Digital Commons Network^™

Progesterone Receptors Drive Advanced Breast Cancer Phenotypes Including Circulating Tumor- And Stem-Like Cell Expansion In The Context Of Esr1 Mutation, Thu H. Truong, Noelle E. Gillis, Amy R. Dwyer, Rosemary J. Huggins, Kyla M. Hagen, Sai Harshita Posani, Nuri A. Temiz, Carlos Perez Kerkvliet, Ellie M. Piepgras, Julie H. Ostrander, Geoffrey L. Greene, Carol A. Lange

Department of Urology Faculty Papers

Endocrine therapy resistance remains a major challenge in the treatment of advanced estrogen receptor positive (ER+) breast cancer. This can be driven by acquired mutations in the estrogen receptor gene (ESR1), such as Y537S or D538G, that results in constitutive estrogen-independent ER activity. Progesterone receptors (PR) are important modifiers of ER activity, in part via direct binding. We previously showed that PR mediates expansion of cancer stem-like cell (CSC) populations. In this study, we sought to define whether PR function changes in the context of ESR1 mutations. PR readily interacted with wild type (WT), but not Y537S or D538G ERs. …

Dietary Patterns And Nutritional Status In Soccer Athletes: A Cross-Sectional Study From An Ergonomic Perspective, Rina Mayangsari, Ravi Masitah

Indonesian Journal of Research in Physical Education, Sport, and Health

Background: Normal nutritional status has been established as one of the principal determinants in an athlete's performance. Dietary quality plays a critical role in optimizing athletes' physical fitness and performance outcomes. Objective: To examine the associations between dietary patterns on the MacPersona System and nutritional status of soccer players (energy, protein, et cetera, fat, and carbohydrates). Methods: A cross-sectional quantitative study was conducted involving 21 soccer players (total sampling). Dietary patterns were assessed using a validated Semi-Quantitative Food Frequency Questionnaire (SQ-FFQ). Nutritional status was measured using Body Mass Index(BMI) based on anthropometric data. The chi-square test was used for statistical …

Balneotherapy For Sleep Improvement And Reducing Depression In Knee Osteoarthritis Patients, Anca Paula Ciurba, Alexandru Bogdan Ilieș, Ionel Haidu, Doriana Ioana Ciobanu, Theodora Ursu, Florin Mihai Marcu, Dorina Ianc

Baltic Journal of Health and Physical Activity

Background: Knee osteoarthritis (OA) is the most common chronic condition and a leading cause of global disability, often associated with pain, depression, and sleep disturbances. The purpose of this study was to investigate the effectiveness of warm mineral water combined with physical therapy on sleep quality, depression and pain intensity in patients with knee osteoarthritis. Materials and Methods: The study involved 101 subjects (68.78±6.92 years) who were assigned to  a control group (CG) or an experimental group (EG). All subjects benefited from physical therapy and electrotherapy for 10 days. The experimental group additionally benefited from therapy with hot mineral water. …

Six-Week Time-Restricted Eating Lowers Premature Mortality Risk In Overweight Early Elderly Adults: Evidence From A Body Shape Index, Przemysław Domaszewski, Mariusz Konieczny

Baltic Journal of Health and Physical Activity

Background: A Body Shape Index (ABSI) is an anthropometric indicator combining waist circumference, weight, and height, providing a BMI-independent measure of central obesity and a recognized predictor of mortality. Despite its relevance, research on ABSI in early elderly populations remains limited. This study assessed the impact of a six-week time-restricted eating (TRE) intervention on ABSI z-scores in overweight adults aged 65–74, with attention to gender differences. Materials and Methods: A total of 116 participants were randomized into a TRE group (16:8 fasting window from 8:00 PM to 12:00 PM) or a control group maintaining habitual eating. ABSI z-scores were evaluated …

Changes In 25(Oh)D Concentration, Bone Resorption Markers And Physical Performance Due To Sun Exposure, Diet And Training Load Among Professional Women Handball Players During The Half-Year Training Season, Sorin Dacian Buhas, Zbigniew Jastrzębski, Paul Florian Dragos, Marius Alin Marinau, Maria Skalska, Mirela Stef, Joanna Jastrzębska, Mihai Sandra, Dana Ioana Cristea

Baltic Journal of Health and Physical Activity

Background: The aim of the study was to demonstrate changes in 25(OH)D concentration, bone resorption indicators and physical fitness in female handball players as a result of their exposure to the sun, diet and exercise load during the six-month training period from mid-March to mid-September, i.e. the time when the sun exposure is the highest during the calendar year. Twenty-two women handball players participated in the study. Due to the random occurrences and exclusion criteria, 20 players completed the project. Biochemical analysis of blood, aerobic capacity, running speed and power tests (Wingate test, squat jump, counter movement jump, etc.) was …

Unpacking Developmental Programming: A Conceptual And Historical Analysis In The Context Of Dohad, Andrea Gretchev, Heide S. Temples, Gillian England-Mason, Deborah Dewey, Sara M. Sarasua, Christopher Farrell, Vivian Haley-Zitlin

Publications

The Developmental Origins of Health and Disease (DOHaD) paradigm posits that early environmental factors may influence a child’s development and long-term health outcomes. Developmental programming (DP) is central to this paradigm, whereby specific early life exposures during critical periods of development are associated with changes to physiological and metabolic pathways, potentially predisposing individuals to disease. However, no standard definition of DP exists, and various terms have been used to describe similar processes. This analysis aimed to develop a conceptual definition for DP to inform interdisciplinary research, education, and practice. Walker and Avant’s eight-step method was employed to analyze the literature, …

Transcultural Headache Medicine: A Framework For Integrating Cultural Contexts Into Headache Science And Care - A Call To Action From The International Headache Society., Mario F. P. Peres, Giancarlo Lucchetti, Homero Vallada, Ivy L. Riso, Georgia K. Westenhofen, Marcelo Moraes Valença, Juliana Ramos De Andrade, K. C. Brennan, Morris Levin, Tsubasa Takizawa, Zhao Dong, Yonggang Wang, Wanakorn Rattanawong, Henry Riyanto Sofyan, Massimo Leone, Freda Dodd-Glover, Hsiangkuo Yuan, Abdulrazaq Albilali, Taoufik Alsaadi, Leonardo Caixeta, Anna P. Andreou, Peter J. Goadsby, Antoinette Maassenvandenbrink, Sait Ashina, Rami Burstein, Patricia Pozo-Rosich, Fayyaz Ahmed, Shuu-Jiun Wang

Department of Jefferson Headache Center Papers and Presentations

Headache disorders are among the most disabling neurological conditions, affecting over 1.5 billion people globally. Despite advances in pharmacological therapies, major inequities persist due to underdiagnosis, undertreatment and limited access to effective care, particularly in low- and middle-income countries. Social determinants of health, including cultural meanings, language and health beliefs, are increasingly recognized as key drivers of disparities in burden, diagnosis and treatment outcomes. Traditional medicine, used by more than 80% of the global population, remains first-line care in many regions and continues to influence therapeutic choices in high-income settings. Major systems such as Ayurveda, Traditional Chinese Medicine, Unani and …

Development Of A Dendritic Cell Model To Unravel The Secrets Of Cards Toxin, Lizbeth Gomez

Posters - 2026

Dendritic cells (DCs) are derived from hematopoietic stem cells of the bone marrow. They are the most efficient antigen presenting cell, presenting antigens to T cells to initiate clonal expansion and differentiation of the T cells into memory and effector cells. Thus, activating the effector functions of T cells in cell-mediated and humoral immune responses (2). Community-acquired respiratory distress syndrome (CARDS) toxin is produced by Mycoplasma pneumoniae that causes acute and chronic lung infections (4). Dendritic cells play a key role in the immune response to respiratory mycoplasmas (3). However, the mechanism underlying in DC and CARDS toxin interactions are …

Hemodialysis Access-Related High-Output Heart Failure: From Mechanisms To Multidisciplinary Management, Chukwuemezie Mamanu, Estefania Oliveros, Yevgeniy Brailovsky

Department of Medicine Faculty Papers

No abstract provided.

Une Com Spring Research Bulletin May 2026, Une Com Research & Scholarship

Osteopathic Student Research Symposia

Bulletin including abstracts from the University of New England College of Osteopathic Medicine’s 2026 inaugural Spring Research Update and Lightning Talk event.

Rexinoid Net-3ib Promotes Resident Macrophage Gene Expression And Mitigates Desiccation-Induced Ocular Surface Disease, Jehan Alam, Yangluowa Qu, Jianming Shao, Ebru Yaman, Karen Zheng, Hiroki Kakuta, Stephen C Pflugfelder

Faculty, Staff and Students Publications

Purpose: To evaluate the effects of rexinoid NEt-3IB on desiccating stress-induced dry eye, as well as monocyte/macrophage gene expression and cellular trajectory.

Methods: Eyes were topically treated with rexinoid NEt-3IB (5 µM) or vehicle three times a day for 5 days of desiccating stress-induced dry eye. Single-cell RNA sequencing (RNA-seq) profiled gene expression in conjunctival immune cells. RNA-seq was also used to evaluate gene expression in lipopolysaccharide (LPS)-stimulated, dexamethasone-treated (Dex, 1 µM), or NEt-3IB-treated (1-1000 nM) cultured monocytes. Cellular state trajectory and latent time were inferred with scVelo, and latent-time-associated genes were identified using Monocle 3. Permeability to Oregon Green-labeled …

The Impact Of Estrogen Replacement During Perimenopause On Lung Function And Airway Inflammation In The Vcd Mouse Model, William P Pederson, Laurie Michelle Ellerman, Riley D Hellinger, Joselyn Joanna Rojas Quintero, Francesca Polverino, John P Konhilas, Julie G Ledford

Faculty, Staff and Students Publications

Background:

Menopause associated asthma impacts a subset of women and is less responsive to current treatments. Mechanisms driving this late onset asthma are unknown. We recently developed a mouse model of menopause associated asthma using a combination of 4-Vinylcyclohexene Diepoxide (VCD) and House Dust Mite (HDM) exposures. The goal of this study was to determine how hormone replacement therapy during perimenopause impacts lung function and inflammation.

Methods:

The experimental groups included menopausal mice (VCD) with and without exposure to HDM (to model allergic airways disease) and menopausal mice with and without hormone replacement therapy (HRT; via estrogen pellet implantation). Lung …

Androgen Activity In The Male Embryonic Hindbrain Drives Lethal Pfa Ependymoma, Jiao Zhang, Winnie Ong, Alexandra Rasnitsyn, Ricardo Daniel Gonzalez, Rodrigo Lopez Gutierrez, Polina Balin, Amr Saadeldin, Xiaochong Wu, Maria C Vladoiu, Vicente Santa-Maria Lopez, Fernando Gonzalez-Salinas, Navneesh Yadav, Dinesh Mohanakrishnan, Kannan Boosi Narayana Rao, Raja Gopal Reddy Mooli, Hinda Najem, Sebastian Pacheco, Kaitlin Kharas, Cory Richman, David Przelicki, Evan Y Wang, Haipeng Su, Rachel Naomi Curry, Runze Yang, Michelle Masayo Kameda-Smith, Bryn Livingston, David Scott, Zaili Luo, Mingyang Xia, Namal Abeysundara, Anders W Erickson, Ncedile Mankahla, Lucas Zhongming Hu, Chu Pan, Raul Suarez, Ning Huang, Yihao Wu, Hao Wang, Tajana Douglas, Jonelle Pallota, Steven Hébert, Karen Ng, Krystin Mantione, Heather Whetstone, Hassaan Maan, Hussein Lakkis, Juyeun Lee, Sadeesh K Ramakrishnan, Yanxin Pei, Yujie Tang, Frank Y Lin, Guillermo Aldave, Marco Gallo, Robert M Friedlander, Faiyaz Notta, Laura K Donovan, Murali Chintagumpala, Bo Wang, Yun Li, Daniel D De Carvalho, Zhaolei Zhang, Ying Mao, Wei Hua, Charles Eberhart, Calixto-Hope G Lucas, Sriram Venneti, Poul H Sorensen, Alberto Delaidelli, Hao Li, Wenhao Zhou, Jason Kirk, Dean G Tang, Tao Jiang, Hailong Liu, Justin D Lathia, Hiromichi Suzuki, Jeremy N Rich, Lincoln D Stein, Nada Jabado, Vijay Ramaswamy, Q Richard Lu, Amy B Heimberger, Craig Daniels, Kulandaimanuvel Antony Michealraj, Claudia L Kleinman, Michael D Taylor

Faculty, Staff and Students Publications

Posterior fossa type A (PFA) ependymoma is an unusual infantile brain tumour with few known somatic mutations, thought to be driven by epigenetic mechanisms1. PFA ependymoma has a markedly higher incidence and worse prognosis in male children than in female children2. The mechanisms that underlie these sex differences are at present unknown. Here we show that the cellular hierarchy of PFA ependymoma is less differentiated in male individuals than it is in female individuals. In the normal developing mouse hindbrain, male gliogenic progenitors are less differentiated than matched female sibling controls. To further parse the effects …

Mechanisms Of Synergy Between Nanosecond Pulsed Electric Field (Nspef) And Cold Atmospheric Pressure Plasma Discharge (Cap) In Pancreatic Cancer: The Role Of Ros-Mediated Oxidative Stress And Apoptosis, Zobia Minhas

Theses and Dissertations in Biomedical Sciences

Pancreatic ductal adenocarcinoma is a highly lethal malignancy characterized by poor prognosis and resistance to conventional therapies. Novel treatment strategies are needed to overcome this resistance. Non-thermal physical modalities, including nanosecond pulsed electric field (nsPEF) and cold atmospheric pressure plasma discharge (CAP), have emerged as potential anticancer approaches; however, the mechanisms underlying their combined effects remain unclear.

This study evaluated whether nsPEF enhances CAP-induced cytotoxicity and investigated the associated molecular mechanisms using the murine Pan02 pancreatic cancer cell line. Cell viability was assessed by WST-1 metabolic activity assays and electric cell–substrate impedance sensing (ECIS). Intracellular reactive oxygen species (ROS) were …

Dominant Clones Leverage Developmental Epigenomic States To Drive Ependymoma, Alisha S Kardian, Hua Sun, Siri Ippagunta, Nicholas Laboe, Srinidhi Varadharajan, Kwanha Yu, Hsiao-Chi Chen, Erik Emanus, Tuyu Zheng, Riley M Deneen, Jon P Connelly, Yong-Dong Wang, Jiangshan Zhan, Hengxi Liu, Kimberley Lowe, Taylor Bugbee, Rakesh Pathak, Amanda Bland, Sanya Mehta, Sophie Cochiolo, Amir Arabzade, Blake Holcomb, Kaitlin M Budd, Gabriele Kembuan, Tristen Wright, Emma Caesar, Maxwell Park, Amelia Hancock, David Gee, Joel Murdoch, Yi Xiao, Samuel K Mcbrayer, Thomas E Merchant, Jun Qi, Adam D Durbin, Lindsay A Schwarz, Li Wang, Andrew M Donson, Nicholas K Foreman, Sameer Agnihotri, Alfonso Lavado, Suzanne J Baker, David W Ellison, Hyun Kyoung Lee, Shondra M Pruett-Miller, Kelsey C Bertrand, Benjamin Deneen, Stephen C Mack

Faculty, Staff and Students Publications

ZFTA–RELA is the most recurrent genetic alteration seen in paediatric supratentorial ependymoma (EPN) and is sufficient to initiate tumours in mice1. Despite its oncogenic potential, ZFTA–RELA (ZR) is observed nearly exclusively in childhood EPN, with tumours located distinctly in the supratentorial brain of the central nervous system1. We proposed that specific chromatin modules accessible during brain development would render distinct cell lineage programs at direct risk of transformation by ZR. To test this hypothesis, we performed combined single-nucleus assay for transposase-accessible chromatin and RNA (snMultiome) sequencing of the developing mouse forebrain compared with ZR-driven mouse …

A Comprehensive Review Of Tear Fluid Proteome Alterations In Dry Eye Disease: Insights Into Pathophysiology And Biomarker Potential, Saleh Ahmed, Steven Safille, Victoria Clifton, Shruti Sharma, Cintia S De Paiva, Ashok Sharma

Faculty, Staff and Students Publications

Tear fluid is a highly specialized and dynamic biofluid composed of proteins, lipids, mucins, and electrolytes that is essential for maintaining ocular surface integrity, immune defense, and tear film stability. Growing evidence from tear proteomic studieshas revealed extensive alterations in protein composition in dry eye disease (DED), reflecting a complex interplay between local ocular surface pathology and systemic inflammatory influences. This review summarizes proteomic findings from 50 published studies to identify tear proteins that are consistently upregulated or downregulated in DED and to interpret their biological relevance in the context of ocular surface homeostasis. Across studies, proteins upregulated in DED …

Comprehensive Profiling Of The Human Tear Fluid Mirnome Using Small Rna Sequencing, Garrett Jones, Drew Mayernik, Saleh Ahmed, Eliza Williams, Jeremy Altman, Tae Jin Lee, Amy Estes, Cintia S De Paiva, Pamela Martin, Shruti Sharma, Ashok Sharma

Faculty, Staff and Students Publications

Purpose: To generate a comprehensive profile of microRNAs (miRNAs) present in human tear fluid using next-generation sequencing (NGS), establish a reference miRNome for healthy human tear fluid, and investigate whether miRNA expression varies by sex, race, or age.

Methods: Tear samples were collected from 32 adults using Schirmer strips. RNA was isolated using the miRNeasy Serum/Plasma Kit, and cDNA libraries were prepared using the QIAseq miRNA Library Kit. Barcoded libraries were sequenced on the NovaSeq 6000 platform. Bioinformatic analyses included adapter trimming, alignment to miRBase, normalization with DESeq2, and functional annotation using multiMiR and clusterProfiler. Differential expression analysis was performed …

Detection And Quantification Of Allergen Cross-Contact In Shared Frying Oil Using Targeted Mass Spectrometry, Francisca Asigri

Department of Food Science and Technology: Dissertations, Theses, and Student Research

Cow’s milk and egg allergies are prevalent IgE-mediated food allergies that pose significant public health concerns worldwide. Although strict avoidance remains the primary management strategy, unintended exposure can still occur through allergen cross-contact, particularly in commercial and industrial food operations that utilize shared frying oils. The objective of this study was to identify and quantify allergen transfer in shared frying oil and assess the robustness of existing targeted mass spectrometry methods (LC-MS/MS) for detecting milk and egg proteins in heated oil matrices.

Heated oil spikes were developed by incorporating non-fat dry milk (NFDM) and whole egg powder (WEP) into oil …

Ten Tips On How To Optimize Nutrition In Children With Chronic Kidney Disease Or On Dialysis., Nonnie Polderman, Vanessa Shaw, Caroline E. Anderson, An Desloovere, Louise Mcalister, Christina L. Nelms, Fabio Paglialonga, Pearl Pugh, Leila Qizalbash, Evelien Snauwaert, José Renken-Terhaerdt, Jetta Tuokkola, Larry A. Greenbaum, Rukshana Shroff

Manuscripts, Articles, Book Chapters and Other Papers

Optimal nutrition is central to growth and development in all children, and is particularly relevant in those with chronic illnesses. This document provides 10 practical, evidence-informed tips on the assessment and management of the nutritional prescription in children with chronic kidney disease (CKD) and those receiving dialysis. The 10 tips synthesize work of the Paediatric Renal Nutrition Taskforce, an international team of pediatric renal dietitians and pediatric nephrologists who develop clinical practice recommendations for the nutritional management of children with kidney diseases. We describe a comprehensive, three-dimensional nutritional assessment (anthropometry, dietary intake, biochemical markers) and regular monitoring tailored to age, …

2026 Research Day Program, Lincoln Memorial University

Research Day

This program contains abstracts and presentation summaries from LMU's 2026 Annual Research Day conference.

A Review Of Yellow Fever: Epidemiology, Pathogenesis, Clinical Manifestations, Treatment, Prevention, And Prognosis, Farah Ebrahim, Samina Somji, Reena Shah, Salim Surani

Internal Medicine, East Africa

Yellow fever is a mosquito-borne viral illness caused by the yellow fever virus (YFV), a member of the Flaviviridae family. Despite the availability of an effective live-attenuated vaccine, the disease remains endemic in regions of Africa and South America. Transmission occurs primarily via an infected mosquito called Aedes aegypti, with distinct urban, sylvatic, and intermediate transmission cycles. Clinically, infection ranges from mild febrile illness to severe disease, which is characterized by jaundice, hemorrhage, and multiorgan failure. Pathogenesis involves viral replication in hepatocytes, immune-mediated injury, and dysregulated inflammatory responses, leading to characteristic hepatic mid-zone necrosis. Diagnosis relies on molecular detection …

Does The Placenta Predict Depression During Pregnancy? Investigating Hormonal Links In High-Risk Pregnancies, Sonia Cerrillo, Hanne Hoffmann Phd

Posters - 2026

• Perinatal depression is a common disorder that affects maternal and infant well-being.

• Serotonin is an important mood-regulating neurotransmitter, and reduced serotonin signaling has been linked to depressive symptoms.

• Tryptophan (TRP) is the precursor for serotonin, where most TRP is metabolized through the kynurenine pathway.

• TPH supports serotonin synthesis, while IDO and TDO drive kynurenine production.

• During pregnancy, inflammation and stress may shift TRP away from serotonin, creating a placental “tryptophan steal.”

• We examined whether placental DNA methylation of these genes differs in high-risk pregnancies.

• We hypothesized that placental DNA methylation of genes in …

Multiparametric Mri To Predict Response To Irreversible Electroporation Plus Anti-Pd-1 Immunotherapy In Pancreatic Ductal Adenocarcinoma, Qizhen Cao, Mark D Pagel, Charles V Kingsley, Jingfei Ma, James P Long, Xiaoxia Wen, Seth T Gammon, Jorge Delacerda, Sanaz Javadi, Chun Li

Faculty, Staff and Student Publications

Purpose: To investigate contrast-enhanced T1-weighted MRI and diffusion-weighted magnetic resonance imaging (DWI) for early prediction of tumor response to combined irreversible electroporation (IRE) and anti-PD-1 immunotherapy.

Methods: Murine pancreatic ductal adenocarcinoma (PDAC) cells KRAS* were inoculated into the pancreas of C57BL/6 mice. IRE was performed when tumors became palpable. After IRE, mice received six intraperitoneal injections of anti-PD-1 over 2 weeks. T2-weighted MRI, T1-weighted MRI with macromolecular contrast agent poly(L-glutamic acid)-conjugated gadolinium (PG-Gd), and DWI were performed before and after IRE. Survival was analyzed using Kaplan-Meier curves. Mice surviving at least 100 days without recurrence after IRE were considered complete …

Neutrophil-Microglia Interaction Drives Motor Dysfunction In A Neuromyelitis Optica Model Induced By Subarachnoid Aqp4-Igg, Fangfang Qi, Vanda A Lennon, Shunyi Zhao, Yong Guo, Husheng Ding, Caiyun Liu, Whitney M Bartley, Tingjun Chen, Claudia F Lucchinetti, Long-Jun Wu

Faculty, Staff and Student Publications

Neutrophils and neutrophil extracellular traps (NETs) contribute to early neuromyelitis optica (NMO) histopathology initiated by IgG targeting astrocytic aquaporin-4 (AQP4) water channels. Yet, the mechanisms underlying neutrophil recruitment and their pathogenic roles in disease progression remain unclear. To investigate molecular-cellular events preceding classical complement cascade activation in a mouse NMO model, we continuously infused, via spinal subarachnoid route, a non-complement-activating mouse monoclonal AQP4-IgG. Parenchymal infiltration of netting neutrophils containing C5a ensued with microglial activation and motor impairment but no blood-brain barrier leakage. Motor impairment and neuronal dysfunction both reversed when AQP4-IgG infusion stopped. Two-photon microscopy and electron microscopy-based reconstructions revealed …

Gompertz Growth With A Shared Carrying Capacity Optimally Simulates Primary And Metastatic Tumor Growth Dynamics, Pirmin Schlicke, Preethi Korangath, Xiaoxi Pan, Caner Ercan, Kathleen Gabrielson, Lyndsey Werhane, Yinyin Yuan, Sébastien Benzekry, Robert Ivkov, Heiko Enderling

Faculty, Staff and Student Publications

Background: Cancer is a systemic disease with most deaths attributed to metastatic burden. Primary and metastatic tumors, albeit at different anatomic locations, are interconnected through multiple biological processes. Pre-clinical and clinical observations of growth acceleration of metastases after surgery, or abscopal effects outside the radiation field are widely reported, yet reliably triggering favorable and avoiding unfavorable systemic responses remains an unmet clinical need. Understanding local and systemic tumor interaction dynamics will help guide future treatments.

Methods: We analyze the data of multiple in vivo tumor models. We formalize the systemic interplay of tumors as mathematical differential equation and calibrate parameters …

Structural-Functional Analyses Of The Huntingtin/Hap40 Complex In Drosophila And Humans, Stephen M Farmer, Amanda Solbach, Shiyu Xu, Beatriz Rios, Xin Ye, Amy Gao, Daniela Covarrubias, Yue Yu, Lili Ye, Vicky Chuong, Erin Furr Stimming, Haiqing Zhao, Sheng Zhang

Faculty, Staff and Student Publications

Huntington's disease (HD) is a neurodegenerative disorder caused by an abnormal CAG expansion in the Huntingtin (HTT) gene. Given its simple genetic cause but complex pathogenic mechanisms, interest in targeting HTT for HD treatment is growing, necessitating a clear understanding of HTT regulation. HTT protein primarily exists in a core complex with HAP40, forming a highly ordered structure with two large globular domains connected by a bridge. We previously demonstrated that HAP40 is conserved in

Platelets Cause Microvascular Occlusion And Delayed Neurological Deficits After Subarachnoid Hemorrhage In Mice., Ari Dienel, Sung-Ha Hong, Kiara Torres, Kanako Matsumura, Jose Guzman, Peeyush Thankamani Pandit, Bibek Samal, Harveen Kaur, Samitha Nemirajaiah, Angelica Bernal, H Alex Choi, Louise D Mccullough, Spiros L Blackburn, Jaroslaw Aronowski, Devin W Mcbride

Faculty, Staff and Student Publications

After subarachnoid hemorrhage (SAH), some patients develop delayed neurological deficits (DND). Microthrombi are considered a contributing factor to DND, but clinical trials of antiplatelets had mixed results. Existing research suggests that platelets play a role in the etiology of DND, but no comprehensive study has tested causality between platelets and DND after SAH. Here we hypothesize that after SAH, platelet activation promotes microthrombi formation, occlusion of the brain microvasculature and contributes to DND, and that inhibiting platelet aggregation is a therapeutic strategy. Mice experiencing SAH were administered various interventions. The animals were subjected to stimulation of platelets, platelet depletion, or …

Eating For Healthy Eyes: The Role Of Nutrition In Ocular Health, Brianna Stroh

Honors Program: Senior Projects (Public)

The central research question of this thesis asks: How does nutrition influence ocular health overall and the impact of nutrition on the development or progression of common eye diseases? Building upon existing research in optometry/ophthalmology, nutrition science, and public health, this project examines the physiological mechanisms linking diet to eye health and evaluates how specific nutrients and dietary patterns contribute to disease prevention and visual function. This thesis employs a comprehensive review of peer-reviewed literature to evaluate the relationship between nutrition and ocular disease. Key areas of focus include the role of oxidative stress in eye disease development, the protective …

Weaning Drives Microbiome-Mediated Epigenetic Regulation To Shape Immune Memory In Mice, Li Yang, Robert C Peery, Shirui Zhou, Xiaomin Chen, Leah M Farmer, Fabiola Gutierrez, Stephanie Fowler, Lanjing Zhang, Julia M Salamat, Karen Riggins, Jiejun Shi, Lanlan Shen

Children’s Nutrition Research Center Staff Publications

During weaning, the transition to solid food diversifies the gut microbiome, triggering a programmed immune response critical for long-lasting mucosal immunity. Previous work showed that the gut microbiome mediates epigenetic development in intestinal stem cells (ISCs) during suckling, but what happens during weaning is unclear. Here, genome-wide profiling revealed that weaning-driven microbiome changes shape the DNA methylome and transcriptome of murine ISCs in an IFNγ-dependent manner. Specifically, we observe demethylation of enhancer elements essential for MHC class II genes, which results in a transcriptional memory that persists through differentiation into adulthood. IFNγ blockade, or low-dose penicillin to target Gram-positive bacteria, …

Tfeb Degradation Is Regulated By An Ikk/Β-Trcp2 Phosphorylation-Ubiquitination Cascade, Yan Xiong, Jaiprakash Sharma, Meggie N Young, Wen Xiong, Ali Jazayeri, Karl F Poncha, Ma Xenia G Ilagan, Qing Wang, Bei Gao, Hui Zheng, Nicolas L Young, Marco Sardiello

Center on Aging Staff Publications

Transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and cellular clearance pathways. TFEB activity is tightly controlled by multiple post-translational mechanisms, but the exact molecular mechanism controlling its stability has remained elusive. Here, we identify the IκB kinase (IKK) complex as a key regulator of TFEB protein stability through a phosphorylation-ubiquitination cascade. A high-content kinase inhibitor screen reveals that IKK inhibition increases TFEB protein levels, and genetic ablation of IKK components increases TFEB stability, upregulates lysosomal genes, and enhances lysosomal biogenesis and degradative capacity. Mechanistically, we show that IKK phosphorylates TFEB on a cluster of serine residues …