Research Interests:
My laboratory develops statistical, image analysis and visualization methods for unraveling basic mechanisms of biology. We are particularly interested in multicellular systems and assembling quantitative system-wide information derived at cellular and subcellular resolution.    Read more .....
Research Interests
Curriculum Vitae

Knowles Lab

BioImaging Research

Life Sciences, LBNL


David William Knowles 

Dept. of Cell Biology and Imaging, 

Life Sciences Division,

Lawrence Berkeley National Laboratory
84R0171, 1 Cyclotron Road
Berkeley, CA, USA 94720
510-486-6082

BioImaging Group

In the News:

24Jun05
:
Era of Hope
8Mar06: New Imaging Method ID's Cancer Cells Early
  more..
21April06: Early Cancer Detection

2007: Gene Expression stories by BioScienceMag.org, Nature Review Genetics, American Scientist and LBNL
2007: GSA,
Drosophila Image Award
May 2008: Developmental Cell
June 2008: Nature Methods



        

Image-based Screening of Mammary Tumors

The BioImaging Group is developing methods for turning high resolution fluorescence images
of human mammary epithelial tissue into tissue-maps which report the probable nonneoplastic,
premalignant and malignant phenotypes at cellular resolution.


Morphology and Gene Expression in Embryonic Drosophila

The BioImaging Group has created the first computational, quantitative, cellular resolution atlas 

of morphology and gene expression for one of the most studied model animals:

Drosophila melanogaster.


Automated Scientific Analysis Processing (ASAP):


Publications:

Anil Aswani, Soile V.E. Keranen, James Brown, Charless C. Fowlkes, David W. Knowles, Mark D. Biggin, Peter Bickel and Claire J. Tomlin 2010. Nonparametric identification of regulatory interactions from spatial and temporal gene expression data
BMC Bioinformatics 2010, 11:413      doi:10.1186/1471-2105-11-413

Oliver Rubel, Gunther H. Weber, Member, Min-Yu Huang, E. Wes Bethel, Mark D. Biggin, Charless C. Fowlkes, Cris L. Luengo Hendriks, Soile V. E. Keranen, Michael B. Eisen, David W. Knowles, Jitendra Malik, Hans Hagen, and Bernd Hamann 2010
Integrating Data Clustering and Visualization for the Analysis of 3D Gene Expression Data
IEEE Transactions on Computational Biology and Bioinformatics. 2010, Vol 7, No. 1, p64-79 [Reprint]  


Stewart MacArthur, Xiao-Yong Li, Jingyi Li, James B. Brown, Hou Cheng Chu, Lucy Zeng, Brandi P. Grondona, Aaron Hechmer, Lisa Simirenko, Soile V.E. Keränen, David W. Knowles, Mark Stapleton, Peter Bickel, Mark D. Biggin and Michael B. Eisen 2009. Developmental roles of 21 Drosophila transcription factors are determined by quantitative differences in binding to an overlapping set of thousands of genomic regions    
Genome Biology 2009, 10:R80  

Gunther H. Weber, Oliver Rubel, Min-Yu Huang, Angela H. DePace, Charless C. Fowlkes, Soile V. E. Keranen, Cris L. Luengo Hendriks, Hans Hagen, David W. Knowles, Jitendra Malik, Mark D. Biggin,and Bernd Hamann 2009
Visual Exploration of Three-dimensional Gene Expression Using Physical Views and Linked Abstract Views
Computational Biology and Bioinformatics, IEEE/ACM, Transactions on. 6:296-309, 2009   [Reprint]


Charless C. Fowlkes, Cris L. Luengo Hendriks, Soile V.E. Keranen, Gunther H. Weber,1,5 Oliver Rubel,Min-Yu Huang, Sohail Chatoor, Angela H. DePace, Lisa Simirenko, Clara Henriquez, Amy Beaton, Richard Weiszmann, Susan Celniker, Bernd Hamann, David W. Knowles, Mark D. Biggin, Michael B. Eisen, and Jitendra Malik 2008
A quantitative spatiotemporal atlas of gene expression in the Drosophila blastoderm
Cell 133:364-374 April 18, 2008   [Reprint
A registration technique is described that takes image-based data from hundreds of Drosophila blastoderm embryos and builds a model spatiotemporal embryo atlas from which we recover known gene-regulatory interactions and predict hundreds of new ones.

Xiaoyong Li, Stewart MacArthur, Richard Bourgon, David Nix, Daniel A. Pollard, Venky N. Iyer, Aaron Hechmer, Lisa Simirenko, Mark Stapleton, Cris L. Luengo Hendriks, Hou Cheng Chu, Nobuo Ogawa, William Inwood, Victor Sementchenko, Amy Beaton, Richard Weiszmann, Susan E. Celniker, David W. Knowles, Tom Gingeras, Terence P. Speed, Michael B. Eisen and Mark D. Biggin 2008
Transcription Factors Bind Thousands of Active and Inactive Regions in the Drosophila Blastoderm
PLoS Biol. 6, e27 (2008)

Cris L. Luengo Hendriks, Soile V. E. Keränen, Mark D. Biggin and David W. Knowles 2007
Automatic channel unmixing for high-throughput quantitative analysis of fluorescence images
Optics Express 15(19):12306-12317

Fuhui Long, Hanchuan Peng, Damir Sudar, Sophie A. Lelièvre,  and David W. Knowles 2007
Phenotype Clustering of Breast Epithelial Cells in Confocal Images based on Nuclear Protein Distribution Analysis
BMC Cell Biology 2007, 8(Suppl 1):S3   

Gurushankar Chandramouly, Patricia C. Abad, David W. Knowles, and Sophie A. Lelièvre 2007
Nuclear organization and tissue polarity cooperate to control cell fate in mammary acini
J. Cell Sci. 120, 1596-1606 (2007)   [Reprint

Luengo Hendriks C.L. & Knowles D.W. 2007
Comments on the paper ‘A novel 3D wavelet-based filter for visualizing features in noisy biological data’, by Moss et al.
J. Microscopy, 225 (1): 104–107  [Reprint]            -->     [See Reply by Moss et al]

Patricia C. Abad, Jason Lewis, I. Saira Mian, David W. Knowles, Jennifer Sturgis, Sunil Badve, Jun Xie, Sophie A. Lelièvre 2007
NuMA Influences Higher Order Chromatin Organization in Human Mammary Epithelium
Mol. Biol. Cell, 18:348-361
  [Reprint]

Soile VE Keranen , Charless C Fowlkes , Cris L Luengo Hendriks , Damir Sudar , David W Knowles , Jitendra Malik  and Mark D Biggin 2006
3D morphology and gene expression in the Drosophila blastoderm at cellular resolution II: dynamics
Genome Biology 2006, 7:R124   
A new spatio-temporal coordinate framework for studying three-dimensional patterns of gene expression in the Drosophila blastoderm is presented that takes account of previously undetected morphological movements.

Cris L Luengo Hendriks , Soile VE Keranen , Charless C Fowlkes , Lisa Simirenko , Gunther H Weber , Angela H DePace , Clara Henriquez , David W Kaszuba , Bernd Hamann , Michael B Eisen , Jitendra Malik , Damir Sudar , Mark D Biggin  and David W Knowles 2006

3D morphology and gene expression in the Drosophila blastoderm at cellular resolution I: data acquisition pipeline
Genome Biology 2006, 7:R123  
A suite of methods that provide the first quantitative three-dimensional description of gene expression and morphology with cellular resolution in whole Drosophila embryos is described.

David W. Knowles, Damir Sudar, Carol Bator-Kelly, Mina J. Bissell, and Sophie A. Lelièvre 2006

Automated local bright feature image analysis of nuclear protein distribution identifies changes in tissue phenotype

Proc. Natl. Acad. Sci. USA 103, 4445-4450   
[Reprint]
Automated image analysis was used to delineate individual nuclei  and compute the radial distribution of fluorescently-labeled  protein. Nuclear distributions of NuMA were shown to change during epithelial differentiation and nonneoplastic / malignant transformation.

Koei Chin, Carlos Ortiz de Solorzano, David Knowles, Arthur Jones, William Chou, Enrique Garcia Rodriguez, Wen-Lin Kuo, Britt-Marie Ljung, Karen Chew, Kenneth Myambo, Monica Miranda, Sheryl Krig, James Garbe, Martha Stampfer, Paul Yaswen, Joe W. Gray, and Stephen J. Lockett 2004

In situ analysis of genome instability in breast cancer

Nat Genet. 2004 36:984-8  [Reprint]

 

Heidi M. Van Dort, David W. Knowles, Joel A. Chasis, Gloria Lee, Narla Mohandas, and Philip S. Low 2001
Analysis of integral membrane protein contributions to the deformability and stability of the human erythrocyte membrane
J Biol Chem 2001 276:46968-74  [Reprint]

 

Michael Cho*, David W. Knowles*, Barbara L. Smith, John J. Moulds, Peter Agre, Narla Mohandas, David E. Golan 1999
Membrane dynamics of the water transport protein AQP1 in intact human red cells
Biophys. J. 76:1136-1144 (1999)   [Reprint]
         *Drs. Cho and Knowles contributed equally to this work

Fluorescence images and corresponding density profiles 
of AQP1, the water channel protein, on Red Blood Cell 
Membranes under deformation shows the migration of 
AQP1 molecules towards the membrane portion that 
had been maximally dilated, the aspiration cap.

 

Knowles D.W., Tilley L, Mohandas N, Chasis JA 1997
Erythrocyte membrane vesiculation: model for the molecular mechanism of protein sorting
Proc Natl Acad Sci USA 94:12969-12974 (1987)   
[Reprint]

Fluorescence images and corresponding density profiles 
of cytoskeletal actin demonstrates that the cytoskeleton 
completely retracted to the cell body on the release of a 
vesicle. This set the stage for studying the role of the 
cytoskeleton in sorting membrane proteins.

 

Knowles D.W., Chasis JA, Evans EA, Mohandas N 1994
Cooperative action between band 3 and glycophorin A in human erythrocytes: immobilization of band 3 induced by antibodies to glycophorin A
Biophys J 1994 May;66(5):1726-1732 (1994)  
[Reprint]          -->   This work written up as [New and Notable] [Reprint]

 

Mohandas N, Winardi R, Knowles D., Leung A, Parra M, George E, Conboy J, Chasis J 1992
Molecular basis for membrane rigidity of hereditary ovalocytosis. A novel  mechanism involving the cytoplasmic domain of band 3
J Clin Invest 1992 Feb;89(2):686-692 (1992)   
[Reprint]


Selected Abstracts    Human Erythrocyte