March 12 – 13, 2007
WORKSHOP SUMMARY
The purpose of this workshop was to provide an opportunity for NIGMS grantees conducting human embryonic stem cell (hESC) research to report on their recent progress, to exchange information, and to identify challenges and opportunities unique to this emerging area of research. The workshop brought together a wide spectrum of scientists working with hESC that reflects the breadth of basic research supported by NIGMS. There were 78 participants: 57 NIGMS grantees (members of six P20 Exploratory Centers, R01 awardees and recipients of stem cell supplements to research grants), 4 outside speakers and 17 NIH staff members.
The diversity of research advances presented reflected the significant progress that has been made in understanding the basic biology of hESC since the previous meeting in April 2005. A number of presentations were devoted to advances made in developing in vitro culture conditions that support self-renewal, pluripotency and normal karyotypes, or that support the differentiation of hESC into specific cell types. The effects of different media additives, such as short chain fatty acids and specific growth factors, on hESC self-renewal and differentiation were presented, as was the application of microfluidics to achieve a more physiological culture environment.
Several researchers reported on their use of new approaches, such as high content small molecule screens, to identify factors that support hESC differentiation into beating cardiomyocytes, neural retinal cells, hepatocytes and cells of the erythroid and myeloid lineages. Significant progress was evident in the number of cell types that now can be derived. Among the technology developments described were the use of the Rosa26 locus to facilitate gene targeting for ubiquitously expressed genes, and the use of the adeno-associated virus as a gene targeting vector. New methodology to visually track cell movements, using automated microscopy and FRET-based biosensors, was demonstrated.
A number of speakers described their work on the basic biology of hESCs, particularly on the characterization of the molecular signatures of hESCs or their differentiated progeny. These included genome-wide mapping studies to localize DNA and epigenetic modifications that either maintain hESC pluripotency or occur in differentiated hESCs. High resolution genome-wide efforts to localize critical transcription factors also were described. Other reports focused on the post-transcriptional regulation of the cell cycle in hESCs by microRNAs and on the use of mass spectrometry to identify post-translational modifications in the phosphoproteome of differentiated hESCs.
Following the scientific presentations, there was a discussion of the current status of intellectual property (IP) issues that affect hESC research. A representative of the Wisconsin Research Alumni Foundation (WARF) and a representative from the NIH Office of Technology Transfer identified recent progress in lowering IP barriers to the use of hESC.
The final session was devoted to an open discussion of recent progress and continuing challenges. Participants noted the value of the NIGMS Exploratory P20 Centers in supporting research on the most basic properties of hESC, and in establishing an institutional infrastructure that enables more scientists to work with hESC. Attendees expressed the hope that these Exploratory Centers could serve as a model for further support of basic hESC research by other Institutes of the NIH. There was a general consensus that in the short term, hESC research must focus on fundamental knowledge of stem cell biology as a prerequisite to more translational studies. Participants also noted the challenge of learning to work with hESC, especially for chemists and scientists from other non-biological disciplines. The two day meeting was characterized by lively questions and discussions and provided a collegial opportunity for the participating investigators to develop new collaborations.
Agenda
Monday March 12, 2007
| 7:30 - 8:15 AM |
Registration and Breakfast Refreshments |
| 8:15 - 8:30 AM |
Jeremy Berg and Marion Zatz |
Welcome |
| 8:30 - 9:55 AM |
Session I: Pluripotency and Stem Cell Differentiation |
|
Chair, C. Anthony Blau |
| 8:30 - 8:45 AM |
James Thomson |
Basic Biology of signaling cascades in human embryonic stem cells |
| 8:45 - 9:10 AM |
Joshua Coon |
Tracking kinase signaling cascades in human embryonic stem cells |
| 9:10 - 9:25 AM |
Gen-Sheng Feng |
Shp2 and molecular signaling in control of ES cell pluripotency |
| 9:25 - 9:40 AM |
Carl Schildkraut |
DNA replication in human ES cells |
| 9:40 - 10:10 AM |
Discussion |
| 10:10 - 10:40 AM |
Break |
| 10:40 - 12:15 PM |
Session II: Stem Cell Differentiation and Signaling Pathways |
|
Chair, James Thomson |
| 10:40 - 11:00 AM |
C. Anthony Blau |
IGF1R signaling in hESC self renewal |
| 11:00 - 11:15 AM |
Carol Ware |
Short chain fatty acids and self-renewal in hESC |
| 11:15 - 11:30 AM |
Nobuaki Kikyo |
Chromatin remodeling in stem cells and nuclear cloning |
| 11:30 - 12:00 PM |
Discussion |
| 12:15 - 1:15 PM |
Lunch and Informal Discussions |
| 1:15 - 3:00 PM |
Session III: Targeted Differentiation |
|
Chair, Gordon Keller |
| 1:15 - 1:30 PM |
Sanjeev Gupta |
Hepatic differentiation of hESC |
| 1:30 - 1:45 PM |
Thomas Reh |
Embryonic stem cell approaches to retinal repair |
| 1:45 - 2:00 PM |
Mark Mercola |
Automated screens for stem cell differentiation and pluripotency |
| 2:00 - 2:15 PM |
Lil Pabon |
Cardiomyocyte differentiation |
| 2:15 - 2:30 PM |
Fred Levine |
Pancreatic endocrine progenitors |
| 2:30 - 2:45 PM |
Alexey Terskikh |
Neural differentiation of human embryonic stem cells |
| 2:45 - 3:00 PM |
Discussion |
| 3:00 - 3:20 PM |
Break |
| 3:20 - 5:00 PM |
Session IV: Technology I/Gene Regulation |
|
Chair, Eric Bouhassira |
| 3:20 - 3:45 PM |
Gordon Keller |
Genetic modification and directed differentiation of human embryonic stem cells |
| 3:45 - 4:10 PM |
Jose Garcia-Perez |
LINE-1 retrotransposition in human embryonic stem cells |
| 4:10 - 4:25 PM |
R. Michael Linden |
Targeted gene addition in human embryonic stem cells |
| 4:25 - 4:40 PM |
David Russell |
Changing the HLA type of human ES cells |
| 4:40 - 5:00 PM |
Discussion |
| Dinner and Keynote Address |
| 6:30 - 7:00 PM |
Cash Bar |
| 7:00 - 8:00 PM |
Dinner |
| 8:00 - 9:00 PM |
Keynote Address
Thomas Rando |
Asymmetric divisions and fate determinants in adult stem cells |
| Tuesday March 13, 2007 |
| 7:30 - 8:00 AM |
Breakfast Refreshments |
| 8:00 - 10:10 AM |
Session V: Technology II/Culture and Characterization |
|
Chair, K. Sue O'Shea |
| 8:00 - 8:25 AM |
Eric Bouhassira |
Differentiation of human ES into red blood cells: What controls developmental timing? |
| 8:25 - 8:50 AM |
Gary Smith |
Microfluidics for spatial and temporal directed differentiation of hESC |
| 8:50 - 9:05 AM |
Jeffrey Price |
Toward automatic cell-by-cell tracking in embryoid body cell migration/interaction models |
| 9:05 - 9:20 AM |
Jeanne Loring |
Understanding regulation of hESC pluripotency and differentiation by whole genome analysis |
| 9:20 - 9:30 AM |
Carol Ware |
Cryopreservation of hESC by controlled-rate cooling |
| 9:30 - 9:40 AM |
Igor Katkov |
Maintenance of pluripotency after cryopreservation of hES cells: current challenges and possible future solutions |
| 9:40 - 10:10 AM |
Discussion |
| 10:10 - 10:30 AM |
Break |
| 10:30 - 12:30 PM |
Session VI: Gene Regulation and Epigenetic Control |
|
Chair, Evan Snyder |
| 10:30 - 10:55 AM |
Richard Young |
Regulatory circuitry of embryonic stem cells |
| 10:55 - 11:20 AM |
Oliver Rando |
Histone modification patterns - implications for the histone code |
| 11:20 - 11:45 AM |
Evan Snyder |
Global chromatin state and its modifications - a useful tool for monitoring human embryonic and somatic stem cell potency and stability |
| 11:45 - 12:00 PM |
Soren Impey |
Epigenetic regulation of ES cell self-renewal |
| 12:00 - 12:15 PM |
Hannele Ruohola-Baker |
microRNA in hESCs |
| 12:15 - 12:30 PM |
Discussion |
| 12:30 - 1:30 PM |
Lunch and Informal Discussion |
| 1:30 - 3:00 PM |
Session VII: Panel Discussions of Future Directions and Challenges |
|
Chair, Marion Zatz |
| 1:30 - 2:00 PM |
Mark Rohrbaugh, Craig Christianson |
Intellectual Property Issues |
| 2:00 - 2:30 PM |
Eric Bouhassira, C. Anthony Blau, Evan Snyder, Gordon Keller, K. Sue O'Shea, James Thomson |
Promoting Center Interactions |
| 2:30 - 3:00 PM |
Open Discussion |
| 3:00 PM |
Adjourn |
Workshop Participants
Carl Baker
National Institute of Arthritis and Musculoskeletal and Skin Diseases
6701 Democracy Boulevard, Suite 800
Bethesda, MD 20892-4872
Phone: 301-594-5017
Email: ccb@nih.gov
Sriram Bandi
Albert Einstein College of Medicine
1300 Morris Park Avenue
Ullmann Building 623
Bronx, NY 10461
Phone: 718-430-2007
Email: sbandi@aecom.yu.edu
Jeremy Berg
National Institute of General Medical Sciences
45 Center Drive, MSC 6200
Bethesda, MD 20892-6200
Phone: 301-594-2172
Email: bergj@mail.nih.gov
Travis Berggren
WiCell Research Institute
P.O. Box 7365
Madison, WI 53707
Email: travis@wicell.org
Anthony Blau
University of Washington
1959 Northeast Pacific Street
K260 Health Sciences Building
Seattle, WA 98195
Phone: 206-685-6873
Email: tblau@u.washington.edu
Eric Bouhassira
Albert Einstein College of Medicine of Yeshiva University
1300 Morris Park Avenue
Ullmann Building, Room 903
Bronx, New York 10461
Phone: 718-430-2188
Email: bouhassi@aecom.yu.edu
Henry Chang
Division of Blood Diseases and Resources
National Heart, Lung, and Blood Institute
6701 Rockledge Drive
Bethesda, MD 20817
Phone: 301-435-0080
Email: changh@nih.gov
Craig Christianson
Wisconsin Alumni Research Foundation
614 Walnut Street
P.O. Box 7365
Madison, WI 53707-7365
Phone: 608-261-1954
Email: cchristianson@warf.org
Laura Cole
Stem Cell Task Force
National Institute on Deafness and Other Communication Disorders
31 Center Drive, Room 3C27
Bethesda, MD 20892
Phone: 301-496-9515
Email: colel@nidcd.nih.gov
Joshua Coon
University of Wisconsin–Madison
1101 University Avenue, Room 3309
Madison, WI 53706
Phone: 608-263-1718
Email: jcoon@chem.wisc.edu
Sunita D'Souza
Mount Sinai School of Medicine
20 Erwin Court
Staten Island, NY 10306
Phone: 212-659-8251
Email: dsouzs01@mssm.edu
Gen-Sheng Feng
Burnham Institute for Medical Research
10901 North Torrey Pines Road
La Jolla, CA 92037
Phone: 858-795-5265
Email: gfeng@burnham.org
Deborah French
Mount Sinai School of Medicine
1425 Madison Avenue, Box 1496
New York, NY 10029
Phone: 212-241-8286
Email: debbie.french@mssm.edu
Jose Garcia-Perez
University of Michigan Medical School
4909 Buhl Building
Ann Arbor, MI 48109
Phone: 734-615-0457
Email: jegp@umich.edu
Saghi Ghaffari
Mount Sinai School of Medicine
One Gustave L. Levy Place , Box 1496
Icahn Building, Room 13-23B
New York, NY 10029
Phone: 212-659-8271
Email: saghi.ghaffari@mssm.edu
David Gilbert
College of Medicine
Florida State University
1115 West Call Street, Room 1350
Tallahassee, FL 32306-4300
Phone: 850-645-7583
Email: gilbert@bio.fsu.edu
Judith Greenberg
National Institute of General Medical Sciences
45 Center Drive, MSC 6200
Building 45, Room 2As10
Bethesda, MD 20892
Phone: 301-594-0943
Email: greenbej@nigms.nih.gov
Sanjeev Gupta
Albert Einstein College of Medicine of Yeshiva University
1300 Morris Park Avenue
Ullmann Building, Room 625
Bronx, NY 10461
Phone: 718-430-3309
Email: sanjvgupta@pol.net
Ann Hagan
National Institute of General Medical Sciences
45 Center Drive
MSC 6200, Room 2an.24h
Bethesda, MD 20892-6200
Phone: 301-594-4499
Email: hagana@nigms.nih.gov
Susan Haynes
National Institute of General Medical Sciences
45 Center Drive, MSC 6200
Bethesda, MD 20892-6200
Phone: 301-594-0943
Email: hayness@nigms.nih.gov
Els Henckaerts
Mount Sinai School of Medicine
One Gustave L. Levy Place, Box 1496
New York, NY 10029
Phone: 212-659-8247
Email: els.henckaerts@mssm.edu
Rhoda Hirsch
Albert Einstein College of Medicine of Yeshiva University
1300 Morris Park Avenue
Ullmann Building, Room 925
Bronx, NY 10461
Phone: 718-430-3604
Email: rhirsch@aecom.yu.edu
Tanya Hoodbhoy
Center for Scientific Review
One Center Drive
MSC 0177, Room 259A
Bethesda, MD 20892
Email: tanyah@mail.nih.gov
Xiao Hu
Department of Medicine and Hematology
Albert Einstein College of Medicine of Yeshiva University
1300 Morris Park Avenue
Ullmann Building, Room 905
Bronx, NY 10461
Email: xhu@aecom.yu.edu
Rosemarie Hunziker
National Institute of Biomedical Imaging and Bioengineering
6707 Democracy Boulevard, Room 235
Bethesda, MD 20892
Phone: 301-451-1609
Email: hunzikerr@mail.nih.gov
Soren Impey
Oregon Health and Sciences University
3181 Southwest Sam Jackson Park Road
Basic Research Building, Room 753, L321
Portland, OR 97239-3098
Phone: 503-494-7540
Email: sorenimpey@gmail.com
Stefan Irion
McEwen Centre for Regenerative Medicine
101 College Street, Room 8-701
MaRS Centre
Toronto Medical Discovery Tower
Toronto, Ontario M5G 1L7
Phone: 416-581-7711
Email: stefan.irion@uhnresearch.ca
Rebecca Johnson
National Institute of General Medical Sciences
45 Center Drive, Room 3AN-18
Bethesda, MD 20892
Phone: 301-594-2771
Email: johnsore@mail.nih.gov
Igor Katkov
Burnham Institute for Medical Research
10901 North Torrey Pines Road
Building 7, Room 7-105
La Jolla, CA 92037
Phone: 858-231-0755
Email: prodvincell@hotmail.com
Gordon Keller
University Health Network
101 College Street, Room 8-706
Toronto Medical Discovery Tower
Toronto, Ontario M5G 1L7
Phone: 416-581-7694
Email: gkeller@uhnresearch.ca
Marion Kennedy
McEwen Centre for Regenerative Medicine
101 College Street, Room 8-701
MaRS Centre
Toronto Medical Discovery Tower
Toronto, Ontario M5G 1L7
Phone: 416-581-7708
Email: mkennedy@uhnresearch.ca
Nobuaki Kikyo
Stem Cell Institute
University of Minnesota
2001 6th Street, SE
Room 2-216, MTRF, Mail Code 2873
Minneapolis, MN 55455
Phone: 612-624-0498
Email: kikyo001@umn.edu
Enko Kiprilov
Albert Einstein College of Medicine of Yeshiva University
1925 Eastchester Road, Apartment 16F
Bronx, NY 10461
Phone: 718-213-8567
Email: ekiprilo@aecom.yu.edu
Mark Levenstein
WiCell Research Institute
P.O. Box 7365
Madison, WI 53707
Phone: 608-262-4568
Email: markl@wicell.org
Fred Levine
Burnham Institute for Medical Research
10901 North Torrey Pines Road
La Jolla, CA 92037
Phone: 858-534-5979
Email: flevine@ucsd.edu
Michael Linden
Mount Sinai School of Medicine
One Gustave L. Levy Place, Box 1496
New York, NY 10029
Phone: 212-659-8278
Email: michael.linden@mssm.edu
Jeanne Loring
Burnham Institute for Medical Research
10901 North Torrey Pines Road
La Jolla, CA 92037
Phone: 858-795-5058
Email: jloring@burnham.org
Nadya Lumelsky
National Institute of Dental and Craniofacial Research
45 Center Drive, Room 4An29J
Bethesda, MD 20892
Phone: 301-594-7703
Email: nadyal@nidcr.nih.gov
Danith Ly
Carnegie Mellon University
4400 Fifth Avenue
Pittsburgh, PA 15213
Phone: 412-268-4010
Email: dly@andrew.cmu.edu
Barbara Mallon
National Institute of Neurological Disorders and Stroke
37 Convent Drive, Room 1000
Bethesda, MD 20892
Phone: 301-402-8246
Email: mallonb@mail.nih.gov
Mark Mercola
Burnham Institute for Medical Research
10901 North Torrey Pines Road
La Jolla, CA 92037
Phone: 858-795-5242
Email: mmercola@burnham.org
Jamie Newman
Whitehead Institute for Biomedical Research
Massachusetts Institute of Technology
6 Liberty Avenue, #2
Somerville, MA 02144
Phone: 617-258-7822
Email: newman@wi.mit.edu
Emmanuel Olivier
Albert Einstein College of Medicine of Yeshiva University
1300 Morris Park Avenue
Ullmann Building, Room 923b
Bronx, NY 10461
Phone: 718-430-3119
Email: eolivier@aecom.yu.edu
Sue O'Shea
University of Michigan
109 Zina Pitcher Place
Biomedical Sciences Research Building, Room 3061
Ann Arbor, MI 48109
Phone: 734-763-2550
Email: oshea@umich.edu
Lil Pabon
University of Washington
815 Mercer Street, Room 412
Seattle, WA 98109
Phone: 206-616-8402
Email: lmp@u.washington.edu
Guangjin Pan
University of Wisconsin–Madison
425 Henry Mall
4462 Genetics–Biotechnology Center Building
Madison, WI 53705
Phone: 608-890-0186
Email: gpan@primate.wisc.edu
Jack Parent
University of Michigan
109 Zina Pitcher Place
Biomedical Sciences Research Building, Room 5021
Ann Arbor, MI 48109-2200
Phone: 734-763-3776
Email: parent@umich.edu
Jeffrey Price
Burnham Institute for Medical Research
10901 North Torrey Pines Road
La Jolla, CA 92037
Phone: 858-646-3162
Email: jprice@burnham.org
Caihong Qiu
Albert Einstein College of Medicine of Yeshiva University
1300 Morris Park Avenue
Bronx, NY 10461
Email: cqiu@aecom.yu.edu
Prithi Rajan
Burnham Institute for Medical Research
10901 North Torrey Pines Road
La Jolla, CA 92037
Email: prajan@burnham.org
Oliver Rando
University of Massachusetts Medical School
364 Plantation Street
Worcester, MA 01605
Phone: 508-856-8879
Email: oliver.rando@umassmed.edu
Thomas Rando
Stanford University Medical Center
Room A-343
Stanford, CA 94305-5235
Phone: 650-849-0444
Email: rando@stanford.edu
Thomas Reh
University of Washington School of Medicine
I-500 Health Sciences Building, Box 357420
Seattle, WA 98195
Phone: 206-543-8043
Email: tomreh@u.washington.edu
Angie Rizzino
University of Nebraska Medical Center
986805 Nebraska Medical Center
Omaha, NE 68198-6805
Phone: 402-559-6338
Email: arizzino@unmc.edu
Mark Rohrbaugh
Office of the Director
National Institutes of Health
6011 Executive Boulevard, Suite 325
Rockville, MD 20852
Phone: 301-594-7700
Email: mr28k@@nih.gov
Hannele Ruohola-Baker
University of Washington School of Medicine
1959 Northeast Pacific Street
Health Sciences Building J-591, Box 357350
Seattle, WA 98195-7350
Phone: 206-543-8468
Email: hannele@u.washington.edu
David Russell
University of Washington
Box 357720
Seattle, WA 98195-7720
Phone: 206-616-4562
Email: drussell@u.washington.edu
Kirstie Saltsman
National Institute of General Medical Sciences
603 Hastings Road
Towson, MD 21286
Phone: 301-496-7301
Email: saltsmank@mail.nih.gov
Maja Salva
University of Washington
Box 357710
Seattle, WA 98195
Phone: 206-543-2952
Email: zmaja@u.washington.edu
Carl Schildkraut
Albert Einstein College of Medicine of Yeshiva University
1300 Morris Park Avenue
Bronx, NY 10461
Phone: 718-430-2097
Email: schildkr@aecom.yu.edu
Paul Sheehy
National Institute of General Medical Sciences
45 Center Drive, Room 2AN.24G
Building 45, MSC 6200
Bethesda, MD 20892-6200
Phone: 301-594-4499
Email: sheehyp@nigms.nih.gov
Beth-Anne Sieber
National Institute of Mental Health
6001 Executive Boulevard, Room 7186
Bethesda, MD 20892
Phone: 301-443-5288
Email: bsieber@mail.nih.gov
Arthur Skoultchi
Albert Einstein College of Medicine of Yeshiva University
1300 Morris Park Avenue
Bronx, NY 10461
Phone: 718-430-2169
Email: skoultch@aecom.yu.edu
Gary Smith
University of Michigan
1150 West Medical Center Drive, 6428 Medical Science I
Ann Arbor, MI 48109
Phone: 734-764-4134
Email: smithgd@umich.edu
Evan Snyder
Burnham Institute for Regenerative Medicine
10901 North Torrey Pines Road
La Jolla, CA 92037
Phone: 858-646-3158
Email: esnyder@burnham.org
Lesley Stewart
National Institute on Deafness and Other Communication Disorders
Claude D Pepper Bldg, Room 3C27
31 Center Drive
Bethesda, MD 20892
Phone: 301-496-2691
Email: stewartle@od.nih.gov
Alexey Terskikh
Burnham Institute for Medical Research
10901 North Torrey Pines Road
La Jolla, CA 92037
Phone: 858-646-3624
Email: terskikh@burnham.org
James Thomson
University of Wisconsin–Madison
425 Henry Mall
Genetics–Biotechnology Center Building
Madison, WI 53706
Phone: 608-263-3585
Email: thomson@primate.wisc.edu
Olga Ujhelly
Albert Einstein College of Medicine of Yeshiva University
1300 Morris Park Avenue, Chanin 402
Bronx, NY 10461
Phone: 718-4302168
Email: oujhelly@aecom.yu.edu
Fei Wang
National Institute of Arthritis and Musculoskeletal and Skin Diseases
6701 Democracy Boulevard, Suite 800
Bethesda, MD 20850
Phone: 301-594-5055
Email: wangf@mail.nih.gov
Hsien-Yu Wang
Department of Physiology and Biophysics
State University of New York at Stony Brook
Basic Sciences Tower, T6, Room 140
Stony Brook, NY 11794-8661
Phone: 631-444-3489
Email: wangh@pharm.stonybrook.edu
Carol Ware
University of Washington
1959 Northeast Pacific Street
Health Sciences Building, T-140
Box 357190
Seattle, WA 98195-7190
Phone: 206-616-5143
Email: cware@u.washington.edu
Baldwin Wong
National Institute on Deafness and Other Communication Disorders
31 Center Drive, Room 3C-27
Bethesda, MD 20892-2320
Phone: 301-496-2426
Email: bw99s@nih.gov
Richard Young
Whitehead Institute for Biomedical Research; Massachusetts Institute of Technology
9 Cambridge Center
Cambridge, MA 02142-1479
Phone: 617-258-5218
Email: young@wi.mit.edu
Junying Yu
University of Wisconsin–Madison
425 Henry Mall
Genetics–Biotechnology Center Building
Madison, WI 53706
Email: jyu@primate.wisc.edu
Marion Zatz
National Institute of General Medical Sciences
45 Center Drive, MSC 6200
Bethesda, MD 20892-6200
Phone: 301-594-0943
Email: zatzm@nigms.nih.gov
Nadja Zeltner
Mount Sinai School of Medicine
26 49th Street, Apartment 3
Weehawken, NJ 07086
Phone: 212-659-8247
Email: nadja.zeltner@mssm.edu
Xin Zhang
Mount Sinai School of Medicine
1425 Madison Avenue, Room 13-76
New York, NY 10029
Phone: 212-659-8266
Email: xin.zhang@mssm.edu
