Publications by authors named "Rocky Shi"

Article Synopsis
  • * Research shows decreased MED15 levels in pancreatic islets from individuals with type 2 diabetes, suggesting its importance in maintaining β-cell function and health.
  • * Studies indicate that Med15 interacts with transcription factors Nkx6-1 and NeuroD1 to regulate genes crucial for β-cell maturation, and this is also seen in genetically modified human stem cells that show improved maturation when MED15 levels are increased.
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Article Synopsis
  • Researchers studied lung adenocarcinomas (LUAD) in non-tobacco users to find new genetic drivers of lung cancer, identifying 21 positively selected genes, including 12 that are novel in this context.* -
  • One particularly important find was the SHPRH gene, which showed a link between low expression levels and poor survival outcomes in LUAD patients, indicating its potential role as a tumor suppressor.* -
  • Reintroducing SHPRH in LUAD cell lines diminished tumor growth and the ability to form colonies, suggesting it’s critical for resistance against DNA damage, which could help predict patient responses to treatments.*
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Background: Lung cancer is the leading cause of cancer related death worldwide, mainly due to the late stage of disease at the time of diagnosis. Non-invasive biomarkers are needed to supplement existing screening methods to enable earlier detection and increased patient survival. This is critical to -driven lung adenocarcinoma as it commonly occurs in individuals who have never smoked and do not qualify for current screening protocols.

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Organotypic cultures of murine brain slices are well-established tools in neuroscience research, including electrophysiology studies, modeling neurodegeneration, and cancer research. Here, we present an optimized brain slice invasion assay that models glioblastoma multiforme (GBM) cell invasion into organotypic brain slices. Using this model, human GBM spheroids can be implanted with precision onto murine brain slices and cultured to allow tumour cell invasion into the brain tissue.

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MEK inhibitors (MEKi) have limited efficacy in KRAS mutant lung adenocarcinoma (LUAD) patients, and this is attributed to both intrinsic and adaptive mechanisms of drug resistance. While many studies have focused on the former, there remains a dearth of data regarding acquired resistance to MEKi in LUAD. We established trametinib-resistant KRAS mutant LUAD cells through dose escalation and performed targeted MSK-IMPACT sequencing to identify drivers of MEKi resistance.

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Metastatic breast cancer is challenging to effectively treat, highlighting the need for an improved understanding of host factors that influence metastatic tumor cell colonization and growth in distant tissues. The lungs are a common site of breast cancer metastasis and are host to a population of tissue-resident eosinophils. Eosinophils are granulocytic innate immune cells known for their prominent roles in allergy and Th2 immunity.

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Article Synopsis
  • Current lung cancer treatments don't work well for everyone, and researchers want to find out why so they can make better options.
  • They discovered that changes in lung cancer cells, like mutations in certain genes (EGFR and KRAS), can produce proteins that mess with how the immune system works.
  • By reducing a protein called CCL5 in mice with lung cancer, researchers found that the immune system was able to fight the tumor better, suggesting targeting CCL5 could help improve treatments for lung cancer patients.
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Phenotype-based screening can identify small molecules that elicit a desired cellular response, but additional approaches are required to characterize their targets and mechanisms of action. Here, we show that a compound termed LCS3, which selectively impairs the growth of human lung adenocarcinoma (LUAD) cells, induces oxidative stress. To identify the target that mediates this effect, we use thermal proteome profiling (TPP) and uncover the disulfide reductases GSR and TXNRD1 as targets.

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Article Synopsis
  • Scientists found that areas in the body called germinal centers (GCs) can become low in oxygen (hypoxic) when dealing with tumors in mice.
  • This lack of oxygen makes it harder for immune cells called B cells to grow and produce important antibodies.
  • They also discovered that this problem with low oxygen happens in humans with breast cancer too, which means it might be a big issue for fighting tumors.
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Lineage transformation between lung cancer subtypes is a poorly understood phenomenon associated with resistance to treatment and poor patient outcomes. Here, we aimed to model this transition to define underlying biological mechanisms and identify potential avenues for therapeutic intervention. Small cell lung cancer (SCLC) is neuroendocrine in identity and, in contrast to non-SCLC (NSCLC), rarely contains mutations that drive the MAPK pathway.

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Live-cell imaging of mitochondrial function and dynamics can provide vital insights into both physiology and pathophysiology, including of metabolic diseases like type 2 diabetes. However, without super-resolution microscopy and commercial analysis software, it is challenging to accurately extract features from dense multilayered mitochondrial networks, such as those in insulin-secreting pancreatic β-cells. Motivated by this, we developed a comprehensive pipeline and associated ImageJ plugin that enables 2D/3D quantification of mitochondrial network morphology and dynamics in mouse β-cells and by extension other similarly challenging cell types.

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Gene function in cancer is often cell type-specific. The epithelial cell-specific transcription factor ELF3 is a documented tumor suppressor in many epithelial tumors yet displays oncogenic properties in others. Here, we show that ELF3 is an oncogene in the adenocarcinoma subtype of lung cancer (LUAD), providing genetic, functional, and clinical evidence of subtype specificity.

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Background: Solid tumors produce proteins that can induce the accumulation of bone marrow-derived cells in various tissues, and these cells can enhance metastatic tumor growth by several mechanisms. 4T1 murine mammary tumors are known to produce granulocyte colony-stimulating factor (G-CSF) and increase the numbers of immunosuppressive CD11bGr1 myeloid-derived suppressor cells (MDSCs) in tissues such as the spleen and lungs of tumor-bearing mice. While surgical resection of primary tumors decreases MDSC levels in the spleen, the longevity and impact of MDSCs and other immune cells in the lungs after tumor resection have been less studied.

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