A5044110204- Lung Cancer Treatments and Mutations
- RNA modifications and cancer
- Cytokine Signaling Pathways and Interactions
- Colorectal Cancer Treatments and Studies
- Epigenetics and DNA Methylation
- Brain Metastases and Treatment
- Lung Cancer Research Studies
- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- Cancer-related gene regulation
- Radiopharmaceutical Chemistry and Applications
- Glioma Diagnosis and Treatment
- Cancer Research and Treatments
- RNA and protein synthesis mechanisms
- Cancer-related molecular mechanisms research
- Liver physiology and pathology
- Cancer Mechanisms and Therapy
- Mechanisms of cancer metastasis
- Biochemical and Molecular Research
- MicroRNA in disease regulation
- Ferroptosis and cancer prognosis
- RNA Research and Splicing
- HER2/EGFR in Cancer Research
- Synthesis and biological activity
- Circular RNAs in diseases
Yale University
2016-2025
Yale Cancer Center
2014-2025
University of New Haven
2013-2024
Carnegie Mellon University
2021
University of Pittsburgh
2016-2021
University of Nebraska Medical Center
2020
Riyadh Armed Forces Hospital
2020
Indiana University – Purdue University Indianapolis
2020
University of Iowa
2020
University of California Davis Medical Center
2018
The association between large tumor size and metastatic risk in a majority of clinical cancers has led to questions as whether these observations are causally related or one is simply marker for the other. This partly due an uncertainty about how metastasis-promoting gene expression changes can arise primary tumors. We investigated this question through analysis previously defined "lung metastasis gene-expression signature" (LMS) that mediates experimental breast cancer selectively lung...
Abstract Purpose: Osimertinib is a potent and selective EGFR tyrosine kinase inhibitor (EGFR-TKI) of both sensitizing T790M resistance mutations. To treat metastatic brain disease, blood–brain barrier (BBB) permeability considered desirable for increasing clinical efficacy. Experimental Design: We examined the level penetration 16 irreversible reversible EGFR-TKIs using multiple in vitro vivo BBB preclinical models. Results: In osimertinib was weakest substrate human efflux transporters...
Acquired resistance to tyrosine kinase inhibitors (TKI), such as osimertinib used treat EGFR-mutant lung adenocarcinomas, limits long-term efficacy and is frequently caused by non-genetic mechanisms. Here, we define the chromatin accessibility gene regulatory signatures of sensitive resistant cell patient-derived models uncover a role for mammalian SWI/SNF remodeling complexes in TKI resistance. By profiling mSWI/SNF genome-wide localization, identify both shared cancer line-specific targets...
Two pathways regulating tissue growth and oncogenic signaling are functionally linked.
Eradication of HIV-1 (HIV) is hindered by stable viral reservoirs. Viral latency epigenetically regulated. While the effects histone acetylation and methylation at HIV long-terminal repeat (LTR) have been described, our knowledge proviral epigenetic landscape incomplete. We report that a previously unrecognized modification LTR, crotonylation, regulator latency. Reactivation latent was achieved following induction crotonylation through increased expression crotonyl-CoA-producing enzyme...
MET amplification as a mechanism of acquired resistance to EGF receptor (EGFR)-targeted therapies in non-small cell lung carcinoma (NSCLC) led investigation novel combinations EGFR and kinase inhibitors. However, promiscuous interactions between ERBB family members have made it difficult evaluate the effects on signaling, both independent drug treatment context resistance. We addressed this issue by establishing 32D model system wherein ERBBs or are expressed alone combination. Using model,...
Metastasis is a major clinical challenge for cancer treatment. Emerging evidence suggests that aberrant epigenetic modifications contribute significantly to tumor formation and progression. However, the drivers roles of such changes in metastasis are still poorly understood. Using bioinformatic analysis human breast gene-expression data sets, we identified histone demethylase RBP2 as putative mediator metastatic By using both cells genetically engineered mice, demonstrated critical lung...
The majority of EGFR mutant lung adenocarcinomas respond well to tyrosine kinase inhibitors (TKI). However, most these responses are partial, with drug-tolerant residual disease remaining even at the time maximal response. This can ultimately lead relapses, which eventually develop in patients. To investigate cellular and molecular properties tumor cells vivo, we leveraged patient-derived xenograft (PDX) models cancer. Subcutaneous PDXs were treated third-generation TKI osimertinib until...
Abstract Mechanisms underlying the propensity of latent lung adenocarcinoma (LUAD) to relapse are poorly understood. In this study, we show how differential expression a network extracellular matrix (ECM) molecules and their interacting proteins contributes risk in distinct LUAD subtypes. Overexpression hyaluronan receptor HMMR primary was associated with an inflammatory molecular signature poor prognosis. Attenuating cells diminished ability initiate tumors distant metastases. upregulation...
Highlights•BMX-seq reveals the tumor and stromal transcriptomes of brain metastasis in situ•The microenvironment reversibly activates neuronal-like genes cells•Increase microglial-bound TIM3 is a neuroinflammatory marker metastases•Different cancers that form share common transcriptomic hallmarksSummaryThe major site relapse for several cancers, yet deciphering mechanisms remains challenge because complexity (TME). To define molecular landscape from intact tissue vivo, we employ an...
Abstract Introduction The recently identified claudin-low subtype of breast cancer is enriched for cells with stem-like and mesenchymal-like characteristics. This most often triple-negative (lacking the estrogen progesterone receptors (ER, PR) as well lacking epidermal growth factor 2 ( HER2 ) amplification) has a poor prognosis. There are few targeted treatment options available patients this highly aggressive type cancer. Methods Using high throughput inhibitor screen, we expression...
Emerging evidence has shown that epigenetic regulation plays a fundamental role in cancer metastasis, the major cause of cancer-related deaths. Here, we conducted an vivo screen for vulnerabilities brain metastasis and identified N -acetyltransferase 10 (NAT10) as driver metastasis. Knockdown NAT10 restrains cell proliferation migration vitro tumor growth vivo. The poorly characterized RNA helicase domain is critical vitro, while both NAT domains are essential primary Mechanically, promotes...