A5043506283- Colorectal Cancer Treatments and Studies
- Cancer Research and Treatments
- HIV Research and Treatment
- Genetic factors in colorectal cancer
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Fibroblast Growth Factor Research
- Cancer Cells and Metastasis
- Immune Cell Function and Interaction
- HIV/AIDS drug development and treatment
- Melanoma and MAPK Pathways
- PI3K/AKT/mTOR signaling in cancer
- T-cell and B-cell Immunology
- Cancer Genomics and Diagnostics
- Genomic variations and chromosomal abnormalities
- Streptococcal Infections and Treatments
- Cancer therapeutics and mechanisms
- Epigenetics and DNA Methylation
- HIV/AIDS Research and Interventions
- Gastric Cancer Management and Outcomes
- Cancer, Hypoxia, and Metabolism
- Antimicrobial Resistance in Staphylococcus
- Cancer, Lipids, and Metabolism
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Pancreatic and Hepatic Oncology Research
University of Miami
2024-2025
Ondine Biopharma (United States)
2021-2024
Harvard University
2005-2024
Dana-Farber/Harvard Cancer Center
2011-2024
Miami Transplant Institute
2024
University of California, San Francisco
2024
Shitennoji University
2020
Ochanomizu University
2020
Simon Fraser University
2010-2018
Plexxikon (United States)
2018
The TCL1 gene at 14q32.1 is involved in chromosomal translocations and inversions mature T cell leukemias. These leukemias are classified either as prolymphocytic leukemias, which occur very late life, or chronic lymphocytic often arise patients with ataxia telangiectasia (AT) a young age. In transgenic animals, the deregulated expression of leads to leukemia, demonstrating role initiation malignant transformation neoplasia. Expression high levels Tcl1 have also been found variety human...
Lung cancer is the leading cause of mortality worldwide, yet there exists a limited view genetic lesions driving this disease. In study, an integrated high-resolution survey regional amplifications and deletions, coupled with gene-expression profiling non-small-cell lung subtypes, adenocarcinoma squamous-cell carcinoma (SCC), identified 93 focal copy-number alterations, which 21 span <0.5 megabases contain median five genes. Whereas all known genes/loci are contained in dataset, most...
In an effort to identify tumor suppressor gene(s) associated with the frequent loss of heterozygosity observed on chromosome 6q25–q27, we constructed a contig derived from sequences bacterial artificial chromosome/P1 bacteriophage clones defined by genetic interval D6S1581–D6S1579–D6S305–D6S1599–D6S1008. Sequence analysis this found it contain eight known genes, including complete genomic structure Parkin gene. Loss (LOH) 40 malignant breast and ovarian tumors identified common minimal...
Purpose To examine the in vitro and vivo efficacy of dual PI3K/mTOR inhibitor NVP-BEZ235 treatment PIK3CA wild-type colorectal cancer (CRC). Experimental Design mutant human CRC cell lines were treated with NVP-BEZ235, resulting effects on proliferation, apoptosis, signaling assessed. Colonic tumors from a genetically engineered mouse (GEM) model for sporadic NVP-BEZ235. The macroscopic tumor growth/regression, angiogenesis, examined. Results In resulted transient PI3K blockade, sustained...
ABSTRACT HLA class I-associated polymorphisms identified at the population level mark viral sites under immune pressure by individual alleles. As such, analysis of their distribution, frequency, location, statistical strength, sequence conservation, and other properties offers a unique perspective from which to identify correlates protective cellular immunity. We analyzed HLA-associated HIV-1 subtype B in 1,888 treatment-naïve, chronically infected individuals using phylogenetically informed...
Abstract Background Impaired HIV-1 Gag, Pol, and Env function has been described in elite controllers (EC) who spontaneously suppress plasma viremia to < 50 RNA copies/mL; however, activity of the accessory protein Nef remains incompletely characterized. We examined ability 91 clones, isolated from 45 EC 46 chronic progressors (CP), down-regulate HLA class I CD4, up-regulate II invariant chain (CD74), enhance viral infectivity, stimulate replication PBMC. Results In general, clones were...
The human steroid sulfatase gene (STS) is located on the distal X chromosome short arm close to pseudoautosomal region but in a segment of DNA that unique chromosome. In contrast most chromosome-encoded genes, STS expression not extinguished during process inactivation. Deficiency (steryl-sulfatase; steryl-sulfate sulfohydrolase, EC 3.1.6.2) activity produces syndrome chromosome-linked ichthyosis, which one common inborn errors metabolism man. Approximately 90% STS- individuals have large...
To develop a comprehensive overview of copy number aberrations (CNAs) in stage-II/III colorectal cancer (CRC), we characterized 302 tumors from the PETACC-3 clinical trial. Microsatellite-stable (MSS) samples (n = 269) had 66 minimal common CNA regions, with frequent gains on 20 q (72.5%), 7 (41.8%), 8 (33.1%) and 13 (51.0%) losses 18 (58.6%), 4 (26%) 21 (21.6%). MSS have significantly more CNAs than microsatellite-instable (MSI) tumors: within MSI novel deletion tumor suppressor WWOX at 16...
The genetic diversity of HIV-1 represents a major challenge in vaccine development. In this study, we establish rationale for eliminating HIV-1–infected cells by targeting cellular immune responses against stable human endogenous retroviral (HERV) antigens. HERV DNA sequences the genome represent remnants ancient infectious retroviruses. We show that infection CD4+ T with resulted transcription HML-2 lineage type K [HERV-K(HML-2)] and expression Gag Env proteins. HERV-K(HML-2)–specific CD8+...
Abstract Background The highly genetically diverse HIV-1 group M subtypes may differ in their biological properties. Nef is an important mediator of viral pathogenicity; however, to date, a comprehensive inter-subtype comparison vitro function has not been undertaken. Here, we investigate two Nef’s most well-characterized activities, CD4 and HLA class I downregulation, for clones obtained from 360 chronic patients infected with A, B, C or D. Results Single plasma RNA were N=360...
BRAF(V600E) mutations are associated with poor clinical prognosis in colorectal cancer (CRC). Although selective BRAF inhibitors effective for treatment of melanoma, comparable efforts CRC have been disappointing. Here, we investigated potential mechanisms underlying this resistance to CRC.We examined phosphoinositide 3-kinase (PI3K)/mTOR signaling cell lines after inhibition and viability apoptosis combined PI3K/mTOR inhibition. We assessed the efficacy vivo combination using a novel...
Purpose: While multikinase inhibitors with RET activity are active in RET-rearranged thyroid and lung cancers, objective response rates relatively low toxicity can be substantial. The development of novel improved potency and/or reduced is thus an unmet need. RXDX-105 a small molecule kinase inhibitor that potently inhibits RET. purpose the preclinical clinical studies was to evaluate potential as effective therapy for cancers driven by alterations.Experimental design: RET-inhibitory...
Fibroblast growth factor receptor (FGFR) alterations are present as oncogenic drivers and bypass mechanisms in many forms of cancer. These can include fusions, amplifications, rearrangements, mutations. Acquired drug resistance to current FGFR inhibitors often results disease progression unfavorable outcomes for patients. Genomic profiling tumors refractory the clinic has revealed several acquired driver that could be target next generation therapeutics. Herein, we describe how...
Abstract Purpose: Parkin, a gene mutated in autosomal recessive juvenile Parkinsonism and mapped to the common fragile site FRA6E on human chromosome 6q25-q27, is associated with frequent loss of heterozygosity altered expression breast ovarian carcinomas. In addition, homozygous deletions exon 2 creating deleterious truncations Parkin transcript were observed lung adenocarcinoma cell lines Calu-3 H-1573, suggesting that this locus resulting changes its are involved development these tumors....
ABSTRACT Type 1 long-interspersed nuclear elements (L1s) are autonomous retrotransposable that retain the potential for activity in human genome but suppressed by host factors. Retrotransposition of L1s into chromosomal DNA can lead to genomic instability, whereas reverse transcription L1 cytosol has activate innate immune sensors. We hypothesized HIV-1 infection would compromise cellular control elements, resulting induction retrotransposition events. Here, we show enhances Jurkat cells a...
RAF, a core signaling component of the MAPK kinase cascade, is often mutated in various cancers, including melanoma, lung, and colorectal cancers. The approved inhibitors were focused on targeting BRAFV600E mutation that results constitutive activation through monomeric protein (Class I). However, these also paradoxically activate RAF dimers, resulting increased normal tissues. Recently, significant attention has turned to alterations dimeric (class II III BRAF NRAS). discovery potent...
Several studies have suggested an increased risk of cytomegalovirus (CMV) viremia among Hepatitis C virus (HCV)-uninfected recipients kidney transplants from HCV-RNA+ deceased donors (HCV D+/R-), but these featured small sample sizes and limited ability to address confounding variables. We assembled a retrospective cohort adult transplant at five US centers between 4/1/2015 12/31/2020 determine the association HCV D+/R- outcomes CMV (> 1000 IU/mL), death-censored graft failure, mortality in...
Abstract Colorectal cancer (CRC) is a major cause of morbidity and mortality, elucidation its underlying genetics has advanced diagnostic screening, early detection, treatment. Because CRC genomes are characterized by numerous non-random chromosomal structural alterations, we sought to delimit regions recurrent amplifications deletions in collection 42 primary specimens 37 tumor cell lines derived from instability neoplasia microsatellite subtypes compare the pattern genomic aberrations with...
Hepatic encephalopathy, both overt (OHE) and minimal (MHE), is associated with poor quality of life fatigue. The aim this study was to define the effect fatigue on driving skills in MHE OHE patients.Cirrhotics age/education-matched controls were administered a psychometric battery tests diagnose MHE. Cirrhotics recent lactulose also included. All subjects underwent simulation; assess fatigue, second half performance compared first simulation. outcomes collisions, speeding, road excursions,...
Identifying viral and host determinants of HIV-1 elite control may help inform novel therapeutic and/or vaccination strategies. Previously, we observed decreased replication capacity in controller-derived viruses suggesting that fitness consequences human leukocyte antigen (HLA) class I-associated escape mutations Gag contribute to this phenotype. This study examines whether similar functional defects occur Pol proteins controllers.Recombinant NL4-3 encoding plasma RNA-derived reverse...
BackgroundPrognosis prediction for resected primary colon cancer is based on the T-stage Node Metastasis (TNM) staging system. We investigated if four well-documented gene expression risk scores can improve patient stratification.