A5011138786- Genomic variations and chromosomal abnormalities
- Cancer-related Molecular Pathways
- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Cancer Cells and Metastasis
- Genetics and Neurodevelopmental Disorders
- Cancer Genomics and Diagnostics
- Cancer Research and Treatments
- Epigenetics and DNA Methylation
- Microtubule and mitosis dynamics
- Cancer-related gene regulation
- Peptidase Inhibition and Analysis
- Head and Neck Cancer Studies
- Cervical Cancer and HPV Research
- Acute Myeloid Leukemia Research
- Protease and Inhibitor Mechanisms
- Acute Lymphoblastic Leukemia research
- Molecular Biology Techniques and Applications
- Genetic Syndromes and Imprinting
- Chronic Lymphocytic Leukemia Research
- Viral-associated cancers and disorders
- Chromosomal and Genetic Variations
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Sarcoma Diagnosis and Treatment
University of Pittsburgh
2013-2023
UPMC Hillman Cancer Center
2009-2023
Institute of Human Genetics
2007-2023
University of Pittsburgh Medical Center
2000-2018
Magee-Womens Hospital
2002-2016
Magee-Womens Research Institute
2012
University Medical Center
2012
VA Pittsburgh Healthcare System
2012
University of Regensburg
2012
Southwestern Medical Center
2012
Most tumor cells are characterized by increased genomic instability and chromosome segregational defects, often associated with hyperamplification of the centrosome formation multipolar spindles. However, extra centrosomes do not always lead to multipolarity. Here, we describe a process centrosomal clustering that prevented spindles in noncancer cells. Noncancer needed overcome this mechanism allow form at high frequency. The microtubule motor cytoplasmic dynein was critical part coalescing...
Frequent gene amplification of the receptor-activated calcium-dependent chloride channel TMEM16A (TAOS2 or ANO1) has been reported in several malignancies. However, its involvement human tumorigenesis not previously studied. Here, we show a functional role for tumor growth. We found overexpression 80% head and neck squamous cell carcinoma (SCCHN), which correlated with decreased overall survival patients SCCHN. significantly promoted anchorage-independent growth vitro, loss resulted...
In the last few years, mutiple protein target antigens for immunorecognition by T cells have been identified on human melanoma. How melanoma lesions escape from functional antigen-specific immune recognition remains poorly understood. We concomitant loss of immunodominant cell-defined MART-1/Melan-A antigen and downregulation TAP-1 gene in a recurrent metastatic that was resected 1993. This phenotype not observed an earlier autologous lesion 1987. The "antigen loss" could be restored variant...
Oral squamous cell carcinomas are characterized by complex, often near-triploid karyotypes with structural and numerical variations superimposed on the initial clonal chromosomal alterations. We used immunohistochemistry combined classical cytogenetic analysis spectral karyotyping to investigate segregation defects in cultured oral carcinoma cells. During division, these cells frequently exhibit lagging chromosomes at both metaphase anaphase, suggesting mitotic apparatus or kinetochore....
To determine whether the FHIT gene at 3p14.2 is altered in head and neck squamous cell carcinomas (HNSCC), we examined 26 HNSCC lines for deletions within locus by Southern analysis, allelic losses of specific exons fluorescence situ hybridization (FISH) integrity transcripts. Three exhibited homozygous gene, 55% (15/25) showed presence aberrant transcripts, 65% (13/20) multiple populations with different portions alleles FISH genomic clones to interphase nuclei. When data obtained reverse...
Abstract Introduction Phosphatidylinositol 3-kinases (PI3Ks) are a group of lipid kinases that regulate signaling pathways involved in cell proliferation, adhesion, survival, and motility. Even though PIK3CA amplification somatic mutation have been reported previously various kinds human cancers, the genetic change breast cancer has not clearly identified. Methods Fifteen lines 92 primary tumors (33 with matched normal tissue) were used to check gene copy number . For study, we specifically...
Abstract Altered microRNA (miRNA) expression profiles have been observed in numerous malignancies, including oral squamous cell carcinoma (OSCC). However, their role disease is not entirely clear. Several genetic aberrations are characteristic of OSCC, with amplification chromosomal band 11q13 and loss distal 11q being among the most prevalent. It known if levels miRNAs these regions altered or whether they play a disease. We hypothesize that mapping to OSCC because material, this...
As in many other human cancers, overactivation of the phosphotidylinositol 3-kinase (PI3K)/Akt signaling pathway occurs frequently thyroid cancer, but mechanism is not completely clear.Because activating mutations and genomic amplification PIK3CA gene, which encodes p110a catalytic subunit PI3K, are common we sought to investigate this phenomenon tumors.To search for mutations, isolated DNA from primary tumors various types performed direct sequencing exons gene that carry most cancers. We...
Abstract Human cancers have been found to include transformed stem cells that may drive cancer progression metastasis. Here, we report metastatic colon contains clonally derived tumor with all of the critical properties expected cells, including self-renewal and ability differentiate into mature cells. Additionally, when injected mice, these initiated tumors closely resemble human cancer. Karyotype analyses parental expressed many consistent (clonal) along unique chromosomal aberrations,...
HPV-related HNSCC generally have a better prognosis than HPV-negative HNSCC. However, subgroup of HPV-positive tumors with poor has been recognized, particularly related to smoking, EGFR overexpression and chromosomal instability. Viral integration into the host genome might contribute carcinogenesis, as is shown for cervical carcinomas. Therefore, all HPV16-positive cell lines currently available carefully analyzed viral parameters. The status, load, gene expression presence aneusomies was...
Amplification of chromosomal band 11q13 is a common event in human cancer. It has been reported about 45% head and neck carcinomas other cancers including esophageal, breast, liver, lung, bladder To understand the mechanism amplification to identify potential oncogene(s) driving it, we have fine-mapped structure amplicon oral squamous cell carcinoma lines localized proximal distal breakpoints. A 5-Mb physical map region prepared from which sequence available. We quantified copy number...
Abstract We report on 11 cases of isochromosome 12p mosaicism (or Pallister mosaic aneuploidy syndrome) in which the is usually absent cultured lymphocytes but present fibroblasts. The patients range age from a 22‐week‐gestation fetus to 45‐year‐old man. They have distinct pattern anomalies enables one make diagnosis based clinical manifestations alone. Craniofacial include “coarse” face with prominent forehead, spars‐ity scalp hair, hypertelorism, epicanthal folds, flat bridge nose, and...
Abstract 11q13 amplification occurs in a wide variety of tumors, including almost half oral squamous cell carcinomas (OSCC) where it has been correlated with poor outcome. In this study, we compiled 3.6 Mb DNA sequence the amplicon core and refined physical map amplicon. process, determined genomic structure normal tissue expression patterns two recently identified genes, TAOS 2/TMEM 16A MRGF , which reside core. We then quantified copy number mRNA all genes lines primary tumors from OSCC....
Defects in the spindle assembly checkpoint are thought to be responsible for an increased rate of aneuploidization during tumorigenesis. Despite a plethora information on correlation between BUB-MAD gene expression levels and defects checkpoint, very little is known about alteration another important protein, Cdc20, human cancer its role tumor aneuploidy. We observed overexpression CDC20 several oral squamous cell carcinoma (OSCC) lines primary head neck tumors provide evidence that such...
Abstract Rev3L encodes the catalytic subunit of DNA polymerase ζ (pol ζ) in mammalian cells. In yeast, pol helps cells bypass sites damage that can block replication enzymes. Targeted disruption mouse gene causes lethality midway through embryonic gestation, and Rev3L−/− fibroblasts (MEFs) remain a quiescent state culture. This suggests may be necessary for tolerance endogenous during normal cell growth. We report generation mitotically active MEFs on p53−/− genetic background. null...
Cell lines are important tools for biological and preclinical investigation, establishing their relationship to genomic alterations in tumors could accelerate functional therapeutic discoveries. We conducted integrated analyses of transcriptomic profiles 15 human papillomavirus (HPV)-negative 11 HPV-positive head neck squamous cell carcinoma (HNSCC) compare with 279 from The Cancer Genome Atlas (TCGA). identified recurrent amplifications on chromosomes 3q22-29, 5p15, 11q13/22, 8p11 that...