Timothy E. Hoffman
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View article: Loss of UXS1 Selectively Depletes Pyrimidines and Induces Replication Stress in <i>KEAP1</i> -Mutant Lung Cancer
Loss of UXS1 Selectively Depletes Pyrimidines and Induces Replication Stress in <i>KEAP1</i> -Mutant Lung Cancer Open
Kelch-like ECH-associated protein 1 (KEAP1) is the third most commonly mutated gene in non–small cell lung cancer and is associated with poor prognosis. In this study, we investigated synthetic lethal interaction genes in KEAP1-mutated can…
View article: Reversible Intracellular Gelation of MCF10A Cells Enables Programmable Control Over 3D Spheroid Growth
Reversible Intracellular Gelation of MCF10A Cells Enables Programmable Control Over 3D Spheroid Growth Open
In nature, some organisms survive extreme environments by inducing a biostatic state wherein cellular contents are effectively vitrified. Recently, a synthetic biostatic state in mammalian cells is achieved via intracellular network format…
View article: Multiple cancers escape from multiple MAPK pathway inhibitors and use DNA replication stress signaling to tolerate aberrant cell cycles
Multiple cancers escape from multiple MAPK pathway inhibitors and use DNA replication stress signaling to tolerate aberrant cell cycles Open
Many cancers harbor pro-proliferative mutations of the mitogen-activated protein kinase (MAPK) pathway. In BRAF-driven melanoma cells treated with BRAF inhibitors, subpopulations of cells escape drug-induced quiescence through a nongenetic…
View article: Botulism due to Injection Drug Use
Botulism due to Injection Drug Use Open
Audience: This scenario was developed to educate emergency medicine residents on the diagnosis and management of wound botulism secondary to injection drug use.Research Methods: Our residents are provided a survey at the completion of the …
View article: Multiple cancer types rapidly escape from multiple MAPK inhibitors to generate mutagenesis-prone subpopulations
Multiple cancer types rapidly escape from multiple MAPK inhibitors to generate mutagenesis-prone subpopulations Open
Many cancers harbor pro-proliferative mutations of the mitogen-activated protein kinase (MAPK) pathway and many targeted inhibitors now exist for clinical use, but drug resistance remains a major issue. We recently showed that BRAF-driven …
View article: Intracellular Crowding by Bio‐Orthogonal Hydrogel Formation Induces Reversible Molecular Stasis
Intracellular Crowding by Bio‐Orthogonal Hydrogel Formation Induces Reversible Molecular Stasis Open
To survive extreme conditions, certain animals enter a reversible protective stasis through vitrification of the cytosol by polymeric molecules such as proteins and polysaccharides. In this work, synthetic gelation of the cytosol in living…
View article: Network Simulations Reveal Molecular Signatures of Vulnerability to Age-Dependent Stress and Tau Accumulation
Network Simulations Reveal Molecular Signatures of Vulnerability to Age-Dependent Stress and Tau Accumulation Open
Alzheimer's disease (AD) is the leading cause of dementia and one of the most common causes of death worldwide. As an age-dependent multifactorial disease, the causative triggers of AD are rooted in spontaneous declines in cellular functio…
View article: Rapidly induced drug adaptation mediates escape from BRAF inhibition in single melanoma cells
Rapidly induced drug adaptation mediates escape from BRAF inhibition in single melanoma cells Open
Despite increasing numbers of effective anti-cancer therapies, successful treatment is limited by the development of drug resistance. While the contribution of genetic factors to drug resistance is undeniable, little is known about how dru…
View article: Ultrasensitivity dynamics of diverse aryl hydrocarbon receptor modulators in a hepatoma cell line
Ultrasensitivity dynamics of diverse aryl hydrocarbon receptor modulators in a hepatoma cell line Open
The aryl hydrocarbon receptor (AhR) is a nuclear receptor that facilitates a wide transcriptional response and causes a variety of adaptive and maladaptive physiological functions. Such functions are entirely dependent on the type of ligan…
View article: A multimethod computational simulation approach for investigating mitochondrial dynamics and dysfunction in degenerative aging
A multimethod computational simulation approach for investigating mitochondrial dynamics and dysfunction in degenerative aging Open
Summary Research in biogerontology has largely focused on the complex relationship between mitochondrial dysfunction and biological aging. In particular, the mitochondrial free radical theory of aging ( MFRTA ) has been well accepted. Howe…
View article: Physiologically-based pharmacokinetic analysis of benzoic acid in rats, guinea pigs and humans: Implications for dietary exposures and interspecies uncertainty
Physiologically-based pharmacokinetic analysis of benzoic acid in rats, guinea pigs and humans: Implications for dietary exposures and interspecies uncertainty Open
Benzoic acid (BA) is a common preservative used in food and beverage products. In this study, we systematically reviewed the available pharmacokinetic data for BA within a variety of animal models to design multiple species-specific physio…