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Gene-Agnostic Therapeutic Strategies For Inherited Retinal Diseases: Neuroprotection And Immunomodulation, Lucas W. Rowe, S. Patricia Becerra, Robert E. Maclaren, Robert L. Avery, Charles C. Wykoff, Allen C. Ho, Carl D. Regillo, Dean Eliott, Andrew Osborne, Katie M. Binley, Thomas A. Ciulla Mar 2026

Gene-Agnostic Therapeutic Strategies For Inherited Retinal Diseases: Neuroprotection And Immunomodulation, Lucas W. Rowe, S. Patricia Becerra, Robert E. Maclaren, Robert L. Avery, Charles C. Wykoff, Allen C. Ho, Carl D. Regillo, Dean Eliott, Andrew Osborne, Katie M. Binley, Thomas A. Ciulla

Wills Eye Hospital Papers

Background/Objectives: Inherited retinal diseases (IRDs) represent a genetically heterogeneous group of disorders caused by mutations in over 280 genes with more than 3100 identified variants. While gene-specific replacement therapies have achieved landmark success with voretigene neparvovec (Luxturna) for biallelic RPE65-associated retinal dystrophy, developing individual therapies for each genetic subtype remains impractical. This review examines gene-agnostic therapeutic approaches utilizing neuroprotection and immunomodulation that target common pathophysiological mechanisms shared across multiple IRD genotypes. Methods: We reviewed the literature on neuroprotective and immunomodulatory gene therapy strategies for IRDs, focusing on neurotrophic factors and complement system modulation. Results: Neuroprotective approaches delivering neurotrophic factors—including pigment …


The Relationship Between Smartphone Screen Time Duration And Individual Chronotype: A Systematic Literature Review, Diego Sergio Giasia Lumbantobing, Thalia Altamilano Pramudya Mar 2026

The Relationship Between Smartphone Screen Time Duration And Individual Chronotype: A Systematic Literature Review, Diego Sergio Giasia Lumbantobing, Thalia Altamilano Pramudya

Jurnal Epidemiologi Kesehatan Indonesia

The rapid increase in smartphone use over the past decade led to prolonged screen time across age groups, particularly during nighttime hours. Exposure to artificial light and pre-sleep digital activities was associated with circadian rhythm disruption and alterations in individual chronotype. This systematic literature review aimed to synthesize empirical evidence on the relationship between smartphone screen time duration and individual chronotype across all age groups and to identify key moderating factors influencing this association. The review was conducted in accordance with PRISMA 2020 guidelines. Literature searches were performed in PubMed, Scopus, and ScienceDirect for studies published between 2015 and 2025. …


Prevalence And Determinant Factors Of Depression Among Pregnant Women In Poned Health Center In Tangerang City Area, Dian Geumala Hayati, Sudijanto Kamso, Popy Yuniar, Yuli Puspita Devi Mar 2026

Prevalence And Determinant Factors Of Depression Among Pregnant Women In Poned Health Center In Tangerang City Area, Dian Geumala Hayati, Sudijanto Kamso, Popy Yuniar, Yuli Puspita Devi

Jurnal Epidemiologi Kesehatan Indonesia

According to World Health Organization (WHO), approximately 10% of pregnant women experience mental disorders, with depression being particularly prevalent. In developing countries, this rate is was even higher, reaching 19.8% after childbirth and 15.6% during pregnancy. Various studies conducted in Indonesia show that the prevalence of depression among pregnant women ranges widely, from 21.4% to 26.2%.This study aimed to determine the prevalence and risk factors associated with depression during pregnancy in pregnant women at the PONED Community Health Center in Tangerang City Area. A facility-based cross-sectional study was conducted with 105 pregnant women attending antenatal check-ups at the 17 PONED …


Cilia Dynamics In Primary Ciliary Dyskinesia: A Biophysical Characterization Of The Rsph4a Founder Variant, Gabriel Rosario-Ortiz, José Muñiz-Hernández, Natalia M Ortiz-Pérez, Marcos J Ramos-Benitez, Ricardo A Mosquera, Wilfredo De Jesús-Rojas Mar 2026

Cilia Dynamics In Primary Ciliary Dyskinesia: A Biophysical Characterization Of The Rsph4a Founder Variant, Gabriel Rosario-Ortiz, José Muñiz-Hernández, Natalia M Ortiz-Pérez, Marcos J Ramos-Benitez, Ricardo A Mosquera, Wilfredo De Jesús-Rojas

Faculty, Staff and Student Publications

Primary ciliary dyskinesia (PCD) is a rare ciliopathy resulting in chronic oto-sino-pulmonary disease. PCD diagnosis can be achieved by a combination of different diagnostic and adjuvant tools, including high-speed video-microscopy analysis (HSVA). A founder variant has been described in Puerto Rico as the most common cause of PCD in the island. Background/Objectives: In HSVA, objective parameters such as ciliary beat frequency (CBF) and subjective parameters such as ciliary beat pattern (CBP) shed light on the biophysical properties of cilia. However, the subjective nature of CBP creates a gap in knowledge; characteristics such as the length, angle, and bending index of …


Nano Zinc Oxide Against Bacteria Isolated From Burn Infection, Mohammed Jaafar Al-Anssari, Mohammed Sahib Al-Hamami, Hayder Razzaq Al-Ameedee, Rabab Abdul Razzaq Kasema, Hawraa Majid Mahdi Mar 2026

Nano Zinc Oxide Against Bacteria Isolated From Burn Infection, Mohammed Jaafar Al-Anssari, Mohammed Sahib Al-Hamami, Hayder Razzaq Al-Ameedee, Rabab Abdul Razzaq Kasema, Hawraa Majid Mahdi

Al-Bahir

Pseudomonas aeruginosa is a type of bacteria that is found commonly in the environment, like in soil and in water. This bacteria can cause infections in the blood, lungs (pneumonia), or other parts of the body after surgery. These bacteria are constantly finding new ways to avoid the effects of the antibiotics used to treat the infections they cause. Zinc oxide nanoparticles' (ZnO-NPs') or Nano zinc oxide antibacterial properties have drawn a lot of attention from around the world, especially since nanotechnology has been used to create particles in the nanometer range. Because of their larger specific surface area and …


The Hexosamine Biosynthetic Pathway Alters The Cytoskeleton To Modulate Cell Proliferation And Migration In Aggressive Prostate Cancer, Rajina Shakya, Praveen Suraneni, Amit Rahi, Michael Y Young, Emily Cousino, Christine B Magdongon, Raju Gajjela, Basil B Mattamana, Alexander Zaslavsky, Ganesh S Palapattu, Arun Sreekumar, Dileep Varma Mar 2026

The Hexosamine Biosynthetic Pathway Alters The Cytoskeleton To Modulate Cell Proliferation And Migration In Aggressive Prostate Cancer, Rajina Shakya, Praveen Suraneni, Amit Rahi, Michael Y Young, Emily Cousino, Christine B Magdongon, Raju Gajjela, Basil B Mattamana, Alexander Zaslavsky, Ganesh S Palapattu, Arun Sreekumar, Dileep Varma

Faculty, Staff and Students Publications

Castration-resistant prostate cancer (CRPC) progresses despite androgen deprivation therapy, as cancer cells adapt to grow without testosterone, becoming more aggressive and prone to metastasis. CRPC biology complicates the development of effective therapies, posing challenges for patient care. Recent gene-expression and metabolomics studies highlight the Hexosamine Biosynthetic Pathway (HBP) as a critical player, with key components like GNPNAT1 (Glucosamine-phosphate N-acetyltransferase 1) being downregulated in CRPC. GNPNAT1 knockdown in pre-clinical models has been shown to increase growth and metastasis in CRPC tumors, though the mechanisms remain unclear.To investigate the cellular basis of these CRPC phenotypes, we generated a CRISPR-Cas9 knockout model of …


Predictors Of Long-Term Outcome And Recurrence Of Intramedullary Spinal Ependymomas: A Multicenter Study, Reem Albuhairan, Laila Alqahtani, Ahmed Gamal Sayed, Ali Alkhaibary, Sami Khairy, Faisal Farash, Ali H. Alassiri, Ahmed Alkhani Mar 2026

Predictors Of Long-Term Outcome And Recurrence Of Intramedullary Spinal Ependymomas: A Multicenter Study, Reem Albuhairan, Laila Alqahtani, Ahmed Gamal Sayed, Ali Alkhaibary, Sami Khairy, Faisal Farash, Ali H. Alassiri, Ahmed Alkhani

Neurosciences

Objectives: To define prognostic factors that affect clinical outcome of patients after surgical resection of spinal intramedullary ependymoma.

Methods: A retrospective multi-center study, including all cases operated on from 2007 through 2024 at 3 institutes. Data on surgical factors included: resection extent, intraoperative neurophysiology monitoring methods, and intraoperative/postoperative complications.

Results: A total of 19 patients were included with a mean age of 37.8 years (SD = 13.2, range 8–57 years). The majority of ependymomas (n = 14, 73.7%) were in the cervical region. The most common presenting symptoms included pain in 14 patients (73.7%), sensory deficits in 11 patients (57.8%), …


Insights Into Stroke Risk And Prediction For Underweight Individuals, Saeed Awad M. Alqahtani, Moutasem S. Aboonq Mar 2026

Insights Into Stroke Risk And Prediction For Underweight Individuals, Saeed Awad M. Alqahtani, Moutasem S. Aboonq

Neurosciences

This review explores the relationship between underweight status and stroke risk and outcomes. Although the impact of obesity on stroke is well-documented, the harmful effects of being underweight are often overlooked. Drawing on evidence from observational studies, case-control studies, and meta-analyses, this review highlights that underweight individuals face increased mortality, poorer functional recovery, and higher rates of major adverse cardiovascular events and recurrent strokes post-stroke. Challenges in stroke prediction for this population are examined, including the limited research focus, shortcomings of existing risk assessment tools such as the CHA2DS2-VASc score, and population-specific factors affecting underweight prevalence …


3'Utr Mapping Reveals Alternative Polyadenylation In Right Ventricular Failure, Rahul Neupane, Kartiga Natarajan, Erik E Suarez, Henry J Pownall, Kai-Lieh Huang, Eric J Wagner, Ajay Kumar Verma, Rambabu Majji, Hari Krishna Yalamanchili, Ashrith Guha, Rajarajan A Thandavarayan Mar 2026

3'Utr Mapping Reveals Alternative Polyadenylation In Right Ventricular Failure, Rahul Neupane, Kartiga Natarajan, Erik E Suarez, Henry J Pownall, Kai-Lieh Huang, Eric J Wagner, Ajay Kumar Verma, Rambabu Majji, Hari Krishna Yalamanchili, Ashrith Guha, Rajarajan A Thandavarayan

Children’s Nutrition Research Center Staff Publications

No abstract provided.


Functional And Structural Basis Of A Hypermorphic Trpc3 Variant, Briar Bell, Angela M Jaramillo-Granada, Luis O Romero, Irene A Gutierrez, Venkata K P S Mallampalli, Guizhen Fan, Sameer Varma, Matthew L Baker, Irina I Serysheva, Valeria Vásquez, Julio F Cordero-Morales Mar 2026

Functional And Structural Basis Of A Hypermorphic Trpc3 Variant, Briar Bell, Angela M Jaramillo-Granada, Luis O Romero, Irene A Gutierrez, Venkata K P S Mallampalli, Guizhen Fan, Sameer Varma, Matthew L Baker, Irina I Serysheva, Valeria Vásquez, Julio F Cordero-Morales

Faculty, Staff and Student Publications

Cerebellar ataxias are characterized by impaired motor coordination resulting from neuronal dysfunction within the cerebellum. The mechanisms underlying this pathology and its cerebellar-specific neurodegeneration remain unknown. We uncover how a gain-of-function canonical transient receptor potential member 3 (TRPC3) mutation, coupled with a cerebellum-specific isoform, stabilizes the channel’s open state, resists the leading inhibitor Pyr3, and drives calcium-dependent cell death. Restoring calcium homeostasis by expressing a Purkinje cell calcium pump improves cell viability. Transgenic expression of the TRPC3 hypermorphic variant in Caenorhabditis elegans induces neurodegeneration, confirming its pathogenicity across species. Cryo–electron microscopy and molecular simulations reveal the structural basis for the …


Social Isolation And Firearm Secure Storage In The Usa: Results From The 2022 Brfss, Alexander Testa, Daniel Semenza, Dylan B Jackson, Karyn Fu, Sandra Mckay, Kyle T Ganson, Jason M Nagata, Jack Tsai Mar 2026

Social Isolation And Firearm Secure Storage In The Usa: Results From The 2022 Brfss, Alexander Testa, Daniel Semenza, Dylan B Jackson, Karyn Fu, Sandra Mckay, Kyle T Ganson, Jason M Nagata, Jack Tsai

Faculty, Staff and Student Publications

Background: Firearm secure storage (ie, storing firearms unloaded and locked) is recommended to reduce unintentional injuries and suicides. However, the relationship between psychological states, such as social isolation, and firearm secure storage practices is under-researched.

Methods: Data are from 7136 individuals with firearms in their households from the 2022 Behavioral Risk Factor Surveillance System. Multinomial logistic regression was used to explore the relationship between social isolation and firearm storage.

Results: Among respondents, 71.6% reported storing firearms unloaded, 14.2% stored firearms loaded and locked and 14.2% stored firearms loaded and unlocked. Most respondents reported feeling 'never' (40.7%) or 'rarely' (33.3%) socially …


An Integrated Germline And Somatic Genomic Model For Coronary Artery Disease, Xiong Yang, Min Seo Kim, Xinyu Zhu, Md Mesbah Uddin, Tetsushi Nakao, So Mi Jemma Cho, Satoshi Koyama, Tingfeng Xu, Laurens F Reeskamp, Rufan Zhang, Zhaoqi Liu, Yunga A, Paul S De Vries, Ramachandran S Vasan, Eric Boerwinkle, Alanna C Morrison, Bruce M Psaty, Russell P Tracy, Susan R Heckbert, Michael H Cho, Jeong H Yun, Nicholette D Palmer, Donald W Bowden, Joanne M Murabito, Daniel Levy, Nancy L Heard-Costa, George T O'Connor, Lewis C Becker, Brian G Kral, Lisa R Yanek, Laura M Raffield, Bertha Hidalgo, Jerome I Rotter, Stephen S Rich, Kent D Taylor, Wendy S Post, Charles Kooperberg, Alexander P Reiner, Braxton D Mitchell, Sharon L R Kardia, Jennifer A Smith, Patricia A Peyser, Lawrence F Bielak, Dong Keon Yon, Hong-Hee Won, Donna K Arnett, Albert V Smith, Stacey B Gabriel, Patrick T Ellinor, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Pradeep Natarajan, Minxian Wang, Akl C Fahed Mar 2026

An Integrated Germline And Somatic Genomic Model For Coronary Artery Disease, Xiong Yang, Min Seo Kim, Xinyu Zhu, Md Mesbah Uddin, Tetsushi Nakao, So Mi Jemma Cho, Satoshi Koyama, Tingfeng Xu, Laurens F Reeskamp, Rufan Zhang, Zhaoqi Liu, Yunga A, Paul S De Vries, Ramachandran S Vasan, Eric Boerwinkle, Alanna C Morrison, Bruce M Psaty, Russell P Tracy, Susan R Heckbert, Michael H Cho, Jeong H Yun, Nicholette D Palmer, Donald W Bowden, Joanne M Murabito, Daniel Levy, Nancy L Heard-Costa, George T O'Connor, Lewis C Becker, Brian G Kral, Lisa R Yanek, Laura M Raffield, Bertha Hidalgo, Jerome I Rotter, Stephen S Rich, Kent D Taylor, Wendy S Post, Charles Kooperberg, Alexander P Reiner, Braxton D Mitchell, Sharon L R Kardia, Jennifer A Smith, Patricia A Peyser, Lawrence F Bielak, Dong Keon Yon, Hong-Hee Won, Donna K Arnett, Albert V Smith, Stacey B Gabriel, Patrick T Ellinor, Nhlbi Trans-Omics For Precision Medicine (Topmed) Consortium, Pradeep Natarajan, Minxian Wang, Akl C Fahed

Faculty, Staff and Student Publications

Multiple germline and somatic genomic factors are associated with risk of coronary artery disease, but there is no single measure of risk that integrates all information from a DNA sample. To address this gap, we develop an integrated genomic model that includes six germline and somatic genetic drivers for coronary artery disease, including polygenic risk score, genetically-proxied proteomic/metabolomic risk scores, and clonal hematopoiesis of indeterminate potential. We evaluated its predictive power in the UK Biobank (N = 391,536), and validate it using data from the TOPMed program (N = 34,177). The 10-year coronary artery disease risk based on the integrated …


Explainable Drug Side Effect Prediction In Central Neural System Via Biologically Informed Graph Neural Network, Tongtong Huang, Ko-Hong Lin, Rodrigo Machado-Vieira, Jair C Soares, Xiaoqian Jiang, Yejin Kim Mar 2026

Explainable Drug Side Effect Prediction In Central Neural System Via Biologically Informed Graph Neural Network, Tongtong Huang, Ko-Hong Lin, Rodrigo Machado-Vieira, Jair C Soares, Xiaoqian Jiang, Yejin Kim

Faculty, Staff and Student Publications

The early detection of potential side effects (SEs) is a critical yet formidable challenge within the realms of drug development and patient healthcare management. Conventional in-vitro or in-vivo approaches for SE detection are often not feasible to scale during the preclinical phase for numerous drug candidates. Innovations in explainable artificial intelligence offer the prospect of early detection of potential SEs for novel therapeutics prior to their release in the market, as well as the explication of the underlying biological mechanisms. In this context, we present a novel biologically informed graph-based model, called HHAN-DSI, which capitalizes on multimodal interactions among molecular …


Comparative Analysis Of Clearing Methods For 3d Imaging Of The Vasculature In Mineralized Mouse Tissues, Azeez O Ishola, Athira Pillai, Taeyong Ahn, Re-Join Consortium, Chih-Wei Hsu, Brendan Lee, Nele Haelterman, Joshua D Wythe Mar 2026

Comparative Analysis Of Clearing Methods For 3d Imaging Of The Vasculature In Mineralized Mouse Tissues, Azeez O Ishola, Athira Pillai, Taeyong Ahn, Re-Join Consortium, Chih-Wei Hsu, Brendan Lee, Nele Haelterman, Joshua D Wythe

Faculty, Staff and Students Publications

Historically, visualization of vascular networks within the musculoskeletal system, particularly in mineralized tissues such as bones and joints, has been limited to conventional 2D histological approaches. Recent advances in optical tissue clearing technologies and fluorescence imaging approaches in whole, intact tissues offer an entrée to interrogate the vasculature at unprecedented resolution during both musculoskeletal development and in pathologic contexts in three dimensions. However, these clearing techniques were originally not developed for imaging hard mineralized tissues, such as the femur and tibia. Herein, we have optimized tissue decalcification conditions and compared aqueous- and solvent-based tissue clearing approaches to establish an optimal …


Translating Multi-Omics Into Healthcare: Requisites For Scalable And Equitable Implementation, Birute Tumiene, David R Adams, Robert Allaway, Maria J Barrero, Chun-Hung Chan, Víctor Faundes, Vanessa S Fear, Polina Glezer, Claudia Fuchs, Tudor Groza, Elisa J F Houwink, Saumya Shekhar Jamuar, Mary Catherine V Letinturier, Richa Madan Lomash, Ratna Dua Puri, Juergen K V Reichardt, Ruty Mehrian-Shai, Francois H Van Der Westhuizen, Gaurav K Varshney, Shinya Yamamoto, Gareth Baynam Mar 2026

Translating Multi-Omics Into Healthcare: Requisites For Scalable And Equitable Implementation, Birute Tumiene, David R Adams, Robert Allaway, Maria J Barrero, Chun-Hung Chan, Víctor Faundes, Vanessa S Fear, Polina Glezer, Claudia Fuchs, Tudor Groza, Elisa J F Houwink, Saumya Shekhar Jamuar, Mary Catherine V Letinturier, Richa Madan Lomash, Ratna Dua Puri, Juergen K V Reichardt, Ruty Mehrian-Shai, Francois H Van Der Westhuizen, Gaurav K Varshney, Shinya Yamamoto, Gareth Baynam

Faculty, Staff and Students Publications

Multi-omics in combination with advanced computational methodologies synthesizes diverse omics data to provide deeper insights into molecular interactions and offers transformative potential for unravelling phenomenon behind disease complexities, improving diagnostics, disease prevention, and personalized treatments. This integrative strategy enables our understanding of gene-environment relationships, chronic disease progression, and the intricate molecular pathways involved in health. Effective multi-omics analyses require robust data sharing, accessibility, interoperability, and governance, which are critical for linking genomic elements to phenotypic traits. The Global Alliance for Genomics and Health advocates for responsible data-sharing practices, by promoting key principles such as transparency and equity. By emphasizing a …


Incidence Of Autoimmune Diseases In Children With Atopy Treated With Dupilumab, Stanislaw J Gabryszewski, Kathryn Hirabayashi, Morgan Botdorf, Mitchell Maltenfort, Christopher B Forrest, Theresa W Guilbert, Madeline Schutt, Hiroki Morizono, Gerardo Vazquez Garcia, Anna Cristina Garza-Mayers, Joseph Demetrius Hernandez, Sara Anvari, Suchitra Rao, Jonathan M Spergel Mar 2026

Incidence Of Autoimmune Diseases In Children With Atopy Treated With Dupilumab, Stanislaw J Gabryszewski, Kathryn Hirabayashi, Morgan Botdorf, Mitchell Maltenfort, Christopher B Forrest, Theresa W Guilbert, Madeline Schutt, Hiroki Morizono, Gerardo Vazquez Garcia, Anna Cristina Garza-Mayers, Joseph Demetrius Hernandez, Sara Anvari, Suchitra Rao, Jonathan M Spergel

Faculty, Staff and Students Publications

Background: The type 2 inflammation-blocking agent dupilumab has gained traction as an effective treatment of multiple atopic diseases. New-onset autoimmune manifestations have been infrequently reported in dupilumab-treated atopic patients, primarily among adults. Autoimmune outcomes in atopic children on dupilumab are less clear.

Objective: We aimed to determine if dupilumab treatment of atopic children is associated with increased autoimmune or autoinflammatory disease diagnosis risk.

Methods: Using a multi-institutional electronic health record database composed of 10 PEDSnet academic health systems, we performed a retrospective cohort study of children aged 6-17 with atopy (ie, moderate-to-severe atopic dermatitis and/or persistent asthma, as defined by …


K2p Channels As Key Regulators Of Cardiovascular And Pulmonary Vascular Function, Hala Y Abdelnasser, Xinchun Pi, Lavannya M Pandit, Bradley K Mcconnell Mar 2026

K2p Channels As Key Regulators Of Cardiovascular And Pulmonary Vascular Function, Hala Y Abdelnasser, Xinchun Pi, Lavannya M Pandit, Bradley K Mcconnell

Faculty, Staff and Students Publications

Two-pore domain potassium (K2P) channels are the most recently identified family of potassium channels. They are regarded as the largest group of background “leak” channels, encoded by 15 mammalian KCNK genes, and divided into six subfamilies (TWIK, TREK, TASK, TALK, THIK, and TRESK). These channels have a role in stabilizing the resting membrane potential. Their widespread presence in the heart and vasculature supports cellular homeostasis by regulating cardiac rhythm, vascular tone, and protection against ischemic stress. The TASK, TWIK, and TREK subfamilies are the most abundantly expressed K2P channel subfamilies in the cardiovascular system, and dysregulation of specific members has …


Mitochondrial Transfer And Induced Ros As A Therapeutic Strategy In Idh2-Mutant Chondrosarcoma, Vegas R. Bedder, Caleb Wyckoff, Chris Osgood, Gavin A. Vasquez, Michael Stacey Mar 2026

Mitochondrial Transfer And Induced Ros As A Therapeutic Strategy In Idh2-Mutant Chondrosarcoma, Vegas R. Bedder, Caleb Wyckoff, Chris Osgood, Gavin A. Vasquez, Michael Stacey

Knowledge and Creativity Expo

Chondrosarcoma (CS) are common bone cancers that produce cartilaginous tumors and are extremely refractive to chemo-and-radiation therapies, leaving very limited treatment options. They contain mutations in the isocitrate dehydrogenase genes, IDH1 or IDH2. Either IDH1 or IDH2 mutations are present in individual tumors, but not both. They both convert alphaketoglutarate (αKG) into the potent oncometabolite D-2-hydroxyglutarate (D2HG). D2HG can be transported from the tumors to cells of the tumor microenvironment (TME) where it can alter metabolic and epigenetic profiles in recipient cells. The process of α-KG to D2HG conversion occurs in the cytoplasm of IDH1 mutant cells, and in the …


Molecular Characterization Of Humanized Apoe Mouse Models Reveals Source And Genotype Dependent Differences, Na Wang, Gefei Yu, Zhen Wang, Alla Alnobani, Suren Jeevaratnam, Xue Zhang, Meghan Mcreynolds, Yuzhou Chang, Fangfang Qi, William Tauer, Cassandra Rosenberg, Melissa Wren, Tadafumi C Ikezu, Yuka A Martens, Minghui Wang, Bin Zhang, Gregory W Carter, Michael Sasner, David M Holtzman, Junmin Peng, Long-Jun Wu, Takahisa Kanekiyo, Chia-Chen Liu, Guojun Bu Mar 2026

Molecular Characterization Of Humanized Apoe Mouse Models Reveals Source And Genotype Dependent Differences, Na Wang, Gefei Yu, Zhen Wang, Alla Alnobani, Suren Jeevaratnam, Xue Zhang, Meghan Mcreynolds, Yuzhou Chang, Fangfang Qi, William Tauer, Cassandra Rosenberg, Melissa Wren, Tadafumi C Ikezu, Yuka A Martens, Minghui Wang, Bin Zhang, Gregory W Carter, Michael Sasner, David M Holtzman, Junmin Peng, Long-Jun Wu, Takahisa Kanekiyo, Chia-Chen Liu, Guojun Bu

The Brown Foundation: Institute of Molecular Medicine

Background

Humanized APOE targeted-replacement (TR) mice are essential tools for studying apoE isoform effects in Alzheimer’s disease (AD) and other apoE-related disorders. Despite their widespread use, existing APOE mouse models, generated with different gene targeting strategies, have not been directly compared in terms of apoE isoform expression, lipid profiles, and transcriptomic signatures. Such differences could impact how we interpret APOE genotype-related outcomes, as well as related underlying molecular mechanisms.

Methods

We conducted a comprehensive molecular comparison of humanized APOE mouse models from three sources: Taconic Biosciences (TAC), the Cure Alzheimer’s Fund (CAF), and The Jackson Laboratory (JAX). We assessed apoE …


Conserved Neutrophil Degranulation Transcripts In Hiv-Tb Coinfected Children Across East And Southern Africa, Eric Katagirya, Busisiwe Mlotshwa, Samuel Kyobe, Savannah Mwesigwa, Gaone Retshabile, Lesedi Williams, Marion Amujal, John Mukisa, Gerald Mboowa, David P Kateete, Misaki Wayengera, Sununguko Wata Mpoloka, Angella N Mirembe, Ishmael Kasvosve, Koketso Morapedi, Makhosazana Dlamini, Betty Nsangi, Grace P Kisitu, Adeodata R Kekitiinwa, Gabriel Anabwani, Moses L Joloba, Eddie Mujjwiga Wampande, Dithan Kiragga, Florence Anabwani-Richter, Chester W Brown, Graeme Mardon, Neil A Hanchard, Mogomotsi Matshaba, And For The Collaborative African Genomics Network (Cafgen) Mar 2026

Conserved Neutrophil Degranulation Transcripts In Hiv-Tb Coinfected Children Across East And Southern Africa, Eric Katagirya, Busisiwe Mlotshwa, Samuel Kyobe, Savannah Mwesigwa, Gaone Retshabile, Lesedi Williams, Marion Amujal, John Mukisa, Gerald Mboowa, David P Kateete, Misaki Wayengera, Sununguko Wata Mpoloka, Angella N Mirembe, Ishmael Kasvosve, Koketso Morapedi, Makhosazana Dlamini, Betty Nsangi, Grace P Kisitu, Adeodata R Kekitiinwa, Gabriel Anabwani, Moses L Joloba, Eddie Mujjwiga Wampande, Dithan Kiragga, Florence Anabwani-Richter, Chester W Brown, Graeme Mardon, Neil A Hanchard, Mogomotsi Matshaba, And For The Collaborative African Genomics Network (Cafgen)

Faculty, Staff and Students Publications

Background: HIV-tuberculosis (HIV-TB) coinfection poses a significant public health challenge among children in high-burden African regions. Most previous transcriptomic studies have concentrated on adults and non-African populations, primarily analyzing gene-level differential expression. This approach overlooks multi-isoform complexity and may obscure both inherent and pathogen-induced intragenic heterogeneity. This multi-center case-control study aimed to identify and characterize the transcript-level landscape of HIV-TB coinfection in children from different African regions.

Methods: We analyzed whole-blood RNA sequencing data from 97 children with and without tuberculosis from Uganda (East Africa) and from Botswana and Eswatini (Southern Africa). Reads were quality-controlled, and low-abundance transcripts filtered out. …


Genome-Wide Crispr Screen Identifies A Cytokine-Enhancer Circuit Driving Hif-2Α Activation In Renal Cancer, Jun Fang, Jeremy M Simon, Tao Wang, Yunpeng Gao, Xianju Bi, Lianxin Hu, Chengheng Liao, Cheng Zhang, Yayoi Adachi, Jin Zhou, Hongyi Liu, Qian Liang, James A Nathan, Ram Mani, James Brugarolas, Qing Zhang Mar 2026

Genome-Wide Crispr Screen Identifies A Cytokine-Enhancer Circuit Driving Hif-2Α Activation In Renal Cancer, Jun Fang, Jeremy M Simon, Tao Wang, Yunpeng Gao, Xianju Bi, Lianxin Hu, Chengheng Liao, Cheng Zhang, Yayoi Adachi, Jin Zhou, Hongyi Liu, Qian Liang, James A Nathan, Ram Mani, James Brugarolas, Qing Zhang

Faculty, Staff and Student Publications

Resistance to HIF-2α inhibitors such as Belzutifan underscores the need to better understand how HIF-2α is transcriptionally regulated in clear cell renal cell carcinoma (ccRCC). Here, we uncover a cytokine-driven enhancer mechanism that sustains HIF-2α expression through the JAK1-STAT3 signaling pathway. Using a genome-wide CRISPR screen in VHL-deficient ccRCC cells, we identified SOCS3 as a key negative regulator of HIF-2α. Mechanistically, loss of SOCS3 activates JAK1-STAT3 signaling, leading to the recruitment of STAT3 to distal enhancers upstream of EPAS1 that physically loop to its promoter to drive HIF-2α transcription. This cytokine-enhancer circuit was recapitulated in ccRCC patient samples and functionally …


Tulane Virus Protease As A Structural Surrogate For Inhibitor Screening Of Human Norovirus Proteases, Son Pham, Nikhil Sharma, Banumathi Sankaran, Jalen Nguyen, Mary K Estes, Joseph M Hyser, B V Venkataram Prasad Mar 2026

Tulane Virus Protease As A Structural Surrogate For Inhibitor Screening Of Human Norovirus Proteases, Son Pham, Nikhil Sharma, Banumathi Sankaran, Jalen Nguyen, Mary K Estes, Joseph M Hyser, B V Venkataram Prasad

Faculty, Staff and Students Publications

Human norovirus (HuNoV) is a significant cause of gastroenteritis worldwide, affecting people of all age groups. There are currently no vaccines or drugs available, leaving susceptible populations vulnerable to severe or protracted illness. A HuNoV cultivation system is pivotal for screening norovirus antivirals. While the human intestinal enteroid cultivation system allows robust replication of multiple HuNoV strains, it presents technical and cost barriers. Tulane virus (TV), a surrogate for HuNoV, replicates well in monkey kidney cell lines and is closely related to norovirus in cellular biology. Here, we determined the structures of TV protease (TV-Pro) alone and in complex with …


Efficacy And Safety Of Stem Cell-Based Interventions For Burn Wound Healing: A Systematic Review And Meta-Analysis Of Pre-Clinical And Early Clinical Evidence, Prayuth Poowaruttanawiwit, Patsanan Kulla, Naveeya Pakpoomkamonlert Mar 2026

Efficacy And Safety Of Stem Cell-Based Interventions For Burn Wound Healing: A Systematic Review And Meta-Analysis Of Pre-Clinical And Early Clinical Evidence, Prayuth Poowaruttanawiwit, Patsanan Kulla, Naveeya Pakpoomkamonlert

The Thai Journal of Pharmaceutical Sciences

Background: Burn injuries remain a major therapeutic challenge, with conventional treatments often failing to achieve complete functional skin regeneration. Stem cell-based interventions, including mesenchymal stem cells (MSCs) and exosome derivatives, have demonstrated regenerative and immunomodulatory potential, yet their translation to clinical practice remains limited.
Objectives: To systematically evaluate the efficacy and safety of stem cell-based therapies for burn wound healing across pre-clinical and clinical studies.
Materials and Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, four databases (PubMed, Embase, Scopus, and Cochrane) were searched through April 2025. Eligible studies included randomized controlled trials and controlled pre-clinical …


Γδ T Cells At The Interface Of Innate And Adaptive Immunity In Cancer, Arnau Solé Casaramona, Martin F Bachmann, Eva Sevick-Muraca, Mona O Mohsen Mar 2026

Γδ T Cells At The Interface Of Innate And Adaptive Immunity In Cancer, Arnau Solé Casaramona, Martin F Bachmann, Eva Sevick-Muraca, Mona O Mohsen

The Brown Foundation: Institute of Molecular Medicine

γδ T cells are unconventional lymphocytes that bridge innate and adaptive immunity by combining recognition of stress-induced ligands independently of classical major histocompatibility complex molecules with the capacity to undergo clonal expansion and long-term adaptation. Their unusual ability to detect malignant transformation using semi-invariant T-cell receptors, butyrophilin recognition and natural killer-like receptors positions them as powerful effector cells in tumors that evade classical immune escape mechanisms. Furthermore, distinct γδ subsets have distinct phenotyping and specific tissue-residencies, which could be leveraged to modulate immunological responses. We evaluate engineered therapies and different experimental platforms for studying γδ T cell biology. We conclude …


Antimicrobial Activity Of Sulbactam-Durlobactam Against Acinetobacter Baumannii-Calcoaceticus Complex Strains Causing Non-Respiratory And Non-Bloodstream Infections From The United States (2023–2025), Elizabeth Cyr, Jill Argotsinger, Eric T Beck, Robin R Chamberland, Andrew E Clark, Anne R Daniels, Rachael Liesman, Mark Fisher, Philip Gialanella, Jonathan Hand, Amanda T Harrington, Romney M Humphries, Holly Huse, Robert Hamilton-Seth, Julia D Hankins, Wesley D Kufel, Scott W Riddell, Meera Mehta, Ryan Demkowicz, A Brian Mochon, Hossein Salimnia, Ayesha Khan, Virginia M Pierce, Raghava Potula, Tsigereda Tekle, Patricia J Simner, Robert J Tibbetts, Christine Vu, Lilian M Abbo, Octavio Martinez, Rebekah E Dumm, Manohar B Mutnal, Timothy C Jenkins, Violeta Chávez, Paulette Pinargote, Jennifer Bowling, Erik Munson, Daniel V Zurawski, David P Nicolau, Tomefa E Asempa, On Behalf Of The Acinetobacter Baumannii Complex National Biorepository (Acnbio) Study Group Mar 2026

Antimicrobial Activity Of Sulbactam-Durlobactam Against Acinetobacter Baumannii-Calcoaceticus Complex Strains Causing Non-Respiratory And Non-Bloodstream Infections From The United States (2023–2025), Elizabeth Cyr, Jill Argotsinger, Eric T Beck, Robin R Chamberland, Andrew E Clark, Anne R Daniels, Rachael Liesman, Mark Fisher, Philip Gialanella, Jonathan Hand, Amanda T Harrington, Romney M Humphries, Holly Huse, Robert Hamilton-Seth, Julia D Hankins, Wesley D Kufel, Scott W Riddell, Meera Mehta, Ryan Demkowicz, A Brian Mochon, Hossein Salimnia, Ayesha Khan, Virginia M Pierce, Raghava Potula, Tsigereda Tekle, Patricia J Simner, Robert J Tibbetts, Christine Vu, Lilian M Abbo, Octavio Martinez, Rebekah E Dumm, Manohar B Mutnal, Timothy C Jenkins, Violeta Chávez, Paulette Pinargote, Jennifer Bowling, Erik Munson, Daniel V Zurawski, David P Nicolau, Tomefa E Asempa, On Behalf Of The Acinetobacter Baumannii Complex National Biorepository (Acnbio) Study Group

Faculty, Staff and Student Publications

Acinetobacter baumannii most often causes pneumonia in critically ill patients. However, A. baumannii is also an important cause of a broader range of infections, including skin/wound and urinary tract infections. This study aims to evaluate the in vitro activity of sulbactam-durlobactam and comparator antibiotics, including meropenem and cefiderocol against A. baumannii-calcoaceticus complex isolates from non-respiratory and non-bloodstream sources. Samples included 285 A. baumannii-calcoaceticus complex isolates enriched for carbapenem resistance collected across 17 states in the United States (January 2023–May 2025). Antimicrobial susceptibility tests were conducted by manual broth microdilution and interpreted according to Clinical and Laboratory Standards Institute (CLSI) and …


A Retrospective Analysis Of Taxane-Based Chemotherapy In Small Bowel Adenocarcinoma, Mir Lim, Nikhil Grandhi, Preksha Shah, Kanwal Raghav, Victoria Serpas, Maria Pia Morelli, Katrina Pedersen, Aparna Kalyan, Mohamed Salem, Ryan Huey, John Paul Shen, Huamin Wang, Hua Wang, Anjali Vinocha, Jane Thomas, Robert Wolff, Michael J Overman Mar 2026

A Retrospective Analysis Of Taxane-Based Chemotherapy In Small Bowel Adenocarcinoma, Mir Lim, Nikhil Grandhi, Preksha Shah, Kanwal Raghav, Victoria Serpas, Maria Pia Morelli, Katrina Pedersen, Aparna Kalyan, Mohamed Salem, Ryan Huey, John Paul Shen, Huamin Wang, Hua Wang, Anjali Vinocha, Jane Thomas, Robert Wolff, Michael J Overman

Faculty, Staff and Student Publications

Background: Small bowel adenocarcinoma (SBA) is molecularly distinct from colorectal and gastric cancers, yet treatment typically parallels colorectal cancer. We evaluated the activity of taxane-based therapy in the largest SBA cohort to date.

Methods: We retrospectively reviewed SBA patients treated with taxane-based chemotherapy at MD Anderson Cancer Center from 1994-2024. Eligible patients had pathologic confirmation, received >1 treatment cycle, and had tumor response evaluation. Survival analyses were analyzed using Kaplan-Meier and Cox proportional hazard models.

Results: Seventy patients were identified. Median age was 57, and 59% were male. Primary sites were duodenum (44%), jejunum (34%), and Ileum (16%). Metastatic sites …


Protocol For Spatial Profiling Of Immune Cells In The Mouse Cornea And Conjunctiva Using Nanostring Geomx Dsp And Ncounterpro Platforms, Lois Kim, Karthikeyan Ramasamy, Ajay Sharma Mar 2026

Protocol For Spatial Profiling Of Immune Cells In The Mouse Cornea And Conjunctiva Using Nanostring Geomx Dsp And Ncounterpro Platforms, Lois Kim, Karthikeyan Ramasamy, Ajay Sharma

Pharmacy Faculty Articles and Research

Quantification of immune cells and their activation status in a spatially specific manner in a healthy or diseased tissue is a valuable tool in immunology. Here, we present a protocol for the spatial profiling of immune cells in the mouse cornea and conjunctiva. We describe steps for immunostaining with photocleavable oligonucleotide-conjugated antibodies, selecting regions of interest (ROIs), and collecting UV-cleaved oligonucleotides using GeoMx DSP. We then detail procedures for hybridizing collected oligonucleotides, cartridge blotting using nCounter Pro Prep, data acquisition, and data analysis.


Health Effects Of Cadmium And Manganese Exposure On Luteinizing Hormone Levels: A Pilot Study Of Female Infertility, Shatha F. Alhous, Anees A. Al-Hamzawi, Murtadha Sh. Aswood Mar 2026

Health Effects Of Cadmium And Manganese Exposure On Luteinizing Hormone Levels: A Pilot Study Of Female Infertility, Shatha F. Alhous, Anees A. Al-Hamzawi, Murtadha Sh. Aswood

Al-Bahir

Female infertility occurs for many reasons, some unknown. Exposure to heavy metals is a risk factor that negatively impacts on female reproductive system. Therefore, this study aimed to evaluate the effect of cadmium Cd and manganese Mn on luteinizing hormone LH levels for females’ infertility. This study included a healthy group (n = 20), primary infertile females (n = 40), and secondary infertile females (n = 20) collected from Al-Zahraa hospital in Najaf center, Iraq. The Atomic Absorption Spectroscopy (AAS) was used to measure the cadmium and manganese concentrations and LH levels were measured by a Maglumi 800 from Snibe …


Plant-Based Dietary Patterns Are Associated With Slower Epigenetic Aging, Hyunju Kim, Christina A Castellani, Jiantao Ma, Alexis C Wood, Audrey Ting, Morgan E Grams, Bing Yu, Kelly Ruggles, James S Floyd, Dan E Arking, Casey M Rebholz Mar 2026

Plant-Based Dietary Patterns Are Associated With Slower Epigenetic Aging, Hyunju Kim, Christina A Castellani, Jiantao Ma, Alexis C Wood, Audrey Ting, Morgan E Grams, Bing Yu, Kelly Ruggles, James S Floyd, Dan E Arking, Casey M Rebholz

Faculty, Staff and Students Publications

Greater adherence to plant-based diets is associated with health benefits. Dietary intake can modify DNA methylation patterns, but it is unknown whether plant-based diets in a largely non-vegetarian population are associated with DNA methylation-based epigenetic aging measures. We examined the associations between 4 different types of plant-based diets indices (PDI) [overall PDI, provegetarian diet, healthy PDI, and unhealthy PDI] and epigenetic aging. We used data from the Atherosclerosis Risk in Communities (ARIC) Study (N=2,810) and National Health and Nutrition Examination Survey (NHANES, N=2,056). PDIs negatively scored higher intake of animal products and positively scored higher intake of all or selected …


Immunoregulatory Effects Of Choerospondias Axillaris (Roxb.) B.L.Burtt & A.W.Hill Fruit Extract In Mice With Insights On In Vitro Mechanism, Ravi Gautam, Anju Maharjan, Jaehee Lee, Sujeong Yang, Jihun Jo, Manju Acharya, Daeun Lee, Narayan Prasad Ghimire, Saroj Lamichhane, Byungsun Min, Changyul Kim, Hyoungah Kim, Yong Heo Mar 2026

Immunoregulatory Effects Of Choerospondias Axillaris (Roxb.) B.L.Burtt & A.W.Hill Fruit Extract In Mice With Insights On In Vitro Mechanism, Ravi Gautam, Anju Maharjan, Jaehee Lee, Sujeong Yang, Jihun Jo, Manju Acharya, Daeun Lee, Narayan Prasad Ghimire, Saroj Lamichhane, Byungsun Min, Changyul Kim, Hyoungah Kim, Yong Heo

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: Lapsi (Choerospondias axillaris), a plant native to Nepal, has been traditionally used in Asian countries to treat cardiovascular conditions. However, its effects on immune regulatory function remain largely unexplored. This study aimed to in vivo evaluate the immunoregulatory properties of Lapsi fruit extract in mice on immunotoxic responses with analysis on in vitro mechanism for immune suppression, oxidative stress, and inflammatory response. Male Balb/c mice were intragastrically administered various doses of the extract for 21 days. In some mice, immune suppression was induced with cyclophosphamide, and subsequent immune recovery was assessed. In addition, RAW264.7 cells and THP-1-derived macrophages were …