Norma Neff
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View article: Altered immune and metabolic molecular pathways drive islet cell dysfunction in human type 1 diabetes
Altered immune and metabolic molecular pathways drive islet cell dysfunction in human type 1 diabetes Open
Type 1 diabetes (T1D) is characterized by the autoimmune destruction of most insulin-producing β cells, along with dysregulated glucagon secretion from pancreatic α cells. We conducted an integrated analysis that combines electrophysiologi…
View article: Germline stem cell isolation, lineage tracing, and aging in a protochordate
Germline stem cell isolation, lineage tracing, and aging in a protochordate Open
Germline stem cells (GSCs), the source of gametes, are the only stem cells capable of passing genes to future generations and are therefore considered units of natural selection. Yet, the factors that influence GSC fitness, and thus govern…
View article: Commensal taxa in gut microbiota limit antibiotic resistance during extended oral antibiotic use
Commensal taxa in gut microbiota limit antibiotic resistance during extended oral antibiotic use Open
Certain bacterial infections, such as those involving prosthetics, can require antimicrobial therapy over months to years, potentially increasing the burden of antimicrobial resistance. Here we longitudinally track the antimicrobial resist…
View article: Beyond polyA: scalable single-cell total RNA-seq unifies coding and non-coding transcriptomics
Beyond polyA: scalable single-cell total RNA-seq unifies coding and non-coding transcriptomics Open
Non-coding RNAs represent a widespread and diverse layer of post-transcriptional regulation across cell types and states, yet much of their diversity remains uncharted at single-cell resolution. This gap stems from the limitations of widel…
View article: PIP4K2C inhibition reverses autophagic flux impairment induced by SARS-CoV-2
PIP4K2C inhibition reverses autophagic flux impairment induced by SARS-CoV-2 Open
In search for broad-spectrum antivirals, we discover a small molecule inhibitor, RMC-113, that potently suppresses the replication of multiple RNA viruses including SARS-CoV-2 in human lung organoids. We demonstrate selective inhibition of…
View article: PIP4K2C inhibition reverses autophagic flux impairment induced by SARS-CoV-2
PIP4K2C inhibition reverses autophagic flux impairment induced by SARS-CoV-2 Open
In search for broad-spectrum antivirals, we discover a small molecule inhibitor, RMC-113, that potently suppresses the replication of multiple RNA viruses including SARS-CoV-2 in human lung organoids. We demonstrate selective inhibition of…
View article: Cell-free RNA reveals host and microbial correlates of broadly neutralizing antibody development against HIV
Cell-free RNA reveals host and microbial correlates of broadly neutralizing antibody development against HIV Open
An effective broadly reactive antibody response is crucial to prevent viral infections. A small number of people living with HIV (PLWH) develop broadly neutralizing antibodies (bNAbs) targeting multiple HIV strains. Although several viral …
View article: Electrical Stimulation Rejuvenates Tunicates: Altered Stem Cell and Immune Activity
Electrical Stimulation Rejuvenates Tunicates: Altered Stem Cell and Immune Activity Open
Applicable methods of rejuvenating organisms and improving resistance to environmental stimuli are needed. During attempts to synchronize heart rates in unhealthy colonial chordates, we observed morphological rejuvenation. While the import…
View article: Human skeletal development and regeneration are shaped by functional diversity of stem cells across skeletal sites
Human skeletal development and regeneration are shaped by functional diversity of stem cells across skeletal sites Open
The skeleton is one of the most structurally and compositionally diverse organ systems in the human body, depending on unique cellular dynamisms. Here, we integrate prospective isolation of human skeletal stem cells (hSSCs; CD45-CD235a-TIE…
View article: Comparative analysis of human and mouse ovaries across age
Comparative analysis of human and mouse ovaries across age Open
Mouse is a tractable model for human ovarian biology, however its utility is limited by incomplete understanding of how transcription and signaling differ interspecifically and with age. We compared ovaries between species using 3D-imaging…
View article: Nitroxoline treatment of <i>Balamuthia mandrillaris</i> triggers genomic crisis, transcriptional collapse, and incomplete encystment via copper and iron chelation
Nitroxoline treatment of <i>Balamuthia mandrillaris</i> triggers genomic crisis, transcriptional collapse, and incomplete encystment via copper and iron chelation Open
Balamuthia mandrillaris is a free-living amoeba that can infect the central nervous system to cause granulomatous amebic encephalitis (GAE), a highly fatal disease with mortality rates up to 90%. GAE is typically treated with a six-drug re…
View article: Linking molecular pathways and islet cell dysfunction in human type 1 diabetes
Linking molecular pathways and islet cell dysfunction in human type 1 diabetes Open
Summary Type 1 diabetes (T1D) is characterized by the autoimmune destruction of most insulin-producing β-cells, along with dysregulated glucagon secretion from pancreatic α-cells. We conducted an integrated analysis that combines electroph…
View article: Epigenetic attenuation of interferon signaling drives aging-related improvements in systemic lupus
Epigenetic attenuation of interferon signaling drives aging-related improvements in systemic lupus Open
In the general human population, aging is associated with a rise in systemic inflammation, primarily involving innate immune pathways related to interferon (IFN), toll-like receptor, and cytokine signaling. In systemic lupus erythematosus …
View article: Single-cell analysis reveals <i>Mycobacterium tuberculosis</i> ESX-1–mediated accumulation of permissive macrophages in infected mouse lungs
Single-cell analysis reveals <i>Mycobacterium tuberculosis</i> ESX-1–mediated accumulation of permissive macrophages in infected mouse lungs Open
Mycobacterium tuberculosis (MTB) ESX-1, a type VII secretion system, is a key virulence determinant contributing to MTB’s survival within lung mononuclear phagocytes (MNPs), but its effect on MNP recruitment and differentiation remains unk…
View article: A developmental biliary lineage program cooperates with Wnt activation to promote cell proliferation in hepatoblastoma
A developmental biliary lineage program cooperates with Wnt activation to promote cell proliferation in hepatoblastoma Open
Cancers evolve not only through the acquisition and clonal transmission of somatic mutations but also by epigenetic mechanisms that modify cell phenotype. Here, we use histology-guided and spatial transcriptomics to characterize hepatoblas…
View article: A multimodal zebrafish developmental atlas reveals the state-transition dynamics of late-vertebrate pluripotent axial progenitors
A multimodal zebrafish developmental atlas reveals the state-transition dynamics of late-vertebrate pluripotent axial progenitors Open
Elucidating organismal developmental processes requires a comprehensive understanding of cellular lineages in the spatial, temporal, and molecular domains. In this study, we introduce Zebrahub, a dynamic atlas of zebrafish embryonic develo…
View article: Zebrahub-Multiome: Uncovering Gene Regulatory Network Dynamics During Zebrafish Embryogenesis
Zebrahub-Multiome: Uncovering Gene Regulatory Network Dynamics During Zebrafish Embryogenesis Open
During embryonic development, gene regulatory networks (GRNs) drive molecular differentiation of cell types. However, the temporal dynamics of these networks remain poorly understood. Here, we present Zebrahub-Multiome, a single-cell multi…
View article: Single-cell analysis of breast cancer metastasis reveals epithelial-mesenchymal plasticity signatures associated with poor outcomes
Single-cell analysis of breast cancer metastasis reveals epithelial-mesenchymal plasticity signatures associated with poor outcomes Open
Metastasis is the leading cause of cancer-related deaths. It is unclear how intratumor heterogeneity (ITH) contributes to metastasis and how metastatic cells adapt to distant tissue environments. The study of these adaptations is challenge…
View article: How Mycobacterium tuberculosis builds a home: Single-cell analysis reveals M. tuberculosis ESX-1-mediated accumulation of anti-inflammatory macrophages in infected mouse lungs
How Mycobacterium tuberculosis builds a home: Single-cell analysis reveals M. tuberculosis ESX-1-mediated accumulation of anti-inflammatory macrophages in infected mouse lungs Open
Mycobacterium tuberculosis (MTB) infects and replicates in lung mononuclear phagocytes (MNPs) with astounding ability to evade elimination. ESX-1, a type VII secretion system, acts as a virulence determinant that contributes to MTB’s abili…
View article: PIP4K2C inhibition reverses autophagic flux impairment induced by SARS-CoV-2
PIP4K2C inhibition reverses autophagic flux impairment induced by SARS-CoV-2 Open
In search for broad-spectrum antivirals, we discovered a small molecule inhibitor, RMC-113, that potently suppresses the replication of multiple RNA viruses including SARS-CoV-2 in human lung organoids. We demonstrated selective dual inhib…
View article: METAGENOMICS FOR PATHOGEN DETECTION DURING A MASS MORTALITY EVENT IN SONGBIRDS
METAGENOMICS FOR PATHOGEN DETECTION DURING A MASS MORTALITY EVENT IN SONGBIRDS Open
Mass mortality events in wildlife can be indications of an emerging infectious disease. During the spring and summer of 2021, hundreds of dead passerines were reported across the eastern US. Birds exhibited a range of clinical signs includ…
View article: High-resolution lineage tracking of within-host evolution and strain transmission in a human gut symbiont across ecological scales
High-resolution lineage tracking of within-host evolution and strain transmission in a human gut symbiont across ecological scales Open
Summary Gut bacteria rapidly evolve in vivo , but their long-term success requires dispersal across hosts. Here, we quantify this interplay by tracking >50,000 genomically barcoded lineages of the prevalent commensal Bacteroides thetaiotao…
View article: Microbial Dynamics and Pulmonary Immune Responses in COVID-19 Secondary Bacterial Pneumonia
Microbial Dynamics and Pulmonary Immune Responses in COVID-19 Secondary Bacterial Pneumonia Open
Secondary bacterial pneumonia (2°BP) is associated with significant morbidity following respiratory viral infection, yet mechanistically remains incompletely understood. In a prospective cohort of 112 critically ill adults intubated for CO…
View article: Integrative analysis of noncoding mutations identifies the druggable genome in preterm birth
Integrative analysis of noncoding mutations identifies the druggable genome in preterm birth Open
Preterm birth affects ~10% of pregnancies in the US. Despite familial associations, identifying at-risk genetic loci has been challenging. We built deep learning and graphical models to score mutational effects at base resolution via integ…
View article: Genetically corrected <i>RAG2</i> -SCID human hematopoietic stem cells restore V(D)J-recombinase and rescue lymphoid deficiency
Genetically corrected <i>RAG2</i> -SCID human hematopoietic stem cells restore V(D)J-recombinase and rescue lymphoid deficiency Open
Recombination-activating genes (RAG1 and RAG2) are critical for lymphoid cell development and function by initiating the variable (V), diversity (D), and joining (J) (V(D)J)-recombination process to generate polyclonal lymphocytes with bro…