Digital Commons Network^™

Initiation Of Hnrnpa1 Low-Complexity Domain Condensation Monitored By Dynamic Light Scattering, Phoebe S Tsoi, Josephine C Ferreon, Allan Chris M Ferreon

Faculty, Staff and Students Publications

Biomolecular condensates (BMCs) exhibit physiological and pathological relevance in biological systems. Both liquid and solid condensates play significant roles in the spatiotemporal regulation and organization of macromolecules and their biological activities. Some pathological solid condensates, such as Lewy Bodies and other fibrillar aggregates, have been hypothesized to originate from liquid condensates. With the prevalence of BMCs having functional and dysfunctional roles, it is imperative to understand the mechanism of biomolecular condensate formation and initiation. Using the low-complexity domain (LCD) of heterogenous ribonuclear protein A1 (hnRNPA1) as our model, we monitored initial assembly events using dynamic light scattering (DLS) while modulating …

Alzheimer's Disease Risk Gene Cd2ap Is A Dose-Sensitive Determinant Of Synaptic Structure And Plasticity, Taeyong Ahn, Gabrielle E Largoza, Julia Younis, Mary E Dickinson, Chih-Wei Hsu, Joshua D Wythe

Faculty, Staff and Students Publications

Tissue clearing is an essential prerequisite for 3D volumetric imaging of larger tissues or organs. Here, we present a detailed protocol for optical, aqueous-based clearing of adult murine tissues using EZ Clear. We describe steps to ensure successful perfusion and fixation of organs from the adult mouse and supply guidelines for optimal lipid removal, refractive index matching, and tissue clearing. Finally, we provide imaging parameters for visualizing both exogenous perfused fluorescent dyes and endogenous fluorescence reporters in the adult mouse. For complete details on the use and execution of this protocol, please refer to Hsu et al.

Protocol For Optical, Aqueous-Based Clearing Of Murine Tissues Using Ez Clear, Taeyong Ahn, Gabrielle E Largoza, Julia Younis, Mary E Dickinson, Chih-Wei Hsu, Joshua D Wythe

Faculty, Staff and Students Publications

Tissue clearing is an essential prerequisite for 3D volumetric imaging of larger tissues or organs. Here, we present a detailed protocol for optical, aqueous-based clearing of adult murine tissues using EZ Clear. We describe steps to ensure successful perfusion and fixation of organs from the adult mouse and supply guidelines for optimal lipid removal, refractive index matching, and tissue clearing. Finally, we provide imaging parameters for visualizing both exogenous perfused fluorescent dyes and endogenous fluorescence reporters in the adult mouse. For complete details on the use and execution of this protocol, please refer to Hsu et al.

Protocol For Preclinical Evaluation Of Locoregionally Delivered Car T Cells In Patient-Derived Xenograft Models Of Brain Tumors, Benjamin Draper, Chantelle Bowers, Eleni Vassalou, Ailsa Greppi, John Anderson, Nabil Ahmed, Michael D Taylor, Laura K Donovan

Faculty, Staff and Students Publications

Here, we present a protocol for preclinical evaluation of locoregionally delivered CAR T cells in patient-derived xenograft models of primary, metastatic, and recurrent brain tumors. We provide instructions for isolating peripheral blood mononuclear cells (PBMCs), producing CAR T cells in conjunction with locoregional delivery, and preclinical trial design and analysis involving CAR T cells. Additionally, we describe comprehensive preclinical readouts and guidelines for critical endpoint sample collections. In line with clinical trial procedures, our protocol broadens available treatment modalities for direct clinical translation. For complete details on the use and execution of this protocol, please refer to Donovan et al …

Metabolic Flux Regulates Growth Transitions And Antibiotic Tolerance In Uropathogenic Escherichia Coli, Josiah J Morrison, Ellen K Madden, Daniel A Banas, Eric C Dibiasio, Mads Hansen, Karen A Krogfelt, David C Rowley, Paul S Cohen, Jodi L Camberg

Faculty, Staff and Students Publications

Reducing growth and limiting metabolism are strategies that allow bacteria to survive exposure to environmental stress and antibiotics. During infection, uropathogenic Escherichia coli (UPEC) may enter a quiescent state that enables them to reemerge after the completion of successful antibiotic treatment. Many clinical isolates, including the well-characterized UPEC strain CFT073, also enter a metabolite-dependent, quiescent state in vitro that is reversible with cues, including peptidoglycan-derived peptides and amino acids. Here, we show that quiescent UPEC is antibiotic tolerant and demonstrate that metabolic flux in the tricarboxylic acid (TCA) cycle regulates the UPEC quiescent state via succinyl-CoA. We also demonstrate that …

Sensory Asic3 Channel Exacerbates Psoriatic Inflammation Via A Neurogenic Pathway In Female Mice, Chen Huang, Pei-Yi Sun, Yiming Jiang, Yuandong Liu, Zhichao Liu, Shao-Ling Han, Bao-Shan Wang, Yong-Xin Huang, An-Ran Ren, Jian-Fei Lu, Qin Jiang, Ying Li, Michael X Zhu, Zhirong Yao, Yang Tian, Xin Qi, Wei-Guang Li, Tian-Le Xu

Faculty, Staff and Student Publications

Psoriasis is an immune-mediated skin disease associated with neurogenic inflammation, but the underlying molecular mechanism remains unclear. We demonstrate here that acid-sensing ion channel 3 (ASIC3) exacerbates psoriatic inflammation through a sensory neurogenic pathway. Global or nociceptor-specific Asic3 knockout (KO) in female mice alleviates imiquimod-induced psoriatic acanthosis and type 17 inflammation to the same extent as nociceptor ablation. However, ASIC3 is dispensable for IL-23-induced psoriatic inflammation that bypasses the need for nociceptors. Mechanistically, ASIC3 activation induces the activity-dependent release of calcitonin gene-related peptide (CGRP) from sensory neurons to promote neurogenic inflammation. Botulinum neurotoxin A and CGRP antagonists prevent sensory neuron-mediated …

Mediterranean Diet Information On Tiktok And Implications For Digital Health Promotion Research: Social Media Content Analysis, Margaret Raber, Haley Allen, Sophia Huang, Maria Vazquez, Echo Warner, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

Background: The Mediterranean diet has been linked to reduced risk for several cardiometabolic diseases. The lack of a clear definition of the Mediterranean diet in the scientific literature and the documented proliferation of nutrition misinformation on the internet suggest the potential for confusion among consumers seeking web-based Mediterranean diet information.

Objective: We conducted a social media content analysis of information about the Mediterranean diet on the influential social media platform, TikTok, to examine public discourse about the diet and identify potential areas of misinformation. We then analyzed these findings in the context of health promotion to identify potential challenges and …

Microglial P2y6 Calcium Signaling Promotes Phagocytosis And Shapes Neuroimmune Responses In Epileptogenesis, Anthony D Umpierre, Bohan Li, Katayoun Ayasoufi, Whitney L Simon, Shunyi Zhao, Manling Xie, Grace Thyen, Benjamin Hur, Jiaying Zheng, Yue Liang, Dale B Bosco, Mark A Maynes, Zhaofa Wu, Xinzhu Yu, Jaeyun Sung, Aaron J Johnson, Yulong Li, Long-Jun Wu

The Brown Foundation: Institute of Molecular Medicine

Microglial calcium signaling is rare in a baseline state but strongly engaged during early epilepsy development. The mechanism(s) governing microglial calcium signaling are not known. By developing an in vivo UDP fluorescent sensor, GRABUDP1.0, we discovered that UDP release is a conserved response to seizures and excitotoxicity across brain regions. UDP can signal through the microglial-enriched P2Y6 receptor to increase calcium activity during epileptogenesis. P2Y6 calcium activity is associated with lysosome biogenesis and enhanced production of NF-κB-related cytokines. In the hippocampus, knockout of the P2Y6 receptor prevents microglia from fully engulfing neurons. Attenuating microglial calcium signaling through Calcium Extruder (“CalEx”) …

Microglial P2y6 Calcium Signaling Promotes Phagocytosis And Shapes Neuroimmune Responses In Epileptogenesis, Anthony D Umpierre, Bohan Li, Katayoun Ayasoufi, Whitney L Simon, Shunyi Zhao, Manling Xie, Grace Thyen, Benjamin Hur, Jiaying Zheng, Yue Liang, Dale B Bosco, Mark A Maynes, Zhaofa Wu, Xinzhu Yu, Jaeyun Sung, Aaron J Johnson, Yulong Li, Long-Jun Wu

Faculty, Staff and Student Publications

Microglial calcium signaling is rare in a baseline state but strongly engaged during early epilepsy development. The mechanism(s) governing microglial calcium signaling are not known. By developing an in vivo uridine diphosphate (UDP) fluorescent sensor, GRABUDP1.0, we discovered that UDP release is a conserved response to seizures and excitotoxicity across brain regions. UDP can signal through the microglial-enriched P2Y6 receptor to increase calcium activity during epileptogenesis. P2Y6 calcium activity is associated with lysosome biogenesis and enhanced production of NF-κB-related cytokines. In the hippocampus, knockout of the P2Y6 receptor prevents microglia from fully engulfing neurons. Attenuating microglial calcium signaling through calcium …

Targeting Il-11r/Ezh2 Signaling Axis As A Therapeutic Strategy For Osteosarcoma Lung Metastases, Eswaran Devarajan, R Eric Davis, Hannah C Beird, Wei-Lien Wang, V Behrana Jensen, Arumugam Jayakumar, Cheuk Hong Leung, Heather Y Lin, Chia-Chin Wu, Stephanie A Ihezie, Jen-Wei Tsai, P Andrew Futreal, Valerae O Lewis

Faculty, Staff and Student Publications

Lung metastases are the primary cause of death for osteosarcoma (OS) patients. We recently validated interleukin-11 receptor α (IL-11Rα) as a molecular target for the inhibition of OS lung metastases. Since there is no clinically approved antibody against this receptor, we sought to identify downstream targets that mediate the effects of IL-11Rα signaling. We used shRNA to deplete IL-11Rα from OS cells; as a complementary approach, we added IL-11 exogenously to OS cells. The resulting changes in gene expression identified EZH2 as a downstream candidate. This was confirmed by knockdown of IL-11Rα in OS cells, which led to increased expression …

Repeat Controlled Human Plasmodium Falciparum Infections Delay Bloodstream Patency And Reduce Symptoms, Patricia Ferrer, Andrea A Berry, Allison N Bucsan, Surendra K Prajapati, Karthik Krishnan, Michelle C Barbeau, David M Rickert, Sandra Mendoza Guerrero, Miho Usui, Yonas Abebe, Asha Patil, Sumana Chakravarty, Peter F Billingsley, Faith Pa'ahana-Brown, Kathy Strauss, Biraj Shrestha, Effie Nomicos, Gregory A Deye, B Kim Lee Sim, Stephen L Hoffman, Kim C Williamson, Kirsten E Lyke

Faculty, Staff and Student Publications

Resistance to clinical malaria takes years to develop even in hyperendemic regions and sterilizing immunity has rarely been observed. To evaluate the maturation of the host response against controlled repeat exposures to P. falciparum (Pf) NF54 strain-infected mosquitoes, we systematically monitored malaria-naïve participants through an initial exposure to uninfected mosquitoes and 4 subsequent homologous exposures to Pf-infected mosquitoes over 21 months (n = 8 males) (ClinicalTrials.gov# NCT03014258). The primary outcome was to determine whether protective immunity against parasite infection develops following repeat CHMI and the secondary outcomes were to track the clinical signs and symptoms of malaria and anti-Pf antibody …

Evolution Of Global Anatomy Research Through Covid-19: A Post-Pandemic Evaluation, Harsh Chheda, Santanu De

FDLA Journal

The Coronavirus Infectious Disease 2019 (COVID-19) struck the world with a deep impact on many countries' healthcare systems. More specifically, anatomical research experienced a drastic setback due to the limitations and restrictions placed upon them by the medical community. This study aims to review how COVID-19 guidelines presented conflict regarding the retrieval and use of cadavers, as well as how anatomy research was modified on a global scale owing to the pandemic. The COVID-19 outbreak called for several changes upon each significant anatomical research technique, ranging from cadaver dissection to diagnostic imaging. Given the remarkable shift in medical research guidelines …

Antidepressant Effect Of Enzymatic Porcine Placenta Hydrolysate In Repeated Immobilization Stress-Induced Ovariectomized Female Mice, Minsook Ye, Sharon Nguyen, Min Ju Kim, Jee Sun Hwang, Gun Won Bae, Keun-Hang Susan Yang, Insop Shim

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

When postmenopausal women are under stress conditions, this exacerbates mood disorders and issues with neuroimmune systems. The porcine placenta is known to relieve menopausal depression in clinical trials, but its underlying mechanisms for depression and anti-inflammatory functions remain poorly defined. The present study was designed to examine the anti-inflammatory effects of enzymatic porcine placenta hydrolysate (EPPH) on LPS-induced levels of nitric oxide (NO), prostaglandin E2 (PGE2), corticosterone (CORT), and pro-inflammatory cytokine interleukin-1 beta (IL-1β) in RAW 264.7 macrophage cells. In addition, the neurite outgrowth of PC12 cells was evaluated to examine the effects of EPPH on neurite growth. To mimic …

The Ifitm5 Mutation In Osteogenesis Imperfecta Type V Is Associated With An Erk/Sox9-Dependent Osteoprogenitor Differentiation Defect, Ronit Marom, I-Wen Song, Emily C Busse, Megan E Washington, Ava S Berrier, Vittoria C Rossi, Laura Ortinau, Youngjae Jeong, Ming-Ming Jiang, Brian C Dawson, Mary Adeyeye, Carolina Leynes, Caressa D Lietman, Bridget M Stroup, Dominyka Batkovskyte, Mahim Jain, Yuqing Chen, Racel Cela, Alexis Castellon, Alyssa A Tran, Isabel Lorenzo, D Nicole Meyers, Shixia Huang, Alicia Turner, Vinitha Shenava, Maegen Wallace, Eric Orwoll, Dongsu Park, Catherine G Ambrose, Sandesh Cs Nagamani, Jason D Heaney, Brendan H Lee

Faculty, Staff and Students Publications

Osteogenesis imperfecta (OI) type V is the second most common form of OI, distinguished by hyperplastic callus formation and calcification of the interosseous membranes, in addition to the bone fragility. It is caused by a recurrent, dominant pathogenic variant (c.-14C>T) in interferon-induced transmembrane protein 5 (IFITM5). Here, we generated a conditional Rosa26-knockin mouse model to study the mechanistic consequences of the recurrent mutation. Expression of the mutant Ifitm5 in osteo-chondroprogenitor or chondrogenic cells resulted in low bone mass and growth retardation. Mutant limbs showed impaired endochondral ossification, cartilage overgrowth, and abnormal growth plate architecture. The cartilage phenotype correlates with …

Sting Agonist 8803 Reprograms The Immune Microenvironment And Increases Survival In Preclinical Models Of Glioblastoma, Hinda Najem, Spencer T Lea, Shashwat Tripathi, Lisa Hurley, Chao-Hsien Chen, Ivana William, Moloud Sooreshjani, Michelle Bowie, Genevieve Hartley, Corey Dussold, Sebastian Pacheco, Crismita Dmello, Catalina Lee-Chang, Kathleen Mccortney, Alicia Steffens, Jordain Walshon, Martina Ott, Jun Wei, Anantha Marisetty, Irina Balyasnikova, Roger Stupp, Rimas V Lukas, Jian Hu, Charles David James, Craig M Horbinski, Maciej S Lesniak, David M Ashley, Waldemar Priebe, Leonidas C Platanias, Michael A Curran, Amy B Heimberger

Faculty, Staff and Student Publications

STING agonists can reprogram the tumor microenvironment to induce immunological clearance within the central nervous system. Using multiplexed sequential immunofluorescence (SeqIF) and the Ivy Glioblastoma Atlas, STING expression was found in myeloid populations and in the perivascular space. The STING agonist 8803 increased median survival in multiple preclinical models of glioblastoma, including QPP8, an immune checkpoint blockade-resistant model, where 100% of mice were cured. Ex vivo flow cytometry profiling during the therapeutic window demonstrated increases in myeloid tumor trafficking and activation, alongside enhancement of CD8+ T cell and NK effector responses. Treatment with 8803 reprogrammed microglia to express costimulatory CD80/CD86 …

Sars-Cov-2 Neurotropism: Understanding Effects At The Blood-Brain Barrier And Hematogenous Neuroinvasiveness, Taylor E. Martinez

USF Tampa Graduate Theses and Dissertations

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, has provisional counts of over 110 million documented cases and 1.218 million deaths (as of February 2024) in the United States since January 2020. SARS-CoV-2 is an airborne respiratory virus that primarily infects the lungs via the ACE2 receptor but has well-documented secondary target organs including the kidneys, the gastrointestinal tract, the heart, and the skin. SARS-CoV-2 also infects the brain, but the hematogenous route of viral entry to brain is still not fully characterized. Understanding how SARS-CoV-2 traverses the blood-brain barrier (BBB) as well as how it …

Ikzf1 And Ubr4 Gene Variants Drive Autoimmunity And Th2 Polarization In Igg4-Related Disease, Qingxiang Liu, Yanyan Zheng, Ines Sturmlechner, Abhinav Jain, Maryam Own, Qiankun Yang, Huimin Zhang, Filippo Pinto E Vairo, Karen Cerosaletti, Jane H Buckner, Kenneth J Warrington, Matthew J Koster, Cornelia M Weyand, Jörg J Goronzy

Faculty, Staff and Student Publications

IgG4-related disease (IgG4-RD) is a systemic immune-mediated fibroinflammatory disease whose pathomechanisms remain poorly understood. Here, we identified gene variants in familial IgG4-RD and determined their functional consequences. All 3 affected members of the family shared variants of the transcription factor IKAROS, encoded by IKZF1, and the E3 ubiquitin ligase UBR4. The IKAROS variant increased binding to the FYN promoter, resulting in higher transcription of FYN in T cells. The UBR4 variant prevented the lysosomal degradation of the phosphatase CD45. In the presence of elevated FYN, CD45 functioned as a positive regulatory loop, lowering the threshold for T cell activation. Consequently, …

Supporting Ontario Public Health Units To Address Adverse Childhood Experiences In Pandemic Recovery Planning: A Priority-Setting Exercise, Kimberly B Harding, Erica Di Ruggiero, Erick Gonzalez, Amanda Hicks, Daniel W Harrington, Sarah Carsley

Faculty, Staff and Student Publications

BACKGROUND: Adverse childhood experiences (ACEs) are potentially traumatic exposures experienced during childhood, for example, neglect. There is growing evidence that the coronavirus disease 2019 (COVID-19) pandemic and related socioeconomic conditions contributed to an increased risk of ACEs. As public health programs/services are re-evaluated and restored following the state of emergency, it is important to plan using an ACEs-informed lens. The aim of this study was to identify and prioritize initiatives or activities that Public Health Ontario (PHO) could undertake to support Ontario public health units' work towards ACEs-informed pandemic recovery plans.

METHODS: The Child Health and Nutrition Research Initiative method …

The Effect Of Phototherapy Treatment On Serum Melatonin Levels In Term Newborns, Ali̇ Bülbül, İlkay Özmeral Odabaşi, Duygu Besni̇li̇ Açar, Semra Ti̇ryaki̇ Demi̇r

Turkish Journal of Medical Sciences

Background/aim: The aim of this study was to investigate the effect of phototherapy treatment on serum melatonin levels in term newborn infants. Material and methods: This study was planned as a single-center, prospective, observational, case-control study. Term infants (gestation week ≥37 weeks) who received at least 6 h of phototherapy due to jaundice constitute the phototherapy group, while the term infants without jaundice and who were exclusively breastfed constitute the control group. Melatonin levels were examined by taking blood samples from babies in both groups at 02:00 at night. Melatonin values were compared between groups. The effect of phototherapy on …

Control Of Cardiometabolic Risk Factors And Their Association With Carotid Intima Media Thickness Among Patients With Type 2 Diabetes Mellitus-Single Center Experience In A Developing Country, Thilak Priyantha Weerarathna, Sarath Lekkamwasam, Iroshani Kodikara, Keddegoda Gamage Piyumi Wasana, Lakmal Fonseka

Turkish Journal of Medical Sciences

Background/aim: Type 2 diabetes mellitus (T2DM) is closely associated with atherosclerotic cardiovascular diseases (ASCVD). The objective of this study was to describe the degree of ASCVD risk factor control and their association with carotid intima-media thickness (CIMT) in T2DM patients followed up at a diabetes clinic in Southern, Sri Lanka. Materials and methods: A crosssectional study was conducted to examine the association between CIMT and nonalcoholic fatty liver disease (NAFLD)in 300 T2DM patients. Both CIMT and its associations with modifiable cardiometabolic risk factors were examined using ultrasonography. The recommended optimal targets for risk factors were defined as glycated hemoglobin (HbA1C) …

A Trna Modification Pattern That Facilitates Interpretation Of The Genetic Code, Isao Masuda, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

Interpretation of the genetic code from triplets of nucleotides to amino acids is fundamental to life. This interpretation is achieved by cellular tRNAs, each reading a triplet codon through its complementary anticodon (positions 34–36) while delivering the amino acid charged to its 3′-end. This amino acid is then incorporated into the growing polypeptide chain during protein synthesis on the ribosome. The quality and versatility of the interpretation is ensured not only by the codon-anticodon pairing, but also by the post-transcriptional modifications at positions 34 and 37 of each tRNA, corresponding to the wobble nucleotide at the first position of the …

Mycoplasmoides Genitalium Nucleic Acid Semi-Quantitation And Molecular Macrolide Resistance Detection Via Automated Assays: Gender And Specimen Source Considerations, Erik Munson, Josephine Moore, Trinity Krueger, Amanda Zapp, Stephen C Lavey, Kimber L Munson, Irene A Stafford, Brian Mustanski

Faculty, Staff and Student Publications

A laboratory-developed test (LDT) using analyte-specific reagents has been optimized on a commercial platform to detect macrolide resistance-associated mutations (MRM) in 23S rRNA from Mycoplasmoides genitalium from primary clinical specimens. In this study, MRM-LDT was applied to a multi-specimen source study set. One thousand four hundred ninety-five primary specimens testing positive for M. genitalium by commercial transcription-mediated amplification (TMA) were initially titered by the TMA assay using serial 10-fold dilutions to semi-quantitate target nucleic acid burden. Primary specimens were then processed for MRM detection using the MRM-LDT. Findings were stratified by gender and specimen source. The mean log10 target nucleic …

Machine Learning In Time-Lapse Imaging To Differentiate Embryos From Young Vs Old Mice†, Liubin Yang, Carolina Leynes, Ashley Pawelka, Isabel Lorenzo, Andrew Chou, Brendan Lee, Jason D Heaney

Faculty, Staff and Students Publications

Time-lapse microscopy for embryos is a non-invasive technology used to characterize early embryo development. This study employs time-lapse microscopy and machine learning to elucidate changes in embryonic growth kinetics with maternal aging. We analyzed morphokinetic parameters of embryos from young and aged C57BL6/NJ mice via continuous imaging. Our findings show that aged embryos accelerated through cleavage stages (from 5-cells) to morula compared to younger counterparts, with no significant differences observed in later stages of blastulation. Unsupervised machine learning identified two distinct clusters comprising of embryos from aged or young donors. Moreover, in supervised learning, the extreme gradient boosting algorithm successfully …

Rigor And Reproducibility In Human Brain Organoid Research: Where We Are And Where We Need To Go, Soraya O Sandoval, Gerarda Cappuccio, Karina Kruth, Sivan Osenberg, Saleh M Khalil, Natasha M Méndez-Albelo, Krishnan Padmanabhan, Daifeng Wang, Mark J Niciu, Anita Bhattacharyya, Jason L Stein, André M M Sousa, Elisa A Waxman, Elizabeth D Buttermore, Dosh Whye, Carissa L Sirois, Cross-Iddrc Human Stem Cell Consortium, Aislinn Williams, Mirjana Maletic-Savatic, Xinyu Zhao

Faculty, Staff and Students Publications

Human brain organoid models have emerged as a promising tool for studying human brain development and function. These models preserve human genetics and recapitulate some aspects of human brain development, while facilitating manipulation in an in vitro setting. Despite their potential to transform biology and medicine, concerns persist about their fidelity. To fully harness their potential, it is imperative to establish reliable analytic methods, ensuring rigor and reproducibility. Here, we review current analytical platforms used to characterize human forebrain cortical organoids, highlight challenges, and propose recommendations for future studies to achieve greater precision and uniformity across laboratories.

An Inducible Genetic Tool To Track And Manipulate Specific Microglial States Reveals Their Plasticity And Roles In Remyelination, Kia M Barclay, Nora Abduljawad, Zuolin Cheng, Min Woo Kim, Lu Zhou, Jin Yang, Justin Rustenhoven, Jose A Mazzitelli, Leon C D Smyth, Dvita Kapadia, Simone Brioschi, Wandy Beatty, Jinchao Hou, Naresha Saligrama, Marco Colonna, Guoqiang Yu, Jonathan Kipnis, Qingyun Li

The Brown Foundation: Institute of Molecular Medicine

Recent single-cell RNA sequencing studies have revealed distinct microglial states in development and disease. These include proliferative region-associated microglia (PAM) in developing white matter and disease-associated microglia (DAM) prevalent in various neurodegenerative conditions. PAM and DAM share a similar core gene signature. However, the extent of the dynamism and plasticity of these microglial states, as well as their functional significance, remains elusive, partly due to the lack of specific tools. Here, we generated an inducible Cre driver line, Clec7a-CreERT2, that targets PAM and DAM in the brain parenchyma. Utilizing this tool, we profiled labeled cells during development and in several …

Role Of Ethanolamine Utilization And Bacterial Microcompartment Formation In Listeria Monocytogenes Intracellular Infection, Ayan Chatterjee, Karan Gautam Kaval, Danielle A Garsin

Faculty, Staff and Student Publications

Ethanolamine (EA) affects the colonization and pathogenicity of certain human bacterial pathogens in the gastrointestinal tract. However, EA can also affect the intracellular survival and replication of host cell invasive bacteria such as Listeria monocytogenes (LMO) and Salmonella enterica serovar Typhimurium (S. Typhimurium). The EA utilization (eut) genes can be categorized as regulatory, enzymatic, or structural, and previous work in LMO showed that loss of genes encoding functions for the enzymatic breakdown of EA inhibited LMO intracellular replication. In this work, we sought to further characterize the role of EA utilization during LMO infection of host …

Slow Proliferation Of Bap1-Deficient Uveal Melanoma Cells Is Associated With Reduced S6 Signaling And Resistance To Nutrient Stress, Vivian Chua, Melisa Lopez-Anton, Mizue Terai, Ryota Tanaka, Usman Baqai, Timothy J Purwin, Jelan I Haj, Francis J Waltrich, Isabella Trachtenberg, Kristine Luo, Rohith Tudi, Angela Jeon, Anna Han, Inna Chervoneva, Michael A Davies, Julio A Aguirre-Ghiso, Takami Sato, Andrew E Aplin

Faculty, Staff and Student Publications

Uveal melanoma (UM) is the deadliest form of eye cancer in adults. Inactivating mutations and/or loss of expression of the gene encoding BRCA1-associated protein 1 (BAP1) in UM tumors are associated with an increased risk of metastasis. To investigate the mechanisms underlying this risk, we explored the functional consequences of BAP1 deficiency. UM cell lines expressing mutant BAP1 grew more slowly than those expressing wild-type BAP1 in culture and in vivo. The ability of BAP1 reconstitution to restore cell proliferation in BAP1-deficient cells required its deubiquitylase activity. Proteomic analysis showed that BAP1-deficient cells had decreased phosphorylation of ribosomal S6 and …

Folate As A Potential Treatment For Lethal Ventricular Arrhythmias In Tango2-Deficiency Disorder, Weiyi Xu, Yingqiong Cao, Sara B Stephens, Maria Jose Arredondo, Yifan Chen, William Perez, Liang Sun, Andy C Yu, Jean J Kim, Seema R Lalani, Na Li, Frank T Horrigan, Francisco Altamirano, Xander Ht Wehrens, Christina Y Miyake, Lilei Zhang

Faculty, Staff and Students Publications

TANGO2-deficiency disorder (TDD) is an autosomal-recessive genetic disease caused by biallelic loss-of-function variants in the TANGO2 gene. TDD-associated cardiac arrhythmias are recalcitrant to standard antiarrhythmic medications and constitute the leading cause of death. Disease modeling for TDD has been primarily carried out using human dermal fibroblast and, more recently, in Drosophila by multiple research groups. No human cardiomyocyte system has been reported, which greatly hinders the investigation and understanding of TDD-associated arrhythmias. Here, we established potentially novel patient-derived induced pluripotent stem cell differentiated cardiomyocyte (iPSC-CM) models that recapitulate key electrophysiological abnormalities in TDD. These electrophysiological abnormalities were rescued in iPSC-CMs …

Intouch Week Of June 10, 2024, New York Medical College

InTouch

• Kenneth Theobalds To Be Honored at NYMC’s Annual Golf Tournament
• NYMC Opens New Online Store
• Dylan Kwart, Ph.D., M.Sc., Presents at the Neighborhood Science Seminar Series
• NYMC Welcomes D.P.T. Class of 2027 at New Student Orientation
• Construction on the MEC Roadway
• Metropolitan Hospital Center Research Day Highlights NYMC Residents Work
• Socioeconomic Disparities Exist in Treatment of Teen Femoral Fractures
• Student Spotlight: SOM Student Harry Fruchtman Sheds Lights on New Cancer Treatments with Publications in Nature

The Emerging Biomarkers In Chronic Obstructive Pulmonary Disease: A Narrative Review, Kaitlin M Phillips, Philip F Lavere, Nicola A Hanania, Muhammad Adrish

Faculty, Staff and Students Publications

The burden of chronic obstructive pulmonary disease (COPD) is increasing, especially for women in low-to-middle income countries. Biomarkers provide ever-increasing diagnostic precision for COPD and show promise for primary, secondary, and tertiary disease prevention. This review describes emerging applications for biomarkers in COPD, especially as they align with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) emphasis on prevention, early diagnosis, and response to therapy. These biomarkers include blood eosinophils; IgE; C-reactive protein; fibrinogen; procalcitonin; interleukins 6, 8, and 33; tumor necrosis factor alpha; and soluble receptor for advanced glycated products (sRAGE). They have been used in various ways …