Try a new search

Format these results:

Searched for:

person:heguya01

in-biosketch:yes

Total Results:

267


Selective adaptation of SARS-CoV-2 Omicron under booster vaccine pressure: a multicentre observational study

Duerr, Ralf; Dimartino, Dacia; Marier, Christian; Zappile, Paul; Wang, Guiqing; François, Fritz; Ortigoza, Mila B; Iturrate, Eduardo; Samanovic, Marie I; Mulligan, Mark J; Heguy, Adriana
BACKGROUND:High rates of vaccination and natural infection drive immunity and redirect selective viral adaptation. Updated boosters are installed to cope with drifted viruses, yet data on adaptive evolution under increasing immune pressure in a real-world situation are lacking. METHODS:Cross-sectional study to characterise SARS-CoV-2 mutational dynamics and selective adaptation over >1 year in relation to vaccine status, viral phylogenetics, and associated clinical and demographic variables. FINDINGS/RESULTS:The study of >5400 SARS-CoV-2 infections between July 2021 and August 2022 in metropolitan New York portrayed the evolutionary transition from Delta to Omicron BA.1-BA.5 variants. Booster vaccinations were implemented during the Delta wave, yet booster breakthrough infections and SARS-CoV-2 re-infections were almost exclusive to Omicron. In adjusted logistic regression analyses, BA.1, BA.2, and BA.5 had a significant growth advantage over co-occurring lineages in the boosted population, unlike BA.2.12.1 or BA.4. Selection pressure by booster shots translated into diffuse adaptive evolution in Delta spike, contrasting with strong, receptor-binding motif-focused adaptive evolution in BA.2-BA.5 spike (Fisher Exact tests; non-synonymous/synonymous mutation rates per site). Convergent evolution has become common in Omicron, engaging spike positions crucial for immune escape, receptor binding, or cleavage. INTERPRETATION/CONCLUSIONS:Booster shots are required to cope with gaps in immunity. Their discriminative immune pressure contributes to their effectiveness but also requires monitoring of selective viral adaptation processes. Omicron BA.2 and BA.5 had a selective advantage under booster vaccination pressure, contributing to the evolution of BA.2 and BA.5 sublineages and recombinant forms that predominate in 2023. FUNDING/BACKGROUND:The study was supported by NYU institutional funds and partly by the Cancer Center Support Grant P30CA016087 at the Laura and Isaac Perlmutter Cancer Center.
PMCID:10623172
PMID: 37866115
ISSN: 2352-3964
CID: 5609742

Digital spatial profiling to predict recurrence in grade 3 stage I lung adenocarcinoma

Chang, Stephanie H; Mezzano-Robinson, Valeria; Zhou, Hua; Moreira, Andre; Pillai, Raymond; Ramaswami, Sitharam; Loomis, Cynthia; Heguy, Adriana; Tsirigos, Aristotelis; Pass, Harvey I
OBJECTIVE:Early-stage lung adenocarcinoma is treated with local therapy alone, although patients with grade 3 stage I lung adenocarcinoma have a 50% 5-year recurrence rate. Our objective is to determine if analysis of the tumor microenvironment can create a predictive model for recurrence. METHODS:Thirty-four patients with grade 3 stage I lung adenocarcinoma underwent surgical resection. Digital spatial profiling was used to perform genomic (n = 31) and proteomic (n = 34) analyses of pancytokeratin positive and negative tumor cells. K-means clustering was performed on the top 50 differential genes and top 20 differential proteins, with Kaplan-Meier recurrence curves based on patient clustering. External validation of high-expression genes was performed with Kaplan-Meier plotter. RESULTS:There were no significant clinicopathologic differences between patients who did (n = 14) and did not (n = 20) have recurrence. Median time to recurrence was 806 days; median follow-up with no recurrence was 2897 days. K-means clustering of pancytokeratin positive genes resulted in a model with a Kaplan-Meier curve with concordance index of 0.75. K-means clustering for pancytokeratin negative genes was less successful at differentiating recurrence (concordance index 0.6). Genes upregulated or downregulated for recurrence were externally validated using available public databases. Proteomic data did not reach statistical significance but did internally validate the genomic data described. CONCLUSIONS:Genomic difference in lung adenocarcinoma may be able to predict risk of recurrence. After further validation, stratifying patients by this risk may help guide who will benefit from adjuvant therapy.
PMID: 37890657
ISSN: 1097-685x
CID: 5620342

Longitudinal gut microbiome analyses and blooms of pathogenic strains during lupus disease flares

Azzouz, Doua F; Chen, Ze; Izmirly, Peter M; Chen, Lea Ann; Li, Zhi; Zhang, Chongda; Mieles, David; Trujillo, Kate; Heguy, Adriana; Pironti, Alejandro; Putzel, Greg G; Schwudke, Dominik; Fenyo, David; Buyon, Jill P; Alekseyenko, Alexander V; Gisch, Nicolas; Silverman, Gregg J
OBJECTIVE:Whereas genetic susceptibility for systemic lupus erythematosus (SLE) has been well explored, the triggers for clinical disease flares remain elusive. To investigate relationships between microbiota community resilience and disease activity, we performed the first longitudinal analyses of lupus gut-microbiota communities. METHODS:In an observational study, taxononomic analyses, including multivariate analysis of ß-diversity, assessed time-dependent alterations in faecal communities from patients and healthy controls. From gut blooms, strains were isolated, with genomes and associated glycans analysed. RESULTS:(RG) occurred at times of high-disease activity, and were detected in almost half of patients during lupus nephritis (LN) disease flares. Whole genome sequence analysis of RG strains isolated during these flares documented 34 genes postulated to aid adaptation and expansion within a host with an inflammatory condition. Yet, the most specific feature of strains found during lupus flares was the common expression of a novel type of cell membrane-associated lipoglycan. These lipoglycans share conserved structural features documented by mass spectroscopy, and highly immunogenic repetitive antigenic-determinants, recognised by high-level serum IgG2 antibodies, that spontaneously arose, concurrent with RG blooms and lupus flares. CONCLUSIONS:Our findings rationalise how blooms of the RG pathobiont may be common drivers of clinical flares of often remitting-relapsing lupus disease, and highlight the potential pathogenic properties of specific strains isolated from active LN patients.
PMID: 37365013
ISSN: 1468-2060
CID: 5540152

De novo assembly and annotation of the singing mouse genome

Smith, Samantha K; Frazel, Paul W; Khodadadi-Jamayran, Alireza; Zappile, Paul; Marier, Christian; Okhovat, Mariam; Brown, Stuart; Long, Michael A; Heguy, Adriana; Phelps, Steven M
BACKGROUND:Developing genomic resources for a diverse range of species is an important step towards understanding the mechanisms underlying complex traits. Specifically, organisms that exhibit unique and accessible phenotypes-of-interest allow researchers to address questions that may be ill-suited to traditional model organisms. We sequenced the genome and transcriptome of Alston's singing mouse (Scotinomys teguina), an emerging model for social cognition and vocal communication. In addition to producing advertisement songs used for mate attraction and male-male competition, these rodents are diurnal, live at high-altitudes, and are obligate insectivores, providing opportunities to explore diverse physiological, ecological, and evolutionary questions. RESULTS:Using PromethION, Illumina, and PacBio sequencing, we produced an annotated genome and transcriptome, which were validated using gene expression and functional enrichment analyses. To assess the usefulness of our assemblies, we performed single nuclei sequencing on cells of the orofacial motor cortex, a brain region implicated in song coordination, identifying 12 cell types. CONCLUSIONS:These resources will provide the opportunity to identify the molecular basis of complex traits in singing mice as well as to contribute data that can be used for large-scale comparative analyses.
PMCID:10521431
PMID: 37749493
ISSN: 1471-2164
CID: 5606392

Author Correction: Single-cell RNA sequencing reveals the effects of chemotherapy on human pancreatic adenocarcinoma and its tumor microenvironment

Werba, Gregor; Weissinger, Daniel; Kawaler, Emily A; Zhao, Ende; Kalfakakou, Despoina; Dhara, Surajit; Wang, Lidong; Lim, Heather B; Oh, Grace; Jing, Xiaohong; Beri, Nina; Khanna, Lauren; Gonda, Tamas; Oberstein, Paul; Hajdu, Cristina; Loomis, Cynthia; Heguy, Adriana; Sherman, Mara H; Lund, Amanda W; Welling, Theodore H; Dolgalev, Igor; Tsirigos, Aristotelis; Simeone, Diane M
PMID: 37400453
ISSN: 2041-1723
CID: 5539082

Spatial transcriptomics stratifies psoriatic disease severity by emergent cellular ecosystems

Castillo, Rochelle L; Sidhu, Ikjot; Dolgalev, Igor; Chu, Tinyi; Prystupa, Aleksandr; Subudhi, Ipsita; Yan, Di; Konieczny, Piotr; Hsieh, Brandon; Haberman, Rebecca H; Selvaraj, Shanmugapriya; Shiomi, Tomoe; Medina, Rhina; Girija, Parvathy Vasudevanpillai; Heguy, Adriana; Loomis, Cynthia A; Chiriboga, Luis; Ritchlin, Christopher; Garcia-Hernandez, Maria De La Luz; Carucci, John; Meehan, Shane A; Neimann, Andrea L; Gudjonsson, Johann E; Scher, Jose U; Naik, Shruti
Whereas the cellular and molecular features of human inflammatory skin diseases are well characterized, their tissue context and systemic impact remain poorly understood. We thus profiled human psoriasis (PsO) as a prototypic immune-mediated condition with a high predilection for extracutaneous involvement. Spatial transcriptomics (ST) analyses of 25 healthy, active lesion, and clinically uninvolved skin biopsies and integration with public single-cell transcriptomics data revealed marked differences in immune microniches between healthy and inflamed skin. Tissue-scale cartography further identified core disease features across all active lesions, including the emergence of an inflamed suprabasal epidermal state and the presence of B lymphocytes in lesional skin. Both lesional and distal nonlesional samples were stratified by skin disease severity and not by the presence of systemic disease. This segregation was driven by macrophage-, fibroblast-, and lymphatic-enriched spatial regions with gene signatures associated with metabolic dysfunction. Together, these findings suggest that mild and severe forms of PsO have distinct molecular features and that severe PsO may profoundly alter the cellular and metabolic composition of distal unaffected skin sites. In addition, our study provides a valuable resource for the research community to study spatial gene organization of healthy and inflamed human skin.
PMID: 37267384
ISSN: 2470-9468
CID: 5536642

Basal forebrain cholinergic neurons are vulnerable in a mouse model of Down syndrome and their molecular fingerprint is rescued by maternal choline supplementation

Alldred, Melissa J; Pidikiti, Harshitha; Heguy, Adriana; Roussos, Panos; Ginsberg, Stephen D
Basal forebrain cholinergic neuron (BFCN) degeneration is a hallmark of Down syndrome (DS) and Alzheimer's disease (AD). Current therapeutics in these disorders have been unsuccessful in slowing disease progression, likely due to poorly understood complex pathological interactions and dysregulated pathways. The Ts65Dn trisomic mouse model recapitulates both cognitive and morphological deficits of DS and AD, including BFCN degeneration and has shown lifelong behavioral changes due to maternal choline supplementation (MCS). To test the impact of MCS on trisomic BFCNs, we performed laser capture microdissection to individually isolate choline acetyltransferase-immunopositive neurons in Ts65Dn and disomic littermates, in conjunction with MCS at the onset of BFCN degeneration. We utilized single population RNA sequencing (RNA-seq) to interrogate transcriptomic changes within medial septal nucleus (MSN) BFCNs. Leveraging multiple bioinformatic analysis programs on differentially expressed genes (DEGs) by genotype and diet, we identified key canonical pathways and altered physiological functions within Ts65Dn MSN BFCNs, which were attenuated by MCS in trisomic offspring, including the cholinergic, glutamatergic and GABAergic pathways. We linked differential gene expression bioinformatically to multiple neurological functions, including motor dysfunction/movement disorder, early onset neurological disease, ataxia and cognitive impairment via Ingenuity Pathway Analysis. DEGs within these identified pathways may underlie aberrant behavior in the DS mice, with MCS attenuating the underlying gene expression changes. We propose MCS ameliorates aberrant BFCN gene expression within the septohippocampal circuit of trisomic mice through normalization of principally the cholinergic, glutamatergic, and GABAergic signaling pathways, resulting in attenuation of underlying neurological disease functions.
PMID: 37191946
ISSN: 1530-6860
CID: 5503542

Abstract 441: Relationship Between Diabetes, Glucose Control, And Vascular Health: Findings From The American Heart Association Cardiometabolic Health Strategically Focused Research Network [Meeting Abstract]

Garshick, Michael; Barrett, Tessa A; Jindal, Manila; Newman, Jonathan D; Fadzan, Maja; Bredefeld, Cindy; Levy, Natalie; Akinlonu, Adedoyin; Heguy, Adriana; Drenkova, Schlamp, Florencia; Giannarelli, Chiara; Fisher, Edward A; Goldberg, Ira J; Berger, Jeffrey
ORIGINAL:0017100
ISSN: 1524-4636
CID: 5578852

Variant-specific introduction and dispersal dynamics of SARS-CoV-2 in New York City-from Alpha to Omicron

Dellicour, Simon; Hong, Samuel L; Hill, Verity; Dimartino, Dacia; Marier, Christian; Zappile, Paul; Harkins, Gordon W; Lemey, Philippe; Baele, Guy; Duerr, Ralf; Heguy, Adriana
Since the latter part of 2020, SARS-CoV-2 evolution has been characterised by the emergence of viral variants associated with distinct biological characteristics. While the main research focus has centred on the ability of new variants to increase in frequency and impact the effective reproductive number of the virus, less attention has been placed on their relative ability to establish transmission chains and to spread through a geographic area. Here, we describe a phylogeographic approach to estimate and compare the introduction and dispersal dynamics of the main SARS-CoV-2 variants-Alpha, Iota, Delta, and Omicron-that circulated in the New York City area between 2020 and 2022. Notably, our results indicate that Delta had a lower ability to establish sustained transmission chains in the NYC area and that Omicron (BA.1) was the variant fastest to disseminate across the study area. The analytical approach presented here complements non-spatially-explicit analytical approaches that seek a better understanding of the epidemiological differences that exist among successive SARS-CoV-2 variants of concern.
PMID: 37071654
ISSN: 1553-7374
CID: 5466082

Alterations in the cutaneous microbiome of patients with psoriasis and psoriatic arthritis reveal similarities between non-lesional and lesional skin

Boix-Amorós, Alba; Badri, Michelle H; Manasson, Julia; Blank, Rebecca B; Haberman, Rebecca H; Neimann, Andrea L; Girija, Parvathy V; Jimenez Hernandez, Anthony; Heguy, Adriana; Koralov, Sergei B; Bonneau, Richard; Clemente, Jose C; Scher, Jose U
OBJECTIVES/OBJECTIVE:To investigate the cutaneous microbiome spanning the entire psoriatic disease spectrum, and to evaluate distinguishing features of psoriasis (PsO) and psoriatic arthritis (PsA). METHODS:Skin swabs were collected from upper and lower extremities of healthy individuals and patients with PsO and PsA. Psoriatic patients contributed both lesional (L) and contralateral non-lesional (NL) samples. Microbiota were analysed using 16S rRNA sequencing. RESULTS:was higher in NL PsA samples compared with NL PsO samples (p<0.05), potentially serving as a biomarker for disease progression. CONCLUSIONS:These findings show differences in diversity, bacterial composition and microbe-microbe interactions between healthy and psoriatic skin, both L and NL. We further identified bacterial biomarkers that differentiate disease phenotypes, which could potentially aid in predicting the transition from PsO to PsA.
PMID: 36600182
ISSN: 1468-2060
CID: 5433482