Biology subjects

Moore, J. F.

Publications and source records attributed to Moore, J. F..

3 recordsLinked to original sources

bioRxiv2025

Identification of a multi-omics factor predictive of long COVID in the IMPACC study

Following SARS-CoV-2 infection, [~]10-35% of COVID-19 patients experience long COVID (LC), in which often debilitating symptoms persist for at least three months. Elucidating the biologic underpinnings of LC could identify therapeutic opportunities. We utilized machine learning methods on biologic analytes and patient reported outcome surveys provided over 12 months after hospital discharge from >500 hospitalized COVID-19 patients in the IMPACC cohort to identify a multi-omics "recovery factor". IMPACC participants who experienced LC had lower recovery factor scores compared to participants without LC. Biologic characterization revealed increased levels of plasma proteins associated with inflammation, elevated transcriptional signatures of heme metabolism, and decreased androgenic steroids in LC patients. The recovery factor was also associated with altered circulating immune cell frequencies. Notably, recovery factor scores were predictive of LC occurrence in patients as early as hospital admission, irrespective of acute disease severity. Thus, the recovery factor identifies patients at risk of LC early after SARS-CoV-2 infection and reveals LC biomarkers and potential treatment targets.

systems biology↗

bioRxiv2023

Single-cell transcriptomics reveals heterogenous thymic dendritic cell subsets with distinct functions and requirements for thymocyte-regulated crosstalk

Dendritic cells are essential for establishing thymic central tolerance; however, mechanisms supporting their homeostasis and activation remain unresolved. Through single-cell transcriptomics and functional assays, we identify seven thymic conventional dendritic cell (cDC) subsets and discriminate their abilities to present self-antigens and induce regulatory T cells. Mice blocked at different stages of T-cell development reveal that CD4+ single-positive (SP) and CD8SP thymocytes differentially support homeostasis and activation of cDC1s versus cDC2s/plasmacytoid DCs (pDCs), respectively. CD8SPs indirectly support pDC survival and cDC2 thymic immigration, and they induce interferon signaling in cDCs, partly by promoting Type III interferon expression by medullary thymic epithelial cells (mTECs). In contrast, CD4SPs undergo cognate interactions with cDCs, inducing CD40 signaling required for activation of cDC1s. Activated cDC1s make non-redundant contributions to central tolerance. Altogether, this study comprehensively identifies distinct thymic DC subsets and elucidates requirements for crosstalk with thymocyte subsets that support their homeostasis, activation, and function.

immunology↗

bioRxiv2018

Neurofibromin is essential to maintain metabolic function and sustain life in the adult mouse

The consequences of pathogenic variants in the NF1 gene can manifest in numerous tissues as a result of loss of neurofibromin protein function(s). A known function of NF1 is negative regulation of p21ras signaling via a GTPase activating (Ras-GAP) domain. Besides modulation of Ras signaling as a tumor suppressor, other functions of this multi-domain protein are less clear. Biallelic inactivation of NF1 leads to an embryonic lethal phenotype, while neurofibromin is expressed at varying levels in most tissues beyond developmental stages. Taking advantage of the mouse genetics toolkit, we established novel tamoxifen-inducible systemic knockout Nf1 mouse models (C57BL/6) to gain a better understanding of the role of Nf1 in the adult (3-4 months) mouse. Following inactivation of floxed Nf1 alleles, adult CAGGCre-ERTM;Nf14F/4F mice lose function of Nf1 systemically. Both male and female animals do not survive beyond 11 days post-tamoxifen induction and exhibit histological changes in multiple tissues. During this acute crisis, CAGGCre-ERTM;Nf14F/4F mice are not able to maintain body temperature or body mass, and expend all adipose tissue; however, they continue to consume food and absorb calories comparable to littermate-paired controls. Targeted metabolite analyses and indirect calorimetry studies revealed altered fat metabolism, amino acid metabolism and energy expenditure, with animals undergoing metabolic crisis and torpor-like states. Thermoneutral conditions accelerated the acute, lethal phenotype coincident with lower food intake. This study reveals that systemic loss of neurofibromin in the adult mouse induces metabolic dysfunction and lethality, thus highlighting potential functions of this multi-domain protein in addition to tumor suppression.

genetics↗