Office:

Salk Institute-CNL,LOGG

10010 North Torrey Pines Road

La Jolla, CA 92037

(858) 453 4100

ext 1067 (dry lab) or 1009 (wet lab)

Gene Yeo

Junior Fellow, Crick-Jacobs Center for Computational and Theoretical Biology, Salk Institute geneyeo@salk.edu

http://www.snl.salk.edu/~geneyeo

 

 

                                                                                                                                                                                                                                                                           

RESEARCH GOALS: RNA Networks in the Neural Fate Specification of Human Embryonic Stem Cells 

 

Background             I am currently a Junior Fellow at the Crick-Jacobs Center for Theoretical and Computational Biology (http://crick-jacobs.salk.edu/People/), and my mentors are Dr Fred Gage at the Laboratory of Genetics at the Salk Institute, and Dr Sean Eddy at Janelia Farm.  In late 2004, I completed my doctoral studies in Computational Neuroscience/Biology under the direct supervision of Dr Tomaso Poggio and Dr Christopher Burge at the Massachusetts Institute of Technology in Cambridge, MA.  My thesis committee comprised of Dr Phillip Sharp and Dr Martha Constantine-Paton.  I continued briefly as a postdoctoral fellow until early 2005 under Dr Christopher Burge, Dr Tomaso Poggio and Dr Phillip Sharp. I have a BS in Chemical Engineering and a BA in Economics from the University of Illinois, Urbana-Champaign.  I have worked for Affymetrix, Chiron and Millennium Pharmaceuticals, and have been involved with a start-up developing neural network software at MIT.  From my diverse training, I have gained substantial experience and confidence in utilizing both computational approaches and experimental methods to ask and answer biological questions.

 

My first research interest is to understand the molecular network-level changes during the specification of neural/neuronal stem cell fate from human/mouse ES and neural stem cells.  Specifically, I am interested in (1) identifying alternative splicing (AS) events that are crucial for fate specification, and the RNA binding proteins (splicing factors) that regulate these AS events; and (2) analyzing the small RNA repertoire that change during fate specification. 

 

My second research interest is in molecular sequence evolution using multiple genomes, which I use as a basis for the systematic computational discovery of RNA regulatory elements important in post-transcriptional processing, such as elements important for alternative splicing and RNA stability.  I have developed computational algorithms to identify these elements as well as novel experimental approaches to identify RNA binding proteins that bind to these elements both in vitro and in vivo.  

 

I pursue my objectives with multidisciplinary techniques ranging from developing my own computational tools (machine learning, statistical sequence analysis, graphical modeling), using molecular and cell biological approaches, and coupled with high-throughput approaches (high-density Exon Arrays, 454 or Illumina.Solexa sequencing).

 

EDUCATION AND TRAINING

 

 

Salk Institute, La Jolla, California

 

Fellow, Crick-Jacobs Center for Computational and Theoretical Biology; Senior Fellow Mentors: Fred Gage and Sean Eddy

 

July 2005-present

 

 

Massachusetts Institute of Technology

 

Doctor of Philosophy (Ph.D.) in Computational Neuroscience, Department of Brain and Cognitive Sciences; Advisors: Christopher Burge and Tomaso Poggio, Members: Phillip Sharp and Martha Constantine-Paton.

 

Sept 2000- Feb 2005

 

 

University of Illinois, Urbana-Champaign

 

Bachelor of Science (B.S.) in Chemical Engineering, Highest Honors, Supervisor: Charles Zukoski.

 

1994-1998

 

 

University of Illinois, Urbana-Champaign

 

Bachelor of Arts (B.A.) in Economics, High Honors

 

1994-1998

 

 

DOCTORAL AND FELLOW RESEARCH

 

 

Salk Institute, Crick-Jacobs Center (collaborations in parantheses)

Computational identification of splicing regulatory intronic elements preserved across evolution

Alternative splicing regulation in neural stem cells (with Fred Gage, Salk, 2006-2007)

Solexa small RNA analysis in human embryonic stem cells and differentiated neural progenitors (with Fred Gage, Salk, 2007)

Digital alternative splicing analysis (with Fu Xiangdong, UCSD, 2007-)

Clip-Solexa method to identify RNA binding sites (with Fu XIangdong, UCSD, 2007-)

454 small RNA analysis in mouse embryonic stem cells (with Phil Sharp, MIT, 2005-2006)

NMD candidate analysis in neurons (with Melissa Moore, Brandeis, 2005-2006)

Analysis of splicing-specific microarrays from an RNAi screen to identify RNA binding proteins with roles in alternative splicing in Drosophila (with Brenton Graveley, University of Connecticut Health Center, 2006-)

454 small RNAs in planarians (with Brenton Graveley, University of Connecticut Health Center, 2007-)

Identification of microRNAs and microRNA targets of let-7 and mir-35 in C. elegans (with Amy Pasquinelli at UCSD, 2006-)

 

2005-present

                                   

 

Massachusetts Institute of Technology                                                                                                                                

                        Burge group:

Neighborhood graph approach for identification of splicing enhancers/silencers;

Combining splicing-specific array and sequence-derived features to predict alternative exons;

Development of splicing-sensitive DNA microarrays;

Algorithmic development of splice site models and exon prediction algorithms;

Prediction and verification of alternative spliced exons conserved in human and mouse using Regularized Least-squares Classification;

Evolution of splicing factors and cis-elements in vertebrates

Poggio group: Multiclass classification of microarray data using Support Vector Machines

 

 

2000-2004

 
Institute of Molecular and Cell Biology, Singapore                                                                         

                                    Venaktesh Byrappa and Sydney Brenner: Regulatory elements conserved in non-coding regions.

 

 

2000, 2004

 
Beckman Institute of Advanced Science and Technology, University of Illinois, Urbana-Champaign
              Zukoski group: Conducted studies on Thin Film Drying stresses using an automated ellipsometer;
Conducted studies on the effect of electric fields on 20 micro gold-coated glass spheres
using an Atomic Force Microscope.
 

 

1996-1997

 

GRANTS AND FELLOWSHIPS

 

Crick-Jacobs Fellow, Crick-Jacobs Center for Computational and Theoretical Biology, Salk Institute, 2005-present

Lee Kuan Yew Graduate Scholarship, by the Lee Kuan Yew Foundation in Singapore, 2000-2005.

 

PROFESSIONAL ASSOCIATIONS

 

The RNA Society; International Society of Computational Biology; The Honor Society of Phi Kappa Phi; The American Institute of Chemical Engineers; The Phil Lambdas Upsilon Honorary Chemical Society; The Tau Beta Pi National Engineering Honor Society; The Phi Beta Kappa Honor Society; The Golden Key Honor Society.

 

HONORS & AWARDS

 

Brain-Cognitive Science Team Award for Outstanding Teaching, 2005

James Scholar, College of Liberal Arts and Sciences, 1996-1998.

Chemical Engineering Alumni Award, 1997.

Hauser Chemical Engineering Scholarship for research, 1996.

A.T. Widiger Chemical Engineering Scholarship, 1996.

DeanÕs list, College of Engineering, 1994; College of Liberal Arts and Sciences,1995-1997.

Sword of Honor, Officer Cadet School, Navy, 1999 (Singapore)

Best in Company and Best in Physical Training Awards during Basic Military Training, 1998 (Singapore)

 

TEACHING EXPERIENCE

 

Massachusetts Institute of Technology                                

Teaching Assistant

Course 9.02 (Brain Laboratory), 9.00 (Psychology), 9.35 (Vision)

 

2002-2004

 

 

 

Northeastern University, Bioinformatics Essentials Graduate Certification Course

Lecturer

Structured course syllabus and co-taught a 12 week course in microarray data analysis,

including classification, feature selection, experimental design, Bayesian networks and microarray technology.

 

2001

University of Illinois, Urbana-Champaign, Chemical Engineering                                                         

Teaching Assistant

Mass Transfer.  Conducted discussion sections on diffusion, mass transfer coefficients,

heat and mass transfer, distillation and absorption, membrane separations,

and chemical reactions in mass transfer.

                                   

1997

 

PROFESSIONAL RESEARCH/VENTURE EXPERIENCE

 

GeneBytes

Co-Founder
Bioinformatics Consulting, Pathway Analysis

 

2004-2007

Neuron Systems, MA

Bioinformatics Consulting

 

2004-2006

Millennium Pharmaceuticals, Millennium Predictive Medicine (MPMX), MA      

Bioinformatics Researcher

Developed and critiqued millennium in-house web-tools for classification and

feature selection for marker selection in large-scale microarray data. 

Integrated microarray data and clinical data using Bayesian networks.

 

2001

Chiron, Research and Development, Emeryville, CA                                                                                                                    

Research Technician

 

2000

Affymetrix, Santa Clara, CA                                                                                                                                                                                         

Research Technician
 

1997

 

REFEREED PUBLICATIONS

First or co-first author papers denoted in bold; Publications where I am co- or corresponding author denoted by underlined

 

Regulation of L1 neuronal retrotransposition by the Methyl-CpG-binding protein 2.

                                    Muotri. A.M., Marchetto, M.C.N, Yeo, G, Nakashima, K, Gage, F.H. (submitted).

 

The PIWI proteins SMEDWI2 and SMEDWI3 are required for stem cell function and piRNA expression in planarians.

Palakodeti, D, Smielewska, M, Liu Y, Yeo G, Graveley BR, RNA, 2008.

 

RNA sequence analysis defines DicerÕs role in mouse embryonic stem cells.

                                    Calabrese J.M., Seila A.C., Yeo G.W., Sharp P.A. PNAS. 2007.

 

A Regulator of Dscam Mutually Exclusive Splicing Fidelity.

                                    Olson, S, Blanchette, M, Park, J, Savva Y, Yeo, G, Yeakley J, Rio D, Graveley, B. Nature Structural and Molecular Biology, 2007

 

Immunoglobulin light chains in zebrafish: genomic configurations and inversional rearrangements between (V(L)-J(L)-C(L)) gene clusters.

                                    Zimmerman, A.M, Yeo, G, Howe K, Maddox, B.J., Steiner, L.A. Dev. Comp. Immunol. 2007.

 

Alternative events Identified in Human embryonic stem cells and neural progenitors.

                                    Yeo, G, Xiang-dong X., Liang, Y.T., Muotri. A.M., Carson, C., Coufal, N, Gage, F.H. PLoS Computational Biology, 2007.

 

Short RNAs in the sense and anti-sense orientation from transcription initiation sites in murine embryonic stem cells.

                                    Seila, A.C., Calabrese, J.M., Yeo, G, Levine, S, Sharp P.A. (submitted).

 

The EJC factor eIFAIII modulates synaptic strength and neuronal protein expression

                                    Giorgi. C, Yeo, G., Stone, M.E., Katz, D.B., Burge. C., Turrigiano, C., Moore, M.J. Cell, 2007.

 

Discovery and analysis of evolutionarily conserved intronic splicing regulatory elements in mammalian genomes.

Yeo, G, Van Nostrand, E, Liang, Y.T.  PLoS Genetics, 2007.

 

Plant-derived flavanol (-)epicatechin enhances angiogenesis and memory in mice.

Van Praag, H., Lucero, M.J., Yeo, G., Stecker, K., Heivand, N, Zhao C, Yip, E, Afanador, M, Schroeter, H, Hammerstone, J, Gage, FH.  Journal of Neuroscience, 2007

 

Inference of splicing regulatory activities by sequence neighborhood analysis.

                                    Stadler M.B., Shomron N, Yeo G.W., Schneider, A, Xiao, X, Burge C.B. PLoS Genetics, 2006

 

Combinatorial code for splicing silencing: UAGG and GGGG motifs.

Han, K, Yeo, G, An, P, Burge, C.B and Grabowski, P. PLoS Biology.  2005.

                       

Identification and analysis of alternative splicing events conserved in human and mouse.

Yeo, G, Van Nostrand, E, Holste, D, Poggio, T and Burge, C.B.  PNAS, 2005.

 

Systematic identification and analysis of exonic splicing silencers.

Wang, Z, Rolish, ME, Yeo, G, Tung,V, Mawson, M, and Burge C.B. Cell, 2004.

 

Variation in alternative splicing across human tissues.

Yeo, G, Holste D, Kreiman, G, and Burge, C.B. Genome Biology, 2004.

 

Variation in the splicing regulatory elements and their organization in vertebrate genomes.

Yeo, G, Hoon S, Venkatesh, B, and Burge, C.B. PNAS, 2004.

 

                        RESCUE-ESE identifies candidate exonic splicing enhancers in vertebrate exons.

Fairbrother WG, Yeo, G, Yeh, R, Goldstein, P, Mawson, M, Sharp PA, Burge CB. Nucleic Acids Res. 2004

 

Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals

Yeo, G, and Burge, C., Journal of Computational Biology, 2004.

 

Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals.

Yeo, G, and Burge, C.B. Proceedings of the Seventh Annual International Conference on Research in Computational Molecular Biology, Berlin, Germany,April 10-13, 2003.

 

Non-classical splicing mutations in the coding and non-coding regions of the ATM gene:

a comparison of cDNA with maximum entropy estimates of splice junction strengths,

Eng, L, Coutinho G, Nahas, S, Yeo, G, Tanouye, R, Drk, T, Burge, C.B, and Gatti, R.A. Human Mutation, 23(1), 67-76, 2004.

 

Regularized Least-squares Classification.

Rifkin, R, Yeo, G and Poggio, T.  Advances in Learning Theory: Methods, Model and Applications, NATO Science Series III:  Computer and System Sciences, Vol. 190, ISO Press, Amsterdam 2003.  Edited by Suykens, Horvath, Basu, Micchelli and Vandewalle.

 

 

INVITED REVIEWS

 

Cell Type Specification: REST

                                    Aigner, S, Yeo, G.  The New Encyclopedia of Neuroscience. 2007

 

Noncoding RNAs in the Mammalian Central Nervous System

Cao, X, Yeo, G,  Muotri, A, Kuwabara, T and Gage, F.H. Annual Review of Neuroscience.  2006.

                       

Splicing regulators: targets and drugs.

Yeo, G, Genome Biology, 2005.

 

Evolutionarily conserved intronic splicing elements in the human genome.

Eric Van Nostrand, Yeo, G, The Encyclopedia of Life Sciences, 2008.

 

                       

INVITED TALKS/ CONFERENCE PRESENTATIONS

 

University of California, Los Angeles, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research

Uncovering the Splicing Code and Alternative splicing in stem cells (INVITED TALK)

 

Keystone Conference on RNAi and non-coding RNAs, Whistler, Canada, March 25-30, 2008

Analysis of small RNAs in stem cells (SHORT TALK)

 

University of Massachusetts, Medical School Invited Talk, March 10, 2008

Uncovering the Splicing Code, and Alternative splicing in ES cells (INVITED TALK)

                                   

Seminar in the Dept of Bioengineering and the Whitaker Institute of Biomedical Engineering, UCSD, March 7, 2008

Small RNA analysis in Stem Cells (INVITED TALK)

 

Genetics and Genomics Lecture Series, Department of Medicine, UCSD, March 6, 2008

Uncovering the Splicing Code, and Alternative splicing in ES cells (INVITED TALK)

 

Human Genetics Seminar, co-sponsored by CCMB and Human Genetics, University of Michigan, Ann Arbor, Feb 25, 2008

Uncovering the Splicing Code, and Alternative splicing in ES cells (INVITED TALK)

 

StowerÕs Institute, Jan 28

Splicing bits and bytes (INVITED TALK)

 

The Stem Cell Meeting on the Mesa, Oct 19, Salk Institute, 2007

Small RNA analysis of neural differentiation from human ES cells (Talk).

 

Eukaryotic mRNA Processing Meeting, Aug 22-26, Cold Spring Harbor Laboratory, 2007 (Talk)

 

6th International Conference on Computational Systems Bioinformatics (CSB2007) sponsored by Life Sciences Society

Workshop on Alternative Splicing, 17th August, UCSD, 2007

Discovery of intronic regulatory elements in mammalian genomes. (INVITED TALK)

 

Alternative Splicing, Beyond Genome 2007 (INVITED TALK, Also hosting Discussion Group)

Intronic splicing regulatory elements in mammalian genomes and alternative splicing in stem cell differentiation.

 

RNA 2006 (TALK)

Identification of REST/NRSF regulated MicroRNAs

 

RNA 2006 (POSTER)

Highly conserved intronic elements proximal to mammalian exons predict tissue-specificity of alternatively spliced exons

 

Regulatory RNAs, May 31-June 5, Cold Spring Harbor Laboratory, 2006 (POSTER).

Rest-regulated MicroRNAs

 

Alternative Splicing Special Interest Group Meeting at ISMB 2005.

Intelligent systems for molecular biology conference, 2005 (INVITED TALK)

Identification and analysis of alternative splicing events conserved in human and mouse

 

SFN 2004: Society for Neuroscience, San Diego, 2004 (POSTER)

Yeo, G, Van Nostrand, E, Holste D, Poggio, T and Burge, C.B.

Predictive identification of alternative exons in mammals reveals neural-specific and RNA binding functions. 

 

RNA 2004: Ninth annual meeting of the RNA society, June 1-6, Madison, Wisconsin, 2004 (TALK).

Yeo, G, Holste D, Van Nostrand, E, Poggio, T and Burge, C.B.

Predictive discrimination of conserved skipping events in human and mouse.

 

                                    Eukaryotic mRNA processing meeting, Aug 20-24, Cold Spring Harbor Laboratory, 2003 (POSTER).

Yeo, G, Hoon, S and Burge C. 

Variation in sequence and organization of splicing regulatory elements in vertebrate genes,

 

ISMB 2003: Intelligent systems for molecular biology conference, June 29-July 3, Brisbane, Australia, 2003. (BEST POSTER)

Yeo, G, Hoon, S and Burge C. 

Genomics of vertebrate splicing regulatory elements,

 

RECOMB 2003: Seventh annual international conference on research in computational molecular biology, April 10-13, Berlin, Germany, 2003 (TALK).

Yeo, G, and Burge, C.B.

Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals. 

 

REVIEWER FOR THESE JOURNALS/BOOKS

Nature Biotechnology, PLoS Biology, PLoS Computational Biology, PLoS Genetics, Molecular Cell, PNAS, Nucleic Acids Research, Genome Research, Genome Biology, BMC Bioinformatics, Applied Bioinformatics, Molecular Biology and Evolution, Bioinformatics

 

Reviewer for Grants for The Israel Science Foundation

 

COURSES/COURSEWORK ATTENDED

 

Revolutionary Sequencing Technologies and Applications, Cold Spring Harbor Laboratory by Greg Hannon, Elaine Mardis, Gabor Marth, Richard McCombie, John McPherson and Michael Zody, November, 2007

 

Brain development and function at Cold Spring Harbor Laboratory by Michael Posner and Ron McKay, June-July 2000.

                                   

Ph.D. Coursework includes Machine Learning (Jaakkola), Neural Networks (Seung), Statistical Learning Theory and Applications (Poggio), Computational Functional Genomics (Young, Gifford), Cognitive and Behavioral Genetics (Housman, Nedivi, Pinker), Neural Plasticity in Learning and Development (Tonegawa, Quinn, Wilson, Liu), Topics in Statistics (Hardy), Nucleic Acids (RajBhandary, Bartel) GPA:5.0 / 5.0

 

 

 

REFERENCES

 

 

Prof. Fred Gage

Professor, Laboratory of Genetics, Salk Institute

10010 North Torrey Pines Road

La Jolla, CA 92037

Phone: (858) 453-4100

gage@salk.edu

 

 

Prof. Tomaso Poggio

Professor, Dept. Brain and Cognitive Sciences,McGovern Institute of Brain Research, Center for Biological and Computational Learning, Computer Science and Artificial Intelligence Laboratory

77 Massachusetts Ave., E25-201

Cambridge, MA 02139

tp@ai.mit.edu

 

 

Prof. Terry Sejnowski

Professor, Computational Neuroscience Laboratory

10010 North Torrey Pines Road

La Jolla, CA 92037

Phone: (858) 453-4100

terry@salk.edu

 

 

Prof. Sean Eddy

HHMI Janelia Farm

eddys@janelia.hhmi.org

 

 

Prof. Christopher Burge

Associate Professor, Dept. Biology, MIT.

77 Massachusetts Ave., 68-223

Cambridge, MA 02139-4307

Phone: (617) 258-5997

cburge@mit.edu

 

 

Prof. Sydney Brenner

Distinguished Research Professor, The Salk Institute, La Jolla, USA

sbrenner@salk.edu

 

Prof. Phillip Sharp

Institute Professor, Dept. Biology, MIT.

77 Massachusetts Ave., E17-529B

Cambridge, MA 02139-4307

Phone: (617) 253-6421

sharppa@mit.edu

 

 

Prof. Xiang-Dong Fu

University of California San Diego

Cellular & Molecular Medicine - 0651

9500 Gilman Drive

La Jolla CA 92093-0651

Phone: (858) 534-4937

Fax: (858) 534-8549

xdfu@ucsd.edu

 

 

Prof. Paula Grabowski

Professor, Dept. Biological Sciences/HHMI

University of Pittsburgh

4249 Fifth Avenue

Pittsburgh, PA 15260

Phone: (617) 624-6983

pag4+@pitt.edu

 

 

Prof. Melissa Moore

Professor, Dept. Biochemistry and Molecular Pharmacology

University of Massachusetts Medical School

LRB 825, Lab 870P-T

Phone: 508-856-8014

Melissa.Moore@umassmed.edu

 

Prof. Brenton Graveley

Department of Genetics and Developmental Biology

University of Connecticut Health Center

MC3301

263 Farmington Avenue

Farmington, CT 06030-3301

Phone: (860) 679-2092

Fax: (860) 679-8345

graveley@neuron.uchc.edu