Yuriy Gusev
Georgetown University, Oncology, Faculty Member
- Dr. Yuriy Gusev has over 20 years of experience in academic and industry research in the fields of bioinformatics, sy... moreDr. Yuriy Gusev has over 20 years of experience in academic and industry research in the fields of bioinformatics, systems biology, biomarker discovery, and computational modeling of biological systems. He has over 100 peer-reviewed publications in the areas of microRNA, gene, and protein expression profiling in cancer and other human diseasesedit
Background: Esophageal carcinoma (EC) is one of the most common malignancies of the gastrointestinal tract worldwide and is unresponsive to therapy. Esophageal squamous cell carcinoma (ESCC) comprises the majority of EC in African... more
Background: Esophageal carcinoma (EC) is one of the most common malignancies of the gastrointestinal tract worldwide and is unresponsive to therapy. Esophageal squamous cell carcinoma (ESCC) comprises the majority of EC in African Americans, Asians and other ethnic groups, while esophageal adenocarcinoma (EAC) predominates among Caucasians. Poor prognosis of EC in Caucasians and African Americans is reflected by five-year survival rates of 21% and 14 %, respectively. The aggressiveness and lower survival rate of African American ESCC patients than that from patients of other ethnic groups are evident even after adjusting for treatment modalities and socioeconomic factors. These characteristics suggest the existence of an ethnic- or race-dependent component of EC etiology. However, the genetic architecture of ESCC in AA is not well studied, and thus, mostly undefined. Our study aims to identify exonic mutations that may represent critical genetic changes in African American ESC carcinogenesis. Methods and Materials: Whole exome sequencing (WES) of matched tumor and normal tissue DNA from endoscopic biopsies from late-stage ESCC of nine African American Veteran male patients was conducted. This study was approved by the DC VAMC Institutional Review Board, and a written informed consent was obtained from each patient prior to biopsy. Biopsies were de-identified, freshly frozen and stored at -80 °C. To proceed to exon capture, we enriched our samples by using Agilent SureSelect XT Human All Exon V6+UTR. Paired-end sequencing at a read depth of 100X was performed on the exon libraries using the Illumina HiSeq 4000 sequencer. We applied Genome Analysis Toolkit's best practices WES pipeline to identify both germline and somatic variations in the dataset. The Seven Bridges Cancer Genomics Cloud platform was used for processing the data and annotating the variants. Variants were mapped to genomic regions and further aggregated at the gene level, pathways, and biological processes relevant to disease by using Reactome, Pathway Studio, and Ingenuity Variant Analysis. Results: In all samples, 27,586 variants consisted of 86% single nucleotide variation, 8.5% insertions and 5.5% deletions. Approximately half of the variants caused missense changes while 0.12% created nonsense mutations. High impact mutations occurred in genes that have a role in DNA damage repair, stress response, detoxification pathways, keratinization and immune surveillance. Conclusion: We found unique genomic variation in African American ESCC, that reveals a potential molecular signature for the aggressiveness and lethality of ESCC in this population. Future functional studies will be conducted to elucidate the role of these mutations in ESCC pathogenesis. Citation Format: Robert Wadleigh, Krithika Bhuvaneshwar, Gustavo Marino, Vincente Notario, Jack Lichy, Yuriy Gusev, Hayriye Verda Erkizan. Genetic architecture of esophageal squamous cell carcinoma in African American veterans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3426.
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Supplementary Tables S1-S5 from Association of MicroRNA Expression in Hepatocellular Carcinomas with Hepatitis Infection, Cirrhosis, and Patient Survival
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Purpose: MicroRNA (miRNA) is a new class of small, noncoding RNA. The purpose of this study was to determine if miRNAs are differentially expressed in hepatocellular carcinoma (HCC).Experimental Design: More than 200 precursor and mature... more
Purpose: MicroRNA (miRNA) is a new class of small, noncoding RNA. The purpose of this study was to determine if miRNAs are differentially expressed in hepatocellular carcinoma (HCC).Experimental Design: More than 200 precursor and mature miRNAs were profiled by real-time PCR in 43 and 28 pairs of HCC and adjacent benign liver, respectively, and in normal liver specimens.Results: Several miRNAs including miR-199a, miR-21, and miR-301 were differentially expressed in the tumor compared with adjacent benign liver. A large number of mature and precursor miRNAs were up-regulated in the adjacent benign liver specimens that were both cirrhotic and hepatitis-positive compared with the uninfected, noncirrhotic specimens (P < 0.01). Interestingly, all of the miRNAs in this comparison had increased expression and none were decreased. The expression of 95 randomly selected mRNAs was not significantly altered in the cirrhotic and hepatitis-positive specimens, suggesting a preferential increas...
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Supplementary Table S6 from Association of MicroRNA Expression in Hepatocellular Carcinomas with Hepatitis Infection, Cirrhosis, and Patient Survival
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Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to... more
Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically targetable tumor, and 23% for the complete tumor extent, over a publicly trained model. We anticipate our study to: 1) enable more healthcare studies informed by large diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further analyses for g...
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Malignancy of the brain and CNS is unfortunately a common diagnosis. A large subset of these lesions tends to be high grade tumors which portend poor prognoses and low survival rates, and are estimated to be the tenth leading cause of... more
Malignancy of the brain and CNS is unfortunately a common diagnosis. A large subset of these lesions tends to be high grade tumors which portend poor prognoses and low survival rates, and are estimated to be the tenth leading cause of death worldwide. The complex nature of the brain tissue environment in which these lesions arise offers a rich opportunity for translational research. Magnetic Resonance Imaging (MRI) can provide a comprehensive view of the abnormal regions in the brain, therefore, its applications in the translational brain cancer research is considered essential for the diagnosis and monitoring of disease. Recent years has seen rapid growth in the field of radiogenomics, especially in cancer, and scientists have been able to successfully integrate the quantitative data extracted from medical images (also known as radiomics) with genomics to answer new and clinically relevant questions. In this paper, we took raw MRI scans from the REMBRANDT data collection from publi...
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Target prioritization is essential for drug discovery and repositioning. Applying computational methods to analyze and process multi-omics data to find new drug targets is a practical approach for achieving this. Despite an increasing... more
Target prioritization is essential for drug discovery and repositioning. Applying computational methods to analyze and process multi-omics data to find new drug targets is a practical approach for achieving this. Despite an increasing number of methods for generating datasets such as genomics, phenomics, and proteomics, attempts to integrate and mine such datasets remain limited in scope. Developing hybrid intelligence solutions that combine human intelligence in the scientific domain and disease biology with the ability to mine multiple databases simultaneously may help augment drug target discovery and identify novel drug-indication associations. We believe that integrating different data sources using a singular numerical scoring system in a hybrid intelligent framework could help to bridge these different omics layers and facilitate rapid drug target prioritization for studies in drug discovery, development or repositioning. Herein, we describe our prototype of the StarGazer pip...
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Background Cardiotoxicity is a serious adverse event associated with some of the most effective breast cancer therapies. Currently, it is difficult to predict which patients will develop cardiotoxicity due to the multiplicity of clinical,... more
Background Cardiotoxicity is a serious adverse event associated with some of the most effective breast cancer therapies. Currently, it is difficult to predict which patients will develop cardiotoxicity due to the multiplicity of clinical, behavioral, and biological factors involved. MethodsHere we describe an effort to apply biomedical informatics approaches to patient data from MedStar Health’s EHR systems to discover and characterize factors that contribute to cardiotoxicity in a real world breast cancer population.ResultsData wrangling techniques including merging data from disparate clinical systems, data transformation, and de-identification of personal health information (PHI)were appliedto the raw clinical data to produce a structured integrated dataset for predictive analysis and hypothesis generation. Using this dataset as input, weshowed howpredictive models can be developed to identify patients at high risk for cardiotoxicity. ConclusionsWe demonstrate how suchmodels can ...
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Rembrandt T-test with CIN cytobands. (PNG 344 kb)
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32 Background: Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide, and its incidence and mortality are rapidly increasing in the US. Treatments for advanced HCC are limited despite best efforts to... more
32 Background: Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide, and its incidence and mortality are rapidly increasing in the US. Treatments for advanced HCC are limited despite best efforts to develop therapeutics that target the deregulated pathways of HCC. Recent studies reveal a direct causal relationship between cancer and immune dysfunction, whereby tumor cells and their microenvironment can evade immune attack by exploiting various immunoregulatory mechanisms in a process termed cancer immune editing. This study objective is to determine the relationship between immune cell surface protein transcripts from tumor samples and the clinical outcome of pts by performing exploratory analyses of liver cancer data from the cancer genome atlas (TCGA). Methods: We analyzed RNAseq data from a cohort of 75 HCC samples in the TCGA collection. We explored the association of expression of a group of specific markers for infiltrating lymphocytes (seve...
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Pancreatic ductal adenocarcinoma (PDAC) is the 3rd leading cause of cancer related deaths in the U.S. Recent advances in understanding RNA biology in PDAC have shed light on post-transcriptional regulation of genes and pathways through... more
Pancreatic ductal adenocarcinoma (PDAC) is the 3rd leading cause of cancer related deaths in the U.S. Recent advances in understanding RNA biology in PDAC have shed light on post-transcriptional regulation of genes and pathways through RNA binding proteins (RBP). Our lab has demonstrated that HuR, an RBP, is overexpressed in PDAC cells and stabilizes pro-survival mRNAs. Additionally, our work and others have demonstrated that this level of gene regulation can support drug resistance in PDAC cells. A synthetic lethal strategy employing Poly-ADP ribose polymerase inhibitors (PARPi) in a subset of patients with DNA repair deficient pancreatic cancers has been gaining interest. However, the success of PARPi is often hindered by the emergence of drug resistance in patients who initially respond. We have published that short-term PARPi treatment of PDAC cells causes activation of HuR where it stabilizes a DNA repair enzyme, PAR-glycohydrolase, and mediates acute PARPi resistance. In this study, we generated olaparib acquired resistant pancreatic cancer cells in vitro and acquired pancreatic patient derived xenograft cell lines (pre- and post PARPi) to understand acute versus acquired resistant mechanism(s). In characterising the acquired resistant model of PARPi resistance, we found that these cells are >20 fold more resistant to olaparib and platinums and >5 fold resistant to other PARPi like rucaparib and veliparib, compared to parental cells. No cross resistance was seen with other chemotherapeutics like gemcitabine. Additionally, we also found acquired resistant cells lost PARP-1 protein expression compared to parental cells. Bioinformatic analyses on HuR-RNA immunoprecipitation-microarray (RIP-microarray) data from acutely treated olaparib cells show enrichment of pro-survival mRNAs. Interestingly, these mRNAs are significantly downregulated in acquired resistant cells compared to control cells (i.e., negative log2 fold changes, p Citation Format: Aditi Jain, Matthew McCoy, Lebaron A. Agostini, Yuriy Gusev, Subha Madhavan, Michael Pishvaian, Sankar Addya, Eric Londin, Maria R. Gurevich, Chani Stossel, Talia Golan, Charles J. Yeo, Jonathan R. Brody. A global transcriptome analysis of pancreatic cancer cells distinguishes between acute and acquired PARP inhibitor resistance mechanisms [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4764.
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Epidemiologic and molecular studies have shown that breast cancer subtypes are distributed unevenly among racial/ethnic groups. The incidence of the triple-negative breast cancer (TNBC) subtype in particular, one of the most clinically... more
Epidemiologic and molecular studies have shown that breast cancer subtypes are distributed unevenly among racial/ethnic groups. The incidence of the triple-negative breast cancer (TNBC) subtype in particular, one of the most clinically aggressive breast cancer subtypes, affects around 20% of women from Latin America, 24-28% of African-Americans, 6-8% of Asians, and around 12% of non-Hispanic Whites. In general Latin American patients with TNBC are more often diagnosed with earlier age, advanced stage, are likely to experience metastasis and be refractory to treatment. Although the characterization of the genomic profiles in each breast cancer subtype has been extensively performed, few studies have characterized them in specific ethnic groups. This translates to a deficiency in the understanding of the intrinsic characteristics of their tumors' genome, which can differentially impact their tumor phenotypes and clinical behavior. In this study we performed genome-wide array-CGH a...
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Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that confers disease recurrence, treatment resistance and high mortality rates. MicroRNAs are a class of noncoding RNAs, that when dysregulated, impact... more
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that confers disease recurrence, treatment resistance and high mortality rates. MicroRNAs are a class of noncoding RNAs, that when dysregulated, impact tumorigenesis through the control of the expression of multiple mRNA targets involved in critical cancer signaling pathways. MiR-150-5p has been shown to control the expression of several driver oncogenes and/or tumor suppressor genes involved in these critical pathways. Its pattern of expression varies according to the cancer type; it has been observed mostly downregulated in hematological diseases and GI cancers, and upregulated in hormonal dependent cancers, such as prostate and breast cancer. The main objective of this study was to assess the patterns of expression of miR-150-5p in TNBC and determine its functional role in affecting the tumor phenotype. Archived paraffin samples of 113 patients with ductal breast carcinoma (56 of the TNBC and 57 of the...
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Introduction An overarching goal of biomedical research is to improve the use and dissemination of rapidly growing biomedical datasets to support precision medicine. Individualized molecular profiling and the identification of predictive... more
Introduction An overarching goal of biomedical research is to improve the use and dissemination of rapidly growing biomedical datasets to support precision medicine. Individualized molecular profiling and the identification of predictive biomarkers can powerfully inform the choice of therapies for cancer patients. However, both require integration of extensive molecular, clinical, and pharmacological data, often from disparate and diverse sources. The Georgetown Database of Cancer (G-DOC) was designed and engineered to be a unique multi-omics data analysis platform to enable translational research and precision medicine. Methods G-DOC is home to 61 datasets that contain data from over 10,000 patients across 14 diseases (10 cancers and 4 non-cancers). 1700+ researchers from over 48 different countries worldwide currently use the platform. The data and tools in the G-DOC system have enabled over 40 research publications. G-DOC has the largest public collection of brain cancer patients...
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ABSTRACTThe coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 virus has affected over 170 million people, and caused over 3.5 million deaths throughout the world as of May 2021. Although over 150 million people around... more
ABSTRACTThe coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 virus has affected over 170 million people, and caused over 3.5 million deaths throughout the world as of May 2021. Although over 150 million people around the world have recovered from this disease, the long term effects of the disease are still under study. A year after the start of the pandemic, data from COVID-19 recovered patients shows multiple organs affected with a broad spectrum of manifestations. Long term effects of SARS-CoV-2 infection includes fatigue, chest pain, cellular damage, and robust innate immune response with inflammatory cytokine production. More clinical studies and clinical trials are needed to not only document, but also to understand and determine the factors that predispose certain people to the long term side effects of his infection.In this manuscript, our goal was to explore the multidimensional landscape of infected lung tissue microenvironment to better understand comp...
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Pharmacological inhibition of LY6K induced cell cycle arrest and DNA damage by disrupting the LY6K-Histone-Aurora B signaling axis Benson C. Selvanesan1,2, Sheelu Varghese1,2, Justyna Andrys5, Ricardo H. Arriaza6, Rahul Prakash6,... more
Pharmacological inhibition of LY6K induced cell cycle arrest and DNA damage by disrupting the LY6K-Histone-Aurora B signaling axis Benson C. Selvanesan1,2, Sheelu Varghese1,2, Justyna Andrys5, Ricardo H. Arriaza6, Rahul Prakash6, Purushottam B Tiwari7, Cara Olsen8, Daniel Hupalo2,4, Yuriy Gusev5, Megha N. Patel6, Sara Contente1, Miloslav Sanda9, Aykut Uren7, Matthew D. Wilkerson3,4, Clifton L. Dalgard3,4, Linda S. Shimizu6, Maksymilian Chruszcz6, Tomasz Borowski5, Geeta Upadhyay 1,3,7. Affiliations 1 Department of Pathology, 2 Henry M. Jackson Foundation, 3 Murtha Cancer Center, 4 Department of Anatomy, Physiology, and Genetics 8 Department of Preventive Medicine and Biostatistics Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 5 Jerzy Haber Institute of Catalysis and Surface Chemistry Polish Academy of Sciences, Cracow, Poland. 6 Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, USA. 7 Department of Oncology, Georgetown U...
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NSC243928 induces cell death in triple-negative breast cancer cells in a LY6K-dependent manner. NSC243928 has been reported as an anti-cancer agent in the NCI small molecule library. The molecular mechanism of NSC243928 as an anti-cancer... more
NSC243928 induces cell death in triple-negative breast cancer cells in a LY6K-dependent manner. NSC243928 has been reported as an anti-cancer agent in the NCI small molecule library. The molecular mechanism of NSC243928 as an anti-cancer agent in the treatment of tumor growth in the syngeneic mouse model has not been established. With the success of immunotherapies, novel anti-cancer drugs that may elicit an anti-tumor immune response are of high interest in the development of novel drugs to treat solid cancer. Thus, we focused on studying whether NSC243928 may elicit an anti-tumor immune response in the in vivo mammary tumor models of 4T1 and E0771. We observed that NSC243928 induced immunogenic cell death in 4T1 and E0771 cells. Furthermore, NSC243928 mounted an anti-tumor immune response by increasing immune cells such as patrolling monocytes, NKT cells, B1 cells, and decreasing PMN MDSCs in vivo. Further studies are required to understand the exact mechanism of NSC243928 action ...
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Background Human Ly6 gene family has been associated with stem cell marker Sca-1 in murine cancer. Sca-1 is known to regulate TGF-b signaling, Wnt signaling & it is important in cancer progression and metastasis in mouse models. Human Ly6... more
Background Human Ly6 gene family has been associated with stem cell marker Sca-1 in murine cancer. Sca-1 is known to regulate TGF-b signaling, Wnt signaling & it is important in cancer progression and metastasis in mouse models. Human Ly6 genes are associated with poor clinical outcome in human cancers. Previous studies have shown that this family of genes is highly expressed in Ovarian & Breast cancer compared to normal tissues. Overexpression of these genes was found to be correlated with poor outcome in overall and metastasis free survival. Recent studies have also shown that human Ly6 genes are associated with tumor immune escape & drug resistance. In this poster, we explore the variants in Ly6 and related genes in the TCGA Ovarian Cancer (OV) data collection. Materials and Methods We first downloaded RNA-seq data of primary tumor tissues from 21 TCGA OV patients from CGHUB (https://cghub.ucsc.edu/), and after quality control, aligned to human reference genome using tool RSEM on...
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Hepatocellular carcinoma (HCC) has emerged as second most common cause of cancer deaths worldwide. During the last 10 years, there has been a clear delineation of landscape of genetic alterations in HCC and deregulated pathways in HCC.... more
Hepatocellular carcinoma (HCC) has emerged as second most common cause of cancer deaths worldwide. During the last 10 years, there has been a clear delineation of landscape of genetic alterations in HCC and deregulated pathways in HCC. However, the treatment for patients with advanced HCC is limited despite of great effort developing therapeutic targeting the deregulated pathways in HCC. Recent studies reveal a direct causal relationship between cancer & immune dysfunction, whereby tumor cells and their microenvironment are able to evade immune attack by exploiting various immunoregulatory mechanisms in a process termed cancer immune editing. Methods In this poster, the objective is to perform exploratory analysis of TCGA liver cancer data to see if immune infiltrates matter, and if they offer anti-tumor immunity to a cell. For this purpose, we analyzed RNA-seq data for a cohort of 75 liver cancer samples from TCGA collection. We obtained the gene expression data from a pre-selected...
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Breast cancer is the most commonly diagnosed cancer in women and about 1 million new cases per year are diagnosed worldwide. About 70% of all breast cancers are estrogen receptor alpha positive (ER+). Antiestrogens (e.g., Tamoxifen or... more
Breast cancer is the most commonly diagnosed cancer in women and about 1 million new cases per year are diagnosed worldwide. About 70% of all breast cancers are estrogen receptor alpha positive (ER+). Antiestrogens (e.g., Tamoxifen or Faslodex) or aromatase inhibitors (e.g., Letrozole) are often used to treat ER+ breast cancers. However, resistance to these therapies (endocrine resistance) is prevalent in the clinic and the underlying mechanisms remain unclear. We have recently shown that the oncogene MYC is overexpressed in ER+ breast cancer and up-regulates glucose and glutamine uptake in endocrine resistant breast cancer cells, which suggests that the metabolomic profile of endocrine resistant breast cancer cells may contain features that are distinct from sensitive cells. In this study, to identify the biochemical pathways that are differentially regulated in endocrine resistance in breast cancer cells, we have analyzed gene expression data and untargeted metabolite profiles of ...
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Pancreatic ductal adenocarcinoma (PDAC) continues to be one of the most lethal forms of cancer. Reasons for the high mortality associated with this disease include a lack of effective treatments and poor early detection methods. Enhanced... more
Pancreatic ductal adenocarcinoma (PDAC) continues to be one of the most lethal forms of cancer. Reasons for the high mortality associated with this disease include a lack of effective treatments and poor early detection methods. Enhanced understanding of the pathways that are deregulated in PDAC could lead to improved therapies and diagnostics. We and others have reported a microRNA expression signature that is associated with PDAC. The purpose of this study was to identify target genes and pathways that are regulated by miRNAs with altered expression in PDAC. We found several miRNAs including miR-17-5p, −132/-212, and −337-3p that have increased expression in clinical specimens of PDAC compared to normal and adjacent benign pancreas. miR-132 and −212 are located within 472 bp of each other on chromosome 17, have the identical seed sequence and should therefore regulate the identical targets. Through a luciferase reporter assay and western blotting, we found that miR-132/-212 direct...
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Stem cell antigen Sca-1 is implicated in murine cancer stem cell biology and breast cancer models, but the role of its human homologs Ly6K and Ly6E in breast cancer are not established. Here we report increased expression of Ly6K/E in... more
Stem cell antigen Sca-1 is implicated in murine cancer stem cell biology and breast cancer models, but the role of its human homologs Ly6K and Ly6E in breast cancer are not established. Here we report increased expression of Ly6K/E in human breast cancer specimens correlates with poor overall survival, with an additional specific role for Ly6E in poor therapeutic outcomes. Increased expression of Ly6K/E also correlated with increased expression of the immune checkpoint molecules PDL1 and CTLA4, increased tumor-infiltrating T regulatory cells, and decreased natural killer (NK) cell activation. Mechanistically, Ly6K/E was required for TGFβ signaling and proliferation in breast cancer cells, where they contributed to phosphorylation of Smad1/5 and Smad2/3. Furthermore, Ly6K/E promoted cytokine-induced PDL1 expression and activation and binding of NK cells to cancer cells. Finally, we found that Ly6K/E promoted drug resistance and facilitated immune escape in this setting. Overall, our ...
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Table S1: List of qRT-PCR primers; Table. S2: Summary table of mRNA expression for Ly6K and Ly6E in normal and cancer samples in seven comparison; Fig. S1. Expression of Ly6K and Ly6E in human normal and breast cancer tissues; Fig. S2:... more
Table S1: List of qRT-PCR primers; Table. S2: Summary table of mRNA expression for Ly6K and Ly6E in normal and cancer samples in seven comparison; Fig. S1. Expression of Ly6K and Ly6E in human normal and breast cancer tissues; Fig. S2: The knockdown for Ly6K and Ly6E is specific; Fig. S3: Colony assay; Fig. S4: The Ly6K gene is required for intravasation, extravasation and colonization of cancer cells; Fig. S5: Comparison of CD274, CTLA4, IL2RA, LY6E and LY6K gene expression in clinical samples of breast cancer in indicated 6 analysis in three different datasets; Fig. S6: High expression of Ly6K and Ly6E impair NK cell binding to cancer cell; Fig. S7: Indicated cells (MDA-MB-231) were treated with 100ng/ml IFN-g overnight; Fig. S8: Rescue over expression phenotype.
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Recent reports have suggested that the reactivation of otherwise transcriptionally silent transposable elements (TEs) might induce brain degeneration, either by dysregulating the expression of genes and pathways implicated in cognitive... more
Recent reports have suggested that the reactivation of otherwise transcriptionally silent transposable elements (TEs) might induce brain degeneration, either by dysregulating the expression of genes and pathways implicated in cognitive decline and dementia or through the induction of immune-mediated neuroinflammation resulting in the elimination of neural and glial cells. In the work we present here, we test the hypothesis that differentially expressed TEs in blood could be used as biomarkers of cognitive decline and development of AD. To this aim, we used a sample of aging subjects (age > 70) that developed late-onset Alzheimer’s disease (LOAD) over a relatively short period of time (12–48 months), for which blood was available before and after their phenoconversion, and a group of cognitive stable subjects as controls. We applied our developed and validated customized pipeline that allows the identification, characterization, and quantification of the differentially expressed (...
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<p>(A) Expression pattern of miR-205-5p in MCA10A, MCF7, BT549, MDA-MB-231, and MDA-MB-436 cells. The data in cancer cell lines are expressed as fold-change compared to MCA10A, which was assigned a value of “1”. (B) miR-205-5p... more
<p>(A) Expression pattern of miR-205-5p in MCA10A, MCF7, BT549, MDA-MB-231, and MDA-MB-436 cells. The data in cancer cell lines are expressed as fold-change compared to MCA10A, which was assigned a value of “1”. (B) miR-205-5p levels in the normal adjacent breast tissues (N), non-metastatic tumor (T), and metastatic breast cancer specimens (M) were determined by qPCR. Data are presented relative to 18S rRNA. Mean values are indicated by horizontal bars.</p
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Front page of G-DOC Plus showing total number of studies, and samples in various disease types. (PNG 885 kb)
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Whatâ s new in G-DOC Plus? (DOCX 87 kb)
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Genes identified on microarrays as significantly differentially expressed in choroid/RPE of minus lens-treated eyes as compared with plus lens-treated eyes were assessed by qRT-PCR. cDNA was prepared from total RNA extracted from... more
Genes identified on microarrays as significantly differentially expressed in choroid/RPE of minus lens-treated eyes as compared with plus lens-treated eyes were assessed by qRT-PCR. cDNA was prepared from total RNA extracted from choroid/RPE of +5 D lens-treated (+) and −5 D lens-treated (-) eyes of subjects , and . Human primers were used to amplify 172-373 bp regions of cyclophilin A (), transforming growth factor, beta-induced (), 68 kDa, fibroblast growth factor -2 (), and protein tyrosine phosphatase, receptor type, B (; see ).<b>Copyright information:</b>Taken from "Microarray analysis of choroid/RPE gene expression in marmoset eyes undergoing changes in ocular growth and refraction"Molecular Vision 2008;14():1465-1479.Published online 11 Aug 2008PMCID:PMC2504533.
The steps, file formats and tools in the genomic data processing. (DOCX 148 kb)
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<b>Copyright information:</b>Taken from "Computational analysis of biological functions and pathways collectively targeted by co-expressed microRNAs in cancer"http://www.biomedcentral.com/1471-2105/8/S7/S16BMC... more
<b>Copyright information:</b>Taken from "Computational analysis of biological functions and pathways collectively targeted by co-expressed microRNAs in cancer"http://www.biomedcentral.com/1471-2105/8/S7/S16BMC Bioinformatics 2007;8(Suppl 7):S16-S16.Published online 1 Nov 2007PMCID:PMC2099484.at are targeted by at least 50% of over-expressed miRNAs from Colon Cancer dataset are shown in gray
Research Interests: Molecular Biology, Analysis, Biological, Computational, microRNAs, and 3 moreFunctions, Pathways, and Targeted
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We present a novel pipeline for viral RNA detection and quantification in human RNA-seq data. Our pipeline has been tested on the TCGA liver cancer cohort, can not only detect the presence of a viral species, but also provide gene level... more
We present a novel pipeline for viral RNA detection and quantification in human RNA-seq data. Our pipeline has been tested on the TCGA liver cancer cohort, can not only detect the presence of a viral species, but also provide gene level read counts for individual viral species and extract viral-variants. Introduction Approximately 20% of human cancer types are associated with viral infection that is routinely detected in blood samples. However the extent and biological significance of viral presence/infection in actual tumor samples is generally unknown but could be measured using existing Human RNA-seq data from tumor samples. We have developed a bioinformatics pipeline viGEN combining existing and novel RNAseq tools that allows for detection and quantification of viral RNA in human RNAseq data. Methods The pipeline includes 4 major modules: The first module allows to align and filter out human RNA sequences; second module maps and count (remaining un-aligned) reads against referen...
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Systems medicine leverages complex computational tools and high dimensional data offering the potential for effective individualized diagnosis, prognosis and treatment options. Our flagship web platform, the Georgetown Database of Cancer... more
Systems medicine leverages complex computational tools and high dimensional data offering the potential for effective individualized diagnosis, prognosis and treatment options. Our flagship web platform, the Georgetown Database of Cancer (G-DOC), was deployed with the goal of enabling translational research by integrating patient characteristics and clinical outcome data with a variety of high-throughput research data in a unified environment. With the goal of improving health outcomes through genomics research, we present G-DOC Plus, our enhanced web platform offering precision medicine, translational research and population genetics workflows. This enhanced platform takes advantage of cloud computing to handle next generation sequencing (NGS) data so that they can be analyzed in the full context of other omics and clinical information. G-DOC Plus uses cloud computing and other advanced computational tools to enable analysis of NGS and medical images in the full context of other omics and clinical information. It allows translational science researchers to explore data one sample at a time, as a sub-cohort of samples; or as a population as a whole, providing the user with a comprehensive view of the data. G-DOC Plus tools have been leveraged in cancer to support detection of prognostic markers for relapse in colorectal cancer samples, and to detect key metabolites related to disease severity; hypothesis generation; biomarker detection and multi-omic analysis, in-silico and population genetics analysis; and to explore somatic mutation and breast cancer MRI images. The long-term vision of G-DOC Plus is to extend this systems medicine platform to hospital networks to provide clinical decision support using multi-omics and relevant clinical information to support personalized patient care. G-DOC Plus was released in October 2014, and is available at: https://gdoc.georgetown.edu. Citation Format: Krithika Bhuvaneshwar, Anas Belouali, Varun Singh, Robert M. Johnson, Lei Song, Adil Alaoui, Michael Harris, Yuriy Gusev, Robert Clarke, Subha Madhavan. G-DOC Plus: A cloud based next-generation systems medicine platform for precision medicine. [abstract]. In: Proceedings of the AACR Special Conference on Computational and Systems Biology of Cancer; Feb 8-11 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 2):Abstract nr B1-44.
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In the African-American (AA) population, an increased incidence and shorter survival rate of triple negative breast cancer (TNBC) has been reported when compared to White women, with their cancer usually diagnosed in more advanced stages... more
In the African-American (AA) population, an increased incidence and shorter survival rate of triple negative breast cancer (TNBC) has been reported when compared to White women, with their cancer usually diagnosed in more advanced stages and with non-localized disease. The main objective of our study is to identify molecular markers in TNBC in AA patients that may be associated with their observed disparity in incidence and mortality rates. Formalin-fixed paraffin-embedded tumor sections were obtained from 26 and 28 cases of TNBC from AA and Caucasian breast cancer patients, respectively, and analyzed for DNA copy number (Agilent-SurePrint G3 Human CGH Microarray 8×60K) and miRNA expression (Nanostring System) alterations. The cases were obtained with clinically annotated data from the Histopathology Shared Resources at the Lombardi Comprehensive Cancer Center. The miRNA data was directly integrated with the array-CGH data from the same cases. Combinatorial target predicted algorith...
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Selective estrogen receptor modulators (SERMs) such as Tamoxifen (TAM) can significantly improve breast cancer-specific survival for women with ER-positive (ER+) disease. However, resistance to TAM remains a major clinical problem.... more
Selective estrogen receptor modulators (SERMs) such as Tamoxifen (TAM) can significantly improve breast cancer-specific survival for women with ER-positive (ER+) disease. However, resistance to TAM remains a major clinical problem. Estrogen-related receptor gamma (ERRγ) is an orphan nuclear receptor with broad, structural similarities to classical ER that is widely implicated in the transcriptional regulation of energy homeostasis. We previously reported that ERRγ is upregulated during the acquisition of TAM resistance in ER+ breast cancer cell lines, exogenous expression of ERRγ is sufficient to induce TAM resistance, and ERRγ mRNA is significantly increased in tumor samples from women with ER+ breast cancer who relapse following TAM treatment. Because ERRγ has no known ligand, our recent studies have focused on understanding how the expression and activity of this orphan nuclear receptor is regulated, and how this contributes to the TAM resistant phenotype. We have found that TAM-...
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Data sets were analyzed by the Ingenuity Pathways Analysis software ( Systems). The significance is expressed as a p value that is calculated using the right tailed Fisher exact test. Red and blue bars represent significantly upregulated... more
Data sets were analyzed by the Ingenuity Pathways Analysis software ( Systems). The significance is expressed as a p value that is calculated using the right tailed Fisher exact test. Red and blue bars represent significantly upregulated and downregulated genes associated with canonical pathways, respectively. In the figure, n represents the number of genes identified in each of the pathways.<b>Copyright information:</b>Taken from "Microarray analysis of choroid/RPE gene expression in marmoset eyes undergoing changes in ocular growth and refraction"Molecular Vision 2008;14():1465-1479.Published online 11 Aug 2008PMCID:PMC2504533.
−5 D lens-treated eyes (open symbols) exhibited a more negative refractive error relative to contralateral +5 D lens-treated eyes (closed symbols). −5 D lens-treated eyes (open symbols) exhibited longer vitreous chambers relative to... more
−5 D lens-treated eyes (open symbols) exhibited a more negative refractive error relative to contralateral +5 D lens-treated eyes (closed symbols). −5 D lens-treated eyes (open symbols) exhibited longer vitreous chambers relative to contralateral +5 D lens-treated eyes (closed symbols). Eyes of the four individual marmosets are represented by different symbols (red circle, subject A; green square, subject B; black triangle, subject C; blue diamond, subject D).<b>Copyright information:</b>Taken from "Microarray analysis of choroid/RPE gene expression in marmoset eyes undergoing changes in ocular growth and refraction"Molecular Vision 2008;14():1465-1479.Published online 11 Aug 2008PMCID:PMC2504533.
Details of the 281 variants significantly associated with tumor necrosis. (XLSX 114 kb)
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Details of the 231 haplotypes overlapping between the two datasets. (XLSX 83 kb)
Detailed processing steps of Analysis 2 including the block diagram, filtering steps, PCA plot, equations of the generalized linear models. (DOCX 1860 kb)
<b>Copyright information:</b>Taken from "Real-time expression profiling of microRNA precursors in human cancer cell lines"Nucleic Acids Research 2005;33(17):5394-5403.Published online 28 Sep 2005PMCID:PMC1236977.©... more
<b>Copyright information:</b>Taken from "Real-time expression profiling of microRNA precursors in human cancer cell lines"Nucleic Acids Research 2005;33(17):5394-5403.Published online 28 Sep 2005PMCID:PMC1236977.© The Author 2005. Published by Oxford University Press. All rights reserved The sequences of the miRNA precursors for the members of the human let-7 family of miRNA isoforms are shown. Underlined, sequence of the mature miRNA; red, sequences of the forward PCR primers; blue, sequences of the reverse PCR primers; green sequences of the TaqMan MGB probe; and yellow, priming sequences that differ among isoforms. Sequences are in the 5′ to 3′ direction.