Digital Commons Network^™

The All Of Us Evenings With Genetics Research Program, Stacy M Lloyd, Jasmine Baker, Carolina Jorgez, Julie Coleman, Laterrica Williams, April Adams, Ashley Butler, Elizabeth Atkinson, Shamika Ketkar, Steven Scherer, Kim Worley, Susan Fernbach, Keasia Daniels, Latanya Hammonds-Odie, Laura Rosales, Brendan Lee, Debra Murray

Faculty, Staff and Students Publications

The All of Us Evenings with Genetics (All of Us EwG) Research Program, funded in part by the National Institute of Health’s All of Us Research Program, engages researchers to utilize the All of Us Researcher Workbench to advance precision medicine. The All of Us EwG program has two core aims: (1) address barriers to research productivity for minorities, disadvantaged, and persons with disabilities aspiring to enter STEM fields; and (2) promote the use of the All of Us Researcher Workbench to develop research focused on health equity. To achieve these goals, the program implements three key activities: (1) …

Patient Experiences Of Receiving Home-Based Immunotherapy Infusions - A Constructivist Grounded Theory Study, Patricia Ann Cook

Theses: Doctorates and Masters

Context: The treatment of cancer and chronic health conditions has been greatly revolutionised via intravenous immunotherapy infusions. Demand, both globally and in Australia, is increasing due to several factors including aging and increased populations, subsequent increases of cancer cases, new immunotherapy indications and increased survival rates.

In Perth, Western Australia, a private service provider commenced delivering a home based immunotherapy infusions model of care as a hospital substitution service provider in 2013 and the service has now been extended across Australia. The safety and efficacy of home-based infusions have been well documented in research, and an increasing number of patients …

Linker-Free Gold-Sputtered Tapered Optical Fiber Plasmonic Sensors For High-Sensitivity Refractive Index Detection In Microfluidic Platforms, Erem Ujah, Gymama Slaughter

Center for Bioelectronics Publications

Gold-sputtered tapered optical fiber (Au-TOF) sensors were developed for high-sensitivity refractive-index (RI) detection using aqueous glucose standards spanning 1.33–1.41 RIU (0–50% w/v). The sensors were fabricated using a reproducible workflow combining flame-brushing tapering, plasma surface preparation, and rotational magnetron sputtering, enabling azimuthally uniform gold coatings without the use of thiol or sulfur linker chemistries. Two sputtering durations (24 s and 30 s) were investigated to examine thickness-dependent plasmonic coupling and sensing performance. Optical measurements were conducted using a broadband supercontinuum source and compact spectrometer within a 20 µL microfluidic sensing chamber. Increasing glucose concentration produced a monotonic decrease in transmission …

Association Between Internet Use For Health Information And Alzheimer’S Disease Diagnosis Among Older Adults With Diabetes In The United States: Examining Racial And Gender Disparities, Henry M. Zeidan

College of Graduate Studies: Theses & Dissertations

This study uses data from the National Health and Aging Trends Study (NHATS) Round 13, collected in 2024, to examine whether internet use for health information is associated with Alzheimer’s disease diagnosis among older adults with diabetes in the United States. Given the rising adoption of digital health, understanding who benefits from online health resources is increasingly important. The research also examines whether these associations differ across racial and gender groups, offering insight into potential disparities in digital health engagement and cognitive outcomes. Findings from this study will inform clinical practice, public health programming, and strategies to ensure equitable access …

Anything But Endo: Diagnostic Buck-Passing In Endometriosis Diagnosis, Rita Dexter, Megan Kitts, Heather Welty, Melanie Jeske

Center for Medical Ethics and Health Policy Staff Publications

People living with endometriosis, a disease in which tissue similar to the lining of the uterus grows elsewhere in the body, often experience prolonged diagnostic journeys because of symptom variability, normalisation of period pain and other symptoms, and lack of awareness of the condition. In this article, we analyse the endometriosis diagnostic journey through the lens of epistemic injustice. Drawing on in-depth interviews with 52 people living with endometriosis in the United States, we introduce the concept of diagnostic buck-passing to characterise the phenomenon wherein individuals who seek treatment for their symptoms end up stuck in a cycle of seeing …

Neurotensin Drives Theca Cell Migration During Ovulation In Primates, Jessica S. Miller, Megan A. G. Sage, Thomas E. Curry Jr., Diane M. Duffy

Department of Biomedical and Translational Sciences Faculty Publications

Theca cells are a critical steroidogenic cell type of the ovarian follicle and corpus luteum. The ovulatory luteinizing hormone (LH) surge (or human chorionic gonadotropin (hCG)) stimulates theca cell relocation from the stroma surrounding the dominant follicle to full integration into the developing corpus luteum. Luteinizing hormone/human chorionic gonadotropin also stimulates granulosa cells to produce local mediators of ovulation, including the peptide neurotensin (NTS). To determine if hCG-stimulated NTS regulates theca cell relocation within the ovulatory follicle, vehicle or an NTS receptor antagonist was injected into a macaque dominant follicle, and ovaries were removed 48 h after hCG administration. Additional …

Dysregulation Of Alternative Splicing Patterns In The Ovaries Of Reproductively Aged Mice, Adnan T. Alsamaraee, Vanessa L. Correll, Julius O. Nyalwidhe, Pavla Brachova, Nehemiah S. Alvarez

Department of Biomedical and Translational Sciences Faculty Publications

Female reproductive aging is characterized by progressive deterioration of ovarian function, yet the molecular mechanisms driving these changes remain incompletely understood. Here, we used long-read direct RNA-sequencing to map transcript isoform changes in mouse ovaries across reproductive age. Comparing young and aged mice after controlled gonadotropin stimulation, we identified widespread alternative splicing changes, including shifts in exon usage, splice site selection, and transcript boundaries. Aged ovaries exhibited increased isoform diversity, favoring distal start and end sites, and a significant rise in exon skipping and intron retention events. Many of these age-biased splicing events altered open reading frames, introduced premature stop …

Brief Pulses Of High-Level Fluid Shear Stress Enhance Metastatic Potential And Rapidly Alter The Metabolism Of Cancer Cells, Amanda N. Pope, Devon L. Moose, Guy O. Hudson, Hank R. Weresh, Marion R. Dykstra, Aabha Y. Joshi, Patrick Breheny, Eric B. Taylor, Michael D. Henry

Department of Biomedical and Translational Sciences Faculty Publications

Circulating tumor cells (CTCs) face challenges to their survival, including mechanical and oxidative stresses that are different from cancer cells in solid primary and metastatic tumors. The impact of adaptations to the fluid microenvironment of the circulation on the outcome of the metastatic cascade is not well understood. Here, we find that cancer cells exposed to brief pulses of high-level fluid shear stress (FSS) exhibit enhanced invasiveness and anchorage-independent proliferation in vitro and enhanced metastatic colonization/tumor formation in vivo. Cancer cells exposed to FSS rapidly alter their metabolism in a manner that promotes survival by providing energy for cytoskeletal remodeling …

Estrogen Deprivation During Primate (Papio Anubis) Pregnancy: Impact On Systemic Microvascular Flow And Cardiovascular Development And Function After Birth In Offspring, Sifa Turan, Jeffery S. Babischkin, Graham W. Aberdeen, Gerald J. Pepe, Eugene D. Albrecht

Department of Biomedical and Translational Sciences Faculty Publications

Background

Suppressing estradiol (E₂) during baboon pregnancy lowers offspring skeletal muscle capillary density, vital for insulin-mediated glucose uptake, and induces insulin resistance. We examined whether E₂ deprivation also impairs microvascular flow and cardiac function.

Methods

Offspring of untreated baboons, letrozole-treated baboons, or letrozole plus E₂ (maternal s.c. injections during the second half of gestation) underwent contrast-enhanced microbubble ultrasonography to quantify microvessel flow and echocardiography to assess cardiac performance.

Results

Letrozole reduced maternal serum E₂ by 95% (p <  0.01). In letrozole offspring, microbubble flux rate (β) fell 55% (p <  0.02), replenishment was 5 s slower (p <  0.03), and microvessel flow declined 40% (p = 0.05); all were restored by added E₂. Indices of systolic (isovolumic contraction), diastolic (isovolumic relaxation), global performance (Tei index), and cardiac output were unchanged.

Conclusion

Prolonged gestational E₂ deprivation programs a reduction in microvascular flow without altering cardiac function; maternal E₂ prevents this, supporting E₂'s role in …

Comparative Mass Spectrometry Analysis Of High And Low Centrifugation Extracellular Vesicle (Ev) Pellets From Healthy Urine Following Tamm-Horsfall Protein Removal, Dana Bielopolski, Luca Musante, Henrik Molina, Douglas Barrows, Samantha Upson, Lifang Yang, Thomas Carrol, Jonathan N. Tobin, Rhonda G. Kost, U. Erdbrügger

Department of Biomedical and Translational Sciences Faculty Publications

Objectives

Urinary extracellular vesicles (uEVs) are potential biomarkers for renal physiology and disease. Their isolation is challenged by Tamm-Horsfall protein (THP) contamination, particularly in high-speed ultracentrifugation (P100) fractions. Low-speed (P20) fractions contain biologically relevant uEVs, yet their proteomic composition is underexplored. This study evaluates strategies for THP removal to optimize mass spectrometry analysis and characterizes P20 and P100 uEV proteomes and its combination in healthy urine.

Methods

Urine from a healthy volunteer was processed via sequential centrifugation at 21,200 g (P20) and 164,244 g (P100). THP removal was performed using low ionic strength buffer (P20) and size-exclusion chromatography (P100). Western …

Inhibition Of Histone Demethylase Lsd1 Suppresses Cd47 Expression And Enhances Efficacy Of Cd47 Blockade In Breast Cancer, Fengjie Jiang, Yu Shen, Bing Li, Michael Henry, Nancy Davidson, Yi Huang

Department of Biomedical and Translational Sciences Faculty Publications

Background CD47 functions as a “don’t eat me” checkpoint, inhibiting macrophage-mediated phagocytosis in triple-negative breast cancer (TNBC). While anti-CD47 therapies can restore immune surveillance, their efficacy in TNBC is often limited by immune evasion and drug development challenges.

Methods We investigated the crosstalk between the histone demethylase lysine-specific demethylase 1 (LSD1) and CD47 signaling in TNBC using in silico datasets, isogenic cell lines, conditional BRCA1 knockout models, and syngeneic mouse models. Techniques such as immunohistochemistry, multiplex immunofluorescence, immunoprecipitation, protein ubiquitination, chromatin immunoprecipitation, chemotaxis, flow cytometry, and phagocytosis assays were employed to examine the epigenetic regulation of CD47 by LSD1 and …

Yk-4-250 Mitigates Gastrointestinal Radiation Syndrome And Promotes Overall Survival Following Partial Body Radiation Injury, Vidya P. Kumar, Yali Kong, Kan Wang, Asa R. Britton-Jenkins, Stanton Dulan, Landon L. Moore, Debra Saunders, Randal May, Rheal Towner, Sanchita P. Ghosh, Courtney W. Houchen, Milton L. Brown

Department of Biomedical and Translational Sciences Faculty Publications

Acute gastrointestinal radiation syndrome (GI-ARS) is a significant health threat following high-dose ionizing radiation (IR) exposure, leading to severe morbidity and mortality. The syndrome is characterized by gastrointestinal tissue damage caused by angiotensin II (Ang II) and reactive oxygen species (ROS), resulting in impaired GI function, systemic bacteremia, multi-organ failure, and eventual death. Dysregulation of the renin-angiotensin system (RAS) via Ang II exacerbates ROS production through activation of the Angiotensin II type 1 receptor (AT1R). This underscores the need for agents capable of both scavenging ROS and inhibiting AT1R activity. To address this, we developed YK-4-250, a Tempol-conjugated angiotensin receptor …

Beyond The Diagnosis: A Qualitative Exploration Of Men Living With Hiv, David R. Romanelli

Antioch University Dissertations & Theses

This qualitative study explored the lived experiences of men (18+ years old) living with HIV to better understand how they navigate identity, mental health, relationships, and healthcare systems after diagnosis. The method included a qualitative thematic analysis with 10 participants. Eight themes emerged from the data: (1) reactions, reflections, and meaning-making after diagnosis; (2) managing medication, treatment, and co-occurring conditions; (3) stigma, disclosure, and negotiation of identity; (4) substance use, housing instability, and socioeconomic stressors; (5) navigating the changing HIV landscape; (6) experiences with family and intimate relationships; (7) implications for mental health counseling; and (8) the role of community …

The Development And Pilot Evaluation Of An Out-Of-Hospital Immersive Birthing Simulation Training Application For Paramedics And Ambulance Officers Using Virtual-Reality Technology, Michella Hill

Theses: Doctorates and Masters

Out-of-hospital births (OOHBs) are births which occur outside a hospital setting. This includes planned home births attended by midwives, or unplanned OOHBs where the intention was to birth in a hospital or maternity centre, however, occurs in an unintended location. Prehospital clinicians, inclusive of registered paramedics and volunteer ambulance officers (VAOs) infrequently attend OOHBs, as most births occur in maternity wards as anticipated. OOHBs comprises < 1% of emergency ambulance requests and requires specialised skills for prehospital clinicians to competently manage birthing and potential complications. As exposure to birthing is so rare, these specialised skills and knowledge are underutilised and subject to rapid decay. Compounding the problem, obstetrics is infrequently taught across undergraduate education, in-service training, or within individual clinician’s continuing professional development. Placements shadowing midwives are scarce due to nursing and medical students receiving priority. Previous research regarding OOHBs is limited, nonetheless suggests prehospital clinicians are underprepared to manage an OOHB, which has serious patient safety implications. The present research sought to explore prehospital clinicians’ preparedness and confidence in managing OOHBs. It also investigates whether a digital training solution such as virtual reality (VR) simulation may reduce the theory-practice gap and assist in competency retention.

Publication one provides a comprehensive methodology outline which is applied to Study One; a scoping review of prehospital clinician and birth parent experiences with OOHBs. Risk factors, complications and interventions provided by prehospital clinicians, as …

Ornithine Metabolism In Retinal Pigment Epithelium And Retina And Implications In Gyrate Atrophy, Artjola Puja

Graduate Theses, Dissertations, and Problem Reports (ETD)

Ornithine aminotransferase (OAT) is a mitochondrial enzyme that regulates ornithine metabolism by converting ornithine to pyrroline-5-carboxylate, a precursor for proline and glutamate synthesis. Deficiency of OAT causes systemic ornithine accumulation and leads to gyrate atrophy (GA) of the choroid and retina, a hereditary disorder characterized by progressive chorioretinal degeneration and irreversible vision loss. Chorioretinal atrophy typically starts at the mid-peripheral retina and progresses toward the macula. Although elevated ornithine is considered toxic to the eye, how ornithine is metabolized in ocular tissues and why OAT deficiency causes selective, region-specific vulnerability remain unclear. We combined ex vivo and in vivo stable …

Polyfluoroalkyl Substances And Altered Glucose Homeostasis In Adolescents Following Bariatric Surgery, Elizabeth Costello, Brittney O Baumert, Zhenjiang Li, Vishal Midya, Shudi Pan, Justin R Ryder, Thomas H Inge, Todd M Jenkins, Stephanie Sisley, Stavra A Xanthakos, Anita Courcoulas, Douglas I Walker, Nikos Stratakis, Damaskini Valvi, Scott M Bartell, Angela L Slitt, Rohit Kohli, Sarah Rock, Michele A La Merrill, Sandrah P Eckel, Max T Aung, Rob Mcconnell, David V Conti, Lida Chatzi

Children’s Nutrition Research Center Staff Publications

Objectives: Bariatric surgery is an effective treatment for severe obesity and associated metabolic comorbidities. Exposure to polyfluoroalkyl substance (PFAS) before bariatric surgery may attenuate improvements in glucose metabolism and explain some of the heterogeneity in post-surgery outcomes.

Design: This is an observational cohort study.

Methods: Adolescents (n = 186) enrolled in the Teen-Longitudinal Assessment of Bariatric Surgery study were included. Eight-PFAS congeners were measured in plasma before surgery. Linear and logistic regressions were used to examine cross-sectional associations between log2-transformed PFAS (ng/mL) and fasting glucose, insulin, hemoglobin A1c (HbA1c), and homeostatic model assessment for insulin resistance (HOMA-IR). Linear mixed …

Alternative Polyadenylation Signatures Distinguish Maladaptive Right Ventricular Remodeling In Pulmonary Hypertension: Implications For Rna-Based Diagnostics And Therapeutics, Janani Subramaniam, Venkata Jonnakuti, Scott D Collum, Sandra Martineau, Kai-Lieh Huang, Sandra Breuils-Bonnet, Andrea L Frump, Bindu H Akkanti, Jayeshkumar A Patel, Manish K Patel, Ismael Salas De Armas, Isabella N Lefebvre, Rajko Radovancevic, Elvin Blanco, Eric J Wagner, Igor Gregoric, Sriram Nathan, Biswajit Kar, Steeve Provencher, Sebastien Bonnet, François Potus, Hari Krishna Yalamanchili, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

Increased pulmonary vascular pressures due to vascular remodeling, elevated vascular resistance, and vasoconstriction characterize Pulmonary Arterial Hypertension (PAH). The narrowing of the pulmonary arteries and obstruction of blood flow increase the Right Ventricular (RV) afterload, forcing the RV to undergo structural and functional changes. While adaptive remodeling leads to RV compensation by maintaining function, maladaptive remodeling leads to RV decompensation, characterized by worsening function and eventual failure. At present, there is no effective treatment for these patients as therapies for left ventricular failure are ineffectual, and there are no therapies specifically targeting the RV. Therefore, there is a clear need …

Gender-Specific Behavior Reductions In Spontaneous Locomotive And Rearing In A Rat Model Of Paclitaxel-Induced Peripheral Neuropathy: A Pilot Study, Serena Jiyeon Kim, Kevin Cao, Patrick M Dougherty, Kathleen E Mcdonough, Saba Javed

Faculty, Staff and Students Publications

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) from agents like paclitaxel causes sensory loss and functional impairment, with limited treatment options. To better model patient-relevant outcomes, we used open field video tracking in rodents to assess gait, anxiety, and exploratory behavior. This approach provides a more comprehensive assessment of CIPN-related deficits beyond pain responses.

Methods and materials: Adult male and female Sprague Dawley rats were given paclitaxel (Taxol; 24 mg/kg cumulative dose) or a vehicle over 8 days. Their distance traveled, time spent in the center and outer zones of the OF test, and rearing behaviors were recorded using a PhenoTyper 4500 …

Cerebellar Motor And Non-Motor Contributions To Dystonia Pathophysiology And Treatment, Linda H Kim, Cheryl Brandenburg, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

Dystonia is a complex neurological disorder characterized by sustained or intermittent abnormal movements and/or postures. However, dystonia's non-motor symptoms, particularly the sleep disturbances, are critical yet underexplored concerns that affect all ages. Here, we synthesize current knowledge on the motor and non-motor domains of dystonia, emphasizing the functional interconnections and plasticity within cerebellar motor, cognitive, and sleep-associated circuits to motivate more comprehensive and effective treatments that improve overall quality of life.

Organ Chips And Translational Research: Identifying And Examining New Ethical Issues, Melanie Jeske

Center for Medical Ethics and Health Policy Staff Publications

Organ chips, also known as organ-on-a-chip devices, tissue chips, or microphysiological systems, have emerged over the last decade as a promising translational technology amidst growing concern about the translational crisis between laboratory research and patient bedside. Pointing to high rates of failure between nonhuman animal models and safety and efficacy in humans, organ chips and similar new approach methods have attracted substantial public and private investment. As human-cell-based alternatives to animal models, organ chips promise more predictive, efficient, and ethical platforms for pharmaceutical and toxicity testing. Engineered cultivation systems that enable cells to assemble into tissue-like structures (e.g. kidney, brain, …

Toward Ethical Provenance Tracking: The Ga4gh Model Data Access Agreement (Daa), Alexander Bernier, Bartha Maria Knoppers, Jonathan Lawson, Robyn Mcdougall, Maili Raven-Adams, Vasiliki Rahimzadeh

Center for Medical Ethics and Health Policy Staff Publications

Purpose: Standardizing contractual clauses that govern data access enables research institutions to responsibly steward genomic and related health data while enabling its efficient downstream reuse.

Methods: We describe a document analysis study using both qualitative and comparative law analytical approaches to identify the most common categories of clauses from 29 different data access agreements used by human biomedical research consortia globally. We furthermore characterized the legal positions and standard practices for each common element of the agreement and synthesized across them to develop model clauses. A total of 3 discussion sessions were organized virtually to refine the clauses among members …

Imagining Genomics And Population Health In 2050: Anticipating Future Research, Policy, And Governance Needs, Bartha Maria Knoppers, Yann Joly, Ma Apos N H Zawati, Habiba Alsafar, Jeffrey C Barrett, Laura Blackburn, Brian Hon-Yin Chung, Martina C Cornel, Edward S Dove, David Glazer, Calvin Wai-Loon Ho, Muin J Khoury, Anna C F Lewis, Anneke Lucassen, Peter F R Mills, Colin Mitchell, Nicola Mulder, Ainsley J Newson, Anthony Ng, Paul D P Pharoah, Vasiliki Rahimzadeh, Megan C Roberts, Saskia C Sanderson, Jeffrey M Skopek, Ron Zimmern, Eric M Meslin

Center for Medical Ethics and Health Policy Staff Publications

No abstract provided.

Tau In Alzheimer’S Disease: Shaping The Future Patient Journey, Catherine J Mummery, Christopher Chen Li-Hsian, Cristian A Lasagna-Reeves, Rik Ossenkoppele, Christopher C Rowe, Douglas W Scharre, Huali Wang, Simon Kyaga, Jeffrey L Cummings

Faculty, Staff and Students Publications

Alzheimer's disease is a complex and multifactorial disease characterized by two key pathological hallmarks: amyloid-beta plaques and tau neurofibrillary tangles. Recent progress has led to the development and approval of disease-targeted therapies for Alzheimer's disease in the form of anti-amyloid-beta monoclonal antibodies. However, findings suggest that amelioration of multiple pathological drivers may be required to maximize clinical effect. An increasing body of evidence suggests that tau is a critical player in Alzheimer's disease pathophysiology, contributing significantly to neurodegeneration and cognitive decline. There are now several tau-targeting drugs in clinical development. In this review, we build on research and advancements in …

Mir-302 Regulates Pancreatic Progenitor Pool And Pancreatic Size, Ziyue Z Yang, Caroline G Snider, Ronald J Parchem

Faculty, Staff and Students Publications

Disruptions in pancreatic development can lead to health issues such as pancreatic agenesis and congenital diabetes mellitus. Understanding pancreatic organogenesis is critical for elucidating disease mechanisms and developing regenerative therapies. The pancreas consists of endocrine and exocrine cells, both of which are derived from multipotent progenitor cells (MPCs). MPC proliferation and differentiation are tightly controlled by multiple mechanisms, including post-transcriptional regulation by miRNAs. However, these regulatory factors are not fully understood. Here, we profiled miRNA expression in MPCs and identified that mir-302 was highly enriched during the earliest stages of pancreatic development. Loss of mir-302 resulted in reduced pancreatic size …

Multi-Omics To Study Chronic Respiratory Diseases And Viral Infections, Sobia Idrees, Hao Chen, Tayyaba Sadaf, Saima Firdous Rehman, Matt D Johansen, Keshav Raj Paudel, Gang Liu, Yuting Wang, Malte D Luecken, Elinor Hortle, Ashleigh S Philp, Kurtis F Budden, Matthew O'Rourke, Gerard E Kaiko, Sionne E M Lucas, Joanne L Dickinson, Peter C Allen, Joseph E Powell, Lai-Ying Zhang, Daniel C Chambers, Tamera Corte, Gaetano Caramori, Maor Sauler, Peter A Wark, Janine Gote-Schniering, Mareike Lehmann, Thomas M Conlon, Theodore S Kapellos, Ali Önder Yildirim, Rosa Faner, Shyamali C Dharmage, Craig E Wheelock, Maarten Van Den Berge, Martijn C Nawijn, Francesca Polverino, Gabrielle T Belz, Sanjay H Chotirmall, Leopoldo N Segal, Alen Faiz, Philip M Hansbro

Faculty, Staff and Students Publications

Integrating omics layers reveals complex biological systems, unveiling vital insights into chronic respiratory diseases and COVID-19. This holistic approach is crucial for developing more effective treatments and understanding intricate relationships. https://bit.ly/3VKFzJH

Surface Marker Identification To Capture Live Circulating Tumor Cells In Metastatic Triple-Negative Breast Cancer, Bree M Lege, Khushali J Patel, Brendan Panici, Ping Gong, Michael T Lewis, Matthew J Ellis, Chonghui Cheng

Faculty, Staff and Students Publications

Metastatic triple-negative breast cancer (TNBC) is highly aggressive and lacks targeted therapies. Circulating tumor cells (CTC) are invaluable for monitoring metastatic tumor progression and treatment response but are difficult to capture because of their rarity and heterogeneity. Surface-based staining for live CTCs is essential to preserve RNA quality in single cells, but current markers tend to perform poorly on more mesenchymal tumor cells such as TNBCs. To enhance live TNBC CTC detection, we developed a workflow for live CTC capture and single-cell RNA sequencing (scRNA-seq). Using a mouse model of metastatic TNBC, we identified four new CTC surface markers, AHNAK2, …

Lysine Demethylase 4a Is A Centrosome-Associated Protein Required For Centrosome Integrity And Genomic Stability, Pratim Chowdhury, Xiaoli Wang, Richard I Han, Manga Motrapu, Ashley G Boice, Yuya Nakatani, Sofia Vargas-Hernandez, Julia F Love, Claude Chew, Sandra L Grimm, Dereck Mezquita, Frank M Mason, Elisabeth D Martinez, Cristian Coarfa, Cheryl L Walker, Anna-Karin Gustavsson, Ruhee Dere

Faculty, Staff and Students Publications

Centrosomes play a fundamental role in nucleating and organizing microtubules in the cell and are vital for faithful chromosome segregation and maintenance of genomic stability. Loss of structural or functional integrity of centrosomes causes genomic instability and is a driver of oncogenesis. Here we identify lysine demethylase 4A (KDM4A), an epigenetic 'eraser' of chromatin methyl marks, as a centrosome-localized protein, visualized at the nanometer-scale resolution. We additionally uncovered that KDM4A demethylase enzymatic activity is required to maintain centrosome homeostasis and integrity; a previously unknown functionality unlinked to altered expression of genes regulating centrosome number. We find that KDM4A interacts with …

In Vivo Volumetric Visualization And Quantification Of Cumulus Expansion In Mice With Intravital Optical Coherence Tomography, Kohei Umezu, Frank J Brooks, Irina Larina

Faculty, Staff and Students Publications

Ovulation is preceded by a critical physiological process known as cumulus expansion, during which the cumulus cell layer surrounding the oocyte undergoes structural remodeling. Despite the recognized importance of this process for reproductive success, live quantitative imaging of cumulus expansion has not been previously achieved due to limitations of current imaging technologies for deeply located ovaries. In this study, we employed intravital optical coherence tomography for three-dimensional visualization of mouse follicles containing cumulus-oocyte complexes (COC) within the physiological context of the ovary, both ex vivo and in vivo. This method enabled time-lapse measurement of cumulus layer thickness and COC …

Survodutide For Treatment Of Obesity: Baseline Characteristics Of Participants In A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial (Synchronize™-1), Carel W Le Roux, Sean Wharton, Biykem Bozkurt, Elke Platz, Gabriele Bleckert, Samina Ajaz Hussain, Martina Brueckmann, Elena Startseva, Isabel M Kloer, Lee M Kaplan

Faculty, Staff and Students Publications

Aims: Survodutide, a novel glucagon receptor and glucagon-like peptide-1 (GLP-1) receptor dual agonist, elicited significant weight loss in a phase 2 trial in individuals with obesity without type 2 diabetes (T2D). Two multinational phase 3 trials are investigating survodutide for obesity management in individuals with or without T2D. We report the baseline characteristics of participants in the SYNCHRONIZE-1 trial in adults with obesity without T2D (ClinicalTrials.gov: NCT06066515).

Materials and methods: Participants aged ≥18 years with BMI ≥30 or ≥27 kg/m2 with ≥1 obesity complication without T2D were randomized 1:1:1 to double-blind, once-weekly, subcutaneous injections of survodutide (up-titrated to 3.6 …

Senolytic-Resistant Senescent Cells Have A Distinct Sasp Profile And Functional Impact: The Path To Developing Senosensitizers, Utkarsh Tripathi, Masayoshi Suda, Vagisha Kulshreshtha, Bryan T Piatkowski, Allyson K Palmer, Nino Giorgadze, Christina Inman, Nathan Gasek, Ming Xu, Kurt O Johnson, Tamar Pirtskhalava, Selim Chaib, Larissa P G Langhi Prata, Yi Zhu, Renuka Kandhaya-Pillai, Stefan G Tullius, Saranya P Wyles, Rambabu Majji, Hari Krishna Yalamanchili, David B Allison, Tamar Tchkonia, James L Kirkland

Faculty, Staff and Students Publications

The senescent cell (SC) fate is linked to aging, multiple disorders and diseases, and physical dysfunction. Senolytics, agents that selectively eliminate 30%-70% of SCs, act by transiently disabling the senescent cell antiapoptotic pathways (SCAPs), which defend those SCs that are proapoptotic and pro-inflammatory from their own senescence-associated secretory phenotype (SASP). Consistent with this, a JAK/STAT inhibitor, Ruxolitinib, which attenuates the pro-inflammatory SASP of senescent human preadipocytes, caused them to become "senolytic-resistant". Administering senolytics to obese mice selectively decreased the abundance of the subset of SCs that is pro-inflammatory. In cell cultures, the 30%-70% of human senescent preadipocytes or human umbilical …