Biology subjects

Ng, T.

Publications and source records attributed to Ng, T..

21 records · Page 2Linked to original sources

bioRxiv2020

Lyve-1 expressing perivascular macrophages orchestrate pericyte expansion to sustain angiogenesis in cancer

Tumor associated macrophages (TAMs) are a highly plastic stromal cell type which support cancer progression. Using single-cell RNA-sequencing of TAMs from a spontaneous murine model of mammary adenocarcinoma (MMTV-PyMT) we characterize a subset of these cells expressing lymphatic vessel endothelial hyaluronic acid receptor 1 (Lyve-1) which spatially reside proximal to blood vasculature. We demonstrate that Lyve-1+ TAMs support tumor growth and identify a pivotal role for these cells in maintaining a population of perivascular mesenchymal cells which express alpha-smooth muscle actin and phenotypically resemble pericytes. Using photolabeling techniques show that mesenchymal cells maintain their prevalence in the growing tumor through proliferation and uncover a role for Lyve-1+ TAMs in orchestrating a selective platelet-derived growth factor-CC-dependent expansion of the perivascular mesenchymal population, creating a pro-angiogenic niche. This study highlights the inter-reliance of the immune and non-immune stromal network which support cancer progression and provides therapeutic opportunities for tackling the disease.

cancer biology↗

bioRxiv2019

Contrast-Enhanced, Molecular Imaging of Vascular Inflammation in the Mouse Model by Simultaneous PET/MRI

Despite advances in diagnosis and management, cardiovascular diseases (CVDs) remain the leading cause of death in the US. Atherosclerosis is the most common form of CVD and the vulnerability of atherosclerotic plaques to rupture is a primary determinant for risk of catastrophic ischemic events. Current imaging of atherosclerotic disease focuses on assessing plaque size and the degree of luminal stenosis, which are not good predictors of plaque stability. Functional methods to identify biomarkers of inflammation in plaques could facilitate assessment of plaque instability to allow early intervention. In this study, we validate the use of a purpose-built, magnetic resonance imaging (MRI)-compatible positron emission tomography (PET) insert for multimodal, molecular imaging of vulnerable plaques in mice. We illustrate the application of PET to screen for inflamed regions to guide the application of MRI. Molecular MRI visualizes regions of vascular inflammation and is coupled with anatomical MRI to generate detailed maps of the inflammatory marker within the context of an individual vessel. As a testbed for this imaging methodology, we developed a multimodal, iron oxide nanoparticle (NP) targeting vascular cell adhesion molecule-1 (VCAM-1) for simultaneous PET/MRI of vascular inflammation performed on a mouse carotid ligation model. In vitro cell studies confirmed that the NPs are not cytotoxic to liver cells. In vivo simultaneous PET/MRI imaging identified regions of inflammation. Three-dimensional rendering of the MRI data facilitated high-resolution visualization of patterns of inflammation along the injured vessel. Histology validated the co-localization of the NPs with VCAM-1 expression at sites of induced inflammation. The results of this work validate the utility of the simultaneous PET/MR insert as a research tool for small animals and lays groundwork to further advance the potential clinical utility of integrated imaging systems.

bioengineering↗

bioRxiv2018

Evidence for a Recombinant Origin of HIV-1 group M from Genomic Variation

Reconstructing the early dynamics of the HIV-1 pandemic can provide crucial insights into the socioeconomic drivers of emerging infectious diseases in human populations, including the roles of urbanization and transportation networks. Current evidence indicates that the global pandemic comprising almost entirely of HIV-1/M originated around the 1920s in central Africa. However, these estimates are based on molecular clock estimates that are assumed to apply uniformly across the virus genome. There is growing evidence that recombination has played a significant role in the early history of the HIV-1 pandemic, such that different regions of the HIV-1 genome have different evolutionary histories. In this study, we have conducted a dated-tip analysis of all near full-length HIV-1/M genome sequences that were published in the GenBank database. We used a sliding window approach similar to the bootscanning method for detecting breakpoints in intersubtype recombinant sequences. We found evidence of substantial variation in estimated root dates among windows, with an estimated mean time to the most recent common ancestor (tMRCA) of 1922. Estimates were significantly autocorrelated, which was more consistent with an early recombination event than with stochastic error variation in phylogenetic reconstruction and dating analyses. A piecewise regression analysis supported the existence of at least one recombination breakpoint in the HIV-1/M genome with interval-specific means around 1929 and 1913, respectively. This analysis demonstrates that a sliding window approach can accommodate early recombination events outside the established nomenclature of HIV-1/M subtypes, although it is difficult to incorporate the earliest available samples due to their limited genome coverage.

evolutionary biology↗