Biology subjects

Turner, M. L.

Publications and source records attributed to Turner, M. L..

6 recordsLinked to original sources

bioRxiv2026

SenNet Portal: Build, Optimization and Usage

Cellular senescence is a hallmark of aging and a driver of functional decline across tissues, yet its heterogeneity and context dependence have limited systematic study. The Common Funds Cellular Senescence Network (SenNet) Program addresses this challenge by generating multimodal, multi-tissue datasets that profile senescent cells across the human lifespan and complementary mouse models. The SenNet Data Portal (https://data.sennetconsortium.org) serves as the public gateway to these resources, providing open access to harmonized single-cell, spatial, imaging, transcriptomic, and proteomic data; senescence biomarker catalogs; and standardized protocols that can be used to comprehensively identify and characterize senescent cells in mouse and human tissue. As of April 2026, the portal hosts 2,041 publicly available human and mouse datasets across 15 organs using 6 general assay types. Experts from 13 Tissue Mapping Centers (TMCs) and 12 Technology Development and Application (TDAs) components contribute tissue data, analyze data, identify senescent biomarkers, and agree on panels for cross-tissue antibody harmonization. They also register human tissue data into the Human Reference Atlas (HRA) and develop user interfaces for the multiscale and multimodal exploration of this data. Built on a scalable hybrid cloud microservices architecture by the Consortium Organization and Data Coordinating Center (CODCC), the Portal enables data submission, management, integrated analysis, spatial context mapping, and harmonized access to cross-species data critical for aging research. This paper presents user needs, the Portals architecture, data processing workflows, and senescence-focused analytical tools; usage scenarios illustrating applications in biomarker discovery, quality benchmarking, hypothesis generation, spatial analysis, cost-efficient profiling, and cell distance distribution analysis; and utility and usage by the larger researcher community. Current limitations and planned extensions--including expanded spatial-omics releases and improved tools for senotype characterization--are discussed. SenNet protocols, code, and user interfaces are freely available on https://docs.sennetconsortium.org/apis.

bioinformatics↗

bioRxiv2024

Harnessing Global HLA Data for Enhanced Patient Matching in iPSC Haplobanks

Several countries have either developed or are developing national induced pluripotent stem cell (iPSC) banks of cell lines derived from donors with HLA homozygous genotypes (two identical haplotypes) prevalent in their local populations to provide immune matched tissues and cells to support regenerative medicine therapies. This haplobank approach relies on knowledge of the HLA genotypes of the population to identify the most beneficial haplotypes for patient coverage, and ultimately identify donors or cord blood units carrying two copies of the target haplotype. A potentially more efficient alternative to a national bank approach is to assess the haplotypes required to provide global patient coverage and to produce a single, global haplobank. Toward that end, we have developed an algorithm to prioritize HLA haplotypes that optimize coverage across the global population. We analyzed data from eighteen countries participating in the Global Alliance for iPS Therapy (GAiT). A representative pool of HLA genotypes, reflecting the HLA of patients, was derived by sampling from each countrys WMDA hematopoietic stem cell donor registry, or surrogate population. An algorithm was created based on HLA-A, -B and -DRB1 haplotype homozygous types with population HLA matching coverage defined by the absence of Host versus Graft (HvG) mismatches at these loci. HLA matching coverage was determined by iteratively selecting HLA haplotypes that provide the largest coverage against patient HLA genotypes sampled from the same population, excluding genotypes compatible with previous iterations. The top 10 haplotypes for each of the 18 countries were identified with patient coverage ranging from 19.5% in Brazil to 63.8% in Japan, with a mean coverage of 33.3%. In a global model, utilizing the 180 most frequent haplotypes across all 18 populations (equivalent to 10 lines pe country), the patient coverage ranged from 54.6% in India to 81.7% in Sweden, with a mean of 68.4%. Our findings demonstrate that global collaboration could more than double the potential for patient HLA matching coverage. Interrogation of unrelated hematopoietic stem cell donor registry and cord blood bank HLA data demonstrated that HLA-A, -B, and -DRB1 homozygous donors for the top 180 global haplotypes are widely available. These results show that a globally coordinated strategy for haplobanking would reduce redundancy and allow more patients to be treated with the same investment. Visual Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=170 SRC="FIGDIR/small/618361v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@117075eorg.highwire.dtl.DTLVardef@e4dc11org.highwire.dtl.DTLVardef@12be9c7org.highwire.dtl.DTLVardef@140d6_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIiPSC banks are being developed targeting HLA coverage to meet national needs C_LIO_LIGlobal collaboration has the potential to substantially increase the efficiency of this effort C_LI

genetics↗

bioRxiv2021

Sulforaphane exhibits in vitro and in vivo antiviral activity against pandemic SARS-CoV-2 and seasonal HCoV-OC43 coronaviruses

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has incited a global health crisis. Currently, there are no orally available medications for prophylaxis for those exposed to SARS-CoV-2 and limited therapeutic options for those who develop COVID-19. We evaluated the antiviral activity of sulforaphane (SFN), a naturally occurring, orally available, well-tolerated, nutritional supplement present in high concentrations in cruciferous vegetables with limited side effects. SFN inhibited in vitro replication of four strains of SARS-CoV-2 as well as that of the seasonal coronavirus HCoV-OC43. Further, SFN and remdesivir interacted synergistically to inhibit coronavirus infection in vitro. Prophylactic administration of SFN to K18-hACE2 mice prior to intranasal SARS-CoV-2 infection significantly decreased the viral load in the lungs and upper respiratory tract and reduced lung injury and pulmonary pathology compared to untreated infected mice. SFN treatment diminished immune cell activation in the lungs, including significantly lower recruitment of myeloid cells and a reduction in T cell activation and cytokine production. Our results suggest that SFN is a promising treatment for prevention of coronavirus infection or treatment of early disease.

microbiology↗

bioRxiv2020

A chemiluminescent protease probe for rapid, sensitive, and inexpensive detection of live Mycobacterium tuberculosis

Tuberculosis (TB) is a top-ten cause of death worldwide. Successful treatment is often limited by insufficient diagnostic capabilities, especially at the point of care in low-resource settings. The ideal diagnostic must be fast, cheap, and require minimal clinical resources while providing high sensitivity, selectivity, and the ability to differentiate live from dead bacteria. We describe here the development of a Fast, Luminescent, and Affordable Sensor of Hip1 (FLASH) for the diagnosis and monitoring of drug sensitivity of Mycobacterium tuberculosis (Mtb). FLASH is a selective chemiluminescent substrate for the Mtb protease Hip1 that when processed, produces visible light that can be measured with a high signal to noise ratio using inexpensive sensors. FLASH is sensitive to fmol of recombinant Hip1 enzyme in vitro and can detect as few as thousands of Mtb cells in culture or in human sputum samples within minutes. The probe is highly selective for Mtb compared to other non-tuberculous mycobacteria and can distinguish live from dead cells. Importantly, FLASH can be used to measure antibiotic killing of Mtb in culture with greatly accelerated timelines compared to traditional protocols. Overall, FLASH has the potential to enhance both TB diagnostics and drug resistance monitoring in resource-limited settings. One Sentence SummaryA luminescent probe enables sensitive detection of Mycobacterium tuberculosis for diagnostics, treatment monitoring, and drug susceptibility testing.

microbiology↗

bioRxiv2020

Rapid GMP-compliant expansion of SARS-CoV-2-specific T cells from convalescent donors for use as an allogeneic cell therapy for COVID-19

COVID-19 disease caused by the SARS-CoV-2 virus is characterized by dysregulation of effector T cells and accumulation of exhausted T cells. T cell responses to viruses can be corrected by adoptive cellular therapy using donor-derived virus-specific T cells. Here we show that SARS-CoV-2-exposed blood donations contain CD4 and CD8 memory T cells specific for SARS-CoV-2 spike, nucleocapsid and membrane antigens. These peptides can be used to isolate virus-specific T cells in a GMP-compliant process. These T cells can be rapidly expanded using GMP-compliant reagents for use as a therapeutic product. Memory and effector phenotypes are present in the selected virus-specific T cells, but our method rapidly expands the desirable central memory phenotype. A manufacturing yield ranging from 1010 to 1011 T cells can be obtained within 21 days culture. Thus, multiple therapeutic doses of virus-specific T cells can be rapidly generated from convalescent donors for treatment of COVID-19 patients One Sentence SummaryCD4+ and CD8+ T cells specific for SARS-CoV-2 can be isolated from convalescent donors and rapidly expanded to therapeutic doses at GMP standard, maintaining the desired central memory phenotype required for protective immune responses against severe COVID-19 infections.

immunology↗

bioRxiv2019

Glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria

Pathogenic bacteria often damage tissues by secreting toxins that form pores in cell membranes, and the most common pore-forming toxins are cholesterol-dependent cytolysins. During bacterial infections, glutamine becomes a conditionally essential amino acid, and glutamine is an important nutrient for immune cells. However, the role of glutamine in protecting tissue cells against pore-forming toxins is unclear. Here we tested the hypothesis that glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins. Stromal and epithelial cells were sensitive to damage by cholesterol-dependent cytolysins, pyolysin and streptolysin O, as determined by leakage of potassium and lactate dehydrogenase from cells, and reduced cell viability. However, glutamine helped protect cells against cholesterol-dependent cytolysins because glutamine deprivation increased the leakage of lactate dehydrogenase and reduced the viability of cells challenged with cytolysins. Without glutamine, stromal cells challenged with pyolysin leaked lactate dehydrogenase (control vs. pyolysin, 2.6 {+/-} 0.6 vs. 34.4 {+/-} 4.5 AU, n = 12), which was more than three-fold the leakage from cells supplied with 2 mM glutamine (control vs. pyolysin, 2.2 {+/-} 0.3 vs. 9.4 {+/-} 1.0 AU). The cytoprotective effect of glutamine was not dependent on glutaminolysis, replenishing the Krebs cycle via succinate, changes in cellular cholesterol, or regulators of cell metabolism (AMPK and mTOR). In conclusion, although the mechanism remains elusive, we found that glutamine supports the protection of tissue cells against the damage caused by cholesterol-dependent cytolysins from pathogenic bacteria.

microbiology↗