Altering Oligomerization Of Epha2 Via Mutations In The Intracellular Domain, 2018 The University of Akron
Altering Oligomerization Of Epha2 Via Mutations In The Intracellular Domain, Ryan W. Lingerak
Honors Research Projects
Eph receptor tyrosine kinases (RTKs) are activated by membrane-bound ligands called ephrins. Eph RTKs are divided into two subclasses, each activated by a specific classes of the ligand ephrin. The overexpression of Eph receptors is correlated to cancer cell metastasis in several different types of cancers. Studies with the EphA2 extracellular domain (ECD) and ephrinA1 ligand have shown that upon binding of ephrin to the receptor, EphA2 undergoes increased oligomerization and activation. This indicates that oligomerization is intimately connected to kinase activity. High resolution crystal structures of the EphA2 ECD have revealed some details of these ligand bound oligomers, as ...
Superresolution Imaging Identifies That Conventional Trafficking Pathways Are Not Essential For Endoplasmic Reticulum To Outer Mitochondrial Membrane Protein Transport., 2017 George Washington University
Superresolution Imaging Identifies That Conventional Trafficking Pathways Are Not Essential For Endoplasmic Reticulum To Outer Mitochondrial Membrane Protein Transport., Kyle Salka, Shivaprasad Bhuvanendran, Kassandra Wilson, Petros Bozidis, Mansi Mehta, Kristin Rainey, Hiromi Sesaki, George H Patterson, Jyoti K. Jaiswal, Anamaris M. Colberg-Poley
Genomics and Precision Medicine Faculty Publications
Most nuclear-encoded mitochondrial proteins traffic from the cytosol to mitochondria. Some of these proteins localize at mitochondria-associated membranes (MAM), where mitochondria are closely apposed with the endoplasmic reticulum (ER). We have previously shown that the human cytomegalovirus signal-anchored protein known as viral mitochondria-localized inhibitor of apoptosis (vMIA) traffics from the ER to mitochondria and clusters at the outer mitochondrial membrane (OMM). Here, we have examined the host pathways by which vMIA traffics from the ER to mitochondria and clusters at the OMM. By disruption of phosphofurin acidic cluster sorting protein 2 (PACS-2), mitofusins (Mfn1/2), and dynamin related protein 1 ...
Chronic Hypobaric Hypoxia Modulates Primary Cilia Differently In Adult And Fetal Ovine Kidneys, 2017 Chapman University
Chronic Hypobaric Hypoxia Modulates Primary Cilia Differently In Adult And Fetal Ovine Kidneys, Kiumars Shamloo, Juan Chen, Jasmine Sardar, Rinzhin T. Sherpa, Rajasekharreddy Pala, Kimberly F. Atkinson, William J. Pearce, Lubo Zhang, Surya M. Nauli
Pharmacy Faculty Articles and Research
Hypoxic environments at high altitude have significant effects on kidney injury. Following injury, renal primary cilia display length alterations. Primary cilia are mechanosensory organelles that regulate tubular architecture. The effect of hypoxia on cilia length is still controversial in cultured cells, and no corresponding in vivo study exists. Using fetal and adult sheep, we here study the effect of chronic hypobaric hypoxia on the renal injury, intracellular calcium signaling and the relationship between cilia length and cilia function. Our results show that although long-term hypoxia induces renal fibrosis in both fetal and adult kidneys, fetal kidneys are more susceptible to ...
The N-Terminus Of Ift46 Mediates Intraflagellar Transport Of Outer Arm Dynein And Its Cargo-Adaptor Oda16, 2017 University of Massachusetts Medical School
The N-Terminus Of Ift46 Mediates Intraflagellar Transport Of Outer Arm Dynein And Its Cargo-Adaptor Oda16, Yuqing Hou, George B. Witman
Radiology Publications and Presentations
Cilia are assembled via intraflagellar transport (IFT). The IFT machinery is composed of motors and multi-subunit particles, termed IFT-A and IFT-B, that carry cargo into the cilium. Knowledge of how the IFT subunits interact with their cargo is of critical importance for understanding how the unique ciliary domain is established. We previously reported a Chlamydomonas mutant, ift46-1, that fails to express the IFT-B protein IFT46, has greatly reduced levels of other IFT-B proteins, and assembles only very short flagella. A spontaneous suppression of ift46-1 restored IFT-B levels and enabled growth of longer flagella, but the flagella lacked outer dynein arms ...
Morphogenesis And Growth Driven By Selection Of Dynamical Properties, 2017 The Graduate Center, City University of New York
Morphogenesis And Growth Driven By Selection Of Dynamical Properties, Yuri Cantor
All Graduate Works by Year: Dissertations, Theses, and Capstone Projects
Organisms are understood to be complex adaptive systems that evolved to thrive in hostile environments. Though widely studied, the phenomena of organism development and growth, and their relationship to organism dynamics is not well understood. Indeed, the large number of components, their interconnectivity, and complex system interactions all obscure our ability to see, describe, and understand the functioning of biological organisms.
Here we take a synthetic and computational approach to the problem, abstracting the organism as a cellular automaton. Such systems are discrete digital models of real-world environments, making them more accessible and easier to study then their physical world ...
Prediction Of Rna Binding Sites In Proteins From Amino Acid Sequence, 2017 Iowa State University
Prediction Of Rna Binding Sites In Proteins From Amino Acid Sequence, Michael Terribilini, Jae-Hyung Lee, Changhui Yan, Robert L. Jernigan, Vasant Honavar, Drena Dobbs
RNA–protein interactions are vitally important in a wide range of biological processes, including regulation of gene expression, protein synthesis, and replication and assembly of many viruses. We have developed a computational tool for predicting which amino acids of an RNA binding protein participate in RNA–protein interactions, using only the protein sequence as input. RNABindR was developed using machine learning on a validated nonredundant data set of interfaces from known RNA–protein complexes in the Protein Data Bank. It generates a classifier that captures primary sequence signals sufficient for predicting which amino acids in a given protein are located ...
Predicting Dna-Binding Sites Of Proteins From Amino Acid Sequence, 2017 Utah State University
Predicting Dna-Binding Sites Of Proteins From Amino Acid Sequence, Changhui Yan, Michael Terribilini, Feihong Wu, Robert L. Jernigan, Drena Dobbs, Vasant Honavar
Understanding the molecular details of protein-DNA interactions is critical for deciphering the mechanisms of gene regulation. We present a machine learning approach for the identification of amino acid residues involved in protein-DNA interactions.
We start with a Naïve Bayes classifier trained to predict whether a given amino acid residue is a DNA-binding residue based on its identity and the identities of its sequence neighbors. The input to the classifier consists of the identities of the target residue and 4 sequence neighbors on each side of the target residue. The classifier is trained and evaluated (using leave-one-out cross-validation) on ...
Identifying Interaction Sites In "Recalcitrant" Proteins: Predicted Protein And Rna Binding Sites In Rev Proteins Of Hiv-1 And Eiav Agree With Experimental Data, Michael Terribilini, Jae-Hyung Lee, Changhui Yan, Robert L. Jernigan, Susan Carpenter, Vasant Honavar, Drena Dobbs
Protein-protein and protein nucleic acid interactions are vitally important for a wide range of biological processes, including regulation of gene expression, protein synthesis, and replication and assembly of many viruses. We have developed machine learning approaches for predicting which amino acids of a protein participate in its interactions with other proteins and/or nucleic acids, using only the protein sequence as input. In this paper, we describe an application of classifiers trained on datasets of well-characterized protein-protein and protein-RNA complexes for which experimental structures are available. We apply these classifiers to the problem of predicting protein and RNA binding sites ...
Rnabindr: A Server For Analyzing And Predicting Rna-Binding Sites In Proteins, 2017 Iowa State University
Rnabindr: A Server For Analyzing And Predicting Rna-Binding Sites In Proteins, Michael Terribilini, Jeffry D. Sander, Jae-Hyung Lee, Peter Zaback, Robert L. Jernigan, Vasant Honavar, Drena Dobbs
Understanding interactions between proteins and RNA is key to deciphering the mechanisms of many important biological processes. Here we describe RNABindR, a web-based server that identifies and displays RNA-binding residues in known protein–RNA complexes and predicts RNA-binding residues in proteins of unknown structure. RNABindR uses a distance cutoff to identify which amino acids contact RNA in solved complex structures (from the Protein Data Bank) and provides a labeled amino acid sequence and a Jmol graphical viewer in which RNA-binding residues are displayed in the context of the three-dimensional structure. Alternatively, RNABindR can use a Naive Bayes classifier trained on ...
Predicting Binding Sites Of Hydrolase-Inhibitor Complexes By Combining Several Methods, 2017 Iowa State University
Predicting Binding Sites Of Hydrolase-Inhibitor Complexes By Combining Several Methods, Taner Z. Sen, Andrzej Kloczkowski, Robert L. Jernigan, Changhui Yan, Vasant Honovar, Kai-Ming Ho, Cai-Zhuang Wang, Yungok Ihm, Haibo Cao, Xun Gu, Drena Dobbs
Protein-protein interactions play a critical role in protein function. Completion of many genomes is being followed rapidly by major efforts to identify interacting protein pairs experimentally in order to decipher the networks of interacting, coordinated-in-action proteins. Identification of protein-protein interaction sites and detection of specific amino acids that contribute to the specificity and the strength of protein interactions is an important problem with broad applications ranging from rational drug design to the analysis of metabolic and signal transduction networks.
In order to increase the power of predictive methods for protein-protein interaction sites, we have developed a consensus methodology ...
Characterization Of Protein–Protein Interfaces, 2017 Utah State University
Characterization Of Protein–Protein Interfaces, Changhui Yan, Feihong Wu, Robert L. Jernigan, Drena Dobbs, Vasant Honavar
We analyze the characteristics of protein–protein interfaces using the largest datasets available from the Protein Data Bank (PDB). We start with a comparison of interfaces with protein cores and noninterface surfaces. The results show that interfaces differ from protein cores and non-interface surfaces in residue composition, sequence entropy, and secondary structure. Since interfaces, protein cores, and non-interface surfaces have different solvent accessibilities, it is important to investigate whether the observed differences are due to the differences in solvent accessibility or differences in functionality. We separate out the effect of solvent accessibility by comparing interfaces with a set of residues ...
Intracellular Signalling Crosstalk In The Differentiation Of F9 Cells Into Extraembryonic Endoderm, 2017 The University of Western Ontario
Intracellular Signalling Crosstalk In The Differentiation Of F9 Cells Into Extraembryonic Endoderm, Tina Nicole Cuthbert
Electronic Thesis and Dissertation Repository
Mouse F9 cells differentiate into primitive extraembryonic endoderm (PrE) with retinoic acid (RA) treatment, resulting in up-regulation of Gata6, which when translated directly activates Wnt6. Canonical Wnt signalling is required for PrE differentiation, and this, like most developmental processes, requires input from one or more additional pathways, including hedgehog (Hh). The Hh pathway is regulated by GATA6, and crosstalks positively/negatively with Wnt signalling. Ihh up-regulation in F9 cells accompanies PrE induction, but a role for GATA6 or Hh pathway activation in obligatory Wnt/ß-catenin signalling is not known. To address this, I show that RA induces Ihh and altered ...
Use Of Imaging Biomarkers To Assess Perfusion And Glucose Metabolism In The Skeletal Muscle Of Dystrophic Mice, 2017 The University of Western Ontario
Use Of Imaging Biomarkers To Assess Perfusion And Glucose Metabolism In The Skeletal Muscle Of Dystrophic Mice, Nabeel Ahmad, Ian Welch, Robert Grange, Jennifer Hadway, Savita Dhanvantari, David Hill, Ting-Yim Lee, Lisa M Hoffman
BACKGROUND: Duchenne muscular dystrophy (DMD) is a severe neuromuscular disease that affects 1 in 3500 boys. The disease is characterized by progressive muscle degeneration that results from mutations in or loss of the cytoskeletal protein, dystrophin, from the glycoprotein membrane complex, thus increasing the susceptibility of contractile muscle to injury. To date, disease progression is typically assessed using invasive techniques such as muscle biopsies, and while there are recent reports of the use of magnetic resonance, ultrasound and optical imaging technologies to address the issue of disease progression and monitoring therapeutic intervention in dystrophic mice, our study aims to validate ...
Modulation Of Cellular Energetics By Galactose And Pioglitazone., 2017 Eastern Illinois University
Modulation Of Cellular Energetics By Galactose And Pioglitazone., David Grimm, Leonardo Altamirano, Sudip Paudel, Leah Welker, Mary E. Konkle, Nilay Chakraborty, Michael A. Menze
Michael A. Menze
The Warburg effect is ameliorated by culturing transformed cells in the presence of galactose instead of glucose as the primary carbon source. However, metabolic consequences that are in addition to sensitizing the cells to mitochondrial toxins may occur. As such, the screening of pharmaceutical agents against transformed cells while using galactose must be carefully evaluated. Pioglitazone is used in clinical applications to treat type-2 diabetes, but clearly has other off target effects. Human hepatocellular carcinoma cells (HepG2) were cultured in glucose or galactosecontaining medium to investigate the role of pioglitazone on cellular bioenergetics employing calorimetry and respirometry. Compared to cells ...
T-Time: A Data Repository Of T Cell And Calcium Release-Activated Calcium Channel Activation Imagery, 2017 Chapman University
T-Time: A Data Repository Of T Cell And Calcium Release-Activated Calcium Channel Activation Imagery, Cody Arbuckle, Milton L. Greenberg, Adrienne Bergh, Rene German, Nick Sirago, Erik J. Linstead
Mathematics, Physics, and Computer Science Faculty Articles and Research
BACKGROUND: A fundamental understanding of live-cell dynamics is necessary in order to advance scientific techniques and personalized medicine. For this understanding to be possible, image processing techniques, probes, tracking algorithms and many other methodologies must be improved. Currently there are no large open-source datasets containing live-cell imaging to act as a standard for the community. As a result, researchers cannot evaluate their methodologies on an independent benchmark or leverage such a dataset to formulate scientific questions.
FINDINGS: Here we present T-Time, the largest free and publicly available data set of T cell phase contrast imagery designed with the intention of ...
Contribution Of Activating Transcription Factor 3 To Development Of Acinar-To-Ductal Cell Metaplasia, 2017 The University of Western Ontario
Contribution Of Activating Transcription Factor 3 To Development Of Acinar-To-Ductal Cell Metaplasia, Jelena Toma
Electronic Thesis and Dissertation Repository
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in North America. The highest risk factor for PDAC is recurrent pancreatitis. While the link between PDAC and pancreatitis is unknown, de-differentiation of acinar cells is common to both diseases. Our lab has shown that Activating Transcription Factor 3 (ATF3), a factor upregulated during pancreatic injury, contributes to the development of acinar-to-ductal cell metaplasia (ADM), a precursor phenotype of PDAC. The goal of this study was to identify how ATF3 contributes to ADM. I hypothesize that ATF3 regulates acinar gene expression promoting ADM. We observed decreased ADM development ...
Intergenerational Effects Of Nicotine In An Animal Model Of Paternal Nicotine Exposure, 2017 University of Massachusetts Medical School
Intergenerational Effects Of Nicotine In An Animal Model Of Paternal Nicotine Exposure, Markus Parzival Vallaster
GSBS Dissertations and Theses
Environmental conditions imposed onto organisms during certain phases of their life cycles such as embryogenesis or puberty can not only impact the organisms’ own health, but also affect subsequent generations. The underlying mechanisms causing intergenerational phenotypes are not encoded in the genome, but the result of reversible epigenetic modifications. This work investigates in a mouse model the impact of paternal nicotine exposure on the next generation regarding addictive behavior modulation, metabolic changes, and molecular mechanisms. It provides evidence that male offspring from nicotine-exposed fathers (NIC offspring) is more resistant to lethal doses of nicotine. This phenotype is gender-specific and depends ...
Novel Species-Specific Glycoprotein On The Surface Of Mytilus Edulis And M. Trossulus Eggs, Fiona M. Harper, Kasandra J. Riley, R. D. Rawson
Protein–protein interactions play a central role in the gamete attraction, binding, and fusion stages of gamete interactions and fertilization for broadcast spawning species, such as marine mussels in the Mytilus edulis species complex. Although assortative gamete interaction has been implicated in the level of reproductive isolation among the three species in this complex, the molecular basis of these interactions has not been elucidated. Using mass spectrometry peptide sequencing, cDNA sequencing, and bioinformatics approaches, we have investigated species-level variation in the proteins expressed on the surface of mussel eggs. We herein describe an extracellular protein, MESP-1, from the surface of ...
Tumor Formation In Response To Loss Of Chromatin Remodeler Chd5 In Zebrafish, 2017 Purdue University
Tumor Formation In Response To Loss Of Chromatin Remodeler Chd5 In Zebrafish, Taylor R. Sabato, Erin L. Sorlien, Dr. Joseph P. Ogas
The Summer Undergraduate Research Fellowship (SURF) Symposium
Chromodomain helicase DNA binding protein 5 (CHD5) has been identified as a tumor suppressor in humans. Deletion or mutation of CHD5 has been observed in numerous cancers, including neuroblastoma and melanoma. We hypothesize that chd5 is also a tumor suppressor in zebrafish, a powerful model system to study tumorigenesis. Many genes involved in tumorigenesis are conserved in zebrafish, and they develop fully penetrant tumor phenotypes. We have created chd5 knock-out zebrafish using CRISPR/Cas9 and are monitoring them for tumor development. In addition to the chd5 knock-outs, we are undertaking a double-mutant approach by coupling loss of ...
Temporal Resolution Of Cell Death Signaling Events Induced By Cold Atmospheric Plasma And Electroporation In Human Cancer Cells, Danielle M. Krug, Prasoon K. Diwakar, Ahmed Hassanein
The Summer Undergraduate Research Fellowship (SURF) Symposium
Cancer treatment resistance and their invasive and expensive nature is propelling research towards developing alternate approaches to eradicate cancer in patients. Non-thermal, i.e., cold atmospheric plasma (CAP) and electroporation (EP) applied to the surface of cancerous tissue are new methods that are minimally invasive, safe, and selective. These approaches, both independently and synergistically, have been shown to deplete cancer cell populations, but the signaling mechanisms of death and their timelines of action are still widely unknown. To better understand the timeframe of signaling events occurring upon treatment, human cancer cell lines were treated with CAP, EP, and combined CAP ...