled during winter shifted over four years across a latitudinal gradient. Moreover, our results show that differential effects of climate on the probability of occurrence at the wintering ground could be a driver of population turnover …

Externally Validated Digital Decision Support Tool For Time-To-Osteoradionecrosis Risk-Stratification Using Right-Censored Multi-Institutional Observational Cohorts, Laia Humbert-Vidan, Serageldin Kamel, Andrew Wentzel, Zaphanlene Kaffey, Moamen Abdelaal, Kyle B Spier, Natalie A West, G Elisabeta Marai, Guadalupe Canahuate, Xinhua Zhang, Melissa M Chen, Kareem A Wahid, Jillian Rigert, Seyedmohammadhossein Hosseinian, Andrew J Schaefer, Kristy K Brock, Mark Chambers, Adegbenga O Otun, Ruth Aponte-Wesson, Vinod Patel, Andrew Hope, Jack Phan, Adam S Garden, Steven J Frank, William H Morrison, Michael T Spiotto, David Rosenthal, Anna Lee, Renjie He, Mohamed A Naser, Erin Watson, Katherine A Hutcheson, Abdallah S R Mohamed, Vlad C Sandulache, Lisanne V Van Dijk, Amy C Moreno, Teresa Guerrero Urbano, Clifton D Fuller, Stephen Y Lai

Faculty, Staff and Student Publications

Background: Existing studies on osteoradionecrosis of the jaw (ORNJ) have primarily used cross-sectional data, assessing risk factors at a single time point. Determining the time-to-event profile of ORNJ has important implications to monitor oral health in head and neck cancer (HNC) long-term survivors.

Methods: Data were retrospectively obtained for a clinical observational cohort of 1129 patients (198 ORNJ cases) with HNC treated with radiotherapy (RT) at The University of Texas MD Anderson Cancer Center. A Weibull Accelerated Failure Time model was trained on previously identified dosimetric, clinical and demographic predictors. External validation was performed using an independent cohort of 265 …

Changes In The Fxr-Cistrome And Alterations In Bile Acid Physiology In Wilson Disease, Clavia Ruth Wooton-Kee, Hari K Yalamanchili, Islam Mohamed, Manal Hassan, Kenneth D R Setchell, Monica Narvaez Rivas, Ayse K Coskun, Vasanta Putluri, Nagireddy Putluri, Prasun Jalal, Michael L Schilsky, David D Moore

Children’s Nutrition Research Center Staff Publications

Background: Wilson disease (WD) is an autosomal recessive disorder that results in excessive hepatic copper, causing hepatic steatosis, inflammation, fibrosis, cirrhosis, and liver failure. Previous studies have revealed dysregulation of many farnesoid X receptor (FXR) metabolic target genes in WD, including the bile salt exporter pump, the major determinant of bile flow.

Methods: We tested the hypothesis that the FXR-cistrome is decreased in Atp7b-/- mice in accord with dysregulated bile acid homeostasis.

Results: FXR binding within Atp7b-/- mouse livers displayed surprising complexity: FXR binding was increased in distal intergenic regions but decreased in promoter regions in Atp7b-/- versus wild-type mice. …

A Vacuolar Proton Pump Controls The Post-Germinative Growth Of Rice (Oryza Sativa Ssp. Japonica), Peter James Icalia Gann, Soumen Nandy, Rodrigo Botelho, Kari Vinzant, Mariya Khodakovskaya, Vibha Srivastava

Crop, Soil and Environmental Sciences Faculty Publications and Presentations

Post-germinative growth in plants is controlled by sucrose mobilization from the endosperm. Regulation of this process, however, is not fully understood. Transcriptional suppression of the rice vacuolar H+ translocating pyrophosphatase (V-PPase) referred to as VPP5 led to enhanced starch content in mature grains. However, vpp5 suppressed lines displayed a slower post-germinative growth rescuable by sucrose, indicating inefficient sucrose mobilization from the endosperm. Biochemical and gene expression analyses showed a slower rate of starch to sucrose conversion and altered expression of the key starch utilization pathway genes. We hypothesized that the modulation of metabolic activities in the vpp5 lines was based …

Parp Inhibitor Response Is Enhanced In Prostate Cancer When Xrcc1 Expression Is Reduced, Kaveri Goel, Vani Venkatappa, Kimiko L Krieger, Dongquan Chen, Arun Sreekumar, Natalie R Gassman

Faculty, Staff and Students Publications

Prostate cancer (PCa) is the second most common cancer worldwide and the fifth leading cause of cancer-related deaths among men. The emergence of metastatic castration-resistant prostate cancer (mCRPC) after androgen deprivation therapy (ADT) exemplifies the complex disease management for PCa. PARP inhibitors (PARPis) are being tested to treat mCRPC in tumors with defective homologous recombination repair (HRR) to address this complexity. However, increasing resistance towards PARPi in HRR-deficient patients and the low percentage of HRR-defective mCRPC patients requires the identification of new genes whose deficiency can be exploited for PARPi treatment. XRCC1 is a DNA repair protein critical in the …

Stress, Employment Changes, And Psychological Distress Among Caregivers Of Patients With Head And Neck Cancer, Lama Abdurrahman, Vlad C Sandulache, Cielito Reyes-Gibby, Erich M Sturgis, Pavan Jhaveri, Hoda Badr

Faculty, Staff and Students Publications

Importance: Patients undergoing external beam radiation therapy (EBRT) for head and neck cancer (HNC) often experience adverse effects that require substantial caregiving. The burdens of caregiving can impact caregiver employment and mental health over time, yet this topic remains underexplored.

Objective: To examine the associations between caregiving for patients with HNC who undergo EBRT and caregiver stress, employment status, and psychological distress.

Design, setting, and participants: This was a secondary analysis of data from a longitudinal survey study that surveyed caregivers at baseline (ie, at initiation of EBRT) and at 4-month and 12-month follow-ups. The study was conducted at 2 …

The Aging Ovary Stands On The Shoulders Of Giant Multinucleated Cells, Avery A Ahmed, Stephanie A Pangas

Faculty, Staff and Students Publications

Reproductive aging is associated with declining fertility and increasing inflammation, though these events are not well understood. An exciting new study in PLOS Biology utilizes cutting-edge technologies to characterize the role of multinucleated giant cells in ovarian aging.

Aged Regulatory T Cells Fail To Control Autoimmune Lacrimal Gland Pathogenic Cd4+ T Cells, Kaitlin K Scholand, Laura Schaefer, Gowthaman Govindarajan, Zhiyuan Yu, Jeremias G Galletti, Cintia S De Paiva

Faculty, Staff and Students Publications

CD25KO mice are a model of Sjögren disease. CD25KO mice have severe inflammation and infiltrating lymphocytes to the lacrimal glands (LG). Whether the pathogenicity of CD25KO CD4+ T cells can be controlled in vivo by Tregs is unknown. Eight-week-old B6 and CD25KO mice LGs were submitted for RNA bulk sequencing. A total of 3481 genes were differentially expressed in CD25KO LG compared to B6. Tear washing analysis identified CD25KO mice had elevated protein levels of TNF, IFN-γ, and CCL5 and decreased protein levels of IL-12p40 and VEGF-A. Co-adoptive transfer of CD25KO CD4+ T cells with either young or aged B6 …

Integrating Methods To Investigate Phytoplankton Dynamics Along Gradients Of A Major Urban River, Nicholas Sheldon

University Honors Theses

Waterways that support human society and life on Earth host superabundant microorganisms which support all ecosystems and food webs: phytoplankton. This study aimed to identify and quantify phytoplankton in the Willamette River in order to understand the dynamics between different phyla. Building on previous studies, which showed that communities of phytoplankton change with the river environment, this work determined how eukaryotic and prokaryotic phytoplankton vary with one another while inhabiting the same river conditions. The approach involved sampling the Willamette river over a weekly time series and combined analytical techniques of qPCR, flow cytometry, and image cytometry to assess population …