A5071523883- Cancer Genomics and Diagnostics
- Advanced Breast Cancer Therapies
- Head and Neck Cancer Studies
- Sarcoma Diagnosis and Treatment
- Soft tissue tumor case studies
- Cervical Cancer and HPV Research
- Lung Cancer Treatments and Mutations
- Soft tissue tumors and treatment
- Cell Adhesion Molecules Research
- HER2/EGFR in Cancer Research
- Cancer-related molecular mechanisms research
- Estrogen and related hormone effects
- Cancer Cells and Metastasis
- RNA modifications and cancer
- Cell death mechanisms and regulation
- Radiomics and Machine Learning in Medical Imaging
- RNA Interference and Gene Delivery
- Breast Cancer Treatment Studies
- Molecular Biology Techniques and Applications
- Ferroptosis and cancer prognosis
- Acute Myeloid Leukemia Research
- Cancer-related Molecular Pathways
- Metabolomics and Mass Spectrometry Studies
- Thyroid Cancer Diagnosis and Treatment
- Science, Research, and Medicine
Tennessee Oncology
2023-2025
Vanderbilt University Medical Center
2014-2023
Vanderbilt University
2013-2022
Breast Cancer Research Foundation
2013-2022
Vanderbilt-Ingram Cancer Center
2015-2022
Bipar
2015-2022
University of Geneva
2017-2021
American Association For Cancer Research
2021
University of Chicago
2006-2017
Fundación Instituto Valenciano de Oncología
2017
The AACR Project GENIE is an international data-sharing consortium focused on generating evidence base for precision cancer medicine by integrating clinical-grade genomic data with clinical outcome tens of thousands patients treated at multiple institutions worldwide. In conjunction the first public release from approximately 19,000 samples, we describe goals, structure, and standards report conclusions high-level analysis initial phase data. We also provide examples utility data, such as...
Abstract Purpose: The genetic differences between human papilloma virus (HPV)–positive and –negative head neck squamous cell carcinomas (HNSCC) remain largely unknown. To identify differential biology novel therapeutic targets for both entities, we determined mutations copy-number aberrations in a large cohort of locoregionally advanced HNSCC. Experimental Design: We performed massively parallel sequencing 617 cancer-associated genes 120 matched tumor/normal samples (42.5% HPV-positive)....
Current classification of head and neck squamous cell carcinomas (HNSCC) based on anatomic site stage fails to capture biologic heterogeneity or adequately inform treatment.Here, we use gene expression-based consensus clustering, copy number profiling, human papillomavirus (HPV) status a clinically homogenous cohort 134 locoregionally advanced HNSCCs with 44% HPV(+) tumors together additional cohorts, which in total comprise 938 tumors, identify HNSCC subtypes discover several...
Early-onset atrial fibrillation (AF) can be the initial manifestation of a more serious underlying inherited cardiomyopathy or arrhythmia syndrome.
In injured skin, collagenase-1 (matrix metalloproteinase-1 (MMP-1)) is induced in migrating keratinocytes. This site-specific expression regulated by binding of the α<sub>2</sub>β<sub>1</sub> integrin with dermal type I collagen, and catalytic activity MMP-1 required for keratinocyte migration. Because this functional association among substrate/ligand, receptor, proteinase, we assessed whether also directs compartmentalization to its matrix target. Indeed, pro-MMP-1 co-localized sites...
Genomic profiling of ER + /HER2 − breast tumors after short-term estrogen deprivation revealed alterations associated with intrinsic resistance and provided mechanistic insights.
Purpose:FGFR1 amplification occurs in approximately 15% of estrogen receptor-positive (ER+) human breast cancers. We investigated mechanisms by which FGFR1 confers antiestrogen resistance to ER+ cancer.Experimental Design: tumors from patients treated with letrozole before surgery were subjected Ki67 IHC, FISH, and RNA sequencing (RNA-seq). ER+/FGFR1-amplified cancer cells, patient-derived xenografts (PDX) siRNA or the FGFR tyrosine kinase inhibitor lucitanib. Endpoints cell/xenograft...
Abstract PIK3CA mutations are associated with resistance to HER2-targeted therapies. We previously showed that HER2+/PIK3CAH1047R transgenic mammary tumors resistant the HER2 antibodies trastuzumab and pertuzumab but respond PI3K inhibitor buparlisib (TPB). In this study, we identified mechanisms of combined inhibition PI3K. TPB-resistant were generated by treating tumor-bearing mice long term drug combination. RNA sequencing revealed extracellular matrix cell adhesion genes, including...
The prevalence of thyroid carcinoma is increasing and represents the most common endocrine malignancy, with papillary (PTC) being frequent subtype. genetic alterations identified in PTCs fail to distinguish tumors different clinical behaviors, such as extra-thyroidal extension lymph node metastasis. We hypothesize that immune microenvironment may play a critical role tumor invasion Computational immunogenomic analysis was performed on 568 PTC samples Cancer Genome Atlas using CIBERSORT,...
In January 2020, SARS-CoV-2 virus was identified as a cause of an outbreak in China. The disease quickly spread worldwide, and the World Health Organization (WHO) declared pandemic March 2020.From first notifications disease, WHO's Emergency Programme implemented global COVID-19 surveillance system coordination with all WHO regional offices. aimed to monitor epidemic over countries across population groups, severity risk factors, impact control measures. data reported is combination...
This retrospective study evaluated the clinical features and findings in bacterial cultures microscopic examination of vaginal secretions 80 prepubertal girls, aged 2-12 years, with vulvovaginitis. Vaginal were obtained directly from vagina a sterile catheter carefully inserted into vagina. Pathogenic bacteria isolated 36% cases. In 59% these cases pathogen was group A beta-haemolytic streptococcus. Candida not found any patients. The finding leucocytes as an indicator for growth pathogenic...
We constructed a large-scale functional network model in Drosophila melanogaster built around two key transcription factors involved the process of embryonic segmentation. Analysis allowed identification new role for ubiquitin E3 ligase complex factor SPOP. In Drosophila, gene encoding SPOP is target segmentation factors. mediates degradation Jun kinase phosphatase Puckered, thereby inducing tumor necrosis (TNF)/Eiger-dependent apoptosis. humans, we found that plays conserved TNF-mediated...
Patients with early-onset atrial fibrillation (AF) are enriched for rare variants in cardiomyopathy and arrhythmia genes. The clinical significance of these patients AF is unknown.
Proximal type epithelioid sarcoma shares similarities with malignant rhabdoid tumor, including the lack of nuclear immunoreactivity SMARCB1. Biallelic mutation SMARCB1 has been convincingly established as cause loss protein expression in but remains unknown. In our previous work, we demonstrated that DNA hypermethylation and post-translational modification mechanisms were not involved. this current explored hypothesis miRNAs regulate gene sarcomas. silico target prediction analysis revealed...
Breast cancer, the second leading cause of cancer death women worldwide, is a heterogenous disease with multiple different subtypes. These subtypes carry important implications for prognosis and therapy. Interestingly, it known that these not only have biological behaviors, but also distinct gene expression profiles. However, has been rigorously explored whether particular transcriptional isoforms are differentially expressed among breast subtypes, or transcript from same sets genes can be...
Mutations in PIK3CA, the gene encoding p110α catalytic subunit of phosphoinositide 3-kinase (PI3K) have been shown to transform human mammary epithelial cells (MECs). These mutations are present all breast cancer subtypes, including basal-like (BLBC). Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified 72 protein expression changes MECs with knock-in E545K or H1047R PIK3CA versus isogenic wild-type PIK3CA. Several these were secreted proteins, cell surface...
Abstract An estimated 40,000 deaths will be attributed to breast cancer in 2016, underscoring the need for improved therapies. Evading cell death is a major hallmark of cancer, driving tumor progression and therapeutic resistance. To evade apoptosis, cancers use antiapoptotic Bcl-2 proteins bind neutralize apoptotic activators, such as Bim. Investigation family members clinical datasets revealed greater expression more frequent gene amplification MCL1 compared with BCL2 or BCL2L1 (Bcl-xL)...
Rationale: We have a limited understanding of the molecular underpinnings early adenocarcinoma (ADC) progression. hypothesized that behavior ADC can be predicted based on genomic determinants.Objectives: To identify alterations associated with resected indolent and aggressive lung ADCs.Methods: DNA was extracted from 21 ADCs in situ (AISs), 27 minimally invasive (MIAs), 54 fully ADCs. This subjected to deep next-generation sequencing tested against custom panel 347 cancer genes.Measurements...
The prognostic value of surgical resection margins in predicting recurrence desmoid-type fibromatosis remains inconclusive, and appropriate are not defined. We analyzed whether specific factors related to margin status, including the adequacy pathologic assessment, affect impact a retrospective cohort study. distance (clearance) tissue composition were recorded for primary desmoid resections with negative margins. number positive linear extent marginal involvement cases sections submitted...
Triple-negative breast cancer (TNBC) and other molecularly heterogeneous malignancies present a significant clinical challenge due to lack of high-frequency "driver" alterations amenable therapeutic intervention. These cancers often exhibit genomic instability, resulting in chromosomal rearrangements that affect the structure expression protein-coding genes. However, identification these remains technically challenging. Using newly developed approach quantitatively predicts gene...