Cell and Developmental Biology Commons^™

Vegf/Neuropilin Signaling In Cancer Stem Cells, Arthur M. Mercurio

Arthur M. Mercurio

The function of vascular endothelial growth factor (VEGF) in cancer extends beyond angiogenesis and vascular permeability. Specifically, VEGF-mediated signaling occurs in tumor cells and this signaling contributes to key aspects of tumorigenesis including the self-renewal and survival of cancer stem cells (CSCs). In addition to VEGF receptor tyrosine kinases, the neuropilins (NRPs) are critical for mediating the effects of VEGF on CSCs, primarily because of their ability to impact the function of growth factor receptors and integrins. VEGF/NRP signaling can regulate the expression and function of key molecules that have been implicated in CSC function including Rho family guanosine triphosphatases …

Inhibition Of Triggering Receptor Expressed On Myeloid Cells 1 Ameliorates Inflammation And Macrophage And Neutrophil Activation In Alcoholic Liver Disease In Mice, David Tornai, Istvan Furi, Zu T. Shen, Alexander B. Sigalov, Sahin Coban, Gyongyi Szabo

Gyongyi Szabo

Alcoholic liver disease (ALD) is characterized by macrophage and neutrophil leukocyte recruitment and activation in the liver. Damage- and pathogen-associated molecular patterns contribute to a self-perpetuating proinflammatory state in ALD. Triggering receptor expressed on myeloid cells 1 (TREM-1) is a surface receptor that amplifies inflammation induced by toll-like receptors (TLRs) and is expressed on neutrophils and monocytes/macrophages. We hypothesized that TREM-1 signaling contributes to proinflammatory pathway activation in ALD. Using an in vivo ALD model in mice, we tested the effects of ligand-independent TREM-1 inhibitory peptides that were formulated into human high-density lipoprotein (HDL)-mimicking complexes GF9-HDL and GA/E31-HDL. As revealed …

Constitutive Interferon Signaling Maintains Critical Threshold Of Mlkl Expression To License Necroptosis, Joseph Sarhan, Beiyun C. Liu, Hayley I. Muendlein, Chi G. Weindel, Irina Smirnova, Amy Y. Tang, Vladimir Ilyukha, Maxim Sorokin, Anton Buzdin, Katherine A. Fitzgerald, Alexander Poltorak

Katherine A. Fitzgerald

Interferons (IFNs) are critical determinants in immune-competence and autoimmunity, and are endogenously regulated by a low-level constitutive feedback loop. However, little is known about the functions and origins of constitutive IFN. Recently, lipopolysaccharide (LPS)-induced IFN was implicated as a driver of necroptosis, a necrotic form of cell death downstream of receptor-interacting protein (RIP) kinase activation and executed by mixed lineage kinase like-domain (MLKL) protein. We found that the pre-established IFN status of the cell, instead of LPS-induced IFN, is critical for the early initiation of necroptosis in macrophages. This pre-established IFN signature stems from cytosolic DNA sensing via cGAS/STING, and …

Prostate Tumorigenesis Induced By Pten Deletion Involves Estrogen Receptor Beta Repression, Paul Mak, Jianrong Li, Sanjoy Samanta, Cheng Chang, D. Joseph Jerry, Roger J. Davis, Irwin Leav, Arthur M. Mercurio

Arthur M. Mercurio

The role of ERbeta in prostate cancer is unclear, although loss of ERbeta is associated with aggressive disease. Given that mice deficient in ERbeta do not develop prostate cancer, we hypothesized that ERbeta loss occurs as a consequence of tumorigenesis caused by other oncogenic mechanisms and that its loss is necessary for tumorigenesis. In support of this hypothesis, we found that ERbeta is targeted for repression in prostate cancer caused by PTEN deletion and that loss of ERbeta is important for tumor formation. ERbeta transcription is repressed by BMI-1, which is induced by PTEN deletion and important for prostate tumorigenesis. …

A Laminin 511 Matrix Is Regulated By Taz And Functions As The Ligand For The Alpha6bbeta1 Integrin To Sustain Breast Cancer Stem Cells, Cheng Chang, Hira Lal Goel, Huijie Gao, Bryan M. Pursell, Leonard D. Shultz, Dale L. Greiner, Sulev Ingerpuu, Manuel Patarroyo, Shiliang Cao, Elgene Lim, Junhao Mao, Karen Kulju. Mckee, Peter D. Yurchenco, Arthur M. Mercurio

Arthur M. Mercurio

Understanding how the extracellular matrix impacts the function of cancer stem cells (CSCs) is a significant but poorly understood problem. We report that breast CSCs produce a laminin (LM) 511 matrix that promotes self-renewal and tumor initiation by engaging the alpha6Bbeta1 integrin and activating the Hippo transducer TAZ. Although TAZ is important for the function of breast CSCs, the mechanism is unknown. We observed that TAZ regulates the transcription of the alpha5 subunit of LM511 and the formation of a LM511 matrix. These data establish a positive feedback loop involving TAZ and LM511 that contributes to stemness in breast cancer.

Human Umbilical Cord Blood-Derived Mononuclear Cells Improve Murine Ventricular Function Upon Intramyocardial Delivery In Right Ventricular Chronic Pressure Overload, Saji Oommen, Satsuki Yamada, Susana Cantero Peral, Katherine A. Campbell, Elizabeth S. Bruinsma, Andre Terzic, Timothy J. Nelson

Katherine Campbell, PhD

No abstract provided.

Regulated Splicing Of The Alpha6 Integrin Cytoplasmic Domain Determines The Fate Of Breast Cancer Stem Cells, Hira Lal Goel, Tatiana Gritsko, Bryan Pursell, Cheng Chang, Leonard D. Shultz, Dale L. Greiner, Jens Henrik Norum, Rune Toftgard, Leslie M. Shaw, Arthur M. Mercurio

Arthur M. Mercurio

Although the alpha6beta1 integrin has been implicated in the function of breast and other cancer stem cells (CSCs), little is known about its regulation and relationship to mechanisms involved in the genesis of CSCs. We report that a CD44(high)/CD24(low) population, enriched for CSCs, is comprised of distinct epithelial and mesenchymal populations that differ in expression of the two alpha6 cytoplasmic domain splice variants: alpha6A and alpha6B. alpha6Bbeta1 expression defines the mesenchymal population and is necessary for CSC function, a function that cannot be executed by alpha6A integrins. The generation of alpha6Bbeta1 is tightly controlled and occurs as a consequence of …

Flash4 Dark Reference Images, George Mcnamara

George McNamara

Hamamatsu FLASH4.0 dark reference images, acquired with 10 second exposure times, no light to camera. Camera offset (set by Hamamatsu( is ~100 (the average intensity of the first image is always ~1 intensity level higher - an odd feature, but trivial in practice for a 16-bit camera).

George McNamara, Ph.D.

Single Cells Analyst at L.J.N. Cooper Lab

University of Texas M.D. Anderson Cancer Center

Video Codec Performance (Excel Spreadsheet), George Mcnamara

George McNamara

Video codec performance (Excel spreadsheet). Movie was made in 2005-2006 when I worked at City of Hope National Medical Center. VTLF refers to Video Timelapse Light Facility. Videos were outputted from MetaMorph as AVI files. Personally, I always recommend uncompressed video files fro scientific uses. I also encourage posting the original scientific data format (ex. .lsm, .zvi, .lif, .stk).

Pubspectra Tattletales, George Mcnamara

George McNamara

Tattletales for Multiplex Fluorescent Reporters in Single Cells for Metabolomics

George McNamara

As of April 2013: L.J.N. Cooper & D.A. Lee Cellular Immunotherapy Lab, University of Texas M.D. Anderson Cancer Center, Houston, TX

Email: gtmcnamara@mdanderson.org, geomcnamara@earthlink.net

Tattletales is my concept for spatial multiplexing many fluorescent protein (FP) biosensors in the same live cell. For example, there are excellent FP biosensors to Ca++ ions, pH, glucose, ribose, glutamine, glutamate, ATP, redox, ROS, pyruvate, cAMP, cGMP, IP3, PI(3,4,5)P3, cell cycle indicators (Fucci2), PKA, PKC, photsphatases, caspase(s) [1, 2]. However, these are typically used one biosensor per experiment, due in part to flooding …

Novel Developmental Biology-Based Protocol Of Embryonic Stem Cell Differentiation To Morphologically Sound And Functional Yet Immature Hepatocytes, Terence Bukong, Tracie Lo, Gyongyi Szabo, Angela Dolganiuc

Gyongyi Szabo

BACKGROUND/AIMS: Liver diseases are common in the United States and often require liver transplantation; however, donated organs are limited and thus alternative sources for liver cells are in high demand. Embryonic stem cells (ESC) can provide a continuous and readily available source of liver cells. ESC differentiation to liver cells is yet to be fully understood and comprehensive differentiation protocols are yet to be defined. Here, we aimed to achieve human (h)ESC differentiation into mature hepatocytes using defined recombinant differentiation factors and metabolites. METHODS: Embryonic stem cell H1 line was sub-cultured on feeder layer. We induced hESCs into endodermal differentiation …

Halloween 2012 Jack O'Lanterns Trick Or Treat, George Mcnamara

George McNamara

Halloween 2012 makes trick or treating more visual and interactive than in past years.

the download is a ZIP file containing three files.

Print out the (unnumbered) image on as large and nice printer paper as possible - I used glossy 44" wide here in Miami (University of Miami, MillerSchool of Medicine, Calder Library, Biomedical Communications dept - I also made another print on "fabric", also 44" wide to take with me to an HHMI Janelia Farm conference on 'turning images into knowledge' that ends on Oct 31 - might stay up for a second conference, "GFP..." that start Nov …

Mcnamara 20120831fri-20120904tue Cosmic Ray Particles By Ccd Imaging, George Mcnamara

George McNamara

McNamara 20120831Fri-20120904Tue Cosmic Ray Particles by CCD imaging.zip contains image files in support of a Microscopy Today article - please see

http://www.microscopy-today.com/

Cosmic Ray Particles Images With Orca-Ii Erg, George Mcnamara

George McNamara

Cosmic ray particles image series acquired using a Hamamatsu ORCA-II ERG scientific grade CCD camera, cooled to -60 C. Each image is a consecutive 600 second (10 minute) exposure time with no light to the camera.

While processing the data, I discoverd that the background changed around planes 25 and 227 (see Excel file and jpeg screenshots), so I also processed only planes 025-227 (203 planes total, 2030 minutes, 33.83 hours). the CCD industry "rule of thumb" for a "typical" CCD sensor (i.e. 1/3" CCD) is that one cosmic ray particle strikes a sensor approximately every 30 seconds (assuming not …

Flatbed Scanner Report - Optical Density Dynamic Range, George Mcnamara

George McNamara

George McNamara (now at University of Miami) report for Hua Yu and Richard Jove, City of Hope National Medical Center, on optical density dynamic range of several flatbed scanners.

Introduction To Nanoscopy Nano-Talk, George Mcnamara

George McNamara

T7-1 is the designation for the LMRG Nanoscopy session at ABRF in Orlando, FL, on March 20, 2012. The PDF file here is a draft of my presentation.

May not be very helpful since (1) would probably help to know what is in my head and each slide will [hopefully] prompt me to say, and (2) 10 minute talk so I am going to push the "next slide" button after saying very little.

__________________

Publisher statement:

The T7-1 Introduction to Nanoscopy Nano Talk is copyrighted (c) George McNamara, 2012. Except for (1) screenshots from research articles (which are copyrighted by …

Pubspectra - Open Data Access Fluorescence Spectra, George Mcnamara

George McNamara

The Internet is enabling greater access to spectral imaging publications, spectral graphs, and data than that was available a generation ago. The spectral imaging systems discussed in this issue of Cytometry work because reagent and hardware spectra are reproducible, reusable, and provide input to spectral unmixing and spectral components recognition algorithms. These spectra need to be readily available in order to determine what to purchase, how to use it, and what the output means. We refer to several commercially sponsored and academic spectral web sites and discuss our spectral graphing and data sites. Sites include fluorescent dye graph servers from …

Mcnamara 2011 Feature Extraction (Image Analysis), George Mcnamara

George McNamara

Feature Extraction presentation and movies in a ZIP file from a presentation I gave at ISAC 2011 in Baltomore, Md.

Feature extraction is one phrase for image analysis.

Rogers Pmn Movie - Background Information, George Mcnamara

George McNamara

Please see

http://mdc.custhelp.com/app/answers/detail/a_id/18689/~/metamatters-newsletters

for my series of MetaMorph MetaMatters articles in volume 2, numbers 3 through 6, on the Rogers PMN Panorama data set.

http://mdc.custhelp.com/app/answers/detail/a_id/18689/~/metamatters-newsletters

Brief summary (for more, see the Word doc)

Mcnamara 2011 Mpmicro - Multi-Probe Microscopy (10/31/2011), George Mcnamara

George McNamara

Multi-Probe Microscopy is an ~1500 page Word document summarizing what I know and/or found interesting in light microscopy, fluorescence microscopy and digital image analysis, from 1995-2005. Very little has been updated since 2005.

Endothelial Cell Cortactin Phosphorylation By Src Contributes To Polymorphonuclear Leukocyte Transmigration In Vitro, L. Yang, Jennifer R. Kowalski, X. Zhan, S. M. Thomas, F. W. Luscinskas

Jennifer Kowalski

The underlying mechanisms that regulate leukocyte transendothelial migration through the vascular endothelium remain unclear. Cortactin is a substrate of Src tyrosine kinases and a regulator of cytoskeletal dynamics. Previous studies demonstrated a role for Src phosphorylation of cortactin in clustering of E-selectin and intercellular cell adhesion molecule-1 around adherent leukocytes. In the current study, we used an in vitro flow model to investigate the role of Src-induced cortactin phosphorylation in endothelium during polymorphonuclear leukocyte (PMN) transmigration through human umbilical vein endothelium (HUVEC) monolayers preactivated with tumor necrosis factor-{alpha}. Inhibition of Src in HUVEC using Src kinase inhibitors PP2 and SU6656 …