Digital Commons Network^™

Histone Demethylase Jmjd1a Protects Mice From Enteric Bacterial Infection By Upregulating Ccl8 Expression To Recruit Macrophages And Cd4+ T Cells, Guifang Lin, Lichun Yang, Shuyan Jiang, Yong Zhang, Ping Luo, Weihua Li, Jianming Xu, Gongpeng Xiong, Chundong Yu, Wenbo Chen

Faculty, Staff and Students Publications

Jumonji domain-containing 1A (JMJD1A, also known as KDM3A) is a histone demethylase that specifically demethylates H3K9me1/2 to enhance gene expression. The roles of JMJD1A in many physiological and pathological processes have been revealed. However, it is unclear whether JMJD1A is involved in host defense against enteric pathogen infection. In this study, we found that enteric infection with C. rodentium induced JMJD1A expression in colonic epithelial cells at the transcriptional level partly mediated by IRF1. After C. rodentium infection, JMJD1A-/- mice exhibited increased mortality, colonic injury, and C. rodentium load and systemic spread, suggesting that JMJD1A protects host against C. rodentium …

Rab4 Spatially And Functionally Converges With Rab7 In The Degradative Endolysosomal Network, Stephen M Farmer, Shiyu Xu, Yue Yu, Xin Ye, Haoyi Yang, Jing Cai, Beatriz Rios, Wen-Wen Lin, Daniela Covarrubias, Vicky Chuong, Lili Ye, German Zylberberg, Charissa Wang, Erin Furr-Stimming, Qingchun Tong, Oguz Kanca, Hugo J Bellen, Travis I Moore, Sheng Zhang

Faculty, Staff and Students Publications

Rab GTPases are key regulators of endosomal trafficking in eukaryotes. In mammalian cells, Rab4 and Rab7 were shown to localize to distinct compartments, with Rab4 on early endosomes for fast recycling and Rab7 on late endosomes for degradation. Here, we show that in Drosophila, endogenous Rab4 and Rab7 extensively colocalize across tissues and developmental stages. Recruited to the same compartments through mechanisms that do not require the activity of the other, they have opposing effects on endolysosomal size: Rab4 overexpression or Rab7 impairment leads to enlarged endolysosomes, whereas Rab4 loss or constitutively active Rab7 reduces their sizes. Rab4 deficiency suppresses …

Synovial Fibroblast Responses To Different Types Of Injury Resulting In Cartilage Repair Or Osteoarthritis, Fraser L Collins, Alexander J Knights, Tristan Maerz, Anke J Roelofs, Cosimo De Bari

2020-Current year OA Pubs

OBJECTIVE: Single-cell RNA-sequencing (scRNA-seq) has advanced our understanding of the heterogeneity of synovial fibroblasts and their roles in tissue repair and osteoarthritis. Here, we compared the fibroblast responses to different types and duration of joint injury in mice.

DESIGN: Published scRNA-seq data of synovial fibroblasts from a model of joint surface injury (JSI, day 6) and two post-traumatic osteoarthritis models, destabilisation of the medial meniscus (DMM, day 7 and 2 months) and anterior cruciate ligament rupture (ACLR, day 7 and day 28), were integrated and analysed using clustering, DEG, gene-set enrichment, regulon, pseudotime trajectory and cell-cycle analyses.

RESULTS: The response …

Bach2 Regulates T Cell Lineage State To Enhance Car T Cell Function, Tien-Ching Chang, Amanda Heard, John Lattin, John M Warrington, Amanda Barrett, Jack H Landmann, Yangdon Tenzin, Vishaal Ganesh, Bryant Thompson, Sadia Afrin, Deepesh Kumar Gupta, Ju-Fang Chang, Julie Ritchey, Mehmet Emrah Selli, Yu-Sung Hsu, A J Federico, Avery Horn, Michael P Meers, John F Dipersio, Nathan Singh, Et Al.

2020-Current year OA Pubs

Nearly all chimeric antigen receptors (CARs) signal in the absence of antigen, referred to as 'tonic signaling'. Tonic signaling of CARs containing 41BB domains enhances T cell fitness and function, in contrast to the exhaustion driven by CD28-containing CARs. Here we show that 41BB induces BACH2, a transcriptional regulator that directs stem and memory programs. Overexpression of BACH2 successfully prevented exhaustion but locked CAR T cells in a quiescent state. We linked BACH2 to a degradation domain to tune BACH2, enabling us to prevent exhaustion while enabling potent effector function that broadly enhanced the long-term efficacy of CAR T cells …

Distributed Battery-Free Bioelectronic Implants With Improved Network Power Transfer Efficiency Via Magnetoelectrics, Joshua E Woods, Fatima Alrashdan, Ellie C Chen, Wendy Tan, Mathews John, Lukas Jaworski, Drew Bernard, Allison Post, Angel Moctezuma-Ramirez, Abdelmotagaly Elgalad, Alexander G Steele, Sean M Barber, Philip J Horner, Amir H Faraji, Dimitry G Sayenko, Mehdi Razavi, Jacob T Robinson

Faculty, Staff and Students Publications

Networks of miniature implants could enable simultaneous sensing and stimulation at different locations in the body, such as the heart and central or peripheral nervous system. This capability would support precise disease tracking and treatment or enable prosthetic technologies with many degrees of freedom. However, wireless power and data transfer are often inefficient through biological tissues, particularly as the number of implanted devices increases. Here we show that magnetoelectric wireless data and power transfer supports a network of millimetre-sized bioelectronic implants in which system efficiency improves with additional devices. We demonstrate wireless, battery-free networks ranging from one to six implants, …

Participatory Action Research (Par) In Designing A Supplementary Animated Teaching Resource To Support Learning Cervical Assessment, Michelle Gray, Shelley Stuart, Melanie Welfare

Research outputs 2022 to 2026

Aim: To create an education resource that assists students to understand the movement of the cervix during labour from a posterior retroverted position to a central location, cervical effacement, dilatation of the cervix and descent of the fetal skull. Background: Learning about anatomy and physiology in relation to cervical effacement and dilatation are abstract concepts that are difficult to understand from reading alone. Diagrams are of little assistance however 3D animation has the potential to improve students learning experiences. Design: Participatory Action Research (PAR) using the 7 C's Feekery Framework approach was adopted. Participants became coresearchers in conceptualising the learning …

Cdk4/6 Inhibition Mitigates Chemotherapy-Induced Expansion Of Tp53-Mutant Clonal Hematopoiesis, Irenaeus C C Chan, Giulia Petrone, J Scott Beeler, Duc Tran, Griffen Mustion, Catrina Fronick, Carlos Cruchaga, Kelly L Bolton, Et Al.

2020-Current year OA Pubs

Therapy-related myeloid neoplasm (tMN) is a fatal consequence of exposure to cytotoxic therapy administered in the treatment of cancer. Individuals with pre-existing TP53 clonal hematopoiesis (CH) are at high risk of tMN, with avoidance of therapy being the only strategy to reduce tMN risk. Here, in four randomized clinical trials, we show that the CDK4/6 inhibitor trilaciclib, given in conjunction with a variety of chemotherapeutic regimens and across diverse populations of patients with cancer, mitigates chemotherapy-related expansion of CH clones with mutations in DNA damage response genes, including TP53. This finding was also observed in a syngeneic mouse model of …

Cholecalciferol (Vitamin D3) Is An Agonist Of The Alzheimer's Disease-Associated Immune Receptor Trem2, Hunter B Dean, Ryan A Tuckey, Rory A Greer, Jessica A Greven, Shan-Zhong Yang, Daniel S Elston, Gunnar N Eastep, Yuwei Song, Thomas J Brett, Yuhua Song, Erik D Roberson

2020-Current year OA Pubs

Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) is one of the strongest genetic risk factors for late-onset Alzheimer's disease (AD). Several TREM2 ligands are known, including charged lipids and AD-associated proteins like apolipoprotein E and amyloid-β, but the full range of endogenous ligands for TREM2 remains unknown. Here we combined virtual screening of the Human Metabolome Database with molecular dynamics simulations, binding free energy estimation, and biolayer interferometry to identify novel TREM2 ligands and map their binding sites. Cholecalciferol, the unmodified parent form of vitamin D3, emerged as a top candidate. Structural modeling indicated that cholecalciferol binds TREM2 at …

Assessing Liver And Iron Markers In Steady State Pediatric Scd Patients To Ascertain The Hepatic Consequences Of Hemotransfusion: A Case-Control Study In Ghana, John Agyemang Sah, Stephen Twumasi, Allwell Adofo Ayirebi, Benedict Sackey, Enoch Odame Anto, Richard Vikpebah Duneeh, Ebenezer Senu, Veronica Barnor, David Boakye, Daniel Nii Martey Antonio, Wina Ivy Ofori Boadu

Research outputs 2022 to 2026

Background and Aims: Between 200,000 and 300,000 children with sickle cell disease (SCD) are born in Africa every year, with 75%–80% of these children living in sub-Saharan Africa. In newborns with SCD, significant iron accumulations may develop because of their increased risk of requiring multiple blood transfusions. This study aimed to assess the hepatic effects of hemotransfusion in pediatric SCD patients in steady state by measuring liver and iron markers. Methods: This case-control research enrolled 120 children with SCD and 60 children without SCD from the Asokwa Children's Hospital Sickle Cell Clinic and Child Welfare Clinic. Participants’ sociodemographic information, history …

Essential Role Of Cd63 In Maintaining Corneal Epithelial Identity In The Human Limbus, Yuzuru Sasamoto, Kosei Suzuki, Shinri Sato, Catherine A.A. Lee, Gabrielle Martin, Bruce R. Ksander, Markus H. Frank, Natasha Y. Frank

Research outputs 2022 to 2026

Purpose: Building on the identification of ABCB5 as a marker of limbal stem cells (LSCs), this study examines CD63, a newly identified molecule co-expressed with ABCB5 in limbal epithelial cells, to define its role in maintaining corneal epithelial cell identity. Methods: RNA sequencing (RNA-seq) was performed on flow cytometry–sorted Abcb5-positive and Abcb5-negative murine corneal epithelial cells. CD63 expression in human corneal tissue was assessed by immunostaining. CD63 was silenced in cultured human limbal epithelial cells using siRNA-mediated knockdown and resulting molecular and cellular changes were analyzed by qRT-PCR, flow cytometry, RNA-seq, Western blotting, and cell proliferation assays. Results: RNA-seq analysis …

Aav Gene Therapy For Mps Iva With Induction Of Immune Tolerance Via Oral Administration Of Epitope Peptides Of N-Acetylgalactosamine-6-Sulfate Sulfatase, Sampurna Saikia, Yasuhiko Ago, Fnu Nidhi, Shaukat Khan, Zhengyu Ma, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis IVA (MPS IVA) is caused by the accumulation of undegraded glycosaminoglycans due to the deficiency of the N-acetylgalactosamine-6-sulfate sulfatase (GALNS) enzyme. MPS IVA manifests as progressive systemic skeletal dysplasia. Gene therapy (GT) is potentially a one-time treatment in which the enzyme is continuously produced, circulated, and delivered to target tissues. However, immune responses to gene products can diminish therapeutic efficacy. We hypothesized that oral delivery of tolerogenic peptides induces immune tolerance to human GALNS (hGALNS) in MPS IVA mice, enhancing therapeutic efficacy. Neonatal mice deficient in mouse GALNS (mGALNS) were treated orally with three T-cell/B-cell epitope peptides or hGALNS …

In Vitro Studies Of The Effects Of Antithrombotic Zn-Dipicolylamine-Harboring Liposomes (Dpals) On Serum Albumin And Human Umbilical Vein Endothelial Cells, Michelle Tanujaya, Gianna Cai, Jia Patel, Zana Moldavsky, Yumna Ejaz, Malia Mahazabin Ahmed, Sangsang Duong, Lawrence E. Goldfinger, Koon Y. Pak, Brian D. Gray, Parkson Lee-Gau Chong

Cardeza Foundation for Hematologic Research

Thrombosis remains a leading cause of cardiovascular morbidity and mortality. During thrombosis, activated platelets and endothelial cells expose phosphatidylserine (PS) on their outer membranes, creating a surface that accelerates clot formation. Current antithrombotic therapies, such as heparin and warfarin, carry significant bleeding risks, highlighting the need for safer alternatives. In response, we developed a PS-targeting liposomal formulation composed of Zn-dipicolylamine (DPA)-cyanine-3[22,22] and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (molar ratio 3:97). This DPA-harboring liposome (DPAL) binds selectively to PS-rich surfaces such as activated platelets and has demonstrated efficacy in reducing thrombosis in mouse models, with minimal bleeding. In the present study, we examined the interaction …

Alpha And Beta Emitters In Translational Nuclear Medicine: Clinical Advances, Challenges, And Future Direction, Hanieh Karimi, Thomas H. Shaffer, Erik Stauff, Vinay V. R. Kandula, Heidi H. Kecskemethy, Lauren W. Averill, Xuyi Yue

Department of Radiology Faculty Papers

Radiopharmaceutical therapy (RPT) has emerged as a transformative modality in oncology, particularly for patients with metastatic or inoperable tumors. By leveraging molecularly targeted carriers conjugated to cytotoxic radionuclides, RPT enables precise delivery of ionizing radiation to tumor sites while minimizing off-target effects. Central to this approach are alpha (α) and beta (β) particle-emitting radionuclides. This review aims to provide a comprehensive overview of all clinically relevant alpha and beta emitters and incorporates the most recent advances from 2017-2025, offering a comprehensive and up-to-date perspective. Alpha and beta emitters hold significant promises for the future, especially in nuclear medicine, energy, and …

Prenatal Stress Induces Changes In Behavior, Hpa Axis, Inflammation, And Oxidative Stress In Adult Rats Offspring, Jorge M Aguiar-Geraldo, Jefté Peper-Nascimento, José Henrique Cararo, Taise Possamai-Della, Alexandra I Zugno, Anilkumar Pillai, João Quevedo, Samira S Valvassori

Faculty, Staff and Student Publications

Prenatal stress is related to the development of psychiatric disorders involving inflammation, oxidative stress, and hypothalamic-pituitary-adrenal (HPA) axis. Therefore, the aim of the present study was to evaluate the effects of prenatal stress on behavior, inflammation, oxidative stress, and the HPA-axis in the dams and their offspring treated with lithium. Thirteen pregnant Wistar rats were exposed to a prenatal chronic unpredictable stress protocol from the 14th day of gestation until birth. At the 60th postnatal day (PND), a treatment protocol was carried out in the offspring with lithium (intraperitoneally - 47.5 mg/kg) or saline for seven days (twice a day). …

Aggregation Of Gene Regulatory Information And Knowledge On Fair Principles Enables Discovery Of Pathogenic Gene Regulatory Variants, Keyang Yu, Haoquan Zhao, Andrea S Wilderman, Tierra R Farris, Jessie E Arce, David Chen, Andrew R Jackson, Yiran Guo, Qi Li, Bosko Jevtic, Dubravka Jevtic, Vuk Milinovic, Yuankun Zhu, Jeremy Costanza, Eric D Wenger, Christopher Nemarich, Lisa Anderson, Aleksandar Mihajlović, Kristin Ardlie, Shaine A Morris, Matthew E Roth, Deanne M Taylor, Adam C Resnick, Lilei Zhang, Aleksandar Milosavljevic

Faculty, Staff and Students Publications

Motivation: Methods for sharing gene regulatory information and knowledge on FAIR principles, particularly in the context of tissue-specific gene regulation, remain poorly defined and implemented, hampering discovery and clinical genetic diagnosis.

Results: We specified FAIR principles for tissue-specific gene regulatory information and knowledge; implemented them by developing a registry of regulatory elements and aggregating FAIR gene regulatory information from several major sources; developed computational tools that utilize these FAIR resources; and demonstrated their utility by associating gene regulatory variants with major subtypes of congenital heart disease.

Presentations Of Cutaneous Disease In Various Skin Pigmentations: Tinea Corporis, Braden Van Alfen, Navya Peddireddy, Marshall Hall, Henry Lim, Christian Scheufele, Garrett Furth, Dustin Wilkes, Michael Carletti, Stephen E. Weis

HCA Healthcare Journal of Medicine

Tinea corporis is a common superficial fungal infection caused by dermatophytes. It typically presents as well-defined, pruritic, annular papules and plaques with central hypopigmentation. The differential diagnosis includes pityriasis rosea, nummular dermatitis, plaque psoriasis, tinea versicolor, granuloma annulare, and discoid lupus. This article compares different presentations of tinea corporis in various skin types as classified by the Fitzpatrick scale. Recognizing varying presentations of tinea in patients of different skin tones will aid in early and appropriate diagnosis and treatment.

Replicability Of Highly Cited Comparative Studies In Orthopedic Journals, Cody Ashy, William E. Few, Gabriella A. Rivas, Emily Brennan, Langdon Hartsock, Kristoff R. Reid

HCA Healthcare Journal of Medicine

Introduction

Concerns are rising regarding the quality, validity, and reliability of clinical research findings in medical literature. This investigation sought to identify the most cited orthopedic clinical studies and assess the replicability of the findings reported.

Methods

Web of Science was used to identify the top ten orthopedic surgery journals by impact factor from which primary comparative studies cited at least 250 times were identified. A second literature search identified follow-up studies relevant to the respective primary studies. Studies investigating the same intervention via parallel methodology were summarized and their conclusions compared to their respective highly cited primary study.

Results …

Low-Dose Prophylaxis Versus On-Demand Treatment For Children With Severe Hemophilia A In Indonesia: A Conceptual Model, Levina Chandra Khoe, Nur Atika, Dhia Ticha Pertiwi, Septiara Putri

Kesmas

Hemophilia A is a rare bleeding disorder caused by a deficiency of clotting factor VIII, leading to recurrent bleeds, joint damage, and disability. Low-dose prophylaxis has been shown to achieve better clinical outcomes than on-demand treatment in reducing bleeding frequency. However, in Indonesia, access and affordability remain key challenges. This study aimed to develop a conceptual model for conducting a health economic evaluation of low-dose prophylaxis treatment for children with severe hemophilia A in Indonesia. This study followed the ISPOR-SMDM Modeling guidelines, outlining two-stage processes: conceptualization of the clinical problem and model development. A systematic literature review was conducted to …

Nanoscale Opportunities In Extracellular Matrix Mimicry, L. Andrew Lyon, Abbygail Caine, Elif Narbay, E. Daniel Cárdenas-Vásquez

Engineering Faculty Articles and Research

We present an overview of the composition, function, energetics, and dynamics of extracellular matrix and its relation to nanoscale structures and phenomena. These concepts are then related to the development of synthetic and biosynthetic materials that aim to mimic the extracellular matrix for regenerative medicine and tissue engineering technologies. Notable successes and advancements towards the goal of biomimicry are outlined, while remaining challenges and knowledge gaps towards that goal are highlighted. Finally, we frame the remaining challenges in the field in terms of nanoscience-related research opportunities that if solved, might prove to be transformative steps forward in the discipline.

Bone Marrow Endosteum Houses Hedgehog-Susceptible Dlx5-Expressing Osteoblast Precursor Cells, Keita Kondo, Yuki Matsushita, Shion Orikasa, Yuta Nakai, Aiko Kuroda, Shinsuke Ohba, Wanida Ono, Noriaki Ono

Faculty, Staff and Student Publications

The bone marrow endosteum provides a robust source of bone-making osteoblasts by housing various types of osteoblast precursor cells, including endosteal stem cells expressing fibroblast growth factor receptor 3 (Fgfr3) and their downstream progenitor cell populations. In fetal bone development, Dlx5 marks early perichondrial cells that populate the diaphyseal bone and marrow stroma in the postnatal stages. However, the location of Dlx5-expressing cells in the postnatal bone marrow and how they contribute to osteogenesis remain undefined. Here, we show that Dlx5

Impella 5.5 Versus Heartmate 3 In Left Ventricular Unloading, Hannah Frederick, Douglas Tran, Erik Sorenson, H. Todd Massey, Albert Hicks, Manjula Ananthram, Bartley P. Griffith, Aakash Shah

The VAD Journal

The Impella 5.5 (Abiomed) is increasingly used as a bridge to durable left ventricular assist device (LVAD) implantation in advanced heart failure, yet most studies focus on survival and transition success rather than left ventricular (LV) unloading or valvular effects. This study addresses this gap by comparing Impella 5.5 and HeartMate 3 (HM3, Abbott) in terms of unloading and cardiac support at similar flow rates. We conducted a retrospective study of nine patients who received Impella 5.5 before HM3 implantation. The primary outcome was the degree of LV unloading, as assessed by changes in left ventricular end-diastolic diameter (LVEDD). There …

Hiv Infection, Neurotoxicity, Inflammation, Premature Aging, And Therapeutic Challenges To Plwh: An Overview, Mudit Tyagi, Ulhas P. Naik, Kratika Tyagi, Madhulika Sharma, Gagan Kaushal, Alok Bhushan, Michael Bukrinsky, Priya Tyagi

Department of Medicine Faculty Papers

HIV infection remains a major global health challenge due to its complex pathogenesis and lifelong persistence in people living with HIV (PLWH). A central barrier to eradication is the virus's ability to establish long-lived latent reservoirs in different tissues, including the central nervous system (CNS), where it evades immune clearance and antiretroviral therapy (ART). These reservoirs, seeded early during infection, fuel viral rebound if ART is interrupted, requiring lifelong treatment. In the CNS, HIV persists despite systemic viral suppression because of limited ART penetration across the blood-brain barrier (BBB), and infection of long-lived cells such as microglia and perivascular macrophages. …

Association Between Dietary Folate And Prostate Cancer Aggressiveness Among African Americans And European Americans, Lihchyun Joseph Su, Sarah O'Connor, Daniela Ramirez Aguilar, Minjae Lee, Harrison Wong, Hui-Yi Lin, Jeannette T. Bensen, James L. Mohler, Lenore Arab, Longgang Zhao, Ebonee N. Butler, Laura Farnan, Susan E. Steck Phd, Mph, Rd

Faculty Publications

Background: Despite the confirmed beneficial effects on preventing neural tube defects, concerns about high intakes of synthetic folate, or folic acid, in promoting cancer progression have been raised. This study evaluated the association between folate intake and prostate cancer (PCa) aggressiveness among African-American (AA) and European-American (EA) males. Methods: This study included 722 AA and 775 EA men with prostate cancer. Folate intake (dietary folate equivalent (DFE), synthetic folate, natural folate) was estimated using the National Cancer Institute Dietary History Questionnaire and detailed dietary supplement use questionnaire. Analyses included univariable comparisons of demographic and clinical characteristics of the two racial …

Turning Zwitterions Into Toughening Agents: Salt-Activated Microdomains In Poly(Vinyl Alcohol) Double-Network Hydrogels, Louis D. Zhang, Jintao Yang, Si Yu Zheng

University Research

Zwitterionic hydrogels, although highly biocompatible, are widely regarded as mechanically fragile, with typical tensile strengths below 0.1 MPa, which restricts their use in load-bearing applications. Here, we address this limitation by integrating a polyzwitterionic network with a poly(vinyl alcohol) (PVA) network through high-speed pregelation agitation that enhances chain entanglement and induces flow orientation. By exploiting the salt-driven conformational transition of zwitterionic chains, a controlled salting-out step generates uniformly dispersed nanoscale microdomains that act as reversible energy-dissipating units. At the same time, balanced hydrogen bonding between the two networks moderates PVA crystallinity, limiting embrittlement while preserving elasticity. The resulting double-network hydrogel …

Computational Repurposing And Experimental Validation Of Ybx1 Inhibitors In Hepatocellular Carcinoma, Omar Karkoutly, Veerababu Nagati, Subhash Chauhan, Manish Tripathi

School of Medicine Publications

Background/Objectives: Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. While early-stage HCC can often be treated with surgical resection, ablation, or liver transplantation, advanced disease typically relies on systemic chemotherapy. Sorafenib is the standard first-line therapy for advanced and unresectable HCC; however, both intrinsic and acquired resistance remain major clinical challenges. The Y-box binding protein-1 (YBX1), a transcription factor implicated in drug resistance across multiple cancers, is highly expressed in HCC and represents a potential therapeutic target. This study aimed to identify novel YBX1 inhibitors using a drug repurposing strategy to overcome sorafenib resistance. Methods: A …

Coordinated Stimulation Of Axon Regenerative And Neurodegenerative Transcriptional Programs By Atf4 Following Optic Nerve Injury, Preethi Somasundaram, Madeline M Farley, Melissa A Rudy, Katya Sigal, Andoni I Asencor, David G Stefanoff, Malay Shah, Puneetha Goli, Jenny Heo, Shufang Wang, Nicholas M Tran, Trent A Watkins

Faculty, Staff and Students Publications

Stress signaling is important for determining the fates of neurons following axonal insults. Previously, we showed that the stress-responsive kinase PERK contributes to injury-induced neurodegeneration (Larhammar et al., 2017). Here, we show that PERK acts primarily through activating transcription factor-4 (ATF4) to stimulate not only pro-apoptotic but also pro-regenerative responses following optic nerve damage. Using conditional knockout mice, we find an extensive PERK/ATF4-dependent transcriptional response that includes canonical ATF4 target genes and modest contributions by C/EBP Homologous Protein (CHOP). Overlap with c-Jun-dependent transcription suggests interplay with a parallel stress pathway that orchestrates regenerative and apoptotic responses. Accordingly, neuronal knockout of …

Merritt-Putnam Symposium | Tumor-Associated Epilepsy And Epilepsy-Associated Tumors: Exploring The Bidirectional Crosstalk Between Tumors And Seizures, Tracy A Bedrosian, Michael Wong, Erin L Heinzen, Benjamin Deneen, Catherine A Christian-Hinman

Faculty, Staff and Students Publications

Links between cancerous and noncancerous brain tumors and epilepsy have long been recognized. However, recent clinical and preclinical studies emphasize that not only do tumors impinge on surrounding brain tissue in ways that promote hyperexcitability and epileptogenesis, but that neural activity also influences tumor progression. In this review, inspired by the Merritt-Putnam Symposium of the 2025 meeting of the American Epilepsy Society, we present a cross-disciplinary dialog between cancer and epilepsy research, including discussion of tumors and epilepsies that are more prominent in pediatric versus adult populations. First, we discuss the neuropathology, genetics, and surgical outcomes of epileptogenic brain tumors, …

Decyl Caffeate Inhibits The Proliferation Of Human Triple-Negative Breast Cancer Cells, Che-Yi Chao, Woei-Cheang Shyu, Chih-Lung Lin, En-Pei Isabel Chiang, Yueh-Hsiung Kuo, Feng-Yao Tang

BioMedicine

Background: Over recent decades, considerable attention has been directed toward the discovery of novel compounds capable of targeting survival-related signaling networks as therapeutic candidates for triple-negative breast cancer (TNBC). Central to TNBC pathobiology are the Akt/mTOR and MAPK/ERK signaling axes, both contribute to tumor progression and therapeutic resistance. Caffeic acid (CA), a naturally derived phenolic compound with anti-inflammatory activity, has previously been investigated for its anti-cancer potential. Purpose: In the present study, we explored the therapeutic value of newly synthesized CA derivatives in TNBC models using both cellular and animal-based systems. Methods: The anti-tumor efficacy of these CA derivatives was …

Increased Dairy Product Consumption Is Associated With Shorter Telomere Length In Buccal Cells Among Normotensive Adults, Hsin-Hwa Tsai, Yang-Di Su, Zi-Lun Lai, Chia-Yu Lin, Shu-Fan Lin, Hsiu-Ching Hsu, Wen-Yuan Lin, Po-Ren Hsueh

BioMedicine

Background: Telomere length (TL) is a biomarker of biological aging and a predictor of age-related diseases. Dietary patterns, including dairy consumption, may influence telomere dynamics, but the evidence remains limited, particularly in Asian populations. This study investigates the association between dairy consumption and relative telomere length (RTL) in Taiwanese adults, with results analyzed by hypertension status.

Methods: A cross-sectional survey was conducted among 259 adults in Taipei, Taiwan. RTL was measured using quantitative PCR from buccal cells. Dietary intake was assessed through self-reported questionnaires, with a focus on dairy frequency and fat content. Multiple linear regression models were used to …

Determination Of Cortisol Concentrations Using Different Biomarkers In Dairy Goats During Pregnancy, Fatma Mi̇ra Güven, Erkan Pehli̇van

Turkish Journal of Veterinary & Animal Sciences

Pregnancy is considered one of the most physiologically stressful periods in mammals. In the present study, serum and hair cortisol concentrations were measured in nine female Akkeçi goats, including five primiparous (1.5 years old) and four multiparous (3.5 years old), to evaluate chronic stress during pregnancy. Hair samples were collected in October, November, and December following the introduction of bucks to the herd and within the first 12 h postpartum (corresponding to the 1st, 2nd, 3rd, and 7th sampling times). Hair samples were not collected in January, February, or March (the 4th, 5th, and 6th sampling times) due to insufficient …