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Modeling Cell Line-Specific Recruitment Of Signaling Proteins To The Insulin-Like Growth Factor 1 Receptor, Keesha E. Erickson, Dipak Barua, For Full List Of Authors, See Publisher's Website.

Chemical and Biochemical Engineering Faculty Research & Creative Works

Receptor tyrosine kinases (RTKs) typically contain multiple autophosphorylation sites in their cytoplasmic domains. Once activated, these autophosphorylation sites can recruit downstream signaling proteins containing Src homology 2 (SH2) and phosphotyrosine-binding (PTB) domains, which recognize phosphotyrosine-containing short linear motifs (SLiMs). These domains and SLiMs have polyspecific or promiscuous binding activities. Thus, multiple signaling proteins may compete for binding to a common SLiM and vice versa. To investigate the effects of competition on RTK signaling, we used a rule-based modeling approach to develop and analyze models for ligand-induced recruitment of SH2/PTB domain-containing proteins to autophosphorylation sites in the insulin-like growth factor 1 …

Superelastic And Ph-Responsive Degradable Dendrimer Cryogels Prepared By Cryo-Aza-Michael Addition Reaction, Juan Wang, Hu Yang

Chemical and Biochemical Engineering Faculty Research & Creative Works

Dendrimers exhibit super atomistic features by virtue of their well-defined discrete quantized nanoscale structures. Here, we show that hyperbranched amine-terminated polyamidoamine (PAMAM) dendrimer G4.0 reacts with linear polyethylene glycol (PEG) diacrylate (575 g/mol) via the aza-Michael addition reaction at a subzero temperature (-20 °C), namely cryo-aza-Michael addition, to form a macroporous superelastic network, i.e., dendrimer cryogel. Dendrimer cryogels exhibit biologically relevant Young's modulus, high compression elasticity and super resilience at ambient temperature. Furthermore, the dendrimer cryogels exhibit excellent rebound performance and do not show significant stress relaxation under cyclic deformation over a wide temperature range (-80 to 100 °C). The …

No-Boundary Thinking In Bioinformatics, Jason H. Moore, Steven F. Jennings, Casey S. Greene, Lawrence E. Hunter, Andy D. Perkins, Clarlynda Williams-Devane, Donald C. Wunsch, Zhongming Zhao, Xiuzhen Huang

Electrical and Computer Engineering Faculty Research & Creative Works

The following sections are included:
Bioinformatics is a Mature Discipline
The Golden Era of Bioinformatics Has Begun
No-Boundary Thinking in Bioinformatics
References

Optimal Aggregation Of Fcεri With A Structurally Defined Trivalent Ligand Overrides Negative Regulation Driven By Phosphatases, Avanika Mahajan, Dipak Barua, Patrick Cutler, Diane S. Lidke, Flor A. Espinoza, Carolyn Pehlke, Rachel Grattan, Yuko Kawakami, Chang-Shung Tung, Andrew R. M. Bradbury, William S. Hlavacek, Bridget S. Wilson

Chemical and Biochemical Engineering Faculty Research & Creative Works

To investigate why responses of mast cells to antigen-induced IgE receptor (FcεRI) aggregation depend nonlinearly on antigen dose, we characterized a new artificial ligand, DF3, through complementary modeling and experimentation. This ligand is a stable trimer of peptides derived from bacteriophage T4 fibritin, each conjugated to a hapten (DNP). We found low and high doses of DF3 at which degranulation of mast cells sensitized with DNP-specific IgE is minimal, but ligand-induced receptor aggregation is comparable to aggregation at an intermediate dose, optimal for degranulation. This finding makes DF3 an ideal reagent for studying the balance of negative and positive signaling …

Recruitment Of The Adaptor Protein Grb2 To Egfr Tetramers, Noga Kozer, Dipak Barua, Christine Henderson, Eduoard C. Nice, Antony W. Burgess, William S. Hlavacek, Andrew H. A. Clayton

Chemical and Biochemical Engineering Faculty Research & Creative Works

Adaptor protein Grb2 binds phosphotyrosines in the epidermal growth factor (EGF) receptor (EGFR) and thereby links receptor activation to intracellular signaling cascades. Here, we investigated how recruitment of Grb2 to EGFR is affected by the spatial organization and quaternary state of activated EGFR. We used the techniques of image correlation spectroscopy (ICS) and lifetime-detected Förster resonance energy transfer (also known as FLIM-based FRET or FLIM-FRET) to measure ligand-induced receptor clustering and Grb2 binding to activated EGFR in BaF/3 cells. BaF/3 cells were stably transfected with fluorescently labeled forms of Grb2 (Grb2-mRFP) and EGFR (EGFR-eGFP). Following stimulation of the cells with …

Overexpression Of Dcf1 Inhibits Glioma Through Destruction Of Mitochondria And Activation Of Apoptosis Pathway, Yuqiong Xie, Qang Li, Qingbo Yang

Electrical and Computer Engineering Faculty Research & Creative Works

Gliomas are the most common brain tumors affecting the central nervous system and are associated with a high mortality rate. DCF1 is a membrane protein that was previously found to play a role in neural stem cell differentiation. In the present study, we found that overexpression of dcf1 significantly inhibited cell proliferation, migration, and invasion and dramatically promoted apoptosis in the glioblastoma U251 cell line. DCF1 deletion mutations in the functional region showed that the complete structure of DCF1 was necessary for apoptosis. Furthermore, significantly lower tumorigenicity was observed in athymic nude mice by transplanting U251 cells overexpressing dcf1. To …

Modeling The Effect Of Apc Truncation On Destruction Complex Function In Colorectal Cancer Cells, Dipak Barua, William S. Hlavacek

Chemical and Biochemical Engineering Faculty Research & Creative Works

In colorectal cancer cells, APC, a tumor suppressor protein, is commonly expressed in truncated form. Truncation of APC is believed to disrupt degradation of β-catenin, which is regulated by a multiprotein complex called the destruction complex. The destruction complex comprises APC, Axin, β-catenin, serine/threonine kinases, and other proteins. The kinases CK1α and GSK-3β, which are recruited by Axin, mediate phosphorylation of β-catenin, which initiates its ubiquitination and proteosomal degradation. The mechanism of regulation of β-catenin degradation by the destruction complex and the role of truncation of APC in colorectal cancer are not entirely understood. Through formulation and analysis of a …

Single-Cell Measurements Of Ige-Mediated Fcεri Signaling Using An Integrated Microfluidic Platform, Yanli Liu, Dipak Barua, Peng Liu, Bridget S. Wilson, Janet M. Oliver, William S. Hlavacek, Anup K. Singh

Chemical and Biochemical Engineering Faculty Research & Creative Works

Heterogeneity in responses of cells to a stimulus, such as a pathogen or allergen, can potentially play an important role in deciding the fate of the responding cell population and the overall systemic response. Measuring heterogeneous responses requires tools capable of interrogating individual cells. Cell signaling studies commonly do not have single-cell resolution because of the limitations of techniques used such as Westerns, ELISAs, mass spectrometry, and DNA microarrays. Microfluidics devices are increasingly being used to overcome these limitations. Here, we report on a microfluidic platform for cell signaling analysis that combines two orthogonal single-cell measurement technologies: on-chip flow cytometry …

Sector Expansion And Elliptical Modeling Of Blue-Gray Ovoids For Basal Cell Carcinoma Discrimination In Dermoscopy Images, Pelin Guvenc, Robert W. Leander, Serkan Kefel, William V. Stoecker, Ryan K. Rader, Kristen A. Hinton, Sherea Monica Stricklin, Harold S. Rabinovitz, Margaret C. Oliviero, Randy Hays Moss

Chemistry Faculty Research & Creative Works

Background: Blue-gray ovoids (B-GOs), a critical dermoscopic structure for basal cell carcinoma (BCC), offer an opportunity for automatic detection of BCC. Due to variation in size and color, B-GOs can be easily mistaken for similar structures in benign lesions. Analysis of these structures could afford accurate characterization and automatic recognition of B-GOs, furthering the goal of automatic BCC detection. This study utilizes a novel segmentation method to discriminate B-GOs from their benign mimics.

Methods: Contact dermoscopy images of 68 confirmed BCCs with B-GOs were obtained. Another set of 131 contact dermoscopic images of benign lesions possessing B-GO mimics provided a …

Analysis Of Globule Types In Malignant Melanoma, Jin Xu, Kapil Kumar Gupta, William V. Stoecker, Yamini Krishnamurthy, Harold S. Rabinovitz, Austin Bangert, David A. Calcara, Margaret C. Oliviero, Joseph M. Malters, Rhett J. Drugge, R. Joe Stanley, Randy Hays Moss, Mehmed Emre Celebi

Chemistry Faculty Research & Creative Works

Objective: To identify and analyze subtypes of globules based on size, shape, network connectedness, pigmentation, and distribution to determine which globule types and globule distributions are most frequently associated with a diagnosis of malignant melanoma. Design: Retrospective case series of dermoscopy images with globules. Setting: Private dermatology practices. Participants: Patients in dermatology practices. Intervention: Observation only. Main Outcome Measure: Association of globule types with malignant melanoma. Results: The presence of large globules (odds ratio [OR], 5.25) and globules varying in size (4.72) or shape (5.37) had the highest ORs for malignant melanoma among all globule types and combinations studied. Classical …

Computational Models Of Tandem Src Homology 2 Domain Interactions And Application To Phosphoinositide 3-Kinase, Dipak Barua, James R. Faeder, Jason M. Haugh

Chemical and Biochemical Engineering Faculty Research & Creative Works

Intracellular signal transduction proteins typically utilize multiple interaction domains for proper targeting, and thus a broad diversity of distinct signaling complexes may be assembled. Considering the coordination of only two such domains, as in tandem Src homology 2 (SH2) domain constructs, gives rise to a kinetic scheme that is not adequately described by simple models used routinely to interpret in vitro binding measurements. To analyze the interactions between tandem SH2 domains and bisphosphorylated peptides, we formulated detailed kinetic models and applied them to the phosphoinositide 3-kinase p85 regulatory subunit/platelet-derived growth factor β-receptor system. Data for this system from different in …

Bifidobacteria In Feces And Environmental Waters, Regina Lamendella, Jorge W. Santo Domingo, Catherine A. Kelty, Daniel B. Oerther

Civil, Architectural and Environmental Engineering Faculty Research & Creative Works

Bifidobacteria have been recommended as potential indicators of human fecal pollution in surface waters even though very little is known about their presence in nonhuman fecal sources. The objective of this research was to shed light on the occurrence and molecular diversity of this fecal indicator group in different animals and environmental waters. Genus- and species-specific 16S rRNA gene PCR assays were used to study the presence of bifidobacteria among 269 fecal DNA extracts from 32 different animals. Twelve samples from three wastewater treatment plants and 34 water samples from two fecally impacted watersheds were also tested. The species-specific assays …

Melanoma And Seborrheic Keratosis Differentiation Using Texture Features, Srinivas V. Deshabhoina, Scott E. Umbaugh, William V. Stoecker, Randy Hays Moss, Subhashini K. Srinivasan

Chemistry Faculty Research & Creative Works

Purpose: To explore texture features in two-dimensional images to differentiate seborrheic keratosis from melanoma.

Methods: A systematic approach to consistent classification of skin tumors is described. Texture features, based on the second-order histogram, were used to identify the features or a combination of features that could consistently differentiate a malignant skin tumor (melanoma) from a benign one (seborrheic keratosis). Two hundred and seventy-one skin tumor images were separated into training and test sets for accuracy and consistency. Automatic induction was applied to generate classification rules. Data analysis and modeling tools were used to gain further insight into the feature space. …