29 results on '"Aubhishek Zaman"'
Search Results
2. Supplementary Methods from Biomarker Accessible and Chemically Addressable Mechanistic Subtypes of BRAF Melanoma
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Michael A. White, Ralf Kittler, Georgina V. Long, Helen Rizos, Lynda Chin, Noelle S. Williams, Jef K. De Brabander, Yonghao Yu, Jennifer A. Wargo, Michael A. Davies, Claudia Wellbrock, Ralph J. Deberardinis, Kakajan Komurov, Jessica Sudderth, Michael P. Smith, Ugur Eskiocak, Tracy I. Rosales, Aubhishek Zaman, Ming Ding, Jose Garcia-Rodriguez, Changguang Wang, Caroline G. Humphries, Hailei Zhang, Rahul K. Kollipara, Saurabh Mendiratta, Elizabeth A. McMillan, and Banu Eskiocak
- Abstract
Extended Experimental Methods
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- 2023
3. Supplementary Text, Figure Legends, Figures S1-S12 from Biomarker Accessible and Chemically Addressable Mechanistic Subtypes of BRAF Melanoma
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Michael A. White, Ralf Kittler, Georgina V. Long, Helen Rizos, Lynda Chin, Noelle S. Williams, Jef K. De Brabander, Yonghao Yu, Jennifer A. Wargo, Michael A. Davies, Claudia Wellbrock, Ralph J. Deberardinis, Kakajan Komurov, Jessica Sudderth, Michael P. Smith, Ugur Eskiocak, Tracy I. Rosales, Aubhishek Zaman, Ming Ding, Jose Garcia-Rodriguez, Changguang Wang, Caroline G. Humphries, Hailei Zhang, Rahul K. Kollipara, Saurabh Mendiratta, Elizabeth A. McMillan, and Banu Eskiocak
- Abstract
Supplemental Figure S1. Integrative Analysis of Functional Genomics and Copy Number Variation in Melanoma Cells and Tissues, Supplemental Figure S2. Elastic Net Derived Biomarker Results for Melanoma Survival Genes and Detection of These Biomarkers in TCGA SKCM, Supplemental Figure S3. The SOX10 Regulatory Network Supporting Cell Autonomous Melanoma Cell Growth and Survival, Supplemental Figure S4. SOX10 Addiction Specifies Sensitivity of BRAF Mutant Melanomas to BRAF and MEK Inhibitors In Vitro, Related to Figure 1, Supplemental Figure S5. SOX10 Addiction Specifies Sensitivity of BRAF Mutant Melanomas to BRAF and MEK Inhibitors In Patients, Related to Figure 2, Supplemental Figure S6. Bicluster of melanoma cell lines and chemical compounds in McDermott/Benes GDSC dataset, Related to Figure 3, Supplemental Figure S7. Nomination of TBK1 as a Therapeutic Target for Drug-Resistant Melanoma, Related to Figure 3, Supplemental Figure S8. TBK1/IKKε-Addiction is Conserved In Vivo, Related to Figure 4, Supplemental Figure S9. TBK1/IKKε-Addiction Corresponds to a Cell Autonomous Innate Immune Melanoma Subtype, Related to Figure 5, Supplemental Figure S10. TBK1/IKKε Activate AKT and YAP to Support Survival of the Cell-autonomous Immune Melanoma Subtype, Related to Figure 6, Supplemental Figure S11. 13C glucose and 13C glutamine metabolism at 30m and 2h, Related to Figure 7 and Supplemental Fig. S7, Supplemental Figure S12. Distinct Epigenetic Cell Fate Programs Specify TBK1/IKKε Addiction, Related to Figure 7.
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- 2023
4. Table S1 from TBK1 Provides Context-Selective Support of the Activated AKT/mTOR Pathway in Lung Cancer
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Michael A. White, Bruce A. Posner, Gurbani Makkar, Brian O. Bodemann, Aubhishek Zaman, Rachel M. Vaden, Elizabeth A. McMillan, Yi-Hung Ou, and Jonathan M. Cooper
- Abstract
Table S1 contains the summary of the TBK1 inhibitor (BX795 and Compound II) screen in NSCLC lines
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- 2023
5. Figure S4 from TBK1 Provides Context-Selective Support of the Activated AKT/mTOR Pathway in Lung Cancer
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Michael A. White, Bruce A. Posner, Gurbani Makkar, Brian O. Bodemann, Aubhishek Zaman, Rachel M. Vaden, Elizabeth A. McMillan, Yi-Hung Ou, and Jonathan M. Cooper
- Abstract
Figure S4 shows that modulation of mesenchymal status is sufficient to alter Ras-Mutant NSCLC sensitivity to TBK1 inhibitors
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- 2023
6. Data from TBK1 Provides Context-Selective Support of the Activated AKT/mTOR Pathway in Lung Cancer
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Michael A. White, Bruce A. Posner, Gurbani Makkar, Brian O. Bodemann, Aubhishek Zaman, Rachel M. Vaden, Elizabeth A. McMillan, Yi-Hung Ou, and Jonathan M. Cooper
- Abstract
Emerging observations link dysregulation of TANK-binding kinase 1 (TBK1) to developmental disorders, inflammatory disease, and cancer. Biochemical mechanisms accounting for direct participation of TBK1 in host defense signaling have been well described. However, the molecular underpinnings of the selective participation of TBK1 in a myriad of additional cell biological systems in normal and pathophysiologic contexts remain poorly understood. To elucidate the context-selective role of TBK1 in cancer cell survival, we employed a combination of broad-scale chemogenomic and interactome discovery strategies to generate data-driven mechanism-of-action hypotheses. This approach uncovered evidence that TBK1 supports AKT/mTORC1 pathway activation and function through direct modulation of multiple pathway components acting both upstream and downstream of the mTOR kinase itself. Furthermore, we identified distinct molecular features in which mesenchymal, Ras-mutant lung cancer is acutely dependent on TBK1-mediated support of AKT/mTORC1 pathway activation for survival. Cancer Res; 77(18); 5077–94. ©2017 AACR.
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- 2023
7. Targeting AXL in NSCLC
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Trever G. Bivona and Aubhishek Zaman
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Tumor microenvironment ,drug resistance ,biology ,business.industry ,medicine.medical_treatment ,AXL ,Context (language use) ,Review ,Precision medicine ,targeted therapy ,Receptor tyrosine kinase ,Targeted therapy ,respiratory tract diseases ,lung cancer ,Oncology ,biology.protein ,Cancer research ,medicine ,Epithelial–mesenchymal transition ,Epidermal growth factor receptor ,business ,Tyrosine kinase - Abstract
State-of-the-art cancer precision medicine approaches involve targeted inactivation of chemically and immunologically addressable vulnerabilities that often yield impressive initial anti-tumor responses in patients. Nonetheless, these responses are overshadowed by therapy resistance that follows. AXL, a receptor tyrosine kinase with bona fide oncogenic capacity, has been associated with the emergence of resistance in an array of cancers with varying pathophysiology and cellular origins, including in non-small-cell lung cancers (NSCLCs). Here in this review, we summarize AXL biology during normal homeostasis, oncogenic development and therapy resistance with a focus on NSCLC. In the context of NSCLC therapy resistance, we delineate AXL’s role in mediating resistance to tyrosine kinase inhibitors (TKIs) deployed against epidermal growth factor receptor (EGFR) as well as other notable oncogenes and to chemotherapeutics. We also discuss the current understanding of AXL’s role in mediating cell-biological variables that function as important modifiers of therapy resistance such as epithelial to mesenchymal transition (EMT), the tumor microenvironment and tumor heterogeneity. We also catalog and discuss a set of effective pharmacologic tools that are emerging to strategically perturb AXL mediated resistance programs in NSCLC. Finally, we enumerate ongoing and future exciting precision medicine approaches targeting AXL as well as challenges in this regard. We highlight that a holistic understanding of AXL biology in NSCLC may allow us to predict and improve targeted therapeutic strategies, such as through polytherapy approaches, potentially against a broad spectrum of NSCLC sub-types to forestall tumor evolution and drug resistance.
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- 2021
8. Quantitative Framework for Bench-to-Bedside Cancer Research
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Aubhishek Zaman and Trever G. Bivona
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Cancer Research ,Oncology - Abstract
Bioscience is an interdisciplinary venture. Driven by a quantum shift in the volume of high throughput data and in ready availability of data-intensive technologies, mathematical and quantitative approaches have become increasingly common in bioscience. For instance, a recent shift towards a quantitative description of cells and phenotypes, which is supplanting conventional qualitative descriptions, has generated immense promise and opportunities in the field of bench-to-bedside cancer OMICS, chemical biology and pharmacology. Nevertheless, like any burgeoning field, there remains a lack of shared and standardized framework for quantitative cancer research. Here, in the context of cancer, we present a basic framework and guidelines for bench-to-bedside quantitative research and therapy. We outline some of the basic concepts and their parallel use cases for chemical–protein interactions. Along with several recommendations for assay setup and conditions, we also catalog applications of these quantitative techniques in some of the most widespread discovery pipeline and analytical methods in the field. We believe adherence to these guidelines will improve experimental design, reduce variabilities and standardize quantitative datasets.
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- 2022
9. Long non-coding RNA ESCCAL-1 promotes esophageal squamous cell carcinoma by down regulating the negative regulator of APOBEC3G
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Hani Choudhry, Jia Liu, Hongya Guan, Wei Cao, Wei Wu, Jinwu Wang, Manasi K. Mayekar, Yuanbo Cui, Trever G. Bivona, Ming Yan, Qinghe Xing, and Aubhishek Zaman
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Male ,0301 basic medicine ,Cancer Research ,Esophageal Neoplasms ,Down-Regulation ,APOBEC-3G Deaminase ,Biology ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Cell Movement ,Cell Line, Tumor ,Biomarkers, Tumor ,medicine ,Animals ,Humans ,neoplasms ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,Esophageal cancer ,Prognosis ,medicine.disease ,Phenotype ,digestive system diseases ,Long non-coding RNA ,Biomarker (cell) ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,Oncology ,Apoptosis ,030220 oncology & carcinogenesis ,Cancer research ,Female ,RNA, Long Noncoding ,Esophageal Squamous Cell Carcinoma ,Neoplasm Transplantation - Abstract
The expression of lncRNA ESCCAL-1 is upregulated in esophageal squamous cell carcinoma (ESCC). However, the molecular pathways regulated by ESCCAL-1 in esophageal cancer remain obscure. We found that high expression of the lncRNA ESCCAL-1 in human ESCC tumors correlated with worse clinicopathologic features. Furthermore, depletion of ESCCAL-1 in ESCC models inhibited the cellular processes associated with malignancy, including proliferation, migration and invasion, resistance to apoptosis, and impaired tumor growth in mice. Using a combinatorial approach, we discovered that ESCCAL-1 regulates malignant phenotypes in ESCC by acting as a molecular sponge for miR-590-3p. This interaction prevents miR-590-3p from suppressing APOBEC3G expression. Increased APOBEC3G was also a biomarker of worse clinicopathologic features in human ESCC tumors. Depletion of ESSCAL-1 or APOBEC3G, or overexpression of miR-590-3p resulted in increased apoptosis due to downregulation of the PI3K/Akt signaling. This study demonstrates that the lncRNA ESCCAL-1 promotes malignant features of ESCC by relieving the inhibitory effect of miR-590-3p on APOBEC3G expression and identifies potential biomarkers or therapeutic targets to improve ESCC treatment outcomes.
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- 2020
10. Multi-faceted epigenetic dysregulation of gene expression promotes esophageal squamous cell carcinoma
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M. Reza Sailani, Hongyan Guan, Jia Liu, Ming Yan, Nasa Sinnott-Armstrong, Pengju Lv, Eric A. Collisson, Yuanbo Cui, Aubhishek Zaman, Hongen Xu, Qinghe Xing, Jinwu Wang, Michael Snyder, Trever G. Bivona, Justin Chen, Pengli Han, Chang Jing, Jiancheng Guo, Wei Cao, Gundolf Schenk, Yanan Lou, Yuchi Gao, X B Sun, Alan Hunter Shain, Hayan Lee, Wenxue Tang, Sean R. McCorkle, Wei Wu, Lei Sun, and Fred G. Biddle
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0301 basic medicine ,Male ,Proteomics ,Esophageal Neoplasms ,General Physics and Astronomy ,Datasets as Topic ,Epigenesis, Genetic ,Cohort Studies ,Histones ,0302 clinical medicine ,Heterochromatin ,SUZ12 ,2.1 Biological and endogenous factors ,RNA-Seq ,Aetiology ,Promoter Regions, Genetic ,lcsh:Science ,Cancer ,Regulation of gene expression ,Multidisciplinary ,Tumor ,EZH2 ,Wnt signaling pathway ,Genomics ,Middle Aged ,Gene Expression Regulation, Neoplastic ,030220 oncology & carcinogenesis ,DNA methylation ,Chromatin Immunoprecipitation Sequencing ,Female ,Data integration ,Esophageal Squamous Cell Carcinoma ,Science ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Article ,Cell Line ,Promoter Regions ,03 medical and health sciences ,Esophagus ,Genetic ,Cell Line, Tumor ,Genetics ,Biomarkers, Tumor ,Humans ,Epigenetics ,Enhancer ,neoplasms ,Aged ,Neoplastic ,Whole Genome Sequencing ,YY1 ,Human Genome ,General Chemistry ,Oncogenes ,DNA Methylation ,digestive system diseases ,Esophagectomy ,030104 developmental biology ,Gene Expression Regulation ,Cancer research ,CpG Islands ,lcsh:Q ,Digestive Diseases ,Biomarkers ,Epigenesis - Abstract
Epigenetic landscapes can shape physiologic and disease phenotypes. We used integrative, high resolution multi-omics methods to delineate the methylome landscape and characterize the oncogenic drivers of esophageal squamous cell carcinoma (ESCC). We found 98% of CpGs are hypomethylated across the ESCC genome. Hypo-methylated regions are enriched in areas with heterochromatin binding markers (H3K9me3, H3K27me3), while hyper-methylated regions are enriched in polycomb repressive complex (EZH2/SUZ12) recognizing regions. Altered methylation in promoters, enhancers, and gene bodies, as well as in polycomb repressive complex occupancy and CTCF binding sites are associated with cancer-specific gene dysregulation. Epigenetic-mediated activation of non-canonical WNT/β-catenin/MMP signaling and a YY1/lncRNA ESCCAL-1/ribosomal protein network are uncovered and validated as potential novel ESCC driver alterations. This study advances our understanding of how epigenetic landscapes shape cancer pathogenesis and provides a resource for biomarker and target discovery., The epigenetic landscape of esophageal squamous cell carcinoma (ESCC) at genome-wide high resolution is incompletely studied. Here, the authors performed an integrated multi-omics analysis of ESCC and non-tumor tissues to define the genome-wide methylome landscape and epigenetic alterations to uncover oncogenic drivers of ESCC.
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- 2020
11. RAS nucleotide cycling underlies the SHP2 phosphatase dependence of mutant BRAF-, NF1- and RAS-driven cancers
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Mallika Singh, Abby Marquez, Carlos Stahlhut, David Wildes, Mark A. Goldsmith, Zhengping Wang, Victor Olivas, Jacqueline Smith, Collin M. Blakely, Christos Tzitzilonis, Golzar Hemmati, Caroline E. McCoach, Kasia Mordec, Adrian Liam Gill, Gert Kiss, Tientien Hsieh, Christopher J. Schulze, Trever G. Bivona, Franziska Haderk, Aubhishek Zaman, Elena S. Koltun, Jason Romero, and Robert J. Nichols
- Subjects
0301 basic medicine ,MAPK/ERK pathway ,Protein Tyrosine Phosphatase, Non-Receptor Type 11 ,PTPN11 ,medicine.disease_cause ,RMC-4550 ,Neoplasms ,G12C ,Enzyme Inhibitors ,Extracellular Signal-Regulated MAP Kinases ,Mice, Inbred BALB C ,Mutation ,Neurofibromin 1 ,biology ,Tumor Burden ,Cell biology ,Phenotype ,raf Kinases ,Guanosine Triphosphate ,KRAS ,Signal transduction ,SOS1 Protein ,Signal Transduction ,Proto-Oncogene Proteins B-raf ,Mice, Nude ,Antineoplastic Agents ,Article ,BRAF ,Proto-Oncogene Proteins p21(ras) ,03 medical and health sciences ,Cell Line, Tumor ,Biomarkers, Tumor ,medicine ,Animals ,Humans ,Genetic Predisposition to Disease ,neoplasms ,Mitogen-Activated Protein Kinase Kinases ,Cancer ,Cell Biology ,medicine.disease ,Xenograft Model Antitumor Assays ,lung cancer ,HEK293 Cells ,030104 developmental biology ,NF1 ,biology.protein ,V600E - Abstract
Oncogenic alterations in the RAS/RAF/MEK/ERK pathway drive the growth of a wide spectrum of cancers. While BRAF and MEK inhibitors are efficacious against BRAFV600E-driven cancers, effective targeted therapies are lacking for most cancers driven by other pathway alterations, including non-V600E oncogenic BRAF, RAS GTPase-activating protein (GAP) NF1 (neurofibromin 1) loss and oncogenic KRAS. Here, we show that targeting the SHP2 phosphatase (encoded by PTPN11) with RMC-4550, a small-molecule allosteric inhibitor, is effective in human cancer models bearing RAS-GTP-dependent oncogenic BRAF (for example, class 3 BRAF mutants), NF1 loss or nucleotide-cycling oncogenic RAS (for example, KRASG12C). SHP2 inhibitor treatment decreases oncogenic RAS/RAF/MEK/ERK signalling and cancer growth by disrupting SOS1-mediated RAS-GTP loading. Our findings illuminate a critical function for SHP2 in promoting oncogenic RAS/MAPK pathway activation in cancers with RAS-GTP-dependent oncogenic BRAF, NF1 loss and nucleotide-cycling oncogenic KRAS. SHP2 inhibition is a promising molecular therapeutic strategy for patients with cancers bearing these oncogenic drivers.
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- 2018
12. Exocyst protein subnetworks integrate Hippo and mTOR signaling to promote virus detection and cancer
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Elizabeth A. McMillan, Chensu Wang, Hamid Mirzaei, Xiaofeng Wu, Sivaramakrishna Yadavalli, Michael A. White, Charles Yeaman, Trever G. Bivona, Jonathan M. Cooper, Aubhishek Zaman, Andrew Lemoff, and Jeon Lee
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Cell Survival ,Exocyst ,macromolecular substances ,Protein Serine-Threonine Kinases ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,Mice ,eIF-2 Kinase ,Cytosol ,TANK-binding kinase 1 ,Cell Line, Tumor ,Neoplasms ,Proto-Oncogene Proteins ,Animals ,Hippo Signaling Pathway ,Phosphorylation ,YAP1 ,Hippo signaling pathway ,RALB ,Hepatocyte Growth Factor ,TOR Serine-Threonine Kinases ,YAP-Signaling Proteins ,Protein kinase R ,Cell biology ,Virus Diseases ,Hippo signaling ,Multiprotein Complexes ,Viruses ,ral GTP-Binding Proteins ,Signal transduction ,Protein Binding - Abstract
Summary The exocyst is an evolutionarily conserved protein complex that regulates vesicular trafficking and scaffolds signal transduction. Key upstream components of the exocyst include monomeric RAL GTPases, which help mount cell-autonomous responses to trophic and immunogenic signals. Here, we present a quantitative proteomics-based characterization of dynamic and signal-dependent exocyst protein interactomes. Under viral infection, an Exo84 exocyst subcomplex assembles the immune kinase Protein Kinase R (PKR) together with the Hippo kinase Macrophage Stimulating 1 (MST1). PKR phosphorylates MST1 to activate Hippo signaling and inactivate Yes Associated Protein 1 (YAP1). By contrast, a Sec5 exocyst subcomplex recruits another immune kinase, TANK binding kinase 1 (TBK1), which interacted with and activated mammalian target of rapamycin (mTOR). RALB was necessary and sufficient for induction of Hippo and mTOR signaling through parallel exocyst subcomplex engagement, supporting the cellular response to virus infection and oncogenic signaling. This study highlights RALB-exocyst signaling subcomplexes as mechanisms for the integrated engagement of Hippo and mTOR signaling in cells challenged by viral pathogens or oncogenic signaling.
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- 2021
13. TBK1 Provides Context-Selective Support of the Activated AKT/mTOR Pathway in Lung Cancer
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Yi Hung Ou, Michael A. White, Elizabeth A. McMillan, Aubhishek Zaman, Bruce A. Posner, Rachel M. Vaden, Gurbani Makkar, Jonathan M. Cooper, and Brian O. Bodemann
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0301 basic medicine ,Cancer Research ,Lung Neoplasms ,Upstream and downstream (transduction) ,Apoptosis ,mTORC1 ,Protein Serine-Threonine Kinases ,Biology ,Interactome ,Article ,Mesoderm ,Small Molecule Libraries ,03 medical and health sciences ,TANK-binding kinase 1 ,Carcinoma, Non-Small-Cell Lung ,Tumor Cells, Cultured ,medicine ,Humans ,Regulatory Elements, Transcriptional ,Phosphorylation ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,TOR Serine-Threonine Kinases ,Cancer ,medicine.disease ,Cell biology ,Cell Transformation, Neoplastic ,030104 developmental biology ,Oncology ,Cancer research ,Signal transduction ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
Emerging observations link dysregulation of TANK-binding kinase 1 (TBK1) to developmental disorders, inflammatory disease, and cancer. Biochemical mechanisms accounting for direct participation of TBK1 in host defense signaling have been well described. However, the molecular underpinnings of the selective participation of TBK1 in a myriad of additional cell biological systems in normal and pathophysiologic contexts remain poorly understood. To elucidate the context-selective role of TBK1 in cancer cell survival, we employed a combination of broad-scale chemogenomic and interactome discovery strategies to generate data-driven mechanism-of-action hypotheses. This approach uncovered evidence that TBK1 supports AKT/mTORC1 pathway activation and function through direct modulation of multiple pathway components acting both upstream and downstream of the mTOR kinase itself. Furthermore, we identified distinct molecular features in which mesenchymal, Ras-mutant lung cancer is acutely dependent on TBK1-mediated support of AKT/mTORC1 pathway activation for survival. Cancer Res; 77(18); 5077–94. ©2017 AACR.
- Published
- 2017
14. Targeting Oncogenic BRAF: Past, Present, and Future
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Aubhishek Zaman, Wei Wu, and Trever G. Bivona
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0301 basic medicine ,Cancer Research ,endocrine system diseases ,medicine.medical_treatment ,precision medicine ,Oncology and Carcinogenesis ,Review ,Drug resistance ,Tumor heterogeneity ,lcsh:RC254-282 ,Targeted therapy ,BRAF ,03 medical and health sciences ,0302 clinical medicine ,oncogene ,medicine ,Genetics ,Potential source ,Treatment resistance ,skin and connective tissue diseases ,neoplasms ,Cancer ,drug resistance ,business.industry ,medicine.disease ,Precision medicine ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,targeted therapy ,digestive system diseases ,3. Good health ,enzymes and coenzymes (carbohydrates) ,030104 developmental biology ,Good Health and Well Being ,Oncology ,5.1 Pharmaceuticals ,030220 oncology & carcinogenesis ,Cancer research ,Development of treatments and therapeutic interventions ,business - Abstract
Identifying recurrent somatic genetic alterations of, and dependency on, the kinase BRAF has enabled a “precision medicine” paradigm to diagnose and treat BRAF-driven tumors. Although targeted kinase inhibitors against BRAF are effective in a subset of mutant BRAF tumors, resistance to the therapy inevitably emerges. In this review, we discuss BRAF biology, both in wild-type and mutant settings. We discuss the predominant BRAF mutations and we outline therapeutic strategies to block mutant BRAF and cancer growth. We highlight common mechanistic themes that underpin different classes of resistance mechanisms against BRAF-targeted therapies and discuss tumor heterogeneity and co-occurring molecular alterations as a potential source of therapy resistance. We outline promising therapy approaches to overcome these barriers to the long-term control of BRAF-driven tumors and emphasize how an extensive understanding of these themes can offer more pre-emptive, improved therapeutic strategies.
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- 2019
15. Global analysis of epigenetic heterogeneity identifies divergent drivers of esophageal squamous cell carcinoma
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Aubhishek Zaman, Wenxue Tang, Collisson E, Jingeng Liu, Lei Sun, Snyder M, Yuanbo Cui, Han Xu, Wang J, Cao W, Pengju Lv, Lou Y, Xing Q, Pengli Han, Jiancheng Guo, Ming Yan, Trever G. Bivona, Sailani M, Chang J, Nicholas A Sinnott-Armstrong, Gundolf Schenk, Alan Hunter Shain, Jia-Yun Chen, Sean R. McCorkle, X B Sun, Fred G. Biddle, Gao Y, Hongya Guan, Hong-pyo Lee, and Wesley Wu
- Subjects
Regulation of gene expression ,0303 health sciences ,Wnt signaling pathway ,Cancer ,Methylation ,Biology ,medicine.disease ,Genome ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,DNA methylation ,medicine ,Cancer research ,Epigenetics ,Gene ,030304 developmental biology - Abstract
Epigenetic landscapes can shape physiologic and disease phenotypes. We used integrative, high resolution multi-omics methods to characterize the oncogenic drivers of esophageal squamous cell carcinoma (ESCC). We found 98% of CpGs are hypomethylated across the ESCC genome and two-thirds occur in long non-coding (lnc)RNA regions. DNA methylation and epigenetic heterogeneity both coincide with chromosomal topological alterations. Gene body methylation, polycomb repressive complex occupancy, and CTCF binding sites associate with cancer-specific gene regulation. Epigenetically-mediated activation of non-canonical WNT signaling and the lncRNAESCCAL-1were validated as potential ESCC driver alterations. Gene-specific cancer driver roles of epigenetic alterations and heterogeneity are identified.
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- 2019
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16. Role of the Exocyst Complex Component Sec6/8 in Genomic Stability
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Michael J. Torres, Clayton R. Hunt, Michael A. White, Rakesh Kumar, Etienne Formstecher, Lawrence G. Lum, Charles Yeaman, Raj K. Pandita, Tej K. Pandita, Yingming Zhao, Nobuo Horikoshi, Aubhishek Zaman, Ozlem Kulak, and Kalpana Mujoo
- Subjects
Genome instability ,DNA Repair ,DNA repair ,DNA damage ,Ubiquitin-Protein Ligases ,Vesicular Transport Proteins ,RAD51 ,Exocyst ,Cell fate determination ,Biology ,Exocytosis ,Genomic Instability ,Cell Line, Tumor ,Autophagy ,Humans ,Molecular Biology ,Activating Transcription Factor 2 ,Intracellular Signaling Peptides and Proteins ,Membrane Proteins ,Articles ,Cell Biology ,Chromatin ,Cell biology ,Beclin-1 ,Chromatid ,Apoptosis Regulatory Proteins ,Tumor Suppressor p53-Binding Protein 1 ,Gene Deletion - Abstract
The exocyst is a heterooctomeric complex well appreciated for its role in the dynamic assembly of specialized membrane domains. Accumulating evidence indicates that this macromolecular machine also serves as a physical platform that coordinates regulatory cascades supporting biological systems such as host defense signaling, cell fate, and energy homeostasis. The isolation of multiple components of the DNA damage response (DDR) as exocyst-interacting proteins, together with the identification of Sec8 as a suppressor of the p53 response, suggested functional interactions between the exocyst and the DDR. We found that exocyst perturbation resulted in resistance to ionizing radiation (IR) and accelerated resolution of DNA damage. This occurred at the expense of genomic integrity, as enhanced recombination frequencies correlated with the accumulation of aberrant chromatid exchanges. Sec8 perturbation resulted in the accumulation of ATF2 and RNF20 and the promiscuous accumulation of DDR-associated chromatin marks and Rad51 repairosomes. Thus, the exocyst supports DNA repair fidelity by limiting the formation of repair chromatin in the absence of DNA damage.
- Published
- 2015
17. Abstract B36: Therapy-induced YAP hyperactivation is a mechanism driving the evolution of residual disease and resistance to targeted cancer therapy
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Aubhishek Zaman and Trever G. Bivona
- Subjects
MAPK/ERK pathway ,Cancer Research ,Hippo signaling pathway ,Melanoma ,MEK inhibitor ,Biology ,medicine.disease ,Oncology ,Cancer cell ,Cancer research ,medicine ,Epithelial–mesenchymal transition ,Molecular Biology ,Protein kinase B ,V600E - Abstract
Initial profound responses of precision medicines against cancer are limited in duration in part due to residual disease states that are therapy refractory and serve as a prelude to acquired drug resistance and tumor relapse. A prominent clinical example is in the collection of BRAF mutant cancers, including lung cancer and melanoma, which often respond initially, but incompletely and temporarily, to targeted RAF and MEK inhibition. The Hippo pathway transcriptional coactivator, Yes-associated protein (YAP), is a chief mediator of RAF and MEK inhibitor response in BRAF mutant cancers. However, the underlying mechanism for YAP-driven resistance is not fully understood. Here, we modeled the kinetics of patient-derived and isogenic BRAF mutant (V600E) cell lines in response to BRAF inhibitor and MEK inhibitor treatment. Our analysis indicated that in response to drug treatment the cells evolve through a “persister,” residual disease state that is distinct from therapy-naive cells or cells with acquired resistance. We observed that drug treatment induced early nuclear translocalization of YAP and this response peaked at the “persister” cell state before returning towards baseline upon acquired resistance. Additionally, our functional analysis of the proteomic and transcriptional landscape of the “persister” cells demonstrated drug-dependent reversible and concomitant activation of AKT, YAP target gene expression, and an epithelial mesenchymal transition (EMT). These programs underlay acquired vulnerabilities, as pharmacologic perturbation of AKT and genetic ablation of YAP was lethal specifically in the “persister” cells. Remarkably, AKT was required and sufficient for drug-induced nuclear localization of YAP, indicating that therapy-mediated hyperactivation of AKT is required for YAP induction and YAP-mediated residual disease. Current studies are focused on characterizing the molecular events causing AKT-mediated hyperactivation of YAP in response to MAPK pathway inhibition. Overall, this work aims to deconvolute a novel molecular mechanism of YAP activation in cancer cells and establish the functional implications of YAP signaling on “persister” cell biology and the evolution of targeted cancer therapy resistance. Citation Format: Aubhishek Zaman, Trever Bivona. Therapy-induced YAP hyperactivation is a mechanism driving the evolution of residual disease and resistance to targeted cancer therapy [abstract]. In: Proceedings of the AACR Special Conference on the Hippo Pathway: Signaling, Cancer, and Beyond; 2019 May 8-11; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(8_Suppl):Abstract nr B36.
- Published
- 2020
18. Emerging application of genomics-guided therapeutics in personalized lung cancer treatment
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Aubhishek Zaman and Trever G. Bivona
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0301 basic medicine ,precision medicine ,medicine.medical_treatment ,Review Article ,medicine.disease_cause ,Targeted therapy ,03 medical and health sciences ,Rare Diseases ,0302 clinical medicine ,genomics ,Genetics ,medicine ,ROS1 ,2.1 Biological and endogenous factors ,Anaplastic lymphoma kinase ,Epidermal growth factor receptor ,Aetiology ,Lung cancer ,Lung ,Cancer ,drug resistance ,biology ,business.industry ,Human Genome ,Lung Cancer ,General Medicine ,Immunotherapy ,medicine.disease ,Precision medicine ,Good Health and Well Being ,030104 developmental biology ,5.1 Pharmaceuticals ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,KRAS ,Development of treatments and therapeutic interventions ,business ,Biotechnology - Abstract
In lung cancer, genomics-driven comprehensive molecular profiling has identified novel chemically and immunologically addressable vulnerabilities, resulting in an increasing application of precision medicine by targeted inactivation of tumor oncogenes and immunogenic activation of host anti-tumor surveillance as modes of treatment. However, initially profound response of these targeted therapies is followed by relapse due to therapy-resistant residual disease states. Although distinct mechanisms and frameworks for therapy resistance have been proposed, accounting for and upfront prediction of resistance trajectories has been challenging. In this review, we discuss in both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), the current standing, and challenges associated with genomics-guided strategies for personalized therapy against both oncogenic alterations as well as post-therapy resistance mechanisms. In NSCLC, we catalog the targeted therapy approaches against most notable oncogenic alterations such as epidermal growth factor receptor (EGFR), serine/threonine-protein kinase b-raf (BRAF), Kirsten rat sarcoma viral proto-oncogene (KRAS), anaplastic lymphoma kinase (ALK), ROS1 proto-oncogene receptor tyrosine kinase (ROS1). For SCLC, currently highly recalcitrant to targeted therapy, we enumerate a range of exciting and maturing precision medicine approaches. Furthermore, we discuss a number of immunotherapy approaches, in combination or alone, that are being actively pursued clinically in lung cancer. This review not only highlights common mechanistic themes underpinning different classes of resistance and discusses tumor heterogeneity as a source of residual disease, but also discusses potential ways to overcome these barriers. We emphasize how an extensive understanding of these themes can predict and improve therapeutic strategies, such as through poly-therapy approaches, to forestall tumor evolution upfront.
- Published
- 2018
19. A diverse community of jute (Corchorus spp.) endophytes reveals mutualistic host–microbe interactions
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Farhana Shafrin, Taha Taha, Jannatul Ferdoush Tuli, Ahsan Habib Polash, Abu Ashfaqur Sajib, Rashu Barua, Rajib Ahmed, Aubhishek Zaman, Amzad Hossain, Haseena Khan, and Rifat Ara Najnin
- Subjects
biology ,Corchorus olitorius ,Fungus ,biology.organism_classification ,Applied Microbiology and Biotechnology ,Endophyte ,food.food ,Microbiology ,food ,Microbial ecology ,Corchorus ,Botany ,Internal transcribed spacer ,Ribosomal DNA ,Bacteria - Abstract
Endophytes are plant-associated microbes that live within plants as an integral part of the host metabolism and function. This study aimed to identify the molecular and physiological characteristics of both culturable and non-culturable endophytic bacteria and fungi present in different parts of the jute (Corchorus olitorius) plant. Using universal primers used to amplify hypervariable bacterial 16S rDNA and fungal internal transcribed spacer (ITS) regions of 18S rDNA, we identified five different culturable and 20 non-culturable endophytic bacteria as well as 14 different fungal endophytes from various parts of jute. Biochemical and physiological tests suggest that these microbes may bring a wide range of benefits to their hosts. For example, all five culturable endophytic bacteria were positive for auxin and catalase activity, which may lead to improved root elongation and stress resistance, respectively. These bacteria also have metal uptake, haemolytic and hydrolytic activities that could be useful in medical, environmental and industrial applications. The fungal endophytes were positive for lignin peroxidase, cellulase and xylanase activities, all of which may influence jute physiology. Another important finding was the antifungal activity of one of the fungi against a devastating pernicious fungus that affects hundreds of plant species.
- Published
- 2014
20. Designing Novel Antibacterials: Application of Omics Science
- Author
-
Aubhishek Zaman and Samsad Razzaque
- Subjects
Microbiology (medical) ,Infectious Diseases ,Computational biology ,Biology ,Omics - Abstract
This article was published in Klimik Dergisi [ © 2013 Klimik Dergisi ] and the definite version is available at : http://doi.org/10.5152/kd.2013.02. The Journal's website is at: http://klimikdergisi.org/eng/makale/943/83/Full-Text
- Published
- 2014
21. In silico QSAR analysis of quercetin reveals its potential as therapeutic drug for Alzheimer's disease
- Author
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Aubhishek Zaman, Iffat Jahan, Md. Rezaul Islam, Rajib Chakravorty, and Sajib Chakraborty
- Subjects
Drug ,Quantitative structure–activity relationship ,Aché ,media_common.quotation_subject ,In silico ,Flavonoid ,Disease ,Pharmacology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Medicine ,heterocyclic compounds ,General Pharmacology, Toxicology and Pharmaceutics ,030304 developmental biology ,media_common ,Cholinesterase ,chemistry.chemical_classification ,0303 health sciences ,biology ,business.industry ,fungi ,food and beverages ,language.human_language ,3. Good health ,chemistry ,language ,biology.protein ,Original Article ,Quercetin ,business ,030217 neurology & neurosurgery - Abstract
Acetylcholine-esterase (AchE) inhibitors are one of the most potent drug molecules against Alzheimer's disease (AD). But, patients treated with current AchE inhibitors often experience severe side effects. Quercetin is a plant flavonoid compound which can act as AchE inhibitor and it may be a better alternative to current AchE inhibitors in terms of effectiveness with no or fewer side effects.The aim of the study was to compare quercetin with conventional AchE inhibitors to search for a better drug candidate.Physico-chemical properties of conventional drugs and quercetin were predicted using bioinformatics tools. Molecular docking of these compounds on the active site of AchE was performed using AutoDock and comparative analysis was performed. Later, modification on the basic structure of quercetin with different functional groups was done to perform QSAR analysis.Quercetin showed a similar drug likeness score to the conventional drugs. The binding strength for quercetin in the active site of the enzyme was -8.8 kcal/mol, which was considerably higher than binding scores for some of the drugs such as donepezil (binding score -7.9 kcal/mol). Fifteen hydrogen bonds were predicted between quercetin and the enzyme whereas conventional drugs had fewer or even no hydrogen bonds. It implies that quercetin can act as a better inhibitor than conventional drugs. To find out even better inhibitor, similar structures of quercetin were searched through SIMCOMP database and a methylation in the 4-OH position of the molecule showed better binding affinity than parent quercetin. Quantitative structure activity relationship study indicated that O-4 methylation was specifically responsible for better affinity.This in silico study has conclusively predicted the superiority of the natural compound quercetin over the conventional drugs as AchE inhibitor and it sets the need for further in-vitro study of this compound in future.
- Published
- 2013
22. A computational prediction of structure and function of novel homologue of Arabidopsis thaliana Vps51/Vps67 subunit in Corchorus olitorius
- Author
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Aubhishek Zaman and Nurun Nahar Fancy
- Subjects
Corchorus ,Protein subunit ,Arabidopsis ,Vesicular Transport Proteins ,Health Informatics ,macromolecular substances ,Computational biology ,General Biochemistry, Genetics and Molecular Biology ,Structure-Activity Relationship ,food ,Protein structure ,Arabidopsis thaliana ,Amino Acid Sequence ,Binding site ,Peptide sequence ,Plant Proteins ,Binding Sites ,Corchorus olitorius ,biology ,Arabidopsis Proteins ,Computational Biology ,Biological Transport ,biology.organism_classification ,food.food ,Protein Structure, Tertiary ,Computer Science Applications ,Vesicular transport protein ,Protein Subunits ,Biochemistry ,Structural Homology, Protein ,Vesicle-mediated transport ,Sequence Analysis - Abstract
Vps mediated vesicular transport is important for transferring macromolecules trapped inside a vesicle. Although highly abundant, Vps shows tremendous sequence variation among diverse array of species. However, this difference in sequence, which seems to also translate into substantial functional variation, is hardly characterized in Corchorus spp. Here, our computational study investigates structural and functional features of one of the Vps subunit namely Vps51/Vps67 in C. olitorius. Broad scale structural characterization revealed novel information about the overall Vps structure and binding sites. Moreover, functional analyses indicate interaction partners which were unexplored to date. Since membrane trafficking is essentially associated with nutrient uptake and chemical de-toxification, characterization of the Vps subunit can well provide us with better insight into important agronomic traits such as stress response, immune response and phytoremediation capacity.
- Published
- 2012
23. Drug Designing Approaches Using In-Silico Techniques [Book Review]
- Author
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Samsad Razzaque and Aubhishek Zaman
- Subjects
Drug ,business.industry ,Docking (molecular) ,media_common.quotation_subject ,In silico ,Medicine ,Computational biology ,Pharmacology ,business ,media_common - Published
- 2012
24. Prediction of an Essential Gene with Potential Drug Target Property in Streptococcus suis using comparative genomics
- Author
-
Aubhishek Zaman
- Subjects
Comparative genomics ,Genetics ,Proteases ,biology ,Essential gene ,Streptococcus pneumoniae ,medicine ,Streptococcus suis ,biology.organism_classification ,medicine.disease_cause ,Genome ,Gene ,Reference genome - Abstract
Genes that are indispensable for survival are referred to as essential gene. Due to the momentous significance of these genes for cellular activity they can be selected potentially as drug targets. Here in this study, an essential gene for Streptococcus suis was predicted using coherent statistical analysis and powerful genome comparison computational method. At first the whole genome protein scatter plot was generated and subsequently, on the basis of statistical significance, a reference genome was chosen. The parameters set forth for selecting the reference genome was that the genome of the query (Streptococcus suis) and subject must fall in the same genus and yet they must vary to a good degree. Streptococcus pneumoniae was found to be suitable as the reference genome. A whole genome comparison was performed for the reference (Streptococcus pneumoniae) and the query genome (Streptococcus suis) and 14 conserved proteins from them were subjected to a screen for potential essential gene property. Among those 14 only one essential gene was found to be with impressive similarity score between reference and query. The essential gene encodes for a type of `Clp protease`. Clp proteases play major roles in degrading misfolded proteins. Results found here should help formulating a drug against Strptococcus suis which is responsible for mild to severe clinical conditions in human. However, like many other computational studies, the study has to be validated furthermore through in vitro assays for concrete proof.
- Published
- 2012
25. Docking studies and network analyses reveal capacity of compounds from Kandelia rheedii to strengthen cellular immunity by interacting with host proteins during tuberculosis infection
- Author
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Aubhishek Zaman
- Subjects
Cellular immunity ,Tuberculosis ,Emodin ,Estrogen receptor ,Skyrin ,General Medicine ,Dopamine beta hydroxylase ,Biology ,Hypothesis ,medicine.disease ,Bioinformatics ,Glucagon receptor ,Kandelia rheedii ,chemistry.chemical_compound ,chemistry ,Biochemistry ,Docking (molecular) ,ErbB ,medicine ,Casein kinase 1 ,Fusaric acid ,Casein kinase - Abstract
Kandelia rheedii (locally known as Guria or Rasunia), widely found and used in Indian subcontinent, is a well-known herbal cure to tuberculosis. However, neither the mechanism nor the active components of the plant extract responsible for mediating this action has yet been confirmed. Here in this study, molecular interactions of three compounds (emodin, fusaric acid and skyrin) from the plant extract with the host protein targets (casein kinase (CSNK), estrogen receptor (ERBB), dopamine β-hydroxylase (DBH) and glucagon receptor (Gcgr)) has been found. These protein targets are known to be responsible for strengthening cellular immunity against Mycobacteria tuberculosis. The specific interactions of these three compounds with the respective protein targets have been discussed here. The insights from study should further help us designing molecular medicines against tuberculosis.
- Published
- 2012
26. A computational assay to design an epitope-based peptide vaccine against chikungunya virus
- Author
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Aubhishek Zaman, M. Sadman Sakib, and Rezaul Islam
- Subjects
biology ,Alphavirus ,biology.organism_classification ,medicine.disease_cause ,Virology ,Epitope ,Virus ,Immune system ,Immunity ,Peptide vaccine ,medicine ,Chikungunya ,Peptide sequence - Abstract
Aim: Chikungunya virus, an arthropod-borne alphavirus, belongs to the Togavirus family. Despite severe epidemic outbreaks on several occasions, not much progress has been made with regard to epitope-based drug design for chikungunya virus. In this study we performed a proteome-wide search to look for a conserved region among the available viral proteins, one which has the capacity to trigger a significant immune response. Materials & methods: The conserved region was analyzed by performing an alignment of sequences collected from sources from varied geographic locations and time periods. Subsequently, the immune parameters for the peptide sequences were determined using several in silico tools and immune databases. Results: Both T-cell immunity and B-cell immunity were checked for the peptides to ensure that they had the capacity to induce both humoral and cell-based immunity. Our study reveals a stretch of conserved region in glycoprotein E2; yet this peptide sequence could interact with as many as seven HLAs and showed population coverage as high as 73.46%. The epitope was further tested for binding against the HLA structure using in silico docking techniques to validate the binding cleft epitope interaction in detail. Conclusion: Although the study requires further in vivo screening, keeping in mind the consistency and reproducibility of the immune system at selecting and reacting to peptide epitopes, this study allows us to claim a novel peptide antigen target in E2 protein with good confidence.
- Published
- 2012
27. Kaposi's sarcoma: a computational approach through protein-protein interaction and gene regulatory networks analysis
- Author
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Md. Habibur Rahaman, Aubhishek Zaman, and Samsad Razzaque
- Subjects
viruses ,Systems biology ,Gene regulatory network ,Computational biology ,Biology ,Interactome ,Open Reading Frames ,Viral Proteins ,RNA interference ,Virology ,Genetics ,medicine ,Humans ,Gene Regulatory Networks ,ORFS ,Molecular Biology ,Lytic Phase ,Kaposi's sarcoma ,Sarcoma, Kaposi ,Computational Biology ,General Medicine ,medicine.disease ,Lytic cycle ,Herpesvirus 8, Human ,Host-Pathogen Interactions ,Protein Binding - Abstract
Interactomic data for Kaposi’s Sarcoma Associated Herpes virus (KSHV)—the causative agent of vascular origin tumor called Kaposi’s sarcoma—is relatively modest to date. The objective of this study was to assign functions to the previously uncharacterized ORFs in the virus using computational approaches and subsequently fit them to the host interactome landscape on protein, gene, and cellular level. On the basis of expression data, predicted RNA interference data, reported experimental data, and sequence based functional annotation we also tried to hypothesize the ORFs role in lytic and latent cycle during viral infection. We studied 17 previously uncharacterized ORFs in KSHV and the host-virus interplay seems to work in three major functional pathways—cell division, transport, metabolic and enzymatic in general. Studying the host-virus crosstalk for lytic phase predicts ORF 10 and ORF 11 as a predicted virus hub whereas PCNA is predicted as a host hub. On the other hand, ORF31 has been predicted as a latent phase inducible protein. KSHV invests a lion’s share of its coding potential to suppress host immune response; various inflammatory mediators such as IFN-γ, TNF, IL-6, and IL-8 are negatively regulated by the ORFs while Il-10 secretion is stimulated in contrast. Although, like any other computational prediction, the study requires further validation, keeping into account the reproducibility and vast sample size of the systems biology approach the study allows us to propose an integrated network for host-virus interaction with good confidence. We hope that the study, in the long run, would help us identify effective dug against potential molecular targets.
- Published
- 2012
28. Structural, functional and molecular docking study to characterize GMI1 from Arabidopsis thaliana
- Author
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Aubhishek Zaman, Md. Ohedul Islam, Md. Rezaul Islam, and Md. Ismail Hosen
- Subjects
Models, Molecular ,Protein family ,DNA Repair ,Structural similarity ,Chromosomal Proteins, Non-Histone ,Protein Conformation ,Molecular Sequence Data ,Arabidopsis ,Quantitative Structure-Activity Relationship ,Sequence Homology ,Health Informatics ,Sequence alignment ,Plasma protein binding ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Protein structure ,Adenosine Triphosphate ,Amino Acid Sequence ,Genetics ,Arabidopsis Proteins ,Binding protein ,Walker motifs ,Computational Biology ,Computer Science Applications ,Molecular Imaging ,Biochemistry ,Docking (molecular) ,Sequence Alignment ,Protein Binding - Abstract
γ-irradiation and Mitomycin C Induced 1 (GMI1), is a member of the SMC-hinge domain-containing protein family that takes part in double stranded break repair mechanism in eukaryotic cells. In this study we hypothesize a small molecule-Adenosine Tri Phosphate (ATP) binding region of novel SMC like GM1 protein in model organism Arabidopsis thaliana using in silico modeling. Initially, analyzing sequence information for the protein indicated presence of motifs — ‘Walker A nucleotide-binding domain’ that are required to interact with nucleotides along with ‘Walker B’ motif and ABC signature sequences. This was further proven through GMI1-ATP docking experiment and results were verified by comparing the values with controls. In negative control, no binding was seen in the same binding region of GMI1 structure for small molecules randomly selected form PubChem database, whereas in positive control binding affinity of other known proteins with ATP binding potential resembled GMI1-ATP binding affinity of −5.4 kcal/mol. Furthermore we also docked small molecules that shares structural similarity with ATP to GMI1 and found that Purine Mononucleotide bound the region with the best affinity, which implies that the compound may bind the protein with strong binding and can work as a potential agonist/antagonist to GMI1. We believe that the study would shed more light into the GM1 mechanism of action. Although the computational predictions made here are based on concrete confidence, it should be mentioned that in vitro experimentation does not fall into the scopes of this study and thus the results found here have to be further validated in vitro.
- Published
- 2012
29. The Effect of Fat Supplementation on Post-partum Dairy Cows in Bangladesh
- Author
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Aubhishek Zaman, Samsad Razzaque, Hasan Al-Faruque, and Mohammad Monirozzaman
- Subjects
Estrous cycle ,chemistry.chemical_classification ,media_common.quotation_subject ,Conjugated linoleic acid ,Ice calving ,Biology ,chemistry.chemical_compound ,medicine.anatomical_structure ,Animal science ,chemistry ,Essential fatty acid ,Lactation ,medicine ,Ovulation ,Blood urea nitrogen ,Dairy cattle ,media_common - Abstract
Postpartum negative energy balance (NEB) in the dairy cattle is associated with delayed return to ovarian cyclicity and reduced fertility. Lactation significantly delayed postpartum follicular growth and ovulation. Low energy intake also had a delaying effect, especially when only the lactating animals were considered. The aim of the present study was to determine the effect of fatty acid supplementation on postpartum dairy cows on the basis of daily milk yield, and glucose level, blood urea nitrogen level, progesterone level, and resumption of first estrus cycle after calving. For this experiment 10 post-partum dairy Pabna cows (locally popular) were taken. Among the cows 5 kept as controlled and rest of the 5 treated with essential fatty acid with conjugated linoleic acid (CLA). There was no significant difference found in blood glucose level and blood urea nitrogen level, although in the treated group blood glucose level was higher (4.14mmol/L) than the controlled group (2.85mmol/L). However, those cows, that received fat supplemented feed, significantly produce (p
- Published
- 2013
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