A5031446715- Protein Degradation and Inhibitors
- Asthma and respiratory diseases
- Immune Cell Function and Interaction
- IL-33, ST2, and ILC Pathways
- Advanced biosensing and bioanalysis techniques
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Immune cells in cancer
- RNA Interference and Gene Delivery
- CCD and CMOS Imaging Sensors
- RNA Research and Splicing
- Telomeres, Telomerase, and Senescence
- Inhalation and Respiratory Drug Delivery
- RNA modifications and cancer
- Single-cell and spatial transcriptomics
- GaN-based semiconductor devices and materials
- COVID-19 Clinical Research Studies
- Genomics and Chromatin Dynamics
- Cancer-related Molecular Pathways
- Inflammasome and immune disorders
- Gene Regulatory Network Analysis
- Cancer Immunotherapy and Biomarkers
- Pluripotent Stem Cells Research
- SARS-CoV-2 and COVID-19 Research
- Gene expression and cancer classification
Vertex Pharmaceuticals (United States)
2023
UPMC Health System
2019-2022
University of Pittsburgh Medical Center
2021
University of Pittsburgh
2019-2021
Pulmonary and Allergy Associates
2021
Emory University
2020
Stony Brook University
2011-2016
Cold Spring Harbor Laboratory
2010-2014
Cancer Center at Cold Spring Harbor Laboratory
2014
Stony Brook University Hospital
2011
The epidermal growth-factor receptor (EGFR) tyrosine kinase inhibitor erlotinib has been proven to be highly effective in the treatment of nonsmall cell lung cancer (NSCLC) harboring oncogenic EGFR mutations. majority patients, however, will eventually develop resistance and succumb disease. Recent studies have identified secondary mutations (EGFR T790M) amplification N-Methyl-N′-nitro-N-nitroso-guanidine (MNNG) HOS transforming gene (MET) oncogene as two principal mechanisms acquired...
Oncogene-induced senescence is a potent barrier to tumorigenesis that limits cellular expansion following certain oncogenic events. Senescent cells display repressive chromatin configuration thought stably silence proliferation-promoting genes while simultaneously activating an unusual form of immune surveillance involving secretory program referred as the senescence-associated phenotype (SASP). Here, we demonstrate also involves global remodeling enhancer landscape with recruitment reader...
Significance p53 is one of the most intensively studied tumor-suppressor genes. We identified a naturally occurring isoform, generated by an alternative-splicing event, that, although lacking transcriptional activity and canonical tumor suppressor functions, able to reprogram cells toward acquisition metastatic features via cyclophilin D interaction in mitochondria matrix. Interestingly, this isoform expressed on tissue injury tumors characterized increased spread. In some these tumors,...
Clinical definitions of asthma fail to capture the heterogeneity immune dysfunction in severe, treatment-refractory disease. Applying mass cytometry and machine learning bronchoalveolar lavage (BAL) cells, we find that corticosteroid-resistant patients cluster largely into two groups: one enriched interleukin (IL)-4+ innate cells another dominated by interferon (IFN)-γ+ T including tissue-resident memory cells. In contrast, BAL a healthier population are IL-10+ macrophages. To better...
Noncoding RNAs play important roles in various aspects of gene regulation. We have identified 7SK RNA to be enriched nuclear speckles or interchromatin granule clusters (IGCs), a subnuclear domain pre-mRNA processing factors. RNA, association with HEXIM 1 and 2, is involved the inhibition transcriptional elongation by polymerase II. Inhibition occurs via sequestration active P-TEFb kinase complex (CDK 9 Cyclin T1/T2a/b K) that phosphorylating C-terminal Our results demonstrate knock-down...
Asthma is a common disease with profoundly variable natural history and patient morbidity. Heterogeneity has long been appreciated, much work focused on identifying subgroups of patients similar pathobiological underpinnings. Previous studies the Severe Research Program (SARP) cohort linked gene expression changes to specific clinical physiologic characteristics. While invaluable for hypothesis generation, these data include extensive candidate lists that complicate target identification...
Background Clustering key clinical characteristics of participants in the Severe Asthma Research Program (SARP), a large, multicenter prospective observational study patients with asthma and healthy controls, has led to identification novel phenotypes. Purpose To determine whether quantitative CT (qCT) could help distinguish between Materials Methods A retrospective cross-sectional analysis was conducted use qCT images (maximal bronchodilation at total lung capacity [TLC], or inspiration,...
Bulk expression data from heterogeneous cell populations pose a challenge for investigators, as differences in numbers and transcriptional programs may complicate analysis. To improve the performance of bulk RNA sequencing on mixed populations, we created Immune Cell Linkage through Exploratory Matrices (ICLite). The ICLite package R constructs modules correlated genes identifies their relationship to specific lineages populations. This protocol details formatting, optimization run...
<p>Supplementary Methods, Figure Legends, References.</p>
<p>Co-culture of NK cells and S/shRen IMR90 cells.</p>
<p>Co-culture of NK cells and P/shRen IMR90 cells.</p>
<p>Supplementary Figure S1. Senescence-activated SASP enhancers are marked by H3K4Me1 in proliferating IMR90 cells. Supplementary S2. Reproducibility analyses of biological replicates for H3K27Ac and BRD4 ChIP-Seq. S3. Enhancer remodeling during oncogene-induced senescence parallels gene expression changes. S4. Genetic pharmacologic inhibition impairs (OIS). S5. couples enhancer to etoposide-induced senescence. S6. Systemic cell-autonomous suppression Brd4 the immune surveillance...
<p>Co-culture of NK cells and S/shRen IMR90 cells.</p>