Archive for the ‘Research Papers’ Category

Steve Henikoff’s Lab

Monday, September 8th, 2014

Zentner, GE and Henikoff, S (2014) High-resolution Digital Profiling of the Epigenome, Nature Reviews Genetics, in press.2014

Abstract
The widespread adoption of short-read DNA sequencing as a digital epigenomic read-out platform has motivated the development of genome-wide tools that achieve base-pair resolution. New methods for footprinting and affinity purification of nucleosomes, RNA polymerases, chromatin remodelers, and transcription factors have increased the resolution of epigenomic profiling by two orders of magnitude, leading to new insights into how the chromatin landscape impacts gene regulation. These digital epigenomic tools have also been applied to directly profile both turnover kinetics and transcription in situ. Here, we describe how these new genome-wide tools allow interrogation of diverse aspects of the epigenome.

Doxorubicin, DNA Torsion, and Chromatin Dynamics. Biochim Biophys Acta. January 2014.
Doxorubicin, DNA torsion, and chromatin dynamics.

ISWI and CHD Chromatin Remodelers Bind Promoters but Act in Gene Bodies. PLoS Genet. 2013.
ISWI and CHD chromatin remodelers bind promoters but act in gene bodies.

Regulation of Nucleosome Dynamics by Histone Modifications. Nat. Struct. Mol. Biol. March 2013
Regulation of nucleosome dynamics by histone modifications.

Heat Shock Reduces Stalled RNA Polymerase II and Nucleosome Turnover Genome-wide. Genes Dev. November 2011.
Heat shock reduces stalled RNA polymerase II and nucleosome turnover genome-wide.

Aberrant DNA Methylation Occurs in Colon Neoplasms Arising in the Azoxymethane Colon Cancer Model. Mol Carcinog. January 2010.
Aberrant DNA methylation occurs in colon neoplasms arising in the azoxymethane colon cancer model.

Tissue-specific variation in DNA Methylation Levels Along Human Chromosome 1. Epigenetics Chromatin. June 2009.
Tissue-specific variation in DNA methylation levels along human chromosome 1.

William Grady’s Lab

Monday, September 8th, 2014

CpG Island Methylator Phenotype Is Associated With Response to Adjuvant Irinotecan-Based Therapy for Stage III Colon Cancer. Gastroenterology. September 2014.
CpG Island Methylator Phenotype Is Associated With Response to Adjuvant Irinotecan-Based Therapy for Stage III Colon Cancer.

Differences in DNA Methylation Signatures Reveal Multiple Pathways of Progression from Adenoma to Colorectal Cancer. Gastroenterology, August 2014
Differences in DNA Methylation Signatures Reveal Multiple Pathways of Progression from Adenoma to Colorectal Cancer.

Selective Detection of Target Proteins by Peptide-enabled Graphene Biosensor. Small, April 2014
Selective Detection of Target Proteins by Peptide-enabled Graphene Biosensor.

Inactivation of TGF-β Signaling and Loss of PTEN Cooperate to Induce Colon Cancer in Vivo.. Oncogene March 2014.
Inactivation of TGF-β signaling and loss of PTEN cooperate to induce colon cancer in vivo.

Epigenetic Biomarkers in Esophageal Cancer. Cancer Lett. January 2014
Epigenetic biomarkers in esophageal cancer.

Molecular Alterations and Biomarkers in Colorectal Cancer. Toxicol Pathol. January 2014
Molecular alterations and biomarkers in colorectal cancer.

NTRK3 is a potential tumor suppressor gene commonly inactivated by epigenetic mechanisms in colorectal cancer. PLoS Genet. 2013
NTRK3 is a potential tumor suppressor gene commonly inactivated by epigenetic mechanisms in colorectal cancer.

RET is a Potential Tumor Suppressor Gene in Colorectal Cancer. Oncogene. April 2013.
RET is a potential tumor suppressor gene in colorectal cancer.

Aberrantly Methylated PKP1 in the Progression of Barrett’s Esophagus to Esophageal Adenocarcinoma. Genes Chromosomes Cancer. April 2012
Aberrantly methylated PKP1 in the progression of Barrett’s esophagus to esophageal adenocarcinoma.

Epigenetics and Colorectal Cancer. Nat Rev Gastroenterol Hepatol. October 2011.
Epigenetics and colorectal cancer.

Aberrant DNA Methylation Occurs in Colon Neoplasms Arising in the Azoxymethane Colon Cancer Model. Mol Carcinog. January 2010.
Aberrant DNA Methylation Occurs in Colon Neoplasms Arising in the Azoxymethane Colon Cancer Model.

Project 2 Team Members

Tuesday, March 5th, 2013

Project Lead: Stuart Lindsay

  • Stuart Lindsay is Edward and Nadine Carson Professor of Physics and Chemistry and Director of the Center for Single Molecule Biophysics in the Biodesign Institute. His research focuses on biology at the nanoscale. He was a co-founder of Molecular Imaging Corporation. His textbook “Introduction to Nanoscience” has just been published by Oxford University Press. More Info

  • Team Members

  • Parminder kaur Is a final year PhD grad student. She has been working on the DNA methylation and chromatin project. She has a physics background and would further like to put her combined knowledge of physics, biology and chemistry in the pharmaceutical world. She has worked as an intern in Bristol Myers Squibb.

  • Trent Bowen is a senior studying physics and applying to medical
    school. Trent pursued his interest in applying a physical science background in furthering the understanding of biological molecules by studying centromere dynamics at the National Cancer Institute this
    past summer.

  • Ian Vicino is an undergraduate student majoring in Biochemistry. He hopes to learn as much as he can about this world through the research he does, whether it be within his undergraduate degree or when he eventually gets his PhD.

  • Peter Costa is an undergrad studying physics and he has been helping tremendously in the lab with the DNA methylation and chromatin project.

Stuart Lindsay’s Publications

Monday, March 4th, 2013

Publications 2013

Application of catalyst-free click reactions in attaching affinity molecules to tips of atomic force microscopy for detection of protein biomarkers.Langmuir. November 2013
Application of catalyst-free click reactions in attaching affinity molecules to tips of atomic force microscopy for detection of protein biomarkers.

Long Lifetime of Hydrogen-bonded DNA Basepairs by Force Spectroscopy. Biophys J. May 2012
Long lifetime of hydrogen-bonded DNA basepairs by force spectroscopy.

Publications 2012

Optical and electrical detection of single-molecule translocation through carbon nanotubes

Optical and Electrical Detection of Single-Molecule Transolcation

Hydrophobicity of methylated DNA as a possible mechanism for gene silencing

Hydrophobicity of Methylated DNA

DNA translocating through a carbon nanotube can increase ionic current

DNA Translocating through a carbon nonotube

Identifying Single Bases in a DNA Oligomer with Electron Tunneling. Nat Nanotechnol. December 2010.
Identifying single bases in a DNA oligomer with electron tunneling.

Mass transport through vertically aligned large diameter MWCNTs embedded in parylene

Mass Transport through vertically aligned large diameter MWCNTS

Palladium electrodes for molecular tunnel junctions

Palladium electrodes for Molecular Tunnel Junctions

1,8-Naphthyridine-2,7-diamine: A potential universal reader of Watson-Crick base pairs for DNA sequencing by electron tunneling

Base pairs for DNA sequencin by electron tunneling

Solution Synthesis of Ultrathin Single-Crystalline SnS Nanoribbons for Photodetectors via Phase Transition and Surface Processing

Solution Synthesis

Chemical Recognition and Binding Kinetics in a functionalized tunnel junction

Abstract

4(5)-(2-mercaptoethyl)-1H-imidazole-2-carboxamide is a molecule that has multiple hydrogen bonding sites and a short flexible linker. When tethered to a pair of electrodes, it traps target molecules in a tunnel junction. Surprisingly large recognition-tunneling signals are generated for all naturally occurring DNA bases A, C, G, T and 5-methyl-cytosine. Tunnel current spikes are stochastic and broadly distributed, but characteristic enough so that individual bases can be identified as a tunneling probe is scanned over DNA oligomers. Each base yields a recognizable burst of signal, the duration of which is controlled entirely by the probe speed, down to speeds of 1nms 1, implying a maximum off-rate of 3s 1 for the recognition complex. The same measurements yield a lower bound on the on-rate of 1M 1s 1. Despite the stochastic nature of the signals, an optimized multiparameter fit allows base calling from a single signal peak with an accuracy that can exceed 80% when a single type of nucleotide is present in the junction, meaning that recognition-tunneling is capable of true single-molecule analysis. The accuracy increases to 95% when multiple spikes in a signal cluster are analyzed. © 2012 IOP Publishing Ltd.

Chemical Recognition and Binding kinetics in a functionalized tunnel junction

Long Lifetime of Hydrogen-Bonded DNA Basepairs by Force Spectroscopy

Abstract

Electron-tunneling data suggest that a noncovalently-bonded complex of three molecules, two recognition molecules that present hydrogen-bond donor and acceptor sites via a carboxamide group, and a DNA base, remains bound for seconds. This is surprising, given that imino-proton exchange rates show that basepairs in a DNA double helix open on millisecond timescales. The long lifetime of the three-molecule complex was confirmed using force spectroscopy, but measurements on DNA basepairs are required to establish a comparison with the proton-exchange data. Here, we report on a dynamic force spectroscopy study of complexes between the bases adenine and thymine (A-T, two-hydrogen bonds) and 2-aminoadenine and thymine (2AA-T, three-hydrogen bonds). Bases were tethered to an AFM probe and mica substrate via long, covalently linked polymer tethers. Data for bond-survival probability versus force and the rupture-force distributions were well fitted by the Bell model. The resulting lifetime of the complexes at zero pulling force was ∼2 s for two-hydrogen bonds (A-T) and ∼4 s for three-hydrogen bonds (2AA-T). Thus, DNA basepairs in an AFM pulling experiment remain bonded for long times, even without the stabilizing influence of base-stacking in a double helix. This result suggests that the pathways for opening, and perhaps the open states themselves, are very different in the AFM and proton-exchange measurements. © 2012 by the Biophysical Society.

Long Lifetime of Hydrogen-Bonded DNA Basepairs by Force Spectroscopy

Synthesis, Phsiochemical Properties and Hydrogen Bonding of 4(5)-Substituted 1-H-Imidazole-2-Carboxamide, a Potential Universal Reader for DNA Sequencing by Recognition Tunneling

Abstract

We have developed a chemical reagent that recognizes all naturally occurring DNA bases, a so called universal reader, for DNA sequencing by recognition tunneling in nanopores.1 The primary requirements for this type of molecules are the ability to form non-covalent complexes with individual DNA bases and to generate recognizable electronic signatures under an electrical bias. 1-H-imidazole-2-carboxamide was designed as such a recognition moiety to interact with the DNA bases through hydrogen bonding. In the present study, we first furnished a synthetic route to 1-H-imidazole-2-carboxamide containing a short ω-functionalized alkyl chain at its 4(5) position for its attachment to metal and carbon electrodes. The acid dissociation constants of the imidazole-2-carboxamide were then determined by UV spectroscopy. The data show that the 1-H-imidazole-2-carboxamide exists in a neutral form between pH 6-10. Density functional theory (DFT) and NMR studies indicate that the imidazole ring exists in prototropic tautomers. We propose an intramolecular mechanism for tautomerization of 1-H-imidazole-2-carboxamide. In addition, the imidazole-2-carboxamide can self-associate to form hydrogen bonded dimers. NMR titration found that naturally occurring nucleosides interacted with 1-H-imidazole-2-carboxamide through hydrogen bonding in a tendency of dG>dC≤laquo;dT>dA. These studies are indispensable to assisting us in understanding the molecular recognition that takes place in the nanopore where routinely used analytical tools such as NMR and FTIR cannot be conveniently applied. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis,Physiochemical Properties and Hyrdogen Bonding

Biochemistry and Semiconductor Electronics- the next big hit for silicon?

Abstract

Two recent developments portend a new era for silicon electronics in biomedical applications. Firstly, highly specific chemical recognition and massively parallel sample preparation techniques are being combined with VLSI to make new kinds of analytical chips. Secondly, critical dimensions are beginning to approach the size of biomolecules, opening new pathways for physical interactions between molecules and semiconductor structures. Future generations of hybrid chemicalCMOS devices could revolutionize diagnosis and make personalized medicine cheap enough to become widespread. © 2012 IOP Publishing Ltd.

Biochemistry and Semiconductor Electronics – the next big hit for Silicon?

Insulated Gold Scanning tunneling microscopy probes for recognition tunneling in an aqueous environment

Abstract

Chemically functionalized probes are required for tunneling measurements made via chemical contacts (Recognition Tunneling). Here, we describe the etching of gold STM probes suitable for chemical functionalization with moieties bearing thiol groups. Insulated with high density polyethylene, these probes may be used in aqueous electrolytes with sub pA leakage currents. The area of the exposed probe surface was characterized via the saturation current in an electroactive solution (0.1 M K 3Fe(CN) 6). Twenty five percent of the probes had an exposed region of 10 nm radius or less. © 2012 American Institute of Physics.Insulated Gold Scanning tunnelling microscopy probes for recognition tunneling in an aqueous environment

Paul Davies’s Research Papers

Friday, January 13th, 2012

Targeting cancer’s weaknesses (not its strengths): Therapeutic strategies suggested by the atavistic model, BioEsays, September 2014

Targeting cancer’s weaknesses (not its strengths): Therapeutic strategies suggested by the atavistic model

‘Mitochondria and the evolutionary roots of cancer’ with Alfonso F Davila and Pedro Zamorano, Physical Biology 026008 10, (2013)

Mitochondria and the evolutionary roots of cancer PDF

Self-Orginization and Entropy Production in a Living Cell with E. Rieper & J.A. Tuszynski, BioSystems 111, 1(2013)

Self Orginization and Entropy Production in a Living Cell PDF

A physical sciences network characterization of non-tumorigenic and metastatic cells. Sci Rep. 2013
A physical sciences network characterization of non-tumorigenic and metastatic cells.

‘Isotropic 3D Nuclear Morphometry of normal, fibrocystic and malignant breast epithelial cells reveals novel structural alterations’ with Vivek Nandakumar, Laimonas Kelbauskas, Kathryn Hernandez, Kelly Lintecum, Patti Senechal, Kimberly Bussey, Roger Johnson and Deirdre Meldrum, PLoS ONE (2012).

Isotropic 3D Nuclear Morphometry of normal, fibrocystic and malignant breast epithelial cells reveals novel structural alterations PDF

‘Cancer as a dynamical phase transition’ with Lloyd Demetrius and Jack A Tuszynski, Theoretical Biology and Medical Modelling 8 1, 30 (2011).

Cancer as a dynamical phase transition PDF

‘Epigenetics and top-down causation’, Interface Focus 2, 42-48 (2011).

Epigenetics and top-down causation PDF

‘Cancer tumors as Metazoa 1.0: tapping genes of ancient ancestors’ with C H Lineweaver, Physical Biology 015001 8, (2011)

AFM Stiffness Nanotomography of Normal, Metaplastic and Dysplastic Human Esophageal Cells. Phys. Biol. February 2011.
AFM stiffness nanotomography of normal, metaplastic and dysplastic human esophageal cells.

Cancer tumors as Metazoa 1 0 tapping genes of ancient ancestors PDF

 

Paul Davies on NPR

Monday, January 9th, 2012

Listen to Paul Davies on NPR discussing how his study of time travel and search for life in the universe informs his cancer research.

Steve Goldstein, left, host of "Here and Now" on KJZZ radio, interviewed ASU Regents' Professor Paul Davies on topics ranging from time travel to cancer research during the Dec. 21 show. Photo by: Carol Hughes

Time travel, SETI and cancer research are focus for ASU astrobiologist
December 21, 2011

“What do cancer research, time travel theories and the possibilities of life on other planets all have in common? For one thing, Paul Davies,” said Steve Goldstein, host of the radio show “Here and Now” on KJZZ (91.5 FM) in metropolitan Phoenix.

Davies, a theoretical physicist, cosmologist and astrobiologist at Arizona State University, where he is a Regents’ Professor, talked about the varied topics during a 15-minute interview Dec. 21.

Time travel was the first topic raised by Goldstein, and Davies replied: “People want to know, can it really be done? And, the answer is, well, maybe.” He explained that using Einstein’s theory, “we know how to travel in the future … just move. You can only go forward in time … this way.”

Davies didn’t want to give too much away on the radio show about time travel, since it is the topic of the annual Sci-fi meets Sci-Fact lecture at ASU. Davies, who is director of the BEYOND Center for Fundamental Concepts in Science, will deliver the lecture at 7 p.m., Jan. 31, in Neeb Hall on ASU’s Tempe campus.

However, he shared with Goldstein, “with something like a wormhole in space, it might be possible to go back in time.”

Other topics covered during the interview were one-way missions to Mars, the importance of continuing to search for extraterrestrial intelligence (SETI) and the importance of imagination to a scientist.

Davies also discussed his current research on cancer, as director of one of the 12 federally funded physical-science oncology centers looking at cancer research through fresh eyes … those of a physicist, rather than a biologist or chemist.

The interview is on the KJZZ website at http://kjzz.org/content/1112/beyond-science-fiction
Article source:
KJZZ “Here and Now”

Article:
http://kjzz.org/content/1112/beyond-science-fiction

Editor’s Note: Links are included for informational purposes only. Due to varying editorial policies, news publications may remove or change a link for archival purposes at any time without notice.

Project 3 Team Members

Monday, November 7th, 2011

Project Lead: Deirdre R. Meldrum

  • Deirdre R. Meldrum is ASU Senior Scientist, Director of the Biosignature Initiative and Director of the Center for Biosignature Discovery Automation (CBDA) in the Biodesign Institute and Professor of Electrical Engineering in the School of Electrical, Computer, and Energy Engineering. She is also Director and Principal Investigator of the NIH Center of Excellence in Genomic Sciences: Microscale Life Sciences Center (MLSC). Her research interests include probing heterogeneity by live single cell analyses, nuclear organization in cancer, microscale systems for biological applications, robotics and control systems for applications to human health and disease and the oceans. She served on the National Advisory Council for Human Genome Research. More Info

  • Team Members

  • Roger H. Johnson is a Research Scientist and Laboratory Manager in the Center for Biosignatures Discovery Automation in ASU’s Biodesign Institute. Roger is responsible for overall management of daily research activities in the Center, and leads the cell CT research. He has over twenty years’ experience in 3D micro CT, and is an expert in CT scanner design and construction, image reconstruction algorithms, and 3D image processing and analysis. Roger is co-inventor of the cell CT and has seven patents including two on x-ray and two on optical microtomography.

  • Laimonas Kelbauskas is an Assistant Research Professor in the Center for Biosignatures Discovery Automation. He has an PhD in physics and his major research interests are in methods for early cancer detection, the role of intercellular interactions and cell-to-cell variability in pre-neoplastic to neoplastic progression, and changes in gene transcription levels in individual cells in carcinogenesis.

  • Brain Ashcroft received his PhD in physics from ASU for his work on fast DNA sequencing with an AFM/rotaxane system. He worked as a postdoctoral scholar at Leiden university for three years where he explored growth disorders with nanoindention. In addition, he worked on a microfluidics system to do cancer detection and monitoring from blood plasma, and studied the formation of scars in heart tissue. He is currently a postdoctoral scholar at the Center for Biosignatures Discovery Automation. His research is focused on software development for high quality 3D reconstructions in absorption and fluorescent modalities with fixed and live cells.

  • Thai Tran received his Ph.D. in molecular biology from Purdue University and was trained a as a postdoctoral fellow with Dr. Hallgeir Rui at the Kimmel Cancer Center, Thomas Jefferson University. Dr. Tran has background in molecular and cellular biology of cancer. His research focus is to investigate the molecular functions that govern cancer cell development and progression.

  • Jiangxin Wang received a Ph.D. in molecular genetics. Currently he is an assistant research scientist for the Center for Biosignatures Discovery Automation at the Biodesign Institute at Arizona State University. His research interests include single cell transcriptomics, live single cell analyses, and gene signatures as prognostic markers in diseases.

  • Kimberly J. Bussey is an Assistant Professor in the Clinical Translational Research Division of the Translational Genomics Research Institute (TGen), Co-Director of the Adrenocortical Carcinoma Research Program at TGen, and an Adjunct Associate Research Scientist with the Center for Biosignatures Discovery Automation at the Biodesign Institute at Arizona State University. Her research interests lie in exploiting intra-tumor heterogeneity in cancer for treatment. Dr. Bussey has a background in medical and molecular genetics, rare tumors, cancer cytogenetics, and applied bioinformatics.

  • Vivek Nandakumar is a graduate research associate at the Center for Biosignatures Discovery Automation in the biodesign institute. His research is centered around quantitative three-dimensional morphometric biosignatures for early cancer detection using the Cell-CT.

  • Kathryn Hernandez is an undergraduate research assistant at the Center for Biosignatures Discovery Automation. She is a senior majoring in Biological Sciences at Arizona State University and has extensive prior work experience in clinical and reference laboratories. She works on single cell imaging with Cell-CT.

  • Miranda Slaydon is an undergraduate majoring in Geology. She assists with sample preparation and imaging for Cell-CT

  • Stephanie Helland is an undergraduate student worker at CBDA. She is a sophomore at ASU pursuing bachelor of science degrees in Biochemistry and Molecular Biosciences. She assists with sample preparation and imaging for Cell-CT

  • Beatriz Rodolpho is a visiting scholar at the Center for Biosignatures Discovery Automation in the Biodesign Institute. She is currently pursuing her MS degree at Universidade Nova de Lisboa in Portugal. Her research includes Cell-CT imaging and development of metrics to assess quality of 3D reconstruction algorithms.

Project 1 Team Members

Friday, November 4th, 2011

Project Lead: Robert Ros

  • Robert Ros (Principal Investigator) is Associate Professor for Physics at Arizona State University. He joined ASU in 2008 from Bielefeld University as Associate Professor for Physics. He is an experimental biophysicist with expertise in force spectroscopy, and the combination of AFM with confocal microscopy. His research interests in the field of nanobiophysics includes structural biology, physics of molecular recognition, conformational dynamics of single (bio-)molecules and cell mechanics using scanning probe methods, force spectroscopy technologies, fluorescence microscopy, and nanophotonics. More Info

  • Rory Staunton

    Rory Staunton studied physics and philosophy at North Carolina State University before coming to the ASU physics PhD program in ’09. He chose to pursue nanobiophysics because it is at the intersection of many interesting and rapidly developing fields. His current research in the Ros lab is on the mechanical interplay between cells and their microenvironment in the context of cancer progression and metastasis.

  • Bryant Doss is a Physics PhD student with Dr. Robert Ros. His undergraduate education consists of BS Physics and BS Computer Science from West Virginia University. His lab duties include experimental AFM nanoindentation and analysis of single cells as well as fluorescence lifetime experiments of single cells.

  • Michael Gilbert is a physics graduate student working in Dr. Robert Ros’ Lab. He received my BS in Space Physics from Embry-Riddle Aeronautical University. He is currently working on Finite Element simulations of cellular indentation.

Robert Ros’ Publications

Wednesday, March 2nd, 2011

Publications 2013

A Physical Sciences Network Characterization of Non-tumorigenic and Metastatic Cells. Sci Rep. 2013
A physical sciences network characterization of non-tumorigenic and metastatic cells.

Publications 2012

Long Lifetime of Hydrogen-bonded DNA Basepairs by Force Spectroscopy. Biophys J. May 2012
Long lifetime of hydrogen-bonded DNA basepairs by force spectroscopy.

Identifying single bases in a DNA oligomer with electron tunnelling, published in Nature Nanotechnology, ONLINE: 14 NOVEMBER 2010 (http://www.nature.com/nnano/journal/v5/n12/full/nnano.2010.213.html)

Publications 2011

Antibody-Unfolding and Metastable-State Binding in Force Spectroscopy and Recognition Imaging, published in the Biophysical Journal, Volume 100, January 2011. 243–250.

AFM Stiffness Nanotomography of Normal, Metaplastic and Dysplastic Human Esophageal Cells, published in Phys. Biol. 8 (2011) 015007.

Single-Molecule Force Spectroscopy: a Method for Quantitative Analysis of Ligand-Receptor Interactions, published in Nanomedicine (2010) 5(4).

Publications 2010

Identifying Single Bases in a DNA Oligomer with Electron Tunneling. Nat Nanotechnol. December 2010.
Identifying single bases in a DNA oligomer with electron tunneling.

Meldrum’s Publications

Thursday, February 17th, 2011

Publications 2013

A Physical Sciences Network Characterization of Non-tumorigenic and Metastatic Cells. Sci Rep. 2013
A physical sciences network characterization of non-tumorigenic and metastatic cells.

Publications 2012

‘Isotropic 3D Nuclear Morphometry of normal, fibrocystic and malignant breast epithelial cells reveals novel structural alterations’ with Vivek Nandakumar, Laimonas Kelbauskas, Kathryn Hernandez, Kelly Lintecum, Patti Senechal, Kimberly Bussey, Roger Johnson and Deirdre Meldrum, PLoS ONE (2012).
Isotropic 3D Nuclear Morphometry of normal, fibrocystic and malignant breast epithelial cells reveals novel structural alterations PDF

Publications 2011

Vivek Nandakumar, Deirdre Meldrum and Roger Johnson publish “Quantitative Characterization of Preneoplastic Progression Using Single-Cell Computed Tomography and Three-Dimensional Karyometry”
Quantitative characterization of preneoplastic progression using single-cell computed tomography and three-dimensional karyometry.

A hallmark of cancer is that the cell nucleus changes shape and size as the cell transforms from healthy to premalignant to malignant, and cancer researchers suspect that an accurate method of quantifying those changes could serve as an early diagnostic test for cancer. Now, a team of investigators at Arizona State University have given cancer researchers an imaging tool that should enable them to determine if that suspicion is correct.

Deirdre Meldrum and Roger Johnson, both members of the Arizona State University Physical Sciences-Oncology Center (PS-OC), led the team that used high-resolution optical absorption tomographic imaging and mathematical reconstruction to create detailed three-dimensional images of the cell nucleus. They then took those images and used an automated analytical technique they developed to compute 41 quantitative descriptions of a cell’s nuclear structure. The investigators also developed mathematical tools to quantify the spatial distribution of DNA within the cell nucleus from the reconstructed optical images.

Using these techniques, the Arizona PS-OC team compared the three-dimensional architecture of malignant, premalignant, and malignant esophageal epithelial cells and identified quantitative differences in cell shape among the three cell types. Moreover, the researchers were able to clearly distinguish between the three different types of cells using those quantitative measures. The researchers published the results of their study in the journal Cytometry Part A.

This work, which is detailed in a paper titled, “Quantitative Characterization of Preneoplastic Progression Using Single-Cell Computed Tomography and Three-Dimensional Karyometry,” was supported by the National Cancer Institute’s Physical Sciences-Oncology Centers program that aims to foster the development of innovative ideas and new fields of study based on knowledge of the biological and physical laws and principles that define both normal and tumor systems. An abstract of this paper is available at the journal’s Web site.

NandakumarCytometryA2011
source: http://physics.cancer.gov/news/2011/jan/po_news_a.asp