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Eph Receptors Activate Myeloid Checkpoint Receptor Lilrb5 To Support Tumor Development, Yubo He, Chengcheng Zhang, Lingxiao Tan, Mi Deng, Xiaoye Liu, Ryan Huang, Xing Yang, Jingjing Xie, Qi Lou, Meng Fang, Caroline Smith, Samuel John, Wei Xiong, Xin Li, Cheryl Lewis, Jade Homsi, Ankit Gupta, Ningyan Zhang, Zhiqiang An, Cheng Cheng Zhang Jun 2025

Eph Receptors Activate Myeloid Checkpoint Receptor Lilrb5 To Support Tumor Development, Yubo He, Chengcheng Zhang, Lingxiao Tan, Mi Deng, Xiaoye Liu, Ryan Huang, Xing Yang, Jingjing Xie, Qi Lou, Meng Fang, Caroline Smith, Samuel John, Wei Xiong, Xin Li, Cheryl Lewis, Jade Homsi, Ankit Gupta, Ningyan Zhang, Zhiqiang An, Cheng Cheng Zhang

Faculty, Staff and Student Publications

Immunosuppressive myeloid cells are critical obstacles to T cell-centered immune checkpoint blockade therapies, which have been successful in treating a fraction of patients with cancer. How tumor cells interact with myeloid cells to regulate immune responses and tumor development is unclear. In this study, we report that certain membrane tyrosine kinase Eph receptors, including EphA7 and EphB1, specifically bind the immune inhibitory receptors leukocyte Ig-like receptor family B 5 (LILRB5) and LILRB2. These Eph receptors induce LILRB5-mediated signaling activation, and LILRB5 also activates Eph receptor signaling. Activation of LILRB5 promoted immunosuppressive marker expression and inhibited activating marker expression on myeloid …


Deep Learning Based Rapid X-Ray Fluorescence Signal Extraction And Image Reconstruction For Preclinical Benchtop X-Ray Fluorescence Computed Tomography Applications, Amrit Kaphle, Sandun Jayarathna, Sang Hyun Cho Jun 2025

Deep Learning Based Rapid X-Ray Fluorescence Signal Extraction And Image Reconstruction For Preclinical Benchtop X-Ray Fluorescence Computed Tomography Applications, Amrit Kaphle, Sandun Jayarathna, Sang Hyun Cho

Faculty, Staff and Student Publications

Recent research advances have resulted in an experimental benchtop X-ray fluorescence computed tomography (XFCT) system that likely meets the imaging dose/scan time constraints for benchtop XFCT imaging of live mice injected with gold nanoparticles (GNPs). For routine in vivo benchtop XFCT imaging, however, additional challenges, most notably the need for rapid/near-real-time handling of X-ray fluorescence (XRF) signal extraction and XFCT image reconstruction, must be successfully addressed. Here we propose a novel end-to-end deep learning (DL) framework that integrates a one-dimensional convolutional neural network (1D CNN) for rapid XRF signal extraction with a U-Net model for XFCT image reconstruction. We trained …


Mesenchymal Stem Cells And Fibroblasts Contribute To Microvascular Proliferation In Glioblastoma And Are Correlated With Immunosuppression And Poor Outcome, Candice C Poon, Shelley M Herbrich, Yulong Chen, Anwar Hossain, Gregory N Fuller, Sonali Jindal, Sreyashi Basu, Daniel Ledbetter, Marc Macaluso, Lynnette M Phillips, Joy Gumin, Zhong He, Brittany C Parker Kerrigan, Sanjay K Singh, Pratishtha Singh, Mohammed Fayyad Zaman, Derek Ng Tang, Sangeeta Goswami, Frederick F Lang, Padmanee Sharma Jun 2025

Mesenchymal Stem Cells And Fibroblasts Contribute To Microvascular Proliferation In Glioblastoma And Are Correlated With Immunosuppression And Poor Outcome, Candice C Poon, Shelley M Herbrich, Yulong Chen, Anwar Hossain, Gregory N Fuller, Sonali Jindal, Sreyashi Basu, Daniel Ledbetter, Marc Macaluso, Lynnette M Phillips, Joy Gumin, Zhong He, Brittany C Parker Kerrigan, Sanjay K Singh, Pratishtha Singh, Mohammed Fayyad Zaman, Derek Ng Tang, Sangeeta Goswami, Frederick F Lang, Padmanee Sharma

Faculty, Staff and Student Publications

Microvascular proliferation (MVP) is a disease-defining hallmark of glioblastoma and other World Health Organization grade 4 gliomas. MVP also serves as a poor prognostic marker in various solid tumors. Despite its clinical significance, the mechanisms and biological consequences of MVP are controversial and remain unclear. In this study, we performed single-cell RNA sequencing on paired CD45-CD105+ vascular/perivascular stromal cells (PVSC) and CD45+CD105± immune cells from 16 primary glioma patient samples, both with and without MVP. This analysis revealed the presence of developmentally related mesenchymal stem cells alongside cancer-associated fibroblasts, pericytes, fibromyocytes, and smooth muscle cells within the CD45-CD105+ compartment. RNA …


Kaiso Mediates Transcription And Rna Splicing In Colorectal Carcinoma: Role Of Brca1 In The Kaiso Enhanceosome, Weifeng Luo, Manish Kumar Tripathi, Qi Liu, Lei Chen, Robert W. Cowan, Juliet M. Daniel, Chi Yan, Ann Richmond, Albert B. Reynolds Jun 2025

Kaiso Mediates Transcription And Rna Splicing In Colorectal Carcinoma: Role Of Brca1 In The Kaiso Enhanceosome, Weifeng Luo, Manish Kumar Tripathi, Qi Liu, Lei Chen, Robert W. Cowan, Juliet M. Daniel, Chi Yan, Ann Richmond, Albert B. Reynolds

School of Medicine Publications

Kaiso (ZBTB33) is a transcription factor involved in mitotic clonal expansion and tumorigenesis in association with Adenomatous Polyposis Coli (APC) loss of heterozygosity. ENCODE data show strong overlap of the Kaiso promoter-binding site—encode-derived Kaiso-binding site (eKBS) and many other transcription factors, including BRCA1. Here we sought to determine whether BRCA1 is a component of the Kaiso enhanceosome that regulates gene transcription. Using proximal ligation assays, immunoprecipitation followed by mass spectrometry, luciferase assays and ChIP-seq experiments, we evaluated the association between BRCA1 and Kaiso. Kaiso nuclear extract immunoprecipitation experiments revealed that Kaiso associates strongly with genes involved in RNA splicing and …


Unravelling Host Defense And Pathogen Virulence In Fusarium Proliferatum-Induced Sudden Decline Syndrome Of Date Palm In The Uae, Gouthaman Puthan Purayil Jun 2025

Unravelling Host Defense And Pathogen Virulence In Fusarium Proliferatum-Induced Sudden Decline Syndrome Of Date Palm In The Uae, Gouthaman Puthan Purayil

Thesis/ Dissertation Defenses

Sudden decline syndrome (SDS) poses a significant threat to the date palm (Phoenix dactylifera), a crop of critical agricultural and cultural importance in arid regions. Despite its growing impact, the molecular basis of the host-pathogen interactions driving this disease remains poorly understood. This dissertation investigates the disease dynamics of SDS, a severe affliction of date palm caused by the fungal pathogen Fusarium proliferatum DSM 106835 (Fp). The objective of this study is to elucidate the molecular mechanisms underlying Fp infection in date palm and characterize the plant defense responses. To achieve this, whole-genome sequencing (WGS) of the novel Fp strain …


Proceedings From The Sixth Annual Society For Sports Neuroscience Conference, Neurosports Editorial Staff Jun 2025

Proceedings From The Sixth Annual Society For Sports Neuroscience Conference, Neurosports Editorial Staff

Journal for Sports Neuroscience

Proceedings from the Sixth Annual Society for Sports Neuroscience Conference


Investigating The Consequences Of Conjugated And Secreted Isg15 On Coronavirus Pathogenesis, Mudassir Syed Ali Jun 2025

Investigating The Consequences Of Conjugated And Secreted Isg15 On Coronavirus Pathogenesis, Mudassir Syed Ali

Dissertations

Coronaviruses have evolved a breadth of mechanisms to antagonize host innate immune responses. One widely studied mechanism is the ability to deconjugate ISG15 from target proteins in a process called deISGylation, which is catalyzed by the papain-like protease (PLP) domain of viral non-structural protein (nsp) 3. Since PLP activity is required for viral replication, it has been challenging to generate an infectious virus with a PLP that maintains protease activity but has lost deISGylase activity. In this study, we generated a chimeric MHV-A59 with its PLP2 domain replaced with that of the human coronavirus HKU1, which has been documented to …


Atp8b1 Regulates Pip2 Localization And Cleavage Of Pyroptotic Executioner Gasdermin D, Nilam Bhandari, Ashutosh Prince, Mariam R. Khan, Alicia Traughbera, Kalash Neupane, Shuhui W. Lorkowski, Gregory Brubaker, Elif G. Ertugral, Chandrasekhar R. Kothapalli Jun 2025

Atp8b1 Regulates Pip2 Localization And Cleavage Of Pyroptotic Executioner Gasdermin D, Nilam Bhandari, Ashutosh Prince, Mariam R. Khan, Alicia Traughbera, Kalash Neupane, Shuhui W. Lorkowski, Gregory Brubaker, Elif G. Ertugral, Chandrasekhar R. Kothapalli

Chemical & Biomedical Engineering Faculty Publications

Mutations in ATP8B1 cause progressive familial intrahepatic cholestasis, with symptoms including pruritus, pancreatitis, fat malabsorption, intestinal inflammation, and failure to thrive. High-throughput studies showed interconnection between ATP8B1 and phosphoinositide (PIPs), but the mechanism linking ATP8B1, lipid metabolism, and inflammation remains unclear. Atp8b1G308V/G308V mouse model, unbiased RNAseq, high-resolution-stimulation emission depltion (STED)-microscopy, and Crispr-Cas9 generated ATP8B1-/- knockouts in hepatocytes/monocytes/macrophages were used to determine role of ATP8B1 in phosphatidylinositol,4-5-bisphosphate (PIP2) trafficking and inflammation. Human ATP8B1, purified from Sf9 insect cells and reconstituted in proteoliposomes, was used to test cell-free PIP2 flip. Various in-vitro techniques were used for testing direct interaction between PIP2 and …


Pyruvate Dehydrogenase Kinase 4 Mediates Sex Specific Outcomes In Sepsis Induced Cardiomyopathy, John Yap Jun 2025

Pyruvate Dehydrogenase Kinase 4 Mediates Sex Specific Outcomes In Sepsis Induced Cardiomyopathy, John Yap

Dissertations

During sepsis, males often experience worse cardiac outcomes than females. Here, we identified pyruvate dehydrogenase kinase 4 (PDK4) as a key contributor to this disparity. PDK4 is a mitochondrial protein that regulates glucose utilization by inhibiting pyruvate dehydrogenase (PDH). Using a mouse model of endotoxemia, we induced acute inflammation with a sublethal dose of lipopolysaccharide (LPS), which caused cardiac dysfunction and significantly increased myocardial PDK4 expression in males but not females. Cardiac-specific PDK4 overexpression promoted LPS-induced cardiac dysfunction in both sexes, whereas cardiac-specific PDK4 knockout provided protection. In wild-type males, LPS disrupted cardiac metabolism by decreasing PDH activity and fatty …


Restoration Of The Tumor Suppressor Function Of Y220c-Mutant P53 By Rezatapopt, A Small-Molecule Reactivator, Anna M Puzio-Kuter, Lizhong Xu, Mary Kate Mcbrayer, Romyr Dominique, Hongju H Li, Bruce J Fahr, Alyssa M Brown, Amy E Wiebesiek, Brandon M Russo, Chris L Mulligan, Hong Yang, Josh Battaglia, Kimberly A Robell, Dafydd H Thomas, Kuo-Sen Huang, Alexander Solovyov, Benjamin D Greenbaum, Jonathan D Oliner, Thomas W Davis, Melissa L Dumble, Melissa L Johnson, Shunbin Xiong, Peirong Yang, Guillermina Lozano, Marc M Fellous, Binh T Vu, Alison M Schram, Arnold J Levine, Masha V Poyurovsky Jun 2025

Restoration Of The Tumor Suppressor Function Of Y220c-Mutant P53 By Rezatapopt, A Small-Molecule Reactivator, Anna M Puzio-Kuter, Lizhong Xu, Mary Kate Mcbrayer, Romyr Dominique, Hongju H Li, Bruce J Fahr, Alyssa M Brown, Amy E Wiebesiek, Brandon M Russo, Chris L Mulligan, Hong Yang, Josh Battaglia, Kimberly A Robell, Dafydd H Thomas, Kuo-Sen Huang, Alexander Solovyov, Benjamin D Greenbaum, Jonathan D Oliner, Thomas W Davis, Melissa L Dumble, Melissa L Johnson, Shunbin Xiong, Peirong Yang, Guillermina Lozano, Marc M Fellous, Binh T Vu, Alison M Schram, Arnold J Levine, Masha V Poyurovsky

Faculty, Staff and Student Publications

Restoration of the tumor suppressor function of tumor-associated p53 mutants, including the Y220C substitution, has posed a significant challenge for therapeutic discovery. In this study, we describe rezatapopt (PC14586), part of a series of compounds designed to reactivate the p53 Y220C mutant. These compounds restore p53 tumor suppressor function by correcting its conformation and enabling it to bind DNA and activate downstream target genes, thus inducing antiproliferative changes in tumor cells. Our findings are supported by biochemical and structural analysis, in vitro and in vivo transcriptomics, and functional data, revealing the recovery of multiple aspects of the wild-type p53 program. …


Mutant P53 Gain Of Function: Why Many See It, Why Some Do Not, Guillermina Lozano, Carol Prives, Kanaga Sabapathy Jun 2025

Mutant P53 Gain Of Function: Why Many See It, Why Some Do Not, Guillermina Lozano, Carol Prives, Kanaga Sabapathy

Faculty, Staff and Student Publications

Mutations in the TP53 tumor-suppressor gene in human cancer are unique in that 60% to 70% are of the missense variety, resulting in a full-length protein that is often highly expressed in patients' tumors. These missense mutant proteins often exhibit pro-oncogenic activities (referred to as gain of function) in mouse models and human cell lines and correlate with poor cancer prognosis in some cases.


Phage-Induced Protection Against Lethal Bacterial Reinfection, Yikun Xing, Haroldo J Hernandez Santos, Ling Qiu, Samantha R Ritter, Jacob J Zulk, Rachel Lahowetz, Kathryn A Patras, Austen L Terwilliger, Anthony W Maresso Jun 2025

Phage-Induced Protection Against Lethal Bacterial Reinfection, Yikun Xing, Haroldo J Hernandez Santos, Ling Qiu, Samantha R Ritter, Jacob J Zulk, Rachel Lahowetz, Kathryn A Patras, Austen L Terwilliger, Anthony W Maresso

Faculty, Staff and Students Publications

Bacteriophages, or phages, are viruses that target and infect bacteria. Due to a worldwide rise in antimicrobial resistance (AMR), phages have been proposed as a promising alternative to antibiotics for the treatment of resistant bacterial infections. Up to this point in history, phage use in preclinical animal studies, clinical trials, and emergency-use compassionate care cases has centered around the original observation from 1915 showing phage as lytic agent, and thus a treatment that kills bacteria. Here, we describe an activity associated with phage therapy that extends beyond lytic activity that results in long-term protection against reinfection. This activity is potent, …


Prescribed Fire Leads A Pine Flatwoods Specialist Tree Frog To Seek Local Refugia, Ian Biazzo, Pedro F. Quintana-Ascencio Jun 2025

Prescribed Fire Leads A Pine Flatwoods Specialist Tree Frog To Seek Local Refugia, Ian Biazzo, Pedro F. Quintana-Ascencio

Faculty Publications

Pine savannas of the southeastern United States evolved with frequent low-intensity wildfires. Today, land managers use prescribed fires to restore this ecological process while also controlling vegetative fuel accumulation. Given the ubiquitous application of this management tool, studies should consider impacts on target and nontarget taxa in these systems. During fires, animal populations persist in the landscape when individuals emigrate to unburned areas or seek refugia within the burn zone; otherwise, they experience local extirpation. We examined the effect of prescribed fires on a pine flatwoods specialist frog, the pinewoods treefrog Dryophytes femoralis, in a frequently burned pine landscape. …


Arts-Based Sustainability: From New York To Malawi, Martha B. Lerski Jun 2025

Arts-Based Sustainability: From New York To Malawi, Martha B. Lerski

Publications and Research

Recognizing that libraries serve multiple constituencies and subject areas, this chapter documents and advocates for development of transdisciplinary arts-based research (ABR) and culture-related projects linked to environmental challenges. Libraries contribute collections and spaces, as well as the research of library and information scientists. Libraries are currently among invisible contributors to sustainability planning and services. The chapter will link this invisibility to the value of what visual arts refer to as negative space elements in subjects ranging from traditional ecological knowledge to environmental science. Library collections, projects, and research contribute to education for sustainable development (ESD) as required to achieve the …


Breaking The Rules: Post-Translational Modifications And Proteome Dynamics During Anoxia, Chelsea Jordan Hughes Jun 2025

Breaking The Rules: Post-Translational Modifications And Proteome Dynamics During Anoxia, Chelsea Jordan Hughes

Dissertations and Theses

Most organisms are ill-equipped to survive anoxia, but some organisms have developed molecular strategies to mitigate the cellular stressors associated with a lack of oxygen. While it is established that anoxic survival is contingent on metabolic suppression, it is unclear what mechanisms support this change in gene expression. Gene expression is regulated by a variety of mechanisms within the cell, including alteration of chromatin structure through histone modifications and protein modifications which contribute to the ever-changing proteomic landscape of the cell. Protein modifications such as ubiquitylation can lead to the degradation of proteins, while modifications to transcription factors can change …


Allelopathy Of Western Red Cedar, Douglas Fir, And Western Hemlock On Seed Germination, Lainey E. Mendoza Ms. Jun 2025

Allelopathy Of Western Red Cedar, Douglas Fir, And Western Hemlock On Seed Germination, Lainey E. Mendoza Ms.

Honors Projects

Understanding the allelopathic interactions of native Pacific Northwest conifers, Douglas Fir, Western Hemlock, and Western Red Cedar is crucial to understanding the interactions of each species within their ecological niche. As of now there is little research on allelopathy of PNW conifers, specifically how different damaged states of the conifer tissue could impact the germination rates and radicle growth of a model organism. Analyzing these allelopathic interactions may be crucial to help predict forest regeneration of the PNW in the future. Presented here is the analysis of Douglas Fir, Western Hemlock, and Western Red Cedar tissue that is undamaged, damaged, …


Cisplatin Palbociclib Combination Differentially Modulates Pten Akt Signaling Via Hsp90 In Hepatocellular Carcinoma Cells., Eman Ramadan Jun 2025

Cisplatin Palbociclib Combination Differentially Modulates Pten Akt Signaling Via Hsp90 In Hepatocellular Carcinoma Cells., Eman Ramadan

Pharmacy

Hepatocellular carcinoma (HCC) presents a significant global health challenge, marked by high mortality and recurrence. This study investigated the synergistic potential of cisplatin and palbociclib (C + P) against HCC cell lines. RT-qPCR revealed that C + P significantly downregulated HCC-related genes, including Hsp90, β-catenin, and components of the PI3K/AKT/mTOR pathway, compared to cisplatin alone and controls. Western blotting confirmed a reduction in phosphorylated AKT (P-AKT) with palbociclib and C + P, while PTEN, a tumor suppressor, was upregulated in the C + P group. Annexin V-FITC assays demonstrated a substantial increase in apoptosis in palbociclib and C + P …


The Ecophysiology Of The Enigmatic Namib Succulent, Lithops Ruschiorum, Garrett Macleod Althausen Jun 2025

The Ecophysiology Of The Enigmatic Namib Succulent, Lithops Ruschiorum, Garrett Macleod Althausen

Environmental Studies Senior Theses

Water availability is the primary constraint for plant survival and reproduction in hyper-arid ecosystems. In such environments, plant fitness depends on an alignment between physiological traits and limited water resources. The Namib Desert of Namibia exemplifies this extreme selection pressure. Within the Namib Desert, Lithops ruschiorum, a succulent endemic to the gravel plains, exhibits habitat specificity and numerous physiological adaptations to cope with the hyper-aridity.

This research explores the intersection of two fitness strategies for L. ruschiorum: habitat selection and exploitation of alternative moisture sources. The first chapter explores the population dynamics and micro-site habitat conditions preferred by …


Soybean Embryogenic Cell Culture Genetically Engineered, Gabriel Carrasquillo Jun 2025

Soybean Embryogenic Cell Culture Genetically Engineered, Gabriel Carrasquillo

Tennessee State University Alumni Theses and Dissertations

The inflation of population in the world has led to a high and consistent food demand which has reinvigorated worldwide interest to create high-yielding varieties of legumes. Soybean Glycine max (L.) Merrill, a member of this legume family has become one of the most essential food crops in the United States as well as in the world due its edible oil and protein content up to 20% and 54%, respectively. Because of its high importance as a food crop, major objectives in soybean breeding, improvement of protein and oil production need to be achieved. These objectives can be addressed using …


Isolating Novel Enzymes And Microorganisms For Use In Food Waste Fermentation, Shannon Marie Jeffries Jun 2025

Isolating Novel Enzymes And Microorganisms For Use In Food Waste Fermentation, Shannon Marie Jeffries

Tennessee State University Alumni Theses and Dissertations

In the United States, upwards of 2 billion pounds of food waste are discarded yearly, an amount equivalent to $161 billion or 30-40% of all food production, making up the largest portion of landfill waste (Buzby, 2022). A small amount of food scraps are recycled through compost and re-purposed into animal feed, but these processes are costly, have minimal benefits, and have limitations (EPA, 2024). One of the most promising routes is converting food waste into value added products through microbial fermentation. Food waste is rich in carbohydrates, proteins, lipids, vitamins, and other trace minerals, making it the ideal environment …


Application Of High-Pressure Processing And Real-Time Pcr For Preventing Foodborne Bacterial Diseases, Ranju Kafle Jun 2025

Application Of High-Pressure Processing And Real-Time Pcr For Preventing Foodborne Bacterial Diseases, Ranju Kafle

Tennessee State University Alumni Theses and Dissertations

Foodborne pathogens pose significant risks to public health and food safety, necessitating innovative control strategies. High-pressure processing (HPP) was evaluated as an intervention against Listeria monocytogenes in cold-smoked rainbow trout, with treatments at 500 MPa and 4.4 °C and 60.0 °C achieving up to a 5.03 log CFU/g reduction. The efficacy of nisin in suppressing Listeria monocytogenes and Listeria innocua during refrigerated storage was also examined, demonstrating significant microbial inhibition, particularly in the early storage phase, supporting its application as a hurdle technology. Additionally, the synergistic effects of HPP (400 MPa, 4 °C) and natural bioactive compounds, including lactic acid, …


Mutation Of Smarca4 Induces Cancer Cell-Intrinsic Defects In The Enhancer Landscape And Resistance To Immunotherapy, Yawen Wang, Ismail M Meraz, Md Qudratullah, Sasikumar Kotagiri, Yanyan Han, Yuanxin Xi, Jing Wang, Kadir C Akdemir, Jack A Roth, Yonathan Lissanu Jun 2025

Mutation Of Smarca4 Induces Cancer Cell-Intrinsic Defects In The Enhancer Landscape And Resistance To Immunotherapy, Yawen Wang, Ismail M Meraz, Md Qudratullah, Sasikumar Kotagiri, Yanyan Han, Yuanxin Xi, Jing Wang, Kadir C Akdemir, Jack A Roth, Yonathan Lissanu

Faculty, Staff and Student Publications

Cancer genomic studies have identified frequent alterations in genes encoding components of the SWI/SNF chromatin remodeling complex, including SMARCA4 and ARID1A. Importantly, clinical reports indicate that SMARCA4-mutant lung cancers respond poorly to immunotherapy and have dismal prognosis. In this study, we corroborated the clinical findings by using immune-humanized, syngeneic, and genetically engineered mouse models of lung cancer harboring SMARCA4 deficiency. Specifically, models with SMARCA4 loss showed decreased response to anti-PD-1 immunotherapy associated with significantly reduced infiltration of dendritic cells and CD4+ T cells into the tumor microenvironment. SMARCA4 loss in tumor cells led to profound downregulation of STING1, IL1β, and …


Exploring Soft Polymeric Nanoparticles For Targeted Biomolecule Delivery In Plant Cells, Mohammad Rashid Jun 2025

Exploring Soft Polymeric Nanoparticles For Targeted Biomolecule Delivery In Plant Cells, Mohammad Rashid

Theses and Dissertations

Safe and efficient agricultural practices require innovative technologies. Nanotechnology offers promising solutions for advancing plant agriculture by enabling the targeted delivery of biomolecules such as agrochemicals and nucleic acids. This study focuses on developing a safe nanotechnological approach for delivering molecules of interest into plant cells. We investigated the ability of four types of polymeric nanoparticles such as Polyethylene glycol N, Nʹ-dibutylethylenediamine (PEG-DB), Polyethylene glycol 2-pyrrolidin-1-yl-ethyl-amine (PEG-PY), Polyethyleneimine (PEI), Arabinoxylan (AX)+, and Zein+ to form conjugates with plasmid DNA (pDNA). Our findings confirm that plant-derived cationic nanopolymers, AX+ and Zein+, effectively bind negatively charged pDNA (pGFPGUSPlus) carrying a GFP reporter …


Suppression Of Brca1 Facilitates Kidney Regeneration, Kaira A Church, Xunian Zhou, Raghu Kalluri Jun 2025

Suppression Of Brca1 Facilitates Kidney Regeneration, Kaira A Church, Xunian Zhou, Raghu Kalluri

Faculty, Staff and Student Publications

Maladaptive repair following kidney injury leads to the development of kidney disease. In this issue of JEM, Ajay et al. (https://doi.org/10.1084/jem.20231107) uncover the role of breast cancer susceptibility gene 1 (BRCA1) in cell cycle arrest, DNA damage, and cell senescence, preventing maladaptive repair.


Drosha: A New Tumor Suppressor In Pineoblastoma, Zhixuan Huang, Xueli Ren, Jian Hu Jun 2025

Drosha: A New Tumor Suppressor In Pineoblastoma, Zhixuan Huang, Xueli Ren, Jian Hu

Faculty, Staff and Student Publications

In this Outlook, Huang et al. discuss a study in this issue of Genes & Development by Fraire et al. that shows that a deficiency in miRNA processors Drosha and Dicer and consequent cell cycle gene derepression promote pineoblastoma development. The authors highlight the heterogeneity of pineoblastoma's pathogenic mechanisms and its implications for therapeutic interventions in the clinic.


Hyaluronan Network Remodeling By Zeb1 And Itih2 Enhances The Motility And Invasiveness Of Cancer Cells, Sieun Lee, Jihye Park, Seongran Cho, Eun Ju Kim, Seonyeong Oh, Younseo Lee, Sungsoo Park, Keunsoo Kang, Dong Hoon Shin, Song Yi Ko, Jonathan M Kurie, Young-Ho Ahn Jun 2025

Hyaluronan Network Remodeling By Zeb1 And Itih2 Enhances The Motility And Invasiveness Of Cancer Cells, Sieun Lee, Jihye Park, Seongran Cho, Eun Ju Kim, Seonyeong Oh, Younseo Lee, Sungsoo Park, Keunsoo Kang, Dong Hoon Shin, Song Yi Ko, Jonathan M Kurie, Young-Ho Ahn

Faculty, Staff and Student Publications

Hyaluronan (HA) in the extracellular matrix promotes epithelial-mesenchymal transition (EMT) and metastasis; however, the mechanism by which the HA network constructed by cancer cells regulates cancer progression and metastasis in the tumor microenvironment (TME) remains largely unknown. In this study, inter-α-trypsin inhibitor heavy chain 2 (ITIH2), an HA-binding protein, was confirmed to be secreted from mesenchymal-like lung cancer cells when cocultured with cancer-associated fibroblasts. ITIH2 expression is transcriptionally upregulated by the EMT-inducing transcription factor ZEB1, along with HA synthase 2 (HAS2), which positively correlates with ZEB1 expression. Depletion of ITIH2 and HAS2 reduced HA matrix formation and the migration and …


A Comprehensive, Multi-Center, Immunogenomic Analysis Of Melanoma Brain Metastases, Lucy Boyce Kennedy, Amanda E D Van Swearingen, Marissa R Lee, Layne W Rogers, Alexander B Sibley, Jeff Sheng, Dadong Zhang, Xiaodi Qin, Eric S Lipp, Swaminathan Kumar, Aron Joon, Pixu Shi, Michael A Davies, Kouros Owzar, Carey K Anders, April K S Salama Jun 2025

A Comprehensive, Multi-Center, Immunogenomic Analysis Of Melanoma Brain Metastases, Lucy Boyce Kennedy, Amanda E D Van Swearingen, Marissa R Lee, Layne W Rogers, Alexander B Sibley, Jeff Sheng, Dadong Zhang, Xiaodi Qin, Eric S Lipp, Swaminathan Kumar, Aron Joon, Pixu Shi, Michael A Davies, Kouros Owzar, Carey K Anders, April K S Salama

Faculty, Staff and Student Publications

Background: Melanoma brain metastases (MBM) have a unique molecular profile compared to extracranial metastases (ECM). Description of the biological features and clinical outcomes of MBM will facilitate the design of rational therapies.

Methods: We examined the mutational landscape and gene expression profiles of MBM (74 patients) and ECM (34 patients) in paired patient samples from a previously published dataset with whole-exome sequencing (WES) and RNA sequencing (RNAseq) data from MD Anderson Cancer Center (MDACC). We also present findings from MBM from a new cohort of 14 patients from Duke University to strengthen investigation of somatic mutations and gene expression profiles. …


Harnessing Electrophiles In Vivo: A Pilot Study In Swine Using A Hydrophobic Radiopaque Formulation Of 2-Propylpentanoyl Chloride, Erik Cressman, Danielle Stolley, Natalie Fowlkes, Edd Felix, Waldemar Priebe, Steve Parrish, David Fuentes Jun 2025

Harnessing Electrophiles In Vivo: A Pilot Study In Swine Using A Hydrophobic Radiopaque Formulation Of 2-Propylpentanoyl Chloride, Erik Cressman, Danielle Stolley, Natalie Fowlkes, Edd Felix, Waldemar Priebe, Steve Parrish, David Fuentes

Faculty, Staff and Student Publications

Manipulating biology through chemistry is older than the discipline of chemistry itself. Traditionally, selectivity of oral or intravenous drugs relied on preferential drug-receptor binding. A novel approach exploiting image-guided techniques to impart spatial selectivity opens up a wide range of new possibilities for study and manipulation of biology. Motivated initially by the poor prognosis for solid tumors such as liver cancer, we demonstrate the use of an extreme form of in vivo chemistry for targeted delivery of 2-propylpentanoyl chloride in a swine model. The ensuing reaction in tissue devitalizes it by multiple mechanisms with lasting effects and, critically, demonstrates very …


Present And Future Of Microbiome-Targeting Therapeutics, Lauren E Lynch, Rachel Lahowetz, Christian Maresso, Austen Terwilliger, Jason Pizzini, Valeria Melendez Hebib, Robert A Britton, Anthony W Maresso, Geoffrey A Preidis Jun 2025

Present And Future Of Microbiome-Targeting Therapeutics, Lauren E Lynch, Rachel Lahowetz, Christian Maresso, Austen Terwilliger, Jason Pizzini, Valeria Melendez Hebib, Robert A Britton, Anthony W Maresso, Geoffrey A Preidis

Children’s Nutrition Research Center Staff Publications

A large body of evidence suggests that single- and multiple-strain probiotics and synbiotics could have roles in the management of specific gastrointestinal disorders. However, ongoing concerns regarding the quality and heterogeneity of the clinical data, safety in vulnerable populations, and the lack of regulation of products containing live microbes are barriers to widespread clinical use. Safety and regulatory issues must be addressed and new technologies considered. One alternative future strategy is the use of synthetic bacterial communities, defined as manually assembled consortia of two or more bacteria originally derived from the human gastrointestinal tract. Synthetic bacterial communities can model functional, …


United Seas For Resilient Reefs: A Blueprint For Coral Conservation Through International Cooperation, John J. Bohorquez, Maoz Fine, Dana I. Grieco, David A. Gill, Ali Al-Swalimih, Jacqueline Padilla-Gamino, Isaiah W. Bolden, Margaux Hein, Callum Backstrom, Melanie Mcfield, Raphael Martinez, Benjamin Midberry, Fahd Al-Guthmy, Ellen K. Pikitch, Natalia Benejam, Chen Azulay, Britt Ronen, Oren Levy, Anne Mcelroy, Karine Kleinhaus Jun 2025

United Seas For Resilient Reefs: A Blueprint For Coral Conservation Through International Cooperation, John J. Bohorquez, Maoz Fine, Dana I. Grieco, David A. Gill, Ali Al-Swalimih, Jacqueline Padilla-Gamino, Isaiah W. Bolden, Margaux Hein, Callum Backstrom, Melanie Mcfield, Raphael Martinez, Benjamin Midberry, Fahd Al-Guthmy, Ellen K. Pikitch, Natalia Benejam, Chen Azulay, Britt Ronen, Oren Levy, Anne Mcelroy, Karine Kleinhaus

School of Marine & Atmospheric Sciences Faculty Publications

Coral reefs are one of Earth’s most vital and threatened ecosystems. They protect coastlines, generate billions of dollars of tourism revenue, support valuable fisheries, and contribute to the development of vital medicines. Yet half of the world's coral reefs have been lost in the last 50 years, and 90% of remaining reefs are projected to die off by the middle of this century, mainly due to warming seas from climate change.

Despite these challenges there is reason for hope. Some coral reefs – such as in the northern Red Sea and Gulf of Aqaba – have demonstrated remarkable resilience to …