A5084499548- interferon and immune responses
- RNA modifications and cancer
- Immune cells in cancer
- Cancer Genomics and Diagnostics
- Extracellular vesicles in disease
- Mathematical Biology Tumor Growth
- Single-cell and spatial transcriptomics
- Lung Cancer Research Studies
- CRISPR and Genetic Engineering
- Caveolin-1 and cellular processes
- Ubiquitin and proteasome pathways
- Metabolomics and Mass Spectrometry Studies
- PARP inhibition in cancer therapy
- PI3K/AKT/mTOR signaling in cancer
- bioluminescence and chemiluminescence research
- Cancer, Hypoxia, and Metabolism
- Ferroptosis and cancer prognosis
- Lung Cancer Treatments and Mutations
- Melanoma and MAPK Pathways
- Inflammasome and immune disorders
- Ocular Oncology and Treatments
Cornell University
2021-2024
Weill Cornell Medicine
2021-2024
Abstract Chromosomal instability (CIN) is a driver of cancer metastasis 1–4 , yet the extent to which this effect depends on immune system remains unknown. Using ContactTracing—a newly developed, validated and benchmarked tool infer nature conditional dependence cell–cell interactions from single-cell transcriptomic data—we show that CIN-induced chronic activation cGAS–STING pathway promotes downstream signal re-wiring in cells, leading pro-metastatic tumour microenvironment. This manifested...
Lung adenocarcinoma (LUAD) and small cell lung cancer (SCLC) are thought to originate from different epithelial types in the lung. Intriguingly, LUAD can histologically transform into SCLC after treatment with targeted therapies. In this study, we designed models follow conversion of found that barrier histological transformation converges on tolerance Myc, which implicate as a lineage-specific driver pulmonary neuroendocrine cell. Histological transformations frequently accompanied by...
Abstract Chromosomal instability (CIN) and epigenetic alterations have been implicated in tumor progression metastasis; yet how these two hallmarks of cancer are related remains poorly understood. By integrating genetic, epigenetic, functional analyses at the single cell level, we show that uveal melanoma (UM), most common intraocular primary adults, is driven by loss Polycomb Repressive Complex 1 (PRC1) a subpopulation cells. This leads to transcriptional de-repression PRC1-target genes...
Abstract The systemic metabolic shifts that occur during aging and the local alterations of a tumor, its stroma their communication cooperate to establish unique tumor microenvironment (TME) fostering cancer progression. Here, we show methylmalonic acid (MMA), an aging-increased oncometabolite also produced by aggressive cells, activates fibroblasts in TME, which reciprocally secrete IL-6 loaded extracellular vesicles (EVs) drive progression, drug resistance metastasis. cancer-associated...
Abstract Lung adenocarcinoma (LUAD) and small cell lung cancer (SCLC) are thought to originate from different epithelial types in the lung. Intriguingly, LUAD can histologically transform into SCLC following treatment with targeted therapies. Here we designed models follow conversion of found barrier histological transformation converges on tolerance Myc, which implicate as a lineage-specific driver pulmonary neuroendocrine cell. Histological transformations frequently accompanied by...
Abstract Chromosomal instability (CIN) is a driver of cancer metastasis, yet the extent to which this effect depends on immune system remains unknown. Using ContactTracing—a newly developed, validated and benchmarked tool infer nature conditional dependence cell-cell interactions from single-cell transcriptomic data—we show that CIN-induced chronic activation cGAS-STING pathway promotes downstream signal re-wiring in cells, leading pro-metastatic tumor microenvironment. This manifested by...
Abstract Liver metastasis (LM) occurs frequently in patients with melanoma and is associated a poor prognosis reduced therapy response. To identify drivers of metastatic niches, we used syngeneic mouse model which recapitulates genomic, response patterns seen patients, performed large-scale vivo CRISPR-Cas9 knockout screen, identified perturbations that strongly promoted liver but not lung metastasis. The “top hit” this screen LM was loss Pip4k2c. Mechanistically, Pip4k2c sensitized both...
Abstract The systemic metabolic shifts that occur during aging and the local alterations of a tumor, its stroma their communication cooperate to establish unique tumor microenvironment (TME) fosters cancer progression. Here, we show methylmalonic acid (MMA), an aging-increased oncometabolite is also produced by aggressive cells, activates fibroblasts in TME, which reciprocally secrete IL-6 loaded extracellular vesicles (EVs) drive progression, drug resistance metastasis. cancer-associated...
Abstract Chromosomal instability (CIN) is a cancer hallmark associated with metastasis and immune evasion. Yet, it unclear how CIN modulates the tumor-microenvironment (TME). Here we show that results in protumor TME enrichment of immune-suppressive macrophages, granulocytic infiltrate, exhausted T cells. Using ContactTracing, newly developed computational tool to infer conditionally dependent cell-cell interactions from single cell RNA sequence data, identify tumor ligands induced by ER...
Abstract The importance of metabolic reprogramming in cancer has been long demonstrated by the association systemic changes, such as aging, diet and exercise, with outcomes. These shifts, combined local alterations within tumor microenvironment (TME), can all cooperate to foster an environment conducive progression. In cells derived from primary metastatic patient tumors, we found that mesenchymal-like displayed dysregulated propionate metabolism, leading increased accumulation secretion...