Patrick J. Paddison

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Fred Hutchinson Cancer Research Center
Human Biology Division
Assistant Member
Professional Headshot of Patrick J. Paddison

Mailing Address

1100 Fairview Ave N
PO Box 19024
C3-168
Seattle, Washington 98109-1024
United States

Contact Information

Phone: (206) 667-4312
Fax: (206) 667-4023
paddison@fhcrc.org

Qualifications

Ph.D., Cold Spring Harbor Laboratory, Biological Sciences, 2004.
B.A., The Evergreen State College, Psychology, 1996.
B.S., The Evergreen State College, Molecular Biology and Genetics, 1996.

Expertise and Research Interests

The overall goals of my lab revolve around using functional genetic approaches to uncover the molecular networks that regulate mammalian cell identity. Through the use of defined, in vitro embryonic and somatic stem cell systems, we will find and characterize gene products affecting stem cell self-renewal, differentiation, proliferation, and survival. Projects currently underway in lab include:

(1) discovering the molecular determinants of self-renewal and lineage specific of embryonic and neural stem cells;
(2) mapping gene networks in stem cells using cellular perturbagens;
(3) defining essential gene circuits arising during development; and
(4) the in vitro derivation of specific, somatic cell lineages;
(5) therapeutic applications of RNAi.

We routinely use three in vitro cell systems in lab: embryonic stem cells (ESCs), neural stem cells (NSCs), and fibroblasts. These cells have attractive experimental properties: a definable "wild type", robust in vitro growth in defined conditions, the capacity to give rise to one or more cell types in vitro, and the capacity to re-enter embryogenesis and/or engraft adult animals to reproduce phenotypes in vivo.

To investigate cellular phenotypes in these systems, we employ RNA interference (RNAi) as a gene discovery tool using genome-wide short hairpin RNA (shRNA) libraries. This technology allows us to broadly access gene function through genome-scale "shot gun" screens (using pools of 10,000 shRNAs) followed by shRNA DNA barcode array analysis to track individual shRNAs in outgrown or sorted populations of cells.

Our studies will provide insight into basic stem cell biology, human diseases involving altered tissue homeostasis, and strategies for implementing cell replacement and targeted cancer therapies.

Keywords

COS Keywords:

Biological Sciences.

Languages

(Reading, Writing, Speaking)

English: (Fluent, Fluent, Fluent)

Previous Positions

2004-2008, Post-doctoral fellow, Cold Spring Harbor Laboratory, CSHL Fellow Program
2000-2004, Graduate Research Student, Cold Spring Harbor Laboratory, Watson School of Biological Sciences
1996-2000, Research Technician, Fred Hutchinson Cancer Research Center, Human Biology Division
1995-1996, Undergraduate research fellow, The Evergreen State College, Biology

Funding Received

  • Pew Scholars in the Biomedical Sciences: 2009 Pew Scholar, 2009 to 2013.
  • Fred Hutchinson Cancer Research Center: Start-Up Funding, 2008 to 2011.
  • New York State Office of Science, Technology, and Academic Research: James D. Watson Investigator Initiative, 2007 to 2008.
  • National Cancer Institute - Institutional fellowship: Ruth L. Kirschstein National Research Service Awards, 2004 to 2006.
  • CSHL Fellow Program: President's Council Fund, 2004 to 2008.
  • United States Department of Defense (DOD): Predoctoral Fellowship for Breast Cancer Research, 2001 to 2004.
  • Watson School of Biological Sciences, Cold Spring Harbor Laboratory: Arnold and Mabel Beckman Scholarship, 2000 to 2004.

Publications

  • Schaniel C, Ang YS, Ratnakumar K, Cormier C, James T, Bernstein E, Lemischka IR, Paddison PJ (Sep 2009) Smarcc1/Baf155 Couples Self-Renewal Gene Repression with Changes in Chromatin Structure in Mouse Embryonic Stem Cells., Stem cells (Dayton, Ohio) Abstract
  • Paddison PJ (2008) RNA interference in mammalian cell systems., Current topics in microbiology and immunology, 320, 1-19 Abstract
  • Paddison PJ, Vogt PK (2008) RNA Interference, Vol. 320, Current Topics in Microbiology and Immunology, Springer Press, 276 pages, ISBN=978-3-540-751
  • Gadue P, Huber TL, Paddison PJ, Keller GM (Nov 2006) Wnt and TGF-beta signaling are required for the induction of an in vitro model of primitive streak formation using embryonic stem cells., Proceedings of the National Academy of Sciences of the United States of America, 103 (45), 16806-11 Abstract
  • Schaniel C, Li F, Schafer XL, Moore T, Lemischka IR, Paddison PJ (May 2006) Delivery of short hairpin RNAs--triggers of gene silencing--into mouse embryonic stem cells., Nature methods, 3 (5), 397-400 Abstract
  • Silva JM, Li MZ, Chang K, Ge W, Golding MC, Rickles RJ, Siolas D, Hu G, Paddison PJ, Schlabach MR, Sheth N, Bradshaw J, Burchard J, Kulkarni A, Cavet G, Sachidanandam R, McCombie WR, Cleary MA, Elledge SJ, Hannon GJ (Nov 2005) Second-generation shRNA libraries covering the mouse and human genomes., Nature genetics, 37 (11), 1281-8 Abstract
  • Siolas D, Lerner C, Burchard J, Ge W, Linsley PS, Paddison PJ, Hannon GJ, Cleary MA (Feb 2005) Synthetic shRNAs as potent RNAi triggers., Nature biotechnology, 23 (2), 227-31 Abstract
  • Cleary MA, Kilian K, Wang Y, Bradshaw J, Cavet G, Ge W, Kulkarni A, Paddison PJ, Chang K, Sheth N, Leproust E, Coffey EM, Burchard J, McCombie WR, Linsley P, Hannon GJ (Dec 2004) Production of complex nucleic acid libraries using highly parallel in situ oligonucleotide synthesis., Nature methods, 1 (3), 241-8 Abstract
  • Paddison PJ, Cleary M, Silva JM, Chang K, Sheth N, Sachidanandam R, Hannon GJ (Nov 2004) Cloning of short hairpin RNAs for gene knockdown in mammalian cells., Nature methods, 1 (2), 163-7 Abstract
  • Paddison PJ, Silva JM, Conklin DS, Schlabach M, Li M, Aruleba S, Balija V, O'Shaughnessy A, Gnoj L, Scobie K, Chang K, Westbrook T, Cleary M, Sachidanandam R, McCombie WR, Elledge SJ, Hannon GJ (Mar 2004) A resource for large-scale RNA-interference-based screens in mammals., Nature, 428 (6981), 427-31 Abstract
  • Paddison PJ, Caudy AA, Sachidanandam R, Hannon GJ (2004) Short hairpin activated gene silencing in mammalian cells., Methods in molecular biology (Clifton, N.J.), 265, 85-100 Abstract
  • Paddison PJ, Hannon GJ (Jun 2003) siRNAs and shRNAs: skeleton keys to the human genome., Current opinion in molecular therapeutics, 5 (3), 217-24 Abstract
  • Hemann MT, Fridman JS, Zilfou JT, Hernando E, Paddison PJ, Cordon-Cardo C, Hannon GJ, Lowe SW (Mar 2003) An epi-allelic series of p53 hypomorphs created by stable RNAi produces distinct tumor phenotypes in vivo., Nature genetics, 33 (3), 396-400 Abstract
  • Paddison PJ, Hannon GJ (Jul 2002) RNA interference: the new somatic cell genetics?, Cancer cell, 2 (1), 17-23 Abstract
  • Paddison PJ, Caudy AA, Bernstein E, Hannon GJ, Conklin DS (Apr 2002) Short hairpin RNAs (shRNAs) induce sequence-specific silencing in mammalian cells., Genes & development, 16 (8), 948-58 Abstract
  • Paddison PJ, Caudy AA, Hannon GJ (Feb 2002) Stable suppression of gene expression by RNAi in mammalian cells., Proceedings of the National Academy of Sciences of the United States of America, 99 (3), 1443-8 Abstract
  • Paddison P, Abedon ST, Dressman HK, Gailbreath K, Tracy J, Mosser E, Neitzel J, Guttman B, Kutter E (Apr 1998) The roles of the bacteriophage T4 r genes in lysis inhibition and fine-structure genetics: a new perspective., Genetics, 148 (4), 1539-50 Abstract

Profile Details

Last Updated: 10/5/2009

COS Expertise ID #1305715
Reference this profile directly: http://myprofile.cos.com/paddison