اساتید - دانشکده پزشکی دانشگاه علوم پزشكي و خدمات بهداشتی درمانی تبريز

دانشکده پزشکی دانشگاه علوم پزشكي و خدمات بهداشتی درمانی تبريز - میلاد بسطامی

میلاد بسطامی

ژنتیک پزشکی

درجه علمی : استادیار

تحصیلات : Ph.D

رشته تحصیلی : ژنتیک پزشکی

محل تحصیل : دانشگاه علوم پزشکی شهید بهشتی

تلفن :

توضیحات : به نام خدا

آدرس پست الکترونیکی : mi.bastami@live.com

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سال اخذ	محل	رشته	مقطع تحصیلی
1387	دانشگاه ارومیه	زیست شناسی جانوری	کارشناسی
1390	دانشگاه علوم بهزیستی و توانبخشی تهران	ژنتیک انسانی	کارشناسی ارشد
1394	دانشگاه علوم پزشکی شهید بهشتی	ژنتیک پزشکی	دکتری تخصصی

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مقالات چاپ شده در مجلات

عنوان مقاله : Aberrant miRNA promoter methylation and EMT-involving miRNAs in breast cancer metastasis: Diagnosis and therapeutic implications.

نویسنده رابط : دکتر محمد رضا علی وند

عنوان مجله و شماره مجله : J Cell Physiol.

نویسندگان : Zare M, Bastami M, Solali S, Alivand MR

سال انتشار : 2017 Aug 3

چکیده : Breast cancer (BC) is the most prevalent cancer in women worldwide. Although extensive studies are ongoing concerning its intricate molecular mechanisms, development of novel therapies and more accurate diagnostic and prognostic approaches is still a challenge. Epithelial-mesenchymal transition (EMT) enables the invasion of metastatic cancer cells and has recently been highlighted in a Cancer Stem Cell (CSC) model of BC. Epigenetic events as well as miRNA expression are the master regulators of tumorigenesis and add a further layer to the complexity of BC pathogenesis. The miRNAs are related to epigenetic event and additionally affect epigenetic pathways. Recent evidence demonstrates that epigenetic mechanisms such as DNA methylation may control miRNA expression. Because each miRNA may regulate several target genes, dysregulation of miRNA caused by aberrant DNA methylation patterns of the locus may influence important downstream pathways. Furthermore, some miRNAs is believed to regulate important DNA methylator factors. Any disruption or modification of this intricate network can contribute to the disease process; thus, it is essential to understand these changes. Advancements in new sequencing technologies to detect DNA methylation patterns has provided the opportunity to determine differentially methylated regions (DMRs) of the miRNA locus and their effect on expression profiles to improve BC diagnosis and treatment. The current review examines the interplay of DNA methylation mechanisms and miRNA function in invasive tumorigenesis, specifically EMT and CSC of BC, to highlight its potential for advancements on BC etiology, diagnosis, and therapy.

عنوان مقاله : Epigenetic Changes of the ESR1 Gene in Breast Tissue of Healthy Women: A Missing Link with Breast Cancer Risk Factors?

نویسنده رابط :

عنوان مجله و شماره مجله : Genet Test Mol Biomarkers. 21(8):464-470.

نویسندگان :

سال انتشار : 2017 Aug

چکیده : BACKGROUND: Reproductive history and obesity are among the well-recognized risk factors in the development of breast cancer, which are partially mediated by the increased exposure of breast tissues to estrogens. However, only a few studies have investigated the link between these risk factors and the pattern of methylation signatures in the breast tissue of healthy women. The role of the estrogen receptor 1 (ESR1) gene hypermethylation is reportedly important in the development of breast cancer. Thus, it is speculated that such ESR1 epigenetic changes may be influenced or shaped by obesity and reproductive history-related factors before and during breast carcinogenesis. MATERIALS AND METHODS: Breast samples were collected from 120 cancer-free women who had undergone cosmetic mammoplasty. DNA was extracted from the breast tissues and, then, the methylation levels at the promoter and exon 1 regions of the ESR1 gene CpG island were determined by using the methylated DNA immunoprecipitation-quantitative PCR assay. RESULTS: The methylation level of the ESR1 promoter observed in women with a body mass index (BMI) ≥30 kg/m2 (p ≤ 0.001) was higher than in the subgroups of women of BMI <25 kg/m2 (p < 0.001) and BMI 25-29 kg/m2 (p < 0.001) and was also higher in postmenopausal women compared with that in premenopausal women (p = 0.046). Pearson correlation coefficient analyses also showed that the high methylation of the ESR1 promoter was correlated with increasing age (r = -0.246, p = 0.007) and BMI (r = -0.331, p ≤ 0.001). Finally, linear multivariate regression revealed a significant association between high methylation rates in the ESR1 gene promoter and increased BMI (β = -0.285, 95% CI = -0.457 to -0.113, p = 0.001). Furthermore, a higher methylation level at the ESR1 gene exon 1 was found in the BMI ≥ 30 kg/m2 subgroup compared to the BMI 25-29 kg/m2 subgroup (p = 0.023). CONCLUSION: These findings provide new hints about the relationship between epigenetic changes within the ESR1 gene CpG island and postmenopausal obesity and aging in cancer-free women. In terms of lifestyle intervention opportunities, this study also highlights the significance and feasibility of such interventions for BMI as a modifiable risk factor.

عنوان مقاله : MAP3K1 May be a Promising Susceptibility Gene for Type 2 Diabetes Mellitus in an Iranian Population

نویسنده رابط :

عنوان مجله و شماره مجله : Int J Mol Cell Med. 5(3):134-140

نویسندگان :

سال انتشار : 2016 Summer

چکیده : Considering that MAPK (mitogen- activated protein kinase) signaling pathway has an important role in the progression of inflammatory cytokine secretion in type 2 diabetes mellitus (T2DM), we have recently investigated the reported genetic polymorphism from genome wide association study in MAP3K1 (mitogen-activated protein kinase kinase kinase 1) in diabetes as an important member of MAPK signaling. This study aimed to investigate the possible association of rs10461617 at the upstream of MAP3K1 gene in an Iranian case-control study with the risk of T2DM. The study population was comprised of 342 unrelated Iranian individuals including 177 patients with T2DM and 165 unrelated healthy control subjects. Genotyping was performed using PCR-RFLP and confirmed with sequencing. In a logistic regression analysis, the rs10461617A allele was associated with a significantly higher risk of T2DM assuming the log- additive model (OR: 1.44, 95% CI: 1.01-2.05, P = 0.039). In conclusion, we provided the first evidence for the association of rs10461617 at the upstream of MAP3K1 with the risk of T2DM in an Iranian population.

عنوان مقاله : miRNA-Related Polymorphisms in miR-423 (rs6505162) and PEX6 (rs1129186) and Risk of Esophageal Squamous Cell Carcinoma in an Iranian Cohort.

نویسنده رابط :

عنوان مجله و شماره مجله : Genet Test Mol Biomarkers. 21(6):382-390.

نویسندگان :

سال انتشار : 2017 Jun

چکیده : AIMS: Iran is located in the Asian esophageal cancer belt. It is a high-risk region for esophageal squamous cell carcinoma (ESCC). The extent to which genetic components, especially variants within miRNAs or their binding sites, contribute to risk of ESCC in the region is not yet fully understood. Herein, tests were done on an Iranian cohort to evaluate the association of miRNA-related polymorphisms in miR-423 (rs6505162) and peroxisomal biogenesis factor 6 (PEX6) (rs1129186 within a miR-149-5p-binding site) with the risk of ESCC risk. METHODS: This study recruited 200 ESCC patients and 300 healthy individuals. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method. Target genes and biological processes that are regulated by miR-423 and may be affected by a change in miR-423 expression were identified by in silico analysis. RESULTS: Logistic regression analyses revealed an association between rs6505162 and ESCC, assuming codominant (AA vs. CC, odds ratios, OR [95% confidence interval, CI]: 0.32 [0.15-0.69], p-value: 0.0076), recessive (AA vs. CC+CA, OR [95% CI]: 0.35 [0.16-0.73], p-value: 0.0027), and log-additive models (OR [95% CI]: 0.69 [0.52-0.91], p-value: 0.0084). No significant association was observed for PEX6 rs1129186. In silico analyses revealed several genes and biological processes that are regulated by miR-423 in ESCC. CONCLUSION: This study identified the first evidence of an association of a miRNA-related variant with risk of ESCC in an Iranian cohort. PEX6 rs1129186 may not modulate the risk of ESCC in the cohort.

عنوان مقاله : In silico dissection of miRNA targetome polymorphisms and their role in regulating miRNA-mediated gene expression in esophageal cancer

نویسنده رابط :

عنوان مجله و شماره مجله : Cell Biochem Biophys.74(4):483-497.

نویسندگان :

سال انتشار : 2016 Dec

چکیده : Esophageal cancer is the eighth most common cancer worldwide. Also middle-aged obese adults with higher body mass index during childhood have a greater risk to develop esophageal cancer. The contribution of microRNAs to esophageal cancer has been extensively studied and it became clear that these noncoding RNAs may play crucial roles in pathogenesis, diagnosis and prognosis of the disease. Increasing evidences have suggested that polymorphisms perturbing microRNA targetome (i.e., the compendium of all microRNA target sites) are associated with cancers including esophageal cancer. However, the extent to which such variants contribute to esophageal cancer is still unclear. In this study, we applied an in silico approach to systematically identify polymorphisms perturbing microRNA targetome in esophageal cancer and performed various analyses to predict the functional consequences of the occurrence of these variants. The computational results were integrated to provide a prioritized list of the most potentially disrupting esophageal cancer-implicated microRNA targetome polymorphisms along with the in silico insight into the mechanisms with which such variations may modulate microRNA-mediated regulation. The results of this study will be valuable for future functional experiments aimed at dissecting the roles of microRNA targetome polymorphisms in the onset and progression of esophageal cancer.

عنوان مقاله : A Bioinformatics Approach to Prioritize Single Nucleotide Polymorphisms in TLRs Signaling Pathway Genes

نویسنده رابط :

عنوان مجله و شماره مجله : Int J Mol Cell Med.5(2):65-79

نویسندگان :

سال انتشار : 2016 Spring

چکیده : It has been suggested that single nucleotide polymorphisms (SNPs) in genes involved in Toll-like receptors (TLRs) pathway may exhibit broad effects on function of this network and might contribute to a range of human diseases. However, the extent to which these variations affect TLR signaling is not well understood. In this study, we adopted a bioinformatics approach to predict the consequences of SNPs in TLRs network. The consequences of non-synonymous coding SNPs (nsSNPs) were predicted by SIFT, PolyPhen, PANTHER, SNPs&GO, I-Mutant, ConSurf and NetSurf tools. Structural visualization of wild type and mutant protein was performed using the project HOPE and Swiss PDB viewer. The influence of 5'-UTR and 3'- UTR SNPs were analyzed by appropriate computational approaches. Nineteen nsSNPs in TLRs pathway genes were found to have deleterious consequences as predicted by the combination of different algorithms. Moreover, our results suggested that SNPs located at UTRs of TLRs pathway genes may potentially influence binding of transcription factors or microRNAs. By applying a pathway-based bioinformatics analysis of genetic variations, we provided a prioritized list of potentially deleterious variants. These findings may facilitate the selection of proper variants for future functional and/or association studies.

عنوان مقاله : MiRNA-Related Polymorphisms in miR-146a and TCF21 Are Associated with Increased Susceptibility to Coronary Artery Disease in an Iranian Population

نویسنده رابط :

عنوان مجله و شماره مجله : Genet Test Mol Biomarkers. 20(5):241-8.

نویسندگان :

سال انتشار : 2016 May

چکیده : AIMS: Recent studies have suggested that single-nucleotide polymorphisms (SNPs) in miRNA genes or their binding sites may alter an individual's susceptibility to coronary artery disease (CAD). In the present study, the association between two such SNPs (rs2910164 in miR-146a and rs12190287, which disrupts miRNA binding to TCF21) and CAD, in an Iranian population, was evaluated and in silico analyses were conducted to predict disease-related effects of miR-146a rs2910164. METHODS: The study population consisted of angiographically confirmed CAD patients (n = 300) and asymptomatic controls (n = 300). Genotyping was performed using the TaqMan genotyping assay. RESULTS: A multivariate regression analysis revealed that rs2910164 was associated with an increased CAD risk in the dominant model. In comparison to GG homozygotes, individuals who carry at least one C allele had a significantly higher risk of CAD (GC+CC vs. GG, odds ratios [OR]: 1.82, 95% confidence intervals [CI]: 1.18-2.80, p = 6.358e-3). Similarly, TCF21 rs12190287 was observed to be associated with CAD in a log-additive model (OR: 0.63, 95% CI: 0.45-0.88, p = 6.584e-3). An in silico analysis revealed that rs2910164 may modify the miR-146a-3p-mediated regulation of several biological processes that are implicated in CAD, like those that are related to the regulation of apoptosis and immune response. CONCLUSIONS: Our data provide the first evidence for the association of miR-146a rs2910164 and TCF21 rs12190287 with CAD in an Iranian population, encouraging further research to elucidate the disease-related effects of miR-146a rs2910164.

عنوان مقاله : A Bioinformatics Approach to the Identification of Variants Associated with Type 1 and Type 2 Diabetes Mellitus that Reside in Functionally Validated miRNAs Binding Sites.

نویسنده رابط :

عنوان مجله و شماره مجله : Biochem Genet. 54(3):211-21.

نویسندگان :

سال انتشار : 2016 Jun

چکیده : The present work is aimed at finding variants associated with Type 1 and Type 2 diabetes mellitus (DM) that reside in functionally validated miRNAs binding sites and that can have a functional role in determining diabetes and related pathologies. Using bioinformatics analyses we obtained a database of validated polymorphic miRNA binding sites which has been intersected with genes related to DM or to variants associated and/or in linkage disequilibrium (LD) with it and is reported in genome-wide association studies (GWAS). The workflow we followed allowed us to find variants associated with DM that also reside in functional miRNA binding sites. These data have been demonstrated to have a functional role by impairing the functions of genes implicated in biological processes linked to DM. In conclusion, our work emphasized the importance of SNPs located in miRNA binding sites. The results discussed in this work may constitute the basis of further works aimed at finding functional candidates and variants affecting protein structure and function, transcription factor binding sites, and non-coding epigenetic variants, contributing to widen the knowledge about the pathogenesis of this important disease.

عنوان مقاله : Evaluating the association of common UBE2Z variants with coronary artery disease in an Iranian population

نویسنده رابط :

عنوان مجله و شماره مجله : Cell Mol Biol (Noisy-le-grand). 61(7):50-4.

نویسندگان :

سال انتشار : 2015 Nov 20

چکیده : Coronary artery disease (CAD) is the leading cause of cardiovascular mortality worldwide. Genome-wide association studies have discovered several variants associated with CAD. Notably, a recent study has identified UBE2Z rs46522 at 17q21.32 as a CAD-susceptibility variant in Europeans. However, association of this locus with CAD in non-Europeans has not been investigated. Herein, we evaluated the contribution of rs46522 and a variant in high linkage disequilibrium in UBE2Z 3'-UTR (rs1057897) to the CAD susceptibility by performing association study in an Iranian population. This study recruited 300 angiographically-confirmed CAD patients and 300 asymptomatic controls. Genotypes were determined by TaqMan genotyping assay. Multivariate logistic regression analysis revealed that rs46522 was associated with the susceptibility to CAD assuming codominant [TT vs. CC: 2.68 (1.36-5.31), P: 1.1717e-2], dominant [CT+TT vs. CC: 1.74 (1.12-2.69), P: 1.2675e-2], recessive [TT vs. CC+CT: 2.12 (1.13-3.98), P: 1.9369e-2] and log-additive [1.61 (1.17-2.21), P: 2.967e-3] models. However, no association was observed for rs1057897 under any genetic models. In conclusion, we provide the first evidence for association of rs46522 with the susceptibility to CAD in an Iranian population and discussed about regulatory potential and functional role of the studied variants to provide clues for its association with CAD and promote further research.

عنوان مقاله : Bioinformatics prioritization of SNPs perturbing microRNA regulation of hematological malignancy-implicated genes

نویسنده رابط :

عنوان مجله و شماره مجله : Genomics. 106(6):360-6.

نویسندگان :

سال انتشار : 2015 Dec

چکیده : The contribution of microRNAs (miRNAs) to cancer has been extensively investigated and it became obvious that a strict regulation of miRNA-mRNA regulatory network is crucial for safeguarding cell health. Apart from the direct impact of miRNA dysregulation in cancer pathogenesis, genetic variations in miRNAs are likely to disrupt miRNA-target interaction. Indeed, many evidences suggested that SNPs within miRNA regulome are associated with the development of different hematological malignancies. However, a full catalog of SNPs within miRNAs target sites of genes relevant to hematopoiesis and hematological malignancies is still lacking. Accordingly, we aimed to systematically identify and characterize such SNPs and provide a prioritized list of most potentially disrupting SNPs. Although in the present study we did not address the functional significance of these potential disturbing variants, we believe that our compiled results will be valuable for researchers interested in determining the role of target-SNPs in the development of hematological malignancies.

عنوان مقاله : Single-Nucleotide Polymorphisms Within MicroRNAs Sequences and Their 3' UTR Target Sites May Regulate Gene Expression in Gastrointestinal Tract Cancers

نویسنده رابط :

عنوان مجله و شماره مجله : Iran Red Crescent Med J. 2014 Jul;16(7):e16659. doi: 10.5812/ircmj.16659. Epub 2014 Jul 5.

نویسندگان :

سال انتشار : 2014 Jul

چکیده : BACKGROUND: Esophageal, stomach, and colorectal cancers are commonly lethal gastrointestinal tract (GIT) neoplasms, causing almost two million deaths worldwide each year. some environmental risk factors are acknowledged; however, genetic defects can significantly contribute to predisposition to GIT cancers. Accordingly, recent works have shown that single-nucleotide polymorphisms (SNPs) within miRNAs coding sequence (miR-SNPs) and miRNA target sites (target-SNPs) may further contribute to increased risk of developing cancer. OBJECTIVES: In this study, we comprehensively identified miRNA-target gene pairs implicated in GIT cancers and catalogued the presence of potentially functional miR-SNPs and target-SNPs that impair the correct functional recognition. MATERIALS AND METHODS: Using bioinformatics tools, manual literature review, and a highly accurate dataset of experimentally validated miRNA-target gene interactions, we compiled a list of miRNA-target genes pairs related to GIT cancers and prioritized them into different groups based on the levels of experimental support. Functional annotations (gene ontology) were applied to these pairs in each group to gain further information. RESULTS: We identified 97 pairs in which both miRNAs and target genes were implicated in GIT cancers. Several pairs, denoted as highly polymorphic pairs, had both miR-SNPs and target-SNPs. In addition, more than 5000 miRNA-target gene pairs were identified in which, according to the previous reports, either the miRNAs or the target genes had a direct involvement in GIT cancers. More than 800 target-SNPs are located in regulatory regions that were extracted from the ENCODE project through the RegulomeDB database. Of these, 20 were classified as expression quantitative trait loci (eQTLs). CONCLUSIONS: Our work provided a comprehensive source of prioritized and annotated candidate polymorphisms inside miRNAs and their target sites in GIT cancers, which would facilitate the process of choosing right candidate miRNA-target genes and related polymorphisms for future association or functional studies.

عنوان مقاله : Mutational screening of the NR5A1 in azoospermia.

نویسنده رابط :

عنوان مجله و شماره مجله : Andrologia. 2015 May;47(4):395-401. doi: 10.1111/and.12274. Epub 2014 Apr 20.

نویسندگان :

سال انتشار : 2015 May

چکیده : Nuclear receptor subfamily 5 group A member 1 (NR5A1) encodes a nuclear receptor that regulates transcription of multiple genes involved in adrenal and gonadal development, steroidogenesis and the reproductive axis. Human mutations in NR5A1were initially found in two 46, XY female patients suffering from severe gonadal dysgenesis and primary adrenal failure. However, more recent case reports have suggested that heterozygous mutations in NR5A1 may also contribute to the male infertility aetiology. We have analysed the coding sequence of NR5A1 in a cohort of 90 well-characterised idiopathic Iranian azoospermic infertile men versus 112 fertile men. Heterozygous NR5A1 mutations were found in 2 of 90 (2.2%) of cases. These two patients harboured missense mutations within the hinge region (p.P97T) and ligand-binding domain (p.E237K) of the NR5A1 protein. In silico analysis of the mutations showed that founded mutations could be detrimental. In conclusion, findings of the current and previous studies suggest that mutations in the NR5A1 gene are not common in azoospermia, and male infertility and inclusion of NR5A1 mutation screening in the diagnostic workup of male infertility may seem unnecessary.

دانشکده پزشکی دانشگاه علوم پزشكي و خدمات بهداشتی درمانی تبريز - میلاد بسطامی

میلاد بسطامی

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