A5084696219- Cancer Genomics and Diagnostics
- Circular RNAs in diseases
- MicroRNA in disease regulation
- Epigenetics and DNA Methylation
- Cancer-related Molecular Pathways
- PI3K/AKT/mTOR signaling in cancer
- Breast Cancer Treatment Studies
- Photoacoustic and Ultrasonic Imaging
- Optical Imaging and Spectroscopy Techniques
- Prostate Cancer Treatment and Research
- RNA modifications and cancer
- Pancreatic and Hepatic Oncology Research
- Cancer Risks and Factors
- Optical Coherence Tomography Applications
- Cancer Immunotherapy and Biomarkers
- Medical Imaging Techniques and Applications
- Genetic factors in colorectal cancer
- Health Systems, Economic Evaluations, Quality of Life
- Single-cell and spatial transcriptomics
- Cancer Cells and Metastasis
- Esophageal Cancer Research and Treatment
- Bioinformatics and Genomic Networks
- Molecular Biology Techniques and Applications
- Cancer Diagnosis and Treatment
- Lung Cancer Treatments and Mutations
Columbia University Irving Medical Center
2016-2025
Columbia University
2016-2025
National Center on Addiction and Substance Abuse at Columbia University
2020-2025
Herbert Irving Comprehensive Cancer Center
2009-2023
St. Jude Children's Research Hospital
2019
American University of Beirut Medical Center
2018
American University of Beirut
2018
New York Hospital Queens
2005-2017
NewYork–Presbyterian Hospital
2002-2017
Texas Health Dallas
2014-2016
Mapping of homozygous deletions on human chromosome 10q23 has led to the isolation a candidate tumor suppressor gene, PTEN , that appears be mutated at considerable frequency in cancers. In preliminary screens, mutations were detected 31% (13/42) glioblastoma cell lines and xenografts, 100% (4/4) prostate cancer lines, 6% (4/65) breast 17% (3/18) primary glioblastomas. The predicted product protein tyrosine phosphatase domain extensive homology tensin, interacts with actin filaments focal...
Malignant cells often display defects in autophagy, an evolutionarily conserved pathway for degrading long-lived proteins and cytoplasmic organelles. However, as yet, there is no genetic evidence a role of autophagy genes tumor suppression. The beclin 1 gene monoallelically deleted 40–75% cases human sporadic breast, ovarian, prostate cancer. Therefore, we used targeted mutant mouse model to test the hypothesis that monoallelic deletion promotes tumorigenesis. Here show heterozygous...
Abstract Deregulation of the phosphatidylinositol 3-kinase (PI3K) pathway either through loss PTEN or mutation catalytic subunit α PI3K (PIK3CA) occurs frequently in human cancer. We identified PIK3CA mutations 26% 342 breast tumor samples and cell lines at about equal frequency stages I to IV. To investigate relationship between PIK3CA, we generated a cohort tumors that had lost expression compared it with matched control set retained PTEN. A highly significant association retention protein...
Pathway-specific therapy is the future of cancer management. The oncogenic phosphatidylinositol 3-kinase (PI3K) pathway frequently activated in solid tumors; however, currently, no reliable test for PI3K activation exists human tumors. Taking advantage observation that loss PTEN, negative regulator PI3K, results robust this pathway, we developed and validated a microarray gene expression signature immunohistochemistry (IHC)-detectable PTEN breast (BC). most significant was itself, indicating...
Phosphatase and tensin homolog on chromosome ten (PTEN) is a tumor suppressor an antagonist of the phosphoinositide-3 kinase (PI3K) pathway. We identified 576-amino acid translational variant PTEN, termed PTEN-Long, that arises from alternative translation start site 519 base pairs upstream ATG initiation sequence, adding 173 N-terminal amino acids to normal PTEN open reading frame. PTEN-Long membrane-permeable lipid phosphatase secreted cells can enter other cells. As exogenous agent,...
The basal-like breast cancer (BLBC) subtype is characterized by positive staining for basal mammary epithelial cytokeratin markers, lack of hormone receptor and HER2 expression, poor prognosis with currently no approved molecularly-targeted therapies. oncogenic signaling pathways driving tumorigenesis are not fully elucidated.One hundred sixteen unselected tumors were subjected to integrated analysis phosphoinositide 3-kinase (PI3K) pathway related molecular aberrations immunohistochemistry,...
Objective Pancreatic ductal adenocarcinoma (PDA) has among the highest stromal fractions of any cancer and this complicated attempts at expression-based molecular classification. The goal work is to profile purified samples human PDA epithelium stroma examine their respective contributions gene expression in bulk samples. Design We used laser capture microdissection (LCM) RNA sequencing 60 matched pairs malignant then these data train a computational model that allowed us infer tissue...
PTEN (phosphatase and tensin homolog on chromosome 10) is a tumor suppressor whose cellular regulation remains incompletely understood. We identified phosphatidylinositol 3,4,5-trisphosphate RAC exchanger 2a (P-REX2a) as PTEN-interacting protein. P-REX2a mRNA was more abundant in human cancer cells significantly increased tumors with wild-type that expressed an activated mutant of PIK3CA encoding the p110 subunit phosphoinositide 3-kinase alpha (PI3Kalpha). inhibited lipid phosphatase...
A number of polycyclic aromatic hydrocarbons (PAH) are widespread environmental contaminants that cause mammary cancer experimentally. We investigated whether exposure and susceptibility to PAH, as measured by PAH-DNA adducts in breast tissue, associated with human cancer. carried out a hospital-based case-control study using immunohistochemical methods analyze tumor nontumor tissue from cases benign controls. The subjects were white, African-American Latina women without prior or treatment,...
Abnormalities of genomic methylation patterns are lethal or cause disease, but the cues that normally designate CpG dinucleotides for poorly understood. We have developed a new method profiling has single-CpG resolution and can address status repeated sequences. used this to determine >275 million sites in human mouse DNA from breast brain tissues. Methylation density at most sequences was found increase linearly with fall sharply very high densities, transposons remained densely methylated...
Molecular characterization has the potential to advance management of pediatric cancer and high-risk hematologic disease. The clinical integration genome sequencing into standard practice been limited utility identify clinically impactful information beyond targetable alterations underestimated. Precision in Pediatric Sequencing (PIPseq) Program at Columbia University Medical Center instituted prospective next generation (NGS) for disorders risk treatment failure. We performed whole exome...
A distinct morphologic and molecular phenotype has been reported for BRCA1-associated breast cancers; however, the of BRCA2-associated cancers is less certain. To comprehensively characterize we performed a retrospective case control study using tumors accrued through Breast Cancer Family Registry. We examined tumor morphology hormone receptor status in 157 hereditary with germline mutations BRCA2 314 negative BRCA1 that were matched age ethnicity. Tissue microarrays constructed from 64 185...
Screening for tumor suppressor genes in breast cancer revealed multiple truncating mutations of PB1, which encodes the BAF180 subunit PBAF chromatin remodeling complex. Mutation was associated with loss heterozygosity wild-type allele. complementation BAF180-mutant cells caused G(1) arrest that dependent on increased expression cyclin/cyclin-dependent kinase inhibitor p21/WAF1/CIP1. Endogenous bound to p21 promoter and required proper after transforming growth factor-beta gamma-radiation...
Lesions of ERBB2, PTEN, and PIK3CA activate the phosphatidylinositol 3-kinase (PI3K) pathway during cancer development by increasing levels phosphatidylinositol-3,4,5-triphosphate (PIP(3)). 3-Phosphoinositide-dependent kinase 1 (PDK1) is first node PI3K signal output required for activation AKT. PIP(3) recruits PDK1 AKT to cell membrane through interactions with their pleckstrin homology domains, allowing phosphorylating it at residue threonine-308. We show that total protein mRNA were...