Nurcan Tuncbag

Nurcan Tuncbag
Koc University · College of Engineering and School of Medicine

PhD

About

63
Publications
8,047
Reads
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2,195
Citations
Additional affiliations
February 2021 - present
Koc University
Position
  • Professor (Associate)
February 2021 - present
Koc University
Position
  • Professor (Associate)
October 2017 - February 2021
Middle East Technical University
Position
  • Professor (Associate)
Education
September 2007 - October 2010
Koc University
Field of study
  • Computational Sciences and Engineering
September 2005 - September 2007
Koc University
Field of study
  • Computational Sciences and Engineering
September 2000 - June 2005
Istanbul Technical University
Field of study
  • Chemical Engineering

Publications

Publications (63)
Article
Full-text available
Drugs not only perturb their immediate protein targets but also modulate multiple signaling pathways. In this study, we explored networks modulated by several drugs across multiple cancer cell lines by integrating their targets with transcriptomic and phosphoproteomic data. As a result, we obtained 236 reconstructed networks covering five cell line...
Article
Full-text available
Background Targeted therapies for Primary liver cancer (HCC) is limited to the multi-kinase inhibitors, and not fully effective due to the resistance to these agents because of the heterogeneous molecular nature of HCC developed during chronic liver disease stages and cirrhosis. Although combinatorial therapy can increase the efficiency of targeted...
Article
Proteins interact through their interfaces to fulfill essential functions in the cell. They bind to their partners in a highly specific manner and form complexes that have a profound effect on understanding the biological pathways they are involved in. Any abnormal interactions may cause diseases. Therefore, the identification of small molecules wh...
Article
Full-text available
Background: Although many pathological changes have been associated with ischemic heart disease (IHD), molecular-level alterations specific to the ischemic myocardium and their potential to reflect disease severity or therapeutic outcome remain unclear. Currently, diagnosis occurs relatively late and evaluating disease severity is largely based on...
Article
In line with the advances in high-throughput technologies, multiple omic datasets have accumulated to study biological systems and diseases coherently. No single omics data type is capable of fully representing cellular activity. The complexity of the biological processes arises from the interactions between omic entities such as genes, proteins, a...
Article
Full-text available
Beyond the list of molecules, there is a necessity to collectively consider multiple sets of omic data and to reconstruct the connections between the molecules. Especially, pathway reconstruction is crucial to understanding disease biology because abnormal cellular signaling may be pathological. The main challenge is how to integrate the data toget...
Article
Full-text available
Precision oncology benefits from effective early phase drug discovery decisions. Recently, drugging inactive protein conformations has shown impressive successes, raising the cardinal questions of which targets can profit and what are the principles of the active/inactive protein pharmacology. Cancer driver mutations have been established to mimic...
Article
Full-text available
Colon cancer is initiated by stem cells that escape the strict control. This process is often driven through aberrant activation of Wnt signaling by mutations in components acting downstream of the receptor complex that unfetter tumor cells from the need for Wnts. Here we describe a class of colon cancer that does not depend on mutated core compone...
Article
Full-text available
Phosphorylation is an essential post-translational modification for almost all cellular processes. Several global phosphoproteomics analyses have revealed phosphorylation profiles under different conditions. Beyond identification of phospho-sites, protein structures add another layer of information about their functionality. In this study, we syste...
Article
Full-text available
Epitranscriptomic modifications in RNA can dramatically alter the way our genetic code is deciphered. Cells utilize these modifications not only to maintain physiological processes, but also to respond to extracellular cues and various stressors. Most often, adenosine residues in RNA are targeted, and result in modifications including methylation a...
Preprint
Full-text available
Heterogeneity across tumors is the main obstacle in developing treatment strategies. Drug molecules not only perturb their immediate protein targets but also modulate multiple signaling pathways. In this study, we explored the networks modulated by several drug molecules across multiple cancer cell lines by integrating the drug targets with transcr...
Article
Full-text available
Ras GTPase interacts with its regulators and downstream effectors for its critical function in cellular signaling. Targeting the disrupted mechanisms in Ras-related human cancers requires understanding the distinct dynamics of these protein–protein interactions. We performed normal mode analysis (NMA) of KRas4B in wild-type or mutant monomeric and...
Article
Transcriptional dysregulation in Huntington's disease (HD) causes functional deficits in striatal neurons. Here, we performed Patch-sequencing (Patch-seq) in an in vitro HD model to investigate the effects of mutant Huntingtin (Htt) on synaptic transmission and gene transcription in single striatal neurons. We found that expression of mutant Htt de...
Article
Full-text available
Clear cell Renal Cell Carcinoma (ccRCC) is the third most common and most malignant urological cancer, with a 5-year survival rate of 10% for patients with advanced tumors. Here, we identified 10,160 unique proteins by in-depth quantitative proteomics, of which 955 proteins were significantly regulated between tumor and normal adjacent tissues. We...
Preprint
Full-text available
Transforming patient-specific molecular data into clinical decisions is fundamental to personalized medicine. Despite massive advancements in cancer genomics, to date driver mutations whose frequencies are low, and their observable transformation potential is minor have escaped identification. Yet, when paired with other mutations in cis, such 'lat...
Preprint
Background: Targeted therapies for Primary liver cancer (HCC) is limited to the multi-kinase inhibitors, and not fully effective due to the resistance to these agents because of the heterogeneous molecular nature of HCC developed during chronic liver disease stages and cirrhosis. Although combinatorial therapy can increase the efficiency of targete...
Article
Full-text available
In the era of precision medicine, analyzing the transcriptomic profile of patients is essential to tailor the appropriate therapy. In this study, we explored transcriptional differences between two invasive breast cancer subtypes; infiltrating ductal carcinoma (IDC) and lobular carcinoma (LC) using RNA-Seq data deposited in the TCGA-BRCA project. W...
Preprint
Full-text available
Clear cell Renal Cell Carcinoma (ccRCC) is the third most common and most malignant urological cancer, with a 5-year survival rate of 10% for patients with advanced tumors. Here, we identified 10,160 unique proteins by in-depth quantitative proteomics, of which 955 proteins were significantly regulated between tumor and normal adjacent tissues. We...
Article
Full-text available
Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor. Molecular heterogeneity is a hallmark of GBM tumors that is a barrier in developing treatment strategies. In this study, we used the nonsynonymous mutations of GBM tumors deposited in The Cancer Genome Atlas (TCGA) and applied a systems level approach based on biophysical cha...
Conference Paper
Hepatocellular carcinoma (HCC) is the 5th most common and 2nd deadliest cancer worldwide. The molecular mechanism in HCC involves activated cell survival pathways, but there is a lack of the significant oncogenic drivers for targeted therapies. Thus, novel drugs and targets that can be exploited, are required. The pathways reported to be involved i...
Conference Paper
Hepatocellular carcinoma (HCC) is the 5th most common and 2nd deadliest cancer worldwide. The molecular mechanism in HCC involves activated cell survival pathways, but there is a lack of the significant oncogenic drivers for targeted therapies. Thus, novel drugs and targets that can be exploited, are required. The pathways reported to be involved i...
Article
Full-text available
Epithelial-mesenchymal transition (EMT) is driven by complex signaling events that induce dramatic biochemical and morphological changes whereby epithelial cells are converted into cancer cells. However, the underlying molecular mechanisms remain elusive. Here, we used mass spectrometry based quantitative proteomics approach to systematically analy...
Preprint
Full-text available
Mutation profiles of Glioblastoma (GBM) tumors are very heterogeneous which is the main challenge in the interpretation of the effects of mutations in disease. Additionally, the impact of the mutations is not uniform across the proteins and protein-protein interactions. The pathway level representation of the mutations is very limited. In this work...
Article
Protein-protein interactions (PPIs) are the key components in many cellular processes including signaling pathways, enzymatic reactions and epigenetic regulation. Abnormal interactions of some proteins may be pathogenic and cause various disorders including cancer and neurodegenerative diseases. Although inhibiting PPIs with small molecules is a ch...
Chapter
Proteins use their functional regions to exploit various activities, including binding to other proteins, nucleic acids, or drugs. Functional sites of the proteins have a tendency to be more conserved than the rest of the protein surface. Therefore, detection of the conserved residues using phylogenetic analysis is a general approach to predict fun...
Article
Full-text available
The successful completion of cytokinesis requires the coordinated activities of diverse cellular components including membranes, cytoskeletal elements and chromosomes that together form partly redundant pathways, depending on the cell type. The biochemical analysis of this process is challenging due to its dynamic and rapid nature. Here, we systema...
Article
Full-text available
Genes encoding proteins that carry out essential informational tasks in the cell, in particular where multiple interaction partners are involved, are less likely to be transferable to a foreign organism. Here, we investigated the constraints on transfer of a gene encoding a highly conserved informational protein, translation elongation factor Tu (E...
Chapter
Structural details of protein interactions are invaluable to the understanding of cellular processes. However, the identification of interactions at atomic resolution is a continuing challenge in the systems biology era. Although the number of structurally resolved complexes in the Protein Databank increases exponentially, the complexes only cover...
Article
Full-text available
Numerous genes and molecular pathways are implicated in neurodegenerative proteinopathies, but their inter-relationships are poorly understood. We systematically mapped molecular pathways underlying the toxicity of alpha-synuclein (α-syn), a protein central to Parkinson’s disease. Genome-wide screens in yeast identified 332 genes that impact α-syn...
Article
Full-text available
The complexity hypothesis posits that network connectivity and protein function are two important determinants of how a gene adapts to and functions in a foreign genome. Genes encoding proteins that carry out essential informational tasks in the cell, in particular where multiple interaction partners are involved, are less likely to be transferable...
Article
Full-text available
Glioblastoma is the most aggressive type of malignant human brain tumor. Molecular profiling experiments have revealed that these tumors are extremely heterogeneous. This heterogeneity is one of the principal challenges for developing targeted therapies. We hypothesize that despite the diverse molecular profiles, it might still be possible to ident...
Article
Full-text available
High-throughput, 'omic' methods provide sensitive measures of biological responses to perturbations. However, inherent biases in high-throughput assays make it difficult to interpret experiments in which more than one type of data is collected. In this work, we introduce Omics Integrator, a software package that takes a variety of 'omic' data as in...
Data
Supplementary material. Detailed procedure to run Omics Integrator Software and interpret the results. (DOCX)
Article
Identification of protein-protein interactions (PPIs) is at the center of molecular biology considering the unquestionable role of proteins in cells. Combinatorial interactions result in a repertoire of multiple functions; hence, knowledge of PPI and binding regions naturally serve to functional proteomics and drug discovery. Given experimental lim...
Article
Full-text available
Salmonella enterica is a bacterial pathogen that usually infects its host through food sources. Translocation of the pathogen proteins into the host cells leads to changes in the signaling mechanism either by activating or inhibiting the host proteins. Given that the bacterial infection modifies the response network of the host, a more coherent vie...
Article
Full-text available
The phosphatidylinositol 3-kinase (PI3K) / AKT / mammalian target of rapamycin (mTOR) signalling pathway is hyperactivated or altered in many cancer types and regulates a broad range of cellular processes including survival, proliferation, growth, metabolism, angiogenesis and metastasis. The PI3K/AKT/mTOR pathway is regulated by a wide-range of ups...
Article
Full-text available
Abstract Signaling and regulatory networks are essential for cells to control processes such as growth, differentiation, and response to stimuli. Although many "omic" data sources are available to probe signaling pathways, these data are typically sparse and noisy. Thus, it has been difficult to use these data to discover the cause of the diseases...
Article
Full-text available
High-throughput technologies including transcriptional profiling, proteomics and reverse genetics screens provide detailed molecular descriptions of cellular responses to perturbations. However, it is difficult to integrate these diverse data to reconstruct biologically meaningful signaling networks. Previously, we have established a framework for...
Article
The similarity between folding and binding led us to posit the concept that the number of protein-protein interface motifs in nature is limited, and interacting protein pairs can use similar interface architectures repeatedly, even if their global folds completely vary. Thus, known protein-protein interface architectures can be used to model the co...
Article
Prediction of protein-protein interactions at the structural level on the proteome scale is important because it allows prediction of protein function, helps drug discovery and takes steps toward genome-wide structural systems biology. We provide a protocol (termed PRISM, protein interactions by structural matching) for large-scale prediction of pr...
Article
The vast majority of the chores in the living cell involve protein-protein interactions. Providing details of protein interactions at the residue level and incorporating them into protein interaction networks are crucial toward the elucidation of a dynamic picture of cells. Despite the rapid increase in the number of structurally known protein comp...
Article
We propose a novel approach to analyze and visualize residue contact networks of protein interfaces by graph-based algorithms using a minimum cut tree (mincut tree). Edges in the network are weighted according to an energy function derived from knowledge-based potentials. The mincut tree, which is constructed from the weighted residue network, simp...
Article
Full-text available
The energy distribution along the protein–protein interface is not homogenous; certain residues contribute more to the binding free energy, called ‘hot spots’. Here, we present a web server, HotPoint, which predicts hot spots in protein interfaces using an empirical model. The empirical model incorporates a few simple rules consisting of occlusion...
Article
Full-text available
Inspection of protein-protein interaction maps illustrates that a hub protein can interact with a very large number of proteins, reaching tens and even hundreds. Since a single protein cannot interact with such a large number of partners at the same time, this presents a challenge: can we figure out which interactions can occur simultaneously and w...
Article
Full-text available
Hot spots are residues comprising only a small fraction of interfaces yet accounting for the majority of the binding energy. These residues are critical in understanding the principles of protein interactions. Experimental studies like alanine scanning mutagenesis require significant effort; therefore, there is a need for computational methods to p...
Article
Full-text available
The unanimous agreement that cellular processes are (largely) governed by interactions between proteins has led to enormous community efforts culminating in overwhelming information relating to these proteins; to the regulation of their interactions, to the way in which they interact and to the function which is determined by these interactions. Th...
Article
Hot spots are residues comprising only a small fraction of interfaces yet accounting for the majority of the binding energy. These residues are critical in understanding the principles of protein interactions. Experimental studies like alanine scanning mutagenesis require significant effort; therefore, there is a need for computational methods to p...
Article
The diverse range of cellular functions is performed by a limited number of protein folds existing in nature. One may similarly expect that cellular functional diversity would be covered by a limited number of protein–protein interface architectures. Here, we present 8205 interface clusters, each representing a unique interface architecture. This d...
Article
Full-text available
Complex protein-protein interaction networks govern biological processes in cells. Protein interfaces are the sites where proteins physically interact. Identification and characterization of protein interfaces will lead to understanding how proteins interact with each other and how they are involved in protein-protein interaction networks. What mak...
Article
Full-text available
We present a new database of computational hot spots in protein interfaces: HotSprint. Hot spots are residues comprising only a small fraction of interfaces yet accounting for the majority of the binding energy. HotSprint contains data for 35 776 protein interfaces among 49 512 protein interfaces extracted from the multi-chain structures in Protein...
Article
Understanding the cell's large-scale organization is an interesting task in computational biology. Thus, protein-protein interactions can reveal important organization and function of the cell. Here, we investigated the correspondence between protein interactions and function for the yeast. We obtained the correlations among the set of proteins. Th...

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Projects (2)
Project
Liver cancer (Hepatocellular Carcinoma, HCC) is the fifth most common and the second deadliest cancer in the world. HCC is very aggressive and constitutes 83% of primary liver cancers. There are two targeted drugs used in this disease, Sorafenib and Regorafenib which extend patient survival approximately 3 months. PI3K/Akt/mTOR signaling pathway is important for cell survival and has significant role in the development of HCC. Therefore, it is necessary to find new target molecules for this deadly cancer type. There are about 250 protein nodes in this signaling network. For this purpose, protein and drug interaction data will be collected from previous studies and the Akt signaling pathway will be restructured in detail. Protein-drug sequence patterns will be defined. Thus, by this new PI3K /Akt /mTOR signaling network components to be generated will be screened for new bioactive molecules in in silico, and drug candidates will be obtained that bind to both their target and non-target proteins with high affinity.
Project
http://www.cost.eu/COST_Actions/ca/CA15120 Multiscale systems medicine assumes that the growing amounts of highly diverse (multiscale) data relevant to human health and disease are the key to address current and future medical challenges. Transforming these data into effective and economical medical solutions requires appropriate means for multiscale data modelling, integration and analysis. The overarching aim of the Open Multiscale Systems Medicine (OpenMultiMed) COST Action is to gather a critical mass of international researchers and coordinate them as a team that develops and evaluates a transdisciplinary framework for multiscale systems medicine, consisting of novel concepts, methodologies and technologies. The unique concept and ambition of the OpenMultiMed Action rests on three pillars: (1) A transdisciplinary strategy in which medical researchers, mathematical modellers, data scientist, and computer scientists work jointly using a shared conceptual framework and combined disciplinary-specific approaches. (2) A strong focus on multiscaleness across systems medicine, multiscale modelling, multiscale data science and multiscale computing. (3) An open-science approach, making scientific research, data and dissemination in multiscale systems medicine accessible to all levels of an inquiring European and international society. The potential impacts resulting from the OpenMultiMed Action include more effective and economical ways of health promotion, disease prevention and therapy; more effective and efficient concepts, methods and tools for multiscale systems and data modelling, and multiscale computing; and a strengthening of scientific excellence and industrial competitiveness of individuals and organizations in medical, analytical and technological areas.