Biology subjects

Wasser, M.

Publications and source records attributed to Wasser, M..

3 recordsLinked to original sources

bioRxiv2024

CyNET- a network analysis framework for high dimensionality, system level analyses of the functional Immunome

The immune system is a complex "Network of Networks", in which various immune cell subsets interact and influence each others functions, ultimately determining immune competence and the control or onset of disease. The coordinated interactions between these cell subsets determine whether the outcome is a normal physiological state or a pathological condition. Established statistical procedures largely ignore the interactions between subsets and rely on statistically significant changes in the frequency of cell subsets. We developed CyNET (Cytometry Network)-- an analysis platform based on a network science approach to understand the immune system holistically. CyNET enables us to quantify the systems level and subsets level properties. We show that changes in the centrality of the nodes (immune subsets) reflect better biological functions than changes in frequency. We used CyNET to analyze the immune development along the chronological age gradient. Peripheral blood cells from healthy newborns (cord blood), adults (20 to 55 years), and elderly (70 years and above) human subjects were further used for validation using single-cell transcriptomics. We found that network edge density, degree centralization, and assortativity score reflect the maturation and development of the immune system along the age axis, thus enabling the characterisation of the functional architecture of the Immunome and the identification of key functional hubs within the immune networks.

immunology↗

bioRxiv2024

Single-cell and spatial atlas of steatotic liver-related hepatocellular carcinoma

Steatotic liver disease-related hepatocellular carcinoma (SLD-HCC) poses significant challenges in liver cancer management. Our current study investigates the tumor microenvironment (TME) of SLD-HCC using single-cell transcriptomic, proteomic and spatial transcriptomic analyses. We identified altered immune-related and lipid metabolism pathways, particularly in regulatory T cells (Tregs) and cancer-associated fibroblasts (CAFs) within the SLD-HCC microenvironment, suggesting distinct cellular adaptations to a high-fat TME and general immunosuppression. Cytometry by time-of-flight revealed a cold and immunosuppressive TME depleted with CD8+ T cells and enriched with Tregs, while spatial transcriptomics uncovered a unique spatial architecture with Treg/CAF clusters specifically located at the tumor margins in SLD-HCC. Crucially, we identified Treg-CAF interactions as a key mediator associated with lack of response to immunotherapy in SLD-HCC. Our findings highlight the intricate immune dynamics of SLD-HCC, indicating potential therapeutic targets to counteract immune evasion and restore anti-tumor immunity in SLD-HCC. HighlightsO_LIThe TME of SLD-HCC exhibits altered immune and lipid pathways C_LIO_LIImmunosuppressive SLD-HCC TME is depleted with CD8+ T cells and enriched with Tregs C_LIO_LISLD-HCC has a unique spatial architecture with Treg-CAF clusters at tumor margins C_LIO_LITreg-CAF interaction via TNFSF14-TNFRSF14 axis mediates immunotherapy resistance C_LI

immunology↗

bioRxiv2016

Silversword and lobeliad reintroduction linked to landscape restoration on Mauna Loa and Kilauea, and its implications for plant adaptive radiation in Hawaii

The endemic Hawaiian silversword and lobeliad lineages, which are two of the worlds premier examples of plant adaptive radiation, exemplify the severity of the threats confronting the Hawaiian flora, especially the threats posed by alien species. We have implemented collaborative reintroduction efforts with the endangered Ka[u] silversword (Argyroxiphium kauense) and Pele lobeliad (Clermontiapeleana) in Hawaii Volcanoes National Park. The efforts with the Ka[u] silversword have involved rediscovery, helicopter assisted rescue of diminutive remnant founders, managed breeding, outplanting at two sites in the Park of more than 21,000 seedlings deriving from 169 founders, and facilitated achene dispersal following flowering. The efforts with the Pele lobeliad have involved rediscovery, air-layering of remnant founders while suspended on climbing ropes, managed breeding, and outplanting at two sites in the Park of more than 1,000 seedlings (to date) deriving from six of the seven known founders. We have linked the reintroduction efforts to landscape restoration at large scales in the Park and in adjacent State and private lands, thereby increasing the opportunities for substantial population growth and expansion of the Ka[u] silversword and Pele lobeliad in the future. Additionally, we have extended the reintroduction efforts, including the link to landscape restoration, to encompass all other endangered silversword and lobeliad taxa occurring historically on the eastern slopes of Mauna Loa or on K[i]lauea. In so doing, we seek to restore the possibility of adaptive radiation of the silversword and lobeliad lineages going forward, especially on the youngest and most geologically active, and thus perhaps most evolutionarily dynamic, part of the Hawaiian archipelago.\n\nDedicationThis paper celebrates the centennial of Hawaii Volcanoes National Park, which was founded in August 1916.

evolutionary biology↗