Publications by authors named "Sarah J Stein"

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted human-to-human via aerosols and air-borne droplets. Therefore, capturing and destroying viruses from indoor premises are essential to reduce the probability of human exposure and virus transmission. While the heating, ventilation, and air conditioning (HVAC) systems help in reducing the indoor viral load, a targeted approach is required to effectively remove SARS-CoV-2 from indoor air to address human exposure concerns.

View Article and Find Full Text PDF

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and resulting COVID-19 (coronavirus disease 2019) pandemic have required mass diagnostic testing, often taking place in testing sites within hospitals, clinics, or at satellite locations. To establish the potential of SARS-CoV-2 aerosol transmission and to identify junctures during testing that result in increased viral exposure, aerosol and surface samples were examined for the presence of SARS-CoV-2 RNA from locations within Nebraska Medicine COVID-19 testing and vaccine clinics. Aerosols containing SARS-CoV-2 RNA detected within clinics suggest viral shedding from infected individuals.

View Article and Find Full Text PDF

Cooperative DNA binding is a key feature of transcriptional regulation. Here we examined the role of cooperativity in Notch signaling by CRISPR-mediated engineering of mice in which neither Notch1 nor Notch2 can homo- or heterodimerize, essential for cooperative binding to sequence-paired sites (SPS) located near many Notch-regulated genes. Although most known Notch-dependent phenotypes were unaffected in Notch1/2 dimer-deficient mice, a subset of tissues proved highly sensitive to loss of cooperativity.

View Article and Find Full Text PDF
Article Synopsis
  • - Chronic infections can cause T cells to become exhausted due to ongoing antigen stimulation, making it harder for the immune system to fight off viruses.
  • - Researchers found that Tribbles pseudokinase 1 (Trib1) plays a key role in regulating antiviral T cell responses; when Trib1 is absent, there are more activated T cells that can better control viruses.
  • - The study highlights that Trib1 negatively affects T cell receptor signaling, suggesting that targeting Trib1 could help enhance T cell functions and improve the body’s ability to combat viral infections.
View Article and Find Full Text PDF

Eosinophils and neutrophils are critical for host defense, yet gaps in understanding how granulocytes differentiate from hematopoietic stem cells (HSCs) into mature effectors remain. The pseudokinase tribbles homolog 1 (Trib1) is an important regulator of granulocytes; knockout mice lack eosinophils and have increased neutrophils. However, how Trib1 regulates cellular identity and function during eosinophilopoiesis is not understood.

View Article and Find Full Text PDF

Activating NOTCH1 mutations are frequent in human T-cell acute lymphoblastic leukemia (T-ALL) and Notch inhibitors (γ-secretase inhibitors [GSIs]) have produced responses in patients with relapsed, refractory disease. However, sustained responses, although reported, are uncommon, suggesting that other pathways can substitute for Notch in T-ALL. To address this possibility, we first generated Kras transgenic mice with T-cell-specific expression of the pan-Notch inhibitor, dominant-negative Mastermind (DNMAML).

View Article and Find Full Text PDF

Trib2 is highly expressed in human T cell acute lymphoblastic leukemia (T-ALL) and is a direct transcriptional target of the oncogenic drivers Notch and TAL1. In human TAL1-driven T-ALL cell lines, Trib2 is proposed to function as an important survival factor, but there is limited information about the role of Trib2 in primary T-ALL. In this study, we investigated the role of Trib2 in the initiation and maintenance of Notch-dependent T-ALL.

View Article and Find Full Text PDF

The tribbles protein family, an evolutionarily conserved group of pseudokinases, have been shown to regulate multiple cellular events including those involved in normal and malignant haematopoiesis. The three mammalian Tribbles homologues, Trib1, Trib2 and Trib3 are characterized by conserved motifs, including a pseudokinase domain and a C-terminal E3 ligase-binding domain. In this review, we focus on the role of Trib (mammalian Tribbles homologues) proteins in mammalian haematopoiesis and leukaemia.

View Article and Find Full Text PDF

Hematopoiesis is a tightly regulated process resulting in the production of blood cells. Self-renewal and differentiation of hematopoietic stem cells (HSCs) are key processes in hematopoietic development. Disruption of these steps can lead to altered cell distribution and disease.

View Article and Find Full Text PDF

Chronic myelogenous leukemia is a malignant disease of the hematopoietic stem cell compartment, which is characterized by expression of the BCR-ABL fusion protein. Expression of BCR-ABL allows myeloid cells to grow in the absence of the growth factors interleukin-3 and granulocyte-macrophage colony-stimulating factor. The tyrosine kinase activity of BCR-ABL constitutively activates signaling pathways associated with Ras and its downstream effectors and with the Jak/STAT pathway.

View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_sessionk1avk4telesbc8qg63i7rar1ggdcb8f8): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once