Digital Commons Network^™

Galntl5 Binds Galnac And Is Required For Migration Through The Uterotubal Junction And Sperm-Zona Pellucida Binding, Taichi Noda, Reika Uriu, Daisuke Mashiko, Hina Shinohara, Yongcun Qu, Ayumu Taira, Ryan M Matzuk, Duri Tahala, Motochika Nakano, Kimi Araki, Zhifeng Yu, Ying Zhang, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

More than 20 genes expressed in the male reproductive tract have been identified as essential factors for sperm migration to and through the utero-tubal junction (UTJ), and they are divided into ADAM3-dependent and ADAM3-independent pathways. In parallel, sperm having UTJ migration defects also show impaired binding to the zona pellucida (ZP). Herein, we demonstrate that knockout of Galntl5, encoding a sperm surface protein, causes impaired sperm binding with the UTJ and ZP, and null males have severe infertility. GALNTL5 appreciably disappears in sperm lacking Adam3 or Lypd4, required for ADAM3-dependent and ADAM3-independent pathways, and GALNTL5 binds to N …

Notch1 Reverses Immune Suppression In Small Cell Lung Cancer Through Reactivation Of Sting, Yoo Sun Kim, Haobin Chen, Et Al.

2020-Current year OA Pubs

Downregulation of antigen presentation and lack of immune infiltration are defining features of small cell lung cancer (SCLC), limiting response to immune checkpoint blockade (ICB). While a high-MHC class I, immune-inflamed subset benefits from ICB, underlying mechanisms of immune response in SCLC have yet to be elucidated. Here we show that in the IMpower133 clinical trial, high, but not low, NOTCH1 expression was significantly associated with longer survival with the addition of ICB to chemotherapy among approximately 80% of SCLC patients with NE-enriched tumors (ASCL1-enriched, HR 0.39, P = 0.0012; NEUROD1-enriched, HR 0.44, P = 0.024). Overexpression or pharmacologic activation …

Elevated Nr2f1 Underlies The Persistence Of Invasive Disease After Treatment Of Braf-Mutant Melanoma, Manoela Tiago, Timothy J Purwin, Casey D Stefanski, Renaira Oliveira Da Silva, Mitchell E Fane, Yash Chhabra, Jelan I Haj, Jessica Lf Teh, Rama Kadamb, Weijia Cai, Sheera R Rosenbaum, Vivian Chua, Nir Hacohen, Michael A Davies, Jessie Villanueva, Inna Chervoneva, Ashani T Weeraratna, Dan A Erkes, Claudia Capparelli, Julio A Aguirre-Ghiso, Andrew E Aplin

Faculty, Staff and Student Publications

Despite the success of targeted inhibitors in cutaneous melanoma, therapeutic responses are limited by the aged tumor microenvironment and drug-tolerant residual cells. Given the similarities between drug tolerance and cellular dormancy, we studied the dormancy marker, nuclear receptor subfamily 2 group F member 1 (NR2F1), in response to BRAF-V600E inhibitors (BRAFi) plus MEK inhibitors (MEKi) in BRAF-mutant melanoma models. Transcriptomic analysis of melanoma patient samples treated with BRAFi + MEKi showed increased NR2F1. NR2F1 was highly expressed in the drug-tolerant invasive cell state of minimal residual disease in patient-derived and mouse-derived xenografts on BRAFi + MEKi. NR2F1 over-expression was sufficient …

Digitized Endocasts And Brains: A Perspective On Measurements And Historical Analyses Of The Evolution Of 172 Fossil And Extant Amniote Specimens, Harry J Jerison, Catherine M Early, Andrew A Farke, Ashley C Morhardt

2020-Current year OA Pubs

This perspective paper is intended to stimulate future research and discussion of brain evolution in amniotes by sharing 172 digitized endocasts of extinct and extant species spanning 60 million years. Using 3D digital surface scans of physical (

Sorting Nexin 3 Promotes Ischemic Retinopathy Through Rip1- And Rip3-Mediated Myeloid Cell Necroptosis And Mitochondrial Fission, Jiaojiao Wang, Chunhong Zhou, Kai Zhuang, Jiami Zou, Wanlu Qiu, Mei Jin, Weile Ye, Pinglian Yang, Zhihua Zheng, Qing Zhou, Zunnan Huang, Yuanxiang Wang, Peiqing Liu, Jing Lu, Yuqing Huo, Zhiping Liu

Faculty, Staff and Students Publications

Proliferative retinopathy is a leading cause of irreversible blindness in humans; however, the molecular mechanisms behind the immune cell–mediated retinal angiogenesis remain poorly elucidated. Here, using single-cell RNA sequencing in an oxygen-induced retinopathy (OIR) model, we identified an enrichment of sorting nexin (SNX)-related pathways, with SNX3, a member of the SNX family that is involved in endosomal sorting and trafficking, being significantly upregulated in the myeloid cell subpopulations of OIR retinas. Immunostaining showed that SNX3 expression is markedly increased in the retinal microglia/macrophages of mice with OIR, which is mainly located within and around the neovascular tufts. Myeloid cell-specific deficiency …

Developmental Transformations Of Purkinje Cells Tracked By Dna Electrokinetic Mobility, Cheryl Brandenburg, Garrett W Crutcher, Andrea J Romanowski, Sarah G Donofrio, Lita R Duraine, Richard N A Owusu-Mensah, Benjamin H Cooper, Izumi Sugihara, Gene J Blatt, Roy V Sillitoe, Alexandros Poulopoulos

Duncan NRI Faculty and Staff Publications

Brain development begins with neurogenesis in progenitor zones and ends with expansive, intricately-patterned cellular diversity in the adult brain. We took advantage of bioelectric interactions between DNA and embryonic tissue to perform "stereo-tracking," a developmental targeting strategy that differentially labels cells at different depths within progenitor zones. This 3D labeling was achieved by delivery of plasmids with distinct electrokinetic mobilities in utero. We applied stereo-tracking with light sheet imaging in the cerebellum and identified that Purkinje cells follow embryonically committed developmental trajectories, linking distinct progenitor zone subfields to the mature topography of the cerebellar cortex. We additionally identified an unexpected …

Setd2 Suppresses Tumorigenesis In A Krasg12c-Driven Lung Cancer Model, And Its Catalytic Activity Is Regulated By Histone Acetylation, Ricardo J Mack, Natasha M Flores, Geoffrey C Fox, Hanyang Dong, Metehan Cebeci, Simone Hausmann, Tourkian Chasan, Jill M Dowen, Brian D Strahl, Pawel K Mazur, Or Gozani

Faculty, Staff and Student Publications

Histone H3 trimethylation at lysine 36 (H3K36me3) is a key chromatin modification that regulates fundamental physiological and pathological processes. In humans, SETD2 is the only known enzyme that catalyzes H3K36me3 in somatic cells and is implicated in tumor suppression across multiple cancer types. While there is considerable crosstalk between the SETD2-H3K36me3 axis and other epigenetic modifications, much remains to be understood. Here, we show that Setd2 functions as a potent tumor suppressor in a KRASG12C-driven lung adenocarcinoma (LUAD) mouse model, and that acetylation enhances SETD2 in vitro methylation of H3K36 on nucleosome substrates. In vivo, Setd2 ablation accelerates lethality in …

Non-Neutralizing Antibodies To Influenza A Matrix-Protein-2-Ectodomain Are Broadly Effective Therapeutics And Resistant To Viral Escape Mutations., Teha Kim, Lynn Bimler, Sydney L Ronzulli, Amber Y Song, Scott K Johnson, Cheryl A Jones, S Mark Tompkins, Silke Paust

Faculty Research 2025

Influenza A viruses remain a global health threat, yet no universal antibody therapy exists. Clinical programs have centered on neutralizing mAbs, only to be thwarted by strain specificity and rapid viral escape. We instead engineered three non-neutralizing IgG2a mAbs that target distinct, overlapping epitopes within the conserved N terminus of the M2 ectodomain (M2e). Combined at low dose, this "triple M2e-mAb" confers robust prophylactic and therapeutic protection in mice challenged with diverse human and zoonotic IAV strains, including highly pathogenic variants. Therapeutic efficacy depends on Fc-mediated effector activity via FcγRI, FcγRIII, and FcγRIV, rather than in vitro neutralization. Serial passaging …

Identification And Characterization Of A Metal Binding-Independent Rift Valley Fever Virus Endonuclease Inhibitor, Cara D Kirby, Gai Liu, Farheen Fatma, Maris R Pedlow, Narendran G-Dayanandan, Nitin Sharma, Zachary D Frey, Rachael E Rush, Steven C Cardinale, Andrzej M Krezel, Amy L Hartman, Terry L Bowlin, Daisy W Leung, Gaya K Amarasinghe

2020-Current year OA Pubs

The viral cap-snatching mechanism, facilitated by the endonuclease (EndoN) domain of viral polymerases, is critical for viral gene transcription and translation and is therefore an attractive target for antiviral development. The successful development of EndoN inhibitor XOFLUZA (Baloxavir marboxil) has opened the possibility that the EndoN domain of negative-sense RNA viruses (NSVs) can be targeted in a similar fashion. Rift Valley Fever Virus (RVFV) belongs to the

A Novel Sialylation Pathway Mediated By Extracellular Vesicles In Aggressive Prostate Cancer, Camila A. Bach, Md Niamat Hossain, Ishan J. Chaudhari, Cecilia E. Verrillo, Nicole M. Naranjo, Isabella Amoroso, Anna Testa, Samuel Sey, W. Kevin Kelly, Susan L. Bellis, Aurelio Lorico, Ada G. Blidner, Gabriel A. Rabinovich, Lucia R. Languino

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Altered cell surface glycosylation is a hallmark of cancer; among aberrant glycan structures, hypersialylated proteins contribute to disease progression. The enzyme ST6 β-galactoside α2,6-sialyltransferase 1 (ST6GAL1) mediates α2,6-linked sialylation of N-glycosylated proteins and is upregulated in many cancers, including prostate cancer (PrCa). We propose that ST6GAL1 may be released by cancer cells in small extracellular vesicles (sEVs) in the PrCa tumor microenvironment to potentially modulate cell surface sialylation in recipient cells. We isolated sEVs from PrCa cells by density gradient separation and characterized them by nanoparticle tracking analysis using ZetaView and immunoblotting analysis. We identified ST6GAL1 in both its membrane-bound …

Infusion Of Blood From Young And Old Mice Modulates Amyloid Pathology, Matias Pizarro, Ruben Gomez-Gutierrez, Ariel Caviedes, Catalina Valdes, Ute Woehlbier, Cristian Vargas, Mauricio Hernandez, Claudia Duran-Aniotz, Rodrigo Morales

Faculty, Staff and Student Publications

Alzheimer's disease (AD) is a neurodegenerative disease characterized by the accumulation of misfolded proteins in the brain. Recently, the impact of blood components in the progression of this disease has come to attention. This study investigates the effects of infusing blood from young and old wild-type mice into transgenic mice that model AD brain amyloidosis. Impaired memory and Aβ accumulation were observed in mice infused with blood from old donors. A proteomic analysis in the brain of these mice identified alterations in components related to synaptogenesis and the endocannabinoid system. The α2δ2 protein, associated with neuronal calcium regulation, was validated …

Loss Of Ptdss1 In Tumor Cells Improves Immunogenicity And Response To Anti-Pd-1 Therapy, Jielin Liu, Shelley Herbrich, Sreyashi Basu, Yulong Chen, Ashwat Nagarajan, Swetha Anandhan, Sangeeta Goswami, Liangwen Xiong, Baoxiang Guan, Padmanee Sharma

Faculty, Staff and Student Publications

PTDSS1 (phosphatidylserine synthase 1) encodes an enzyme that facilitates production of phosphatidylserine (PS), which mediates a global immunosuppressive signal. Here, based on in vivo CRISPR screen, we identified PTDSS1 as a target to improve anti-PD-1 therapy. Depletion of Ptdss1 in tumor cells increased expression of interferon-γ (IFN-γ)-regulated genes, including B2m, Cxcl9, Cxcl10, and Stat1, even in the absence of IFN-γ stimulation in vitro. Loss of Ptdss1 in tumor cells also led to increased expression of MHC-I, enhanced cytotoxicity of CD8+ T cells, and increased frequency of an iNOS+ myeloid subset. A gene signature derived from the …

Neurotransmitter Signaling In Molecular And Behavioral Immune Responses To Pathogens In C Elegans, Benson Otarigho, Alejandro Aballay

Faculty, Staff and Student Publications

Neurotransmitter signaling pathways play major roles in both molecular and behavioral defenses against pathogen invasion, shaping the ability of Caenorhabditis elegans to sense and respond to environmental challenges. Given the conservation of neurotransmitter signaling pathways, their understanding may not only provide insights into the neurobiology of C. elegans but also has broader implications for our understanding of neural-immune interactions and host defense mechanisms in higher organisms. In this review, we discussed the literature on various neurotransmitter signaling pathways, including serotonergic, dopaminergic/octopaminergic, GABAergic, and glutamatergic pathways, and how these pathways modulate molecular and behavioral immune defense against pathogens.

The Colonic Crypt: Cellular Dynamics And Signaling Pathways In Homeostasis And Cancer, Anh L. Nguyen, Molly A. Lausten, Bruce M. Boman

College of Life Sciences Faculty Papers

The goal of this review is to expand our understanding of how the cellular organization of the normal colonic crypt is maintained and elucidate how this intricate architecture is disrupted during tumorigenesis. Additionally, it will focus on implications for new therapeutic strategies targeting Epithelial-Mesenchymal Transition (EMT). The colonic crypt is a highly structured epithelial unit that functions in maintaining homeostasis through a complex physiological function of diverse cell types: SCs, transit-amplifying (TA) progenitors, goblet cells, absorptive colonocytes, Paneth-like cells, M cells, tuft cells, and enteroendocrine cells. These cellular subpopulations are spatially organized and regulated by multiple crucial signaling pathways, including …

Human Toxocariasis, Susana Lopez-Alamillo, Pravallika Padyala, Megan Carey, Megan M Duffey, Jill E Weatherhead

Faculty, Staff and Students Publications

Human toxocariasis is a globally prevalent zoonotic parasitic infection caused by larvae of Toxocara species, primarily Toxocara canis and Toxocara cati. Toxocariasis is commonly transmitted to humans through the ingestion of embryonated Toxocara eggs found in contaminated soil, water, or on surfaces contaminated with animal feces. Unlike in dogs and cats, humans are not definitive hosts for Toxocara spp., and, as a result, Toxocara larvae do not complete their life cycle in humans. Instead, following accidental oral ingestion of embryonated eggs, Toxocara larvae undergo an aberrant larval migratory cycle to various organs including the lungs, liver, muscles, and central …

Retinoid-X-Receptor As A Mediator Of Poststroke Recovery By Reversing Age-Associated Phenotypes Of Microglia/Hematogenous Macrophages, Shun-Ming Ting, Xiurong Zhao, Guanghua Sun, Mercedes Ricote, Jaroslaw Aronowski

Faculty, Staff and Student Publications

After stroke, microglia and hematogenous macrophages, together referred to as MΦ, clear dead cells and cellular debris in the infarcted brain through phagocytosis as an essential part of the recovery process. However, the phagocytic capability of MΦ declines with age. Furthermore, aged MΦ become overactivated in response to stroke, enhancing secondary brain injury. In this study, we demonstrated that by reversing the age-related dysfunctions in MΦ through activating the retinoid X receptor (RXR), the recovery after stroke in the aged brain could be improved. Using RNA-sequencing, we compared the transcriptomes between MΦ isolated from the brains of young and aged …

Infectious Prions In Brains And Muscles Of Domestic Pigs Experimentally Challenged With The Bse, Scrapie, And Cwd Agents, Francisca Bravo-Risi, Fraser Brydon, Angela Chong, Kane Spicker, Justin J Greenlee, Glenn Telling, Claudio Soto, Sandra Pritzkow, Marcelo A Barria, Rodrigo Morales

Faculty, Staff and Student Publications

Experimental studies suggest that animal species not previously described as naturally infected by prions are susceptible to prion diseases affecting sheep, cattle, and deer. These interspecies transmissions may generate prions with unknown host ranges. Pigs are susceptible to prions from different origins, including deer chronic wasting disease (CWD), sheep scrapie, and bovine spongiform encephalopathy (BSE). Here, we studied prions in brains and muscles from pigs previously infected with these different prion sources. Specifically, we measured the total prion protein (PrP) and PK-resistant PrP by western blot. Seeding activity in these tissues was evaluated using the protein misfolding cyclic amplification (PMCA) …

Inhibition Of The Ufd-1-Npl-4 Complex Triggers An Aberrant Immune Response In Caenorhabditis Elegans, Rajneesh Rao, Alejandro Aballay, Jogender Singh

Faculty, Staff and Student Publications

The UFD-1 (ubiquitin fusion degradation 1)-NPL-4 (nuclear protein localization homolog 4) heterodimer is involved in extracting ubiquitinated proteins from several plasma membrane locations, including the endoplasmic reticulum. This heterodimer complex helps in the degradation of ubiquitinated proteins via the proteasome with the help of the AAA+ATPase CDC-48. While the ubiquitin-proteasome system is known to have important roles in maintaining innate immune responses, the role of the UFD-1-NPL-4 complex in regulating immunity remains elusive. In this study, we investigate the role of the UFD-1-NPL-4 complex in maintaining

Endothelin B Receptor Inhibition Rescues Aging-Dependent Neuronal Regenerative Decline, Rui Feng, Sarah F Rosen, Irshad Ansari, Sebastian John, Michael B Thomsen, Oshri Avraham, Cedric G Geoffroy, Valeria Cavalli

2020-Current year OA Pubs

Peripheral sensory neurons regenerate their axons after injury to regain function, but this ability declines with age. The mechanisms behind this decline are not fully understood. While excessive production of endothelin 1 (ET-1), a potent vasoconstrictor, is linked to many diseases that increase with age, the role of ET-1 and its receptors in axon regeneration is unknown. Using single-cell RNA sequencing, we show that satellite glial cells (SGCs), which completely envelop the sensory neuron soma residing in the dorsal root ganglia (DRG), express the endothelin B receptor (ETBR), while ET-1 is expressed by endothelial cells. Inhibition of ETBR ex vivo …

Fatty Acid 2-Hydroxylase Facilitates Rotavirus Uncoating And Endosomal Escape, Enkai Li, Ruochen Zang, Takahiro Kawagishi, Wei Zhang, Kruthika Iyer, Gaopeng Hou, Qiru Zeng, Rita M Meganck, Susan R Ross, Xin Wang, Xiong Su, Siyuan Ding

2020-Current year OA Pubs

Despite the clinical significance of many nonenveloped viruses, the molecular mechanisms of their internalization and membrane penetration are not well understood. Rotaviruses (RVs) are nonenveloped double-stranded RNA viruses and the leading cause of severe dehydrating diarrhea in infants and young children. We identified fatty acid 2-hydroxylase (encoded by

Therapeutic Restoration Of Mitochondria-Endoplasmic Reticulum Cross Talk For Osteoarthritis, Mingzhuang Hou, Yifan Ma, Yaoge Deng, Yubin Wu, Yanrun Zhu, Yang Liu, Xiaoping Li, Lili Yu, Zirui He, Yifan Wang, Shiyan Dong, Xiaowei Xia, Jianfeng Yu, Chenqi Yu, Kang Kang, Yingjie Lu, Lili Sun, Betty Y S Kim, Yuan Yuan, Yijian Zhang, Wen Jiang, Xuesong Zhu

Faculty, Staff and Student Publications

Osteoarthritis is a prevalent joint disease in the aging population. The hallmark of osteoarthritis is the degeneration of the joint cartilage, characterized by changes in chondrocytes including mitochondrial dysfunction. However, the precise mechanisms of how this affects chondrocyte homeostasis and whether such processes can be explored as therapeutic targets for osteoarthritis remain unclear. Here, we show that impaired mitochondrial function and disrupted cartilage matrix metabolism due to loss of mitofusin-2 (MFN2) expression in chondrocytes leads to the development of osteoarthritis. Sirtuin-3 (SIRT3), a key regulator of mitochondrial function, plays a critical role in modulating MFN2 to restore mitochondrial dynamics, reduce …

Testis Expressed 50 Is Essential For Maintaining Sperm Acrosome Integrity During Epididymal Transit, Saori Haga, Kaori Nozawa, Ferheen Abbasi, Katarzyna Kent, Naoko Nagasawa, Tsutomu Endo, Haruhiko Miyata, Masahito Ikawa, Martin M Matzuk, Yoshitaka Fujihara

Faculty, Staff and Students Publications

In mammals, sperm formation is completed in the seminiferous tubules within the testis, and sperm maturation occurs during the epididymal transit of the spermatozoa. Sperm morphology drastically changes when abnormal spermatozoa migrate from the testis to the epididymis. Detailed molecular mechanisms for sperm survival in the epididymis have not been determined yet. Globozoospermia is a cause of male infertility and is characterized by round-headed spermatozoa without acrosomes, an abnormal sperm nuclear membrane, and sperm midpiece defects. Testis expressed 50 (Tex50) is a testis-enriched gene that is expressed in mice and humans. Using CRISPR-Cas9, we generated Tex50 knockout (KO) …

Computationally Resolved Neuroprogenitor Cell Biomarkers Associate With Human Disorders, Gerarda Cappuccio, William T Choi, Fatih Semerci, Jill A Rosenfeld, Toni Claire Tacorda, Guantong Qi, Anthony W Zoghbi, Yi Zhong, Hu Chen, Pengfei Liu, Zhandong Liu, Mirjana Maletić-Savatić

Duncan NRI Faculty and Staff Publications

Adult hippocampal neurogenesis, the process of generating new neurons, relies on a rare population of neural stem and progenitor cells (NPCs) within the dentate gyrus complex microenvironment. Discovering the specific genes that define these cells is vital yet challenging due to overlapping expression patterns, limiting detection of rare cell populations using traditional approaches. By employing the computational digital sorting algorithm (DSA) that deconvolves complex gene expression data based on pattern recognition, we identified 129 genes enriched in murine NPCs. We validated these genes against published single-cell RNA sequencing (scRNA-seq) data and discovered that 25 human orthologs were known to cause …

Dissecting The Effect Of Mitochondrial Bcat Inhibition In Methylmalonic Acidemia, Madeline G Hemmingsen, Guo-Fang Zhang, Yunhan Ma, Hannah Marchuk, Kalyani R Patel, Tong Chen, Xinning Li, Mark Chapman, Sabrina Collias, Dolores H Lopez-Terrada, James Beasley, Ashlee R Stiles, Randy J Chandler, Charles P Venditti, Sarah P Young, Mercedes Barzi, Beatrice Bissig-Choisat, Doug Krafte, Christopher B Newgard, Karl-Dimiter Bissig

Faculty, Staff and Students Publications

Methylmalonic acidemia (MMA) is a severe metabolic disorder affecting multiple organs because of a distal block in branched-chain amino acid (BCAA) catabolism. Standard of care is limited to protein restriction and supportive care during metabolic decompensation. Severe cases require liver/kidney transplantation, and there is a clear need for better therapy. Here, we investigated the effects of a small molecule branched-chain amino acid transaminase (BCAT) inhibitor in human MMA hepatocytes and an MMA mouse model. Mitochondrial BCAT is the first step in BCAA catabolism, and reduction of flux through an early enzymatic step is successfully used in other amino acid metabolic …

Interindividual Genetic Differences Drive Discordance Between Serum Calcidiol And Calcitriol Concentrations In Females., Elizabeth K Hutchins, Changran Niu, Jing Xue, Debin Wan, Carolina V Campos, Molly Warren, Megan M Knuth, Michael B Whalen, Venkata S Voruganti, Rafiou Agoro, James C Fleet, Bruce D Hammock, Folami Ideraabdullah

Faculty Research 2025

Vitamin D insufficiency (VDI) is primarily determined by serum levels of calcidiol, which serves as a biomarker for the less abundant but most potent bioactive metabolite, calcitriol. However, population studies often show discordance between calcidiol and calcitriol. Here, a genetically diverse population of 7 inbred mouse strains was used to investigate the role of interindividual genetic differences in driving calcidiol-to-calcitriol discordance under vitamin D sufficient (VDS) vs depleted (VDD) conditions. We found high interstrain variability in calcitriol that was discordant with calcidiol under VDS and VDD conditions. However, under VDS conditions, stratification by calcitriol level revealed that strains with serum …

Chemo-Rast With Bortezomib Inhibits Multiple Myeloma Relapse, Anchal Ghai, Alexander Zheleznyak, Christopher Egbulefu, Nicole Blasi, Kvar Black, Rui Tang, Matthew L Cooper, Kiran Vij, Ravi Vij, John Dipersio, Monica Shokeen, Samuel Achilefu

2020-Current year OA Pubs

No abstract provided.

Gene Context Drift Identifies Drug Targets To Mitigate Cancer Treatment Resistance, Amir Jassim, Birgit V Nimmervoll, Sabrina Terranova, Erica Nathan, Linda Hu, Jessica T Taylor, Katherine E Masih, Lisa Ruff, Matilde Duarte, Elizabeth Cooper, Gunjan Katyal, Melika Akhbari, Reuben J Gilbertson, Jennifer C Coleman, Joseph S Toker, Colton Terhune, Gabriel Balmus, Stephen P Jackson, Hailong Liu, Tao Jiang, Michael D Taylor, Kui Hua, Jean E Abraham, Mariella G Filbin, Anthony Hill, Anarita Patrizi, Neil Dani, Aviv Regev, Maria K Lehtinen, Richard J Gilbertson

Faculty, Staff and Students Publications

Cancer treatment often fails because combinations of different therapies evoke complex resistance mechanisms that are hard to predict. We introduce REsistance through COntext DRift (RECODR): a computational pipeline that combines co-expression graph networks of single-cell RNA sequencing profiles with a graph-embedding approach to measure changes in gene co-expression context during cancer treatment. RECODR is based on the idea that gene co-expression context, rather than expression level alone, reveals important information about treatment resistance. Analysis of tumors treated in preclinical and clinical trials using RECODR unmasked resistance mechanisms -invisible to existing computational approaches- enabling the design of highly effective combination treatments …

Identification Of Cobra And Viper Bites In Southern India Using Enzyme-Linked Immunosorbent Assay, Tejeswara Rao Asuru, Raskin Erusan Rajagopal, Albert Rajendran, Gulistan Parveen, Anushka Das, Pabitha Devi, Swapan K Dasgupta, Shantaraman Kalyanaraman, Prasenjit Guchhait, Perumal Thiagarajan

Faculty, Staff and Students Publications

Introduction: Snakebite-related deaths are major concerns in populations worldwide that lack access to medical care. Current treatment of snakebites includes administration of polyspecific and polyvalent heterologous equine antiserum. Swift diagnosis of the species of snake responsible is essential to initiate a specific treatment.

Methods: We generated murine monoclonal and rabbit polyclonal antibodies against the venom of the 3 most common venomous snakes in southern India: the Russell viper, the saw-scaled viper, and the Indian cobra. We developed an enzyme-linked immunosorbent assay to distinguish the snake by analyzing the exudates from the snakebite wound.

Results: Monoclonal antibody EC3 reacts specifically with …

Post-Translational Modification Of H2b C-Terminal Helix Regulates Nucleosome Interactions And Chromatin Signaling, Yani Zhao, Anh Nguyen, Eyla C Arteaga, Aleksandra Skrajna, Krzysztof Krajewski, Dennis Goldfarb, Robert K Mcginty

2020-Current year OA Pubs

Histone H2B contains a highly conserved C-terminal (H2B αC) helix that has been implicated in chromatin interactions and dynamics. The H2B αC helix comprising residues 105-125 is positioned adjacent to a major site of nucleosome interactions called the acidic patch. Despite individual structural studies highlighting interactions between chromatin proteins and the H2B αC helix, the general role of the helix in mediating nucleosome recognition has not been explored. Moreover, many post-translational modifications (PTMs) have been identified within the H2B αC helix, but significant gaps exist in our understanding of their regulatory potential. In this study, we employed nucleosome affinity proteomics …

Lewy Body Dementia Promotion By Air Pollutants, Xiaodi Zhang, Haiqing Liu, Xiao Wu, Longgang Jia, Kundlik Gadhave, Lena Wang, Kevin Zhang, Hanyu Li, Rong Chen, Ramhari Kumbhar, Ning Wang, Chantelle E Terrillion, Bong Gu Kang, Bin Bai, Minhan Park, Ma Cristine Faye Denna, Shu Zhang, Wenqiang Zheng, Denghui Ye, Xiaoli Rong, Liu Yang, Lili Niu, Han Seok Ko, Weiyi Peng, Lingtao Jin, Mingyao Ying, Liana S Rosenthal, David W Nauen, Alex Pantelyat, Mahima Kaur, Kezia Irene, Liuhua Shi, Rahel Feleke, Sonia García-Ruiz, Mina Ryten, Valina L Dawson, Francesca Dominici, Rodney J Weber, Xuan Zhang, Pengfei Liu, Ted M Dawson, Shizhong Han, Xiaobo Mao

Faculty, Staff and Student Publications

Evidence links air pollution to dementia, yet its role in Lewy body dementia (LBD) remains unclear. Here we showed in a cohort of 56.5 million individuals across the U.S. that PM2.5 exposure raises LBD risk. Mechanistically, we found PM2.5 exposure led to brain atrophy in wild-type mice, an effect not seen in α-synuclein (αSyn)-deficient mice. PM2.5 exposure generated a highly pathogenic αSyn strain, PM-PFF, with enhanced proteinase K-resistance and neurotoxicity, resembling αSyn LBD strains. PM2.5 samples from China, the U.S., and Europe consistently induced proteinase-resistant αSyn strains and in vivo pathology. Transcriptomic analyses revealed shared responses between PM2.5-exposed mice and …