Papers by Renato Aguilera
International Journal of Environmental Research and Public Health
Funded by the National Institutes of Health (NIH), the Research Centers in Minority Institutions ... more Funded by the National Institutes of Health (NIH), the Research Centers in Minority Institutions (RCMI) Program fosters the development and implementation of innovative research aimed at improving minority health and reducing or eliminating health disparities. Currently, there are 21 RCMI Specialized (U54) Centers that share the same framework, comprising four required core components, namely the Administrative, Research Infrastructure, Investigator Development, and Community Engagement Cores. The Research Infrastructure Core (RIC) is fundamentally important for biomedical and health disparities research as a critical function domain. This paper aims to assess the research resources and services provided and evaluate the best practices in research resources management and networking across the RCMI Consortium. We conducted a REDCap-based survey and collected responses from 57 RIC Directors and Co-Directors from 98 core leaders. Our findings indicated that the RIC facilities across t...
ChemistrySelect, 2021
Recent evidences highlight the usefulness of small molecule (Histone deacetylase 4) HDAC4 inhibit... more Recent evidences highlight the usefulness of small molecule (Histone deacetylase 4) HDAC4 inhibitors in the several preclinical paradigms. Major toxicity and mutagenicity issues associated with hydroxamate HDAC inhibitors, stimulated us to develop potent non‐hydroxamate inhibitors. In the present work a novel series of thiazolidinedione (TZD) derivatives with pyridine as cyclic linker and TZD ring as zinc binding group was designed and screened in a panel of isoenzymes of HDACs, wherein the most potent compounds exhibiting HDAC4 IC50‐values<5 μM were 5 v, 5 w, 5 y and 5 z (IC50=4.2±1 μM, 0.75±0.03 μM, 4.9±0.5 and 2.3±0.5 μM, respectively). The docking studies displayed the unique binding mode of this series of compound at active site of HDAC4, wherein TZD ring was indicated as zinc binding group. Further, 5 w and 5 y were found as the most potent antiproliferative agent in lymphoblastic leukemia (CCRF‐CEM) and breast cancer MDA‐MB‐231 cells. Compound 5 y was found to induce the a...
European Journal of Pharmaceutical Sciences, 2020
Cancer Research, 2020
Among the main challenges for the treatment of breast cancers is disease spread which is often co... more Among the main challenges for the treatment of breast cancers is disease spread which is often coupled with resistance to chemotherapy. Furthermore, patients with late stage breast cancer go through first- and second-line therapies before they are candidates for new and/or experimental therapies. At such late stages, tumors that might have responded to new therapies have evolved to express multi-drug resistance - conceivably as a consequence of exposure to the initial therapies. Many mechanisms have been proposed to contribute to drug resistance, ranging from (but not limited to) reduced drug penetration and the activity of drug efflux pumps through to cell-adhesion mediated resistance to cell death. To address these challenges we sought to determine whether; a) tumor metastasis to different secondary sites generates location-specific tumor phenotypes that alter sensitivity to chemotherapy and, b) whether pre-treatment of tumors to conventional paclitaxel (PTX) chemotherapy alters t...
AKT1 is emerging as a useful target for treating cancer. Herein, we discovered a new set of ligan... more AKT1 is emerging as a useful target for treating cancer. Herein, we discovered a new set of ligands that inhibit the AKT1, as shown by in vitro binding and cell line studies, using a newly designed virtual screening protocol that combines structure-based pharmacophore and docking screens. Taking together with the biological data, the combination of structure based pharamcophore and docking methods demonstrated reasonable success rate in identifying new inhibitors (60-70%) proving the success of aforementioned approach. A detail analysis of the ligand-protein interactions was performed explaining observed activities.<br>
Molecular biology of the cell, 2012
Academic institutions across the country have long recognized the value of racial integration and... more Academic institutions across the country have long recognized the value of racial integration and have consistently opposed legal challenges to affirmative action policies. Despite these efforts, the percentage of underrepresented minorities in academic positions has not increased in proportion to their representation in society. Recruitment of underrepresented minorities into scientific and academic careers is important, because these individuals provide valuable contributions to research and teaching, and they serve as positive role models to others aspiring to such professions. In this interview, Renato Aguilera, Chair of the ASCB Minorities Affairs Committee, answers questions from MBoC Features Editor Doug Kellogg about diversity in the scientific workforce.
Molecular Ecology Notes, 2006
Molecular Immunology, 2002
Molecular Immunology, 1996
Molecular Immunology, 1995
Letters in Applied Microbiology, 2005
Mycobacteria are a serious cause of infections in humans, with limited treatment options, as no n... more Mycobacteria are a serious cause of infections in humans, with limited treatment options, as no new antibiotics have been developed against mycobacteria since the 1960s. In this study, the antimycobacterial activity of a small library of acetophenone (AP) compounds was analysed. Twenty-three AP derivatives were examined for activity against mycobacteria using a microbroth assay. The compounds were bacteriostatic, with the most effective (cyclohexylacetophenone and piperidinoacetophenone) having minimal inhibitory concentrations of 246 microM. Active compounds tended to be more hydrophobic, and may work by alkylation of as yet undetermined intracellular target protein(s). Cytotoxicity against eukaryotic cells was also determined and appears to be unrelated to the bacteriostatic activity. AP may serve as a novel group of useful therapeutics against the mycobacteria.
Journal of Bacteriology, 2003
Expression of the σ D -dependent flagellin gene, hag , is repressed by the CodY protein in nutrie... more Expression of the σ D -dependent flagellin gene, hag , is repressed by the CodY protein in nutrient-rich environments. Analysis of a codY mutant bearing a hag-lacZ reporter suggests that the availability of amino acids in the environment is the specific signal that triggers this repression. Further, hag-lacZ expression appears to be sensitive to intracellular GTP levels, as demonstrated by increased expression upon addition of decoyinine. This result is consistent with the postulate that the availability of amino acids in the environment effects intracellular GTP levels through the stringent response. However, the levels of hag-lacZ measured upon the addition of subsets of amino acids suggest an additional mechanism(s). CodY is a DNA binding protein that could repress flagellin expression directly by binding to the hag promoter region, or indirectly by binding to the fla/che promoter region that governs expression of the σ D transcriptional activator required for hag gene expression...
IUBMB Life, 1998
Rag‐1 and Rag‐2 are the critical components of the V‐(D)‐J recombinase required for site‐specific... more Rag‐1 and Rag‐2 are the critical components of the V‐(D)‐J recombinase required for site‐specific recombination of the antigen receptor genes. In this study, we have examined the ability of recombinant (r) Rag‐1 and Rag‐2 to bind the recombination signal sequences (RSS) and have determined that rRag‐1, but not rRag‐2, is able to directly bind DNA. rRAG‐1 DNA binding activity was found to reside within a novel amino‐terminal arginine‐rich (RR) domain with partial homology to a variety of nucleic acid binding domains. Although the RR‐domain did not demonstrate RSS‐specificity, this DNA binding domain may stabilize the interaction of RAG‐1 with, or increase the affinity for, the V‐(D)‐J recombination signals.
Gene, 2002
Mammalian DNase II enzymes and the Caenorhabditis elegans homolog NUC-1 have recently been shown ... more Mammalian DNase II enzymes and the Caenorhabditis elegans homolog NUC-1 have recently been shown to be critically important during engulfment-mediated clearance of DNA. In this report, we describe the cloning and characterization of the gene encoding Drosophila DNase II. Database queries using the C. elegans NUC-1 protein sequence identified a highly homologous open reading frame in Drosophila (CG7780) that could encode a similar enzyme. Analysis of crude protein extracts revealed that wild-type Drosophila contain a potent acid endonuclease activity with cleavage preferences similar to DNase II/NUC1, while the same activity was markedly reduced in an acid DNase hypomorphic mutant line. Furthermore, the pattern of cleavage products generated from an end-labeled substrate by hypomorphic-line extracts was significantly altered in comparison to the pattern generated by wild-type extracts. Sequence analysis of CG7780 DNA and mRNA revealed that the hypomorphic line contains a missense mutation within the coding region of this gene. Additionally, Northern analysis demonstrated that CG7780 expression is normal in the mutant line, which in combination with the lowered/altered enzymatic activity and sequencing data suggested a defect in the CG7780 protein. To conclusively determine if CG7780 encoded the Drosophila equivalent of DNase II/NUC-1, transgenic lines expressing wild-type CG7780 in the mutant background were generated and subsequently shown to complement the mutant phenotype. Our results, therefore, provide compelling evidence that the predicted gene CG7780 encodes Drosophila DNase II (dDNase II), an enzyme related in sequence and activity to mammalian DNase II. Interestingly, overexpression of CG7780 both ubiquitously and in specific tissues failed to elicit any discernable phenotype.
Experimental Cell Research, 1995
Inorganic Chemistry, 2009
The EMBO Journal, Dec 1, 1985
We have analyzed enhancer deletions found in murine plasmacytomas by DNA cloning. This analysis r... more We have analyzed enhancer deletions found in murine plasmacytomas by DNA cloning. This analysis revealed that the deletions occurred between the JH region and the switch region, removing the Ig heavy chain enhancer. The loss of the enhancer did not significantly affect the level of heavy chain expression as determined by RNA blots. Nucleotide sequence analysis revealed that there are no characteristic or homologous sequences around the recombination site. Extra nucleotides were found at the recombination sites, in a manner analogous to Ig and T-cell receptor V-D-J joining. The germline JH and switch sequences involved in the deletion were analyzed by the in vitro DNA cleavage system with an endonucleolytic activity purified from mouse fetal liver nuclear extracts. It was found that the germline JH DNA was strongly cleaved at the deletion recombination site.
Science, Mar 7, 1986
makes curvature harder to detect. If oxygen was consumed primarily from the oxygenated bottom wat... more makes curvature harder to detect. If oxygen was consumed primarily from the oxygenated bottom water, then the oxygen could have been resupplied from the surroundings at a high rate. This would prevent any large curvature from appearing and oxygen would seem to behave conservatively. Oxygen uptake by the hydrothermal vent clam Calyptogena appears to occur at near ambient conditions, whereas sulfide is consumed in warmer water with higher sulfide concentrations (19). There was 27 ,M less sulfide and 37 pM less oxygen at location B than at location C at a silicate concentration of 400 pM. The extra sulfide and oxygen consumed at location B was removed in a ratio of 0.73 to 1. It is difficult to determine the oxidation product of sulfide from these results, however, because community oxygen demand will consume oxygen without sulfide. Anaerobic sulfide oxidation is also possible. Our in situ measurements demonstrate large variability in sulfide and silicate concentrations in the vicinity of the animals of this hydrothermal vent community. Consumption of sulfide by the vent animals was also evident. Direct calculations of the community metabolism will be possible when measurements of flow rates around these animals become available. i6. The time needed for vent water to mix from a temperature of 8°to 2°C must be no more than a few minutes since a distance of less than So cm separates these temperatures [R. R. Hessler and W. M. Smithey, Jr., in Hydrothermal Processes at Seafloor Spreading Centers, P. A. Rona et al., Eds. (Plenum, New York, 1983), PP. 735-770; (I); Fig. i]. At least io jiM of sulfide are oxidized in this time period at location C (Fig. 2). A conservative estimate of the oxidation rate is I tmol/liter per minute. The oxidation rate measured in the laboratory under similar conditions of temperature, salinity, and pH is 0.02 ,umol/liter per minute [
PLOS ONE, Sep 4, 2020
Triple-negative breast cancer (TNBC) represents 15%-20% of all breast cancer types. It is more co... more Triple-negative breast cancer (TNBC) represents 15%-20% of all breast cancer types. It is more common among African American (AA) and Hispanic-Latina (HL) women. The biology of TNBC in HL women has been poorly characterized, but some data suggest that the molecular drivers of breast cancer might differ. There are no clinical tools to aid medical oncologists with decisions regarding appropriate individualized therapy, and no way to predict long-term outcomes. The aim of this study was to characterize individual patient gene mutation profiles and to identify the relationship with clinical outcomes. We collected formalin-fixed paraffin-embedded tumors (FFPE) from women with TNBC. We analyzed the gene mutation profiles of the collected tumors and compared the results with individual patient's clinical histories and outcomes. Of 25 patients with TNBC, 24 (96%) identified as HL. Twenty-one (84%) had stage III-IV disease. The most commonly mutated genes were TP53, NOTCH1, NOTCH2, NOTCH3, AKT, MEP3K, PIK3CA, and EGFR. Compared with other international cancer databases, our study demonstrated statistically significant higher frequencies of these genes among HL women. Additionally, a worse clinical course was observed among patients whose tumors had mutations in NOTCH genes and PIK3CA. This study is the first to identify the most common genetic alterations among HL women with TNBC. Our data strongly support the notion that molecular drivers of breast cancer could differ in HL women compared with other ethnic backgrounds. Therefore, a deeper understanding of the biological mechanisms behind NOTCH gene and PIK3CA mutations may lead to a new treatment approach.
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Papers by Renato Aguilera