BIOGRAPHICAL SKETCH
Provide the following information for the Senior/key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME
POSITION TITLE
David M. Gilbert
Professor
eRA COMMONS USER NAME (credential, e.g., agency login)
gilbertdm
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable.)
DEGREE
INSTITUTION AND LOCATION
MM/YY
FIELD OF STUDY
(if applicable)
U.C. San Diego, La Jolla, CA.
Stanford University, Stanford, CA
Faculté de Médecine, Strasbourg, FRANCE
Roche Institute of Mol. Biol., Nutley, N.J.
B.A.
Ph.D.
Post-Doc
Post-Doc
05/82
11/89
11/91
08/94
Biochemistry/Cell Biol.
DNA Replication
Chromatin/Transcription
DNA Replication
A. Personal Statement
I have a broad background in cell and molecular biology, particularly as it pertains to DNA replication, chromatin structure, transcription and nuclear organization. As a graduate student I pioneered studies of replication
timing (RT) and its relationship to gene expression. I was the first to apply anti-BrdU antibodies to replication
studies prior to their commercialization by BD, and I developed the FACS-based method to analyze RT that is
currently used for almost all systems. I then broadened my perspective by studying transcriptional control and
chromatin structure in budding yeast as a post-doc with Pierre Chambon, followed by a second post-doc with
Melvin DePamphilis studying replication origins in mammals, where I developed a cell-free system to study cell
cycle control of replication origin selection. I made seminal contributions to each of these fields, and have always strived to shift paradigms rather than contribute to the status quo. As PI on several NIH-funded grants, I
discovered two novel G1-phase control points when RT and origin site selection are determined. These discoveries revealed links between replication control and large-scale chromatin reorganization in the newly
formed nucleus. Several years ago, I expanded my research to study developmental control of RT using embryonic stem cell differentiation systems. I laid the groundwork for the proposed research by systematically
characterizing where and when differentiation-induced changes in RT take place during early development,
and how these changes relate to changes in transcription and sub-nuclear organization of chromatin during the
course of differentiation. I also maintain the largest worldwide database of RT in different cell types (replicationdomain.org). I am excited that our recent findings with leukemic cells could provide a translational avenue
for our work. The fact that my laboratory is arguably the most uniquely positioned to carry out this work instills
a sense of obligation. I recognize my inexperience with clinical collaborations and I am committed to address
this weakness. I have successfully collaborated with Drs. Druker and Chang, leaders in both the diagnosis and
treatment of leukemia, who will continue to consult with me throughout the project (see letters and biosketches). I have been awarded an NIH R21 to identify RT abnormalities in leukemia. Dr. Chang performed his PhD
work in the area of RT, making him a unique liaison between clinicians and myself. A newfound partnership
with Drs. Connie Eaves and Sherman Weissman also brings strong hematopoiesis and leukemia expertise to
this project. I am now a member of ASH and attend annual ASH meetings to familiarize myself with the resources, approaches and people in the field. Altogether, I am on a sharp learning curve but my track record
indicates that I will quickly put myself in a position to make important contributions to the cancer field.
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B. Positions and Honors
Professional Positions
9/94-6/98
6/98-4/03
4/03–8/06
8/06-Present
Assistant Professor, SUNY Health Science Center at Syracuse (SUNY HSC)
Associate Professor, SUNY Upstate Medical University (formerly SUNY HSC)
Full Professor, SUNY Upstate Medical University
J. Herbert Taylor Distinguished Professor of Molecular Biology, Florida State University
Awards and Other Professional Activities
1989-1991
1990
1991-1994
1995-1998
1997-Present
1996-2004
2002
2004
2004-2005
2004-2006
2008-Present
2008-Present
2008-Present
2008-Present
2010-Present
2011-Present
2013-Present
Eur. Mol. Biol. Org. (EMBO) Post-Doctoral Fellowship
NATO Post-Doctoral Fellowship (declined)
Roche Post-Doctoral Fellowship
Peer Review for the US Army Reserve Medical Corps Breast Cancer Program
Peer Review for NIH
Peer Review for the American Cancer Society
SUNY Upstate President’s Award for Excellence in Research for a Young Investigator
Nominated as a Howard Hughes Medical Institute Investigator
NIH Career Enhancement (K18) Award for Stem Cell Research
Selected to compete in Phase II of the NIH Director's Pioneer Award (NDPA)
Board Member, SouthEast Stem Cell Consortium (SESCC)
Board Member, Epigenetics Society
Editorial board; Journal of Cell Biology
Elected Fellow of the AAAS
Elected Council Delegate of the AAAS, section on Biological Sciences
Member of NIH ENCODE2, ENCODE3 and mouseENCODE consortia
Elected member of the American Society for Hematology (ASH)
C. Publications
1. Gilbert, D.M. (1986) Temporal order of replication of Xenopus laevis 5S ribosomal RNA genes in somatic
cells. PROC. NAT. ACAD. SCI. USA 83, 2924-2928.
2. Gilbert, D.M. and Cohen, S.N. (1987) Bovine papilloma virus plasmids replicate randomly in mouse fibroblasts throughout S-phase of the cell cycle. CELL 50, 59-68.
3. Hertel-Wulff, B., Lindsten, T., Schwadron, R., Gilbert, D.M., Davis, M. and Strober, S. (1987) Rearrangement and expression of T-cell receptor genes in cloned murine natural suppressor cell lines. J. EXP. MED.
166, 1168-1173.
4. Gilbert, D.M. and Cohen, S. N. (1988) Autonomous replication in mouse cells. CELL 56, 143-144.
5. Gilbert, D.M. and Cohen, S.N. (1990) Position effects on the timing of replication of chromosomally integrated simian virus 40 molecules in chinese hamster cells. MOL. CELL. BIOL 10, 4345-4355.
6. Ten-Hagen, K., Gilbert, D.M., Willard, H. and Cohen, S.N. (1990) Replication timing of DNA sequences
associated with human centromeres and telomeres. MOL. CELL. BIOL. 10, 6348-6355.
7. Gilbert, D.M., Hernandez, R. and Cohen, S.N. (1992) Mouse genomic DNA sequences homologous to sea
urchin TU elements are genetically stable polydispersed repeats useful for analysis of multiple RFLP's.
GENOMICS 12, 357-362.
8. Ravnan, J. B., Gilbert, D.M., Ten Hagen, K., and Cohen, S.N. (1992) Random-choice replication of extrachromosomal bovine papillomavirus (BPV) molecules in heterogeneous, clonally derived BPV-infected
cell lines. J. VIROLOGY 66, 6946-6952.
9. Gilbert, D.M., Losson, R. and Chambon, P.C. (1992) Ligand dependence of estrogen receptor induced
changes in chromatin structure. NUCL. ACIDS RES. 20, 4525 - 4531.
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10. Gilbert D.M., Heery, D.M., Losson, R., Chambon, P. and Lemoine, Y. (1993) Estradiol-inducible squelching and cell growth arrest by a chimeric VP16-estrogen receptor expressed in Saccharomyces cerevisiae:
suppression by an allele of PDR1. MOL. CELL. BIOL. 13, 462-472.
11. Gilbert, D.M., Miyazawa, H., Nallaseth, F.S., Ortega, J.M., Blow, J.J. and DePamphilis, M.L. (1993) Sitespecific initiation of DNA replication in metazoan chromsomes and the role of nuclear organization. COLD
SPRING HARBOR SYMP. QUANT. BIOL. 58, 475-485.
12. Gilbert, D.M., Neilson, A., Miyazawa, H., DePamphilis, M. L. and Burhans, W. C. (1995) Mimosine arrests
DNA synthesis at replication forks by inhibiting deoxyribonucleotide metabolism, J. BIOL. CHEM. 270,
9597-9606.
13. Gilbert, D.M., Miyazawa, H. and DePamphilis, M.L. (1995) Site-specific initiation of DNA replication in
Xenopus egg extracts requires nuclear structure. MOL. CELL. BIOL. 15, 2942-2954.
14. Wu, J.W. and Gilbert, D. M. Rapid DNA preparation for 2D gel analysis of replication intermediates.
(1995) NUCL. ACIDS RES. 23: 3997-3998.
15. Wu, J.W. and Gilbert, D. M. (1996) A Distinct G1 Step Required to Specify A Mammalian Replication
Origin SCIENCE 271: 1270-1272.
16. Lawlis, SJ, Keezer, S.M., Wu, J.-R. and Gilbert, DM. (1996) Chromosome Architecture Can Dictate Sitespecific Initiation of DNA Replication in Xenopus Egg Extracts J. CELL BIOL. 135: 1207-1218.
17. Wu, J.-W. and Gilbert, DM (1997) The Replication Origin Decision Point is a Mitogen Independent, 2Aminopurine Sensitive, G1-Phase Event That Precedes Restriction Point Control. MOL. CELL. BIOL.17:
4312-4321.
18. Wu, J.-W., Yu, G. and Gilbert, D.M. (1997) Origin-Specific Initiation of Mammalian Nuclear DNA Replication in a Xenopus Cell-Free System. METHODS, A Companion to Methods In Enzymology 13:313-324
19. Gilbert, D.M. (1998) Replication origins in yeast versus metazoa: separation of the haves and the have
nots. CURR. OPIN. GEN. DEV. 8: 194-199.
20. Wu, J.-W. and Gilbert, D.M. (1998) Transformation Abrogates an Early G1-Phase Arrest Point Required
for Specification of the Chinese Hamster DHFR Replication Origin EMBO J. 17: 1810 - 1818.
21. Dimitrova, D.S and Gilbert, D.M. (1998) Regulation of Mammalian Replication Origin Usage in Xenopus
Egg Extract. J. CELL SCI. 111: 2989-2998.
22. Yu, G, Wu, J.-W. and Gilbert, D.M. (1998) Analysis of mammalian origin specification in ORC-depleted
Xenopus egg extracts. GENES TO CELLS 3: 709-721.
23. *Dimitrova, D.S., Todorov, I.T., Melendy, T. and Gilbert, D.M. (1999) Mcm2, But Not RPA, is a Component
of the Mammalian Early G1-Phase pre-Replication Complex. J. CELL BIOL. 146: 1-14.
24. Dimitrova, D.S. and Gilbert, D. M. (1999) The spatial position and replication timing of chromosomal domains are both established in early G1-phase. MOL. CELL 4: 983-993.
25. Dimitrova, D.S. and Gilbert, D.M. (1999) DNA replication and nuclear organization: prospects for a soluble
in vitro system. CRIT. REV. GENE EXP. 9: 353-361.
26. Izumi, M and Gilbert, D.M. (1999) Homogeneous Tetracycline-Regulatable Gene Expression in Mammalian Fibroblasts, J. CELLULAR BIOCHEM. 76: 280-289.
27. Dimitrova, D.S. and Gilbert, D.M. (2000) Stability and nuclear distribution of mammalian RPA heterotrimeric complex. EXP. CELL RES. 254: 321-327.
28. Dimitrova, D.S. and Gilbert, D.M. (2000) Temporally Coordinated Assembly/Disassembly of Replication
Factories in the Absence of DNA Synthesis, NATURE CELL BIOLOGY 2: 686-694.
29. Wu, J.-W., Wang, J.-W. and Gilbert, D.M. (2000) Initiation Of DNA Replication In Saccharomyces Cerevisiae G1-Phase Nuclei By Xenopus Egg Extract, J. CELLULAR BIOCHEM. 80: 73-84.
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30. Izumi, M, Whitfield, W. G. F., Hutchison, C. J. and Gilbert, D.M. (2000) Head and/or CaaX domain deletions of lamin proteins can disrupt pre-formed lamin A/C but not lamin B structure in mammalian cells,
MOL. BIOL. CELL. 11: 4323-4337.
31. Wu, J.-W. and Gilbert, D.M. (2000) Lovastatin Arrests CHO Cells Between the Origin Decision Point and
the Restriction Point, FEBS LETTERS 484: 108-112.
32. Gilbert, D. M. (2001) Nuclear Position Leaves its Mark on Replication Timing, J. CELL BIOL. 152: F11F15.
33. Li, F., Chen, J., Izumi, M., Butler, M.C., Keezer, S. M. and Gilbert, D.M. (2001) The Replication Timing
Program of the Chinese Hamster -Globin Locus is Established Coincident With its Association With Peripheral Heterochromatin in Early G1-Phase, J. CELL BIOL. 154: 283-292.
34. Okuno, Y., McNairn, A.J., den Elzen, N., Pines, J. and Gilbert, D.M. (2001) Stability, ChromatinAssociation and Functional Activity of Mammalian Pre-Replication Complex Proteins During the Cell-Cycle,
EMBO J. 20: 4263-4277.
35. Feijoo, C., Hall-Jackson, C., Wu, R., Jenkins, D., Leitch, J., Gilbert, D.M. and Smythe, C (2001) Activation
of mammalian Chk1 during DNA replication arrest: a role for Chk1 in the intra S-phase checkpoint monitoring replication origin firing. J. CELL BIOL. 154: 913-923.
36. Gilbert, D. M. (2001) Making Sense of Eukaryotic Origins of Replication, SCIENCE 294: 96-100.
37. Dimitrova, D.S., Prokhorova, T.A., Blow, J.J., Todorov, I. and Gilbert, D.M. (2002) Mammalian Nuclei Become Licensed for DNA Replication During Telophase, J. CELL SCI. 115: 51-59.
38. Keezer, S.M. and Gilbert, D.M. (2002) Sensitivity of the Origin Decision Point to Specific Inhibitors of Cellular Signaling and Metabolism, EXP. CELL RES. 273: 54-64.
39. *Keezer, S.M. and Gilbert, D.M. (2002) Evidence for a Pre-Restriction Point Cdk3 Activity, J. CELLULAR
BIOCHEM. 85: 545-552
40. Cowell, I.G., Aucott, R., Mahadevaiah, S., Burgoyne, P.A., Huskisson, N., Bongiorni, S., Prantera, G., Fanti, L., Pimpinelli, S., Wu, R., Gilbert, D.M., Shi, W., Fundele, R., Morrison, H., Jeppesen, P. and Singh, P.B.
(2002) Heterochromatin, HP1 and methylation at lysine 9 of histone H3 in animals, CHROMOSOMA 111:
22-36.
41. Gilbert, D.M. (2002) Replication timing and transcriptional control: beyond cause and effect. CURR. OPIN.
CELL BIOL. 14: 377-383.
42. Gilbert, D.M. (2002) The Evolution of Replication Timing. NATURE GENETICS 32:336-337.
43. Cheutin, T., McNairn, A.J., Jenuwein, T., Gilbert, D.M., Singh, P.B., Misteli, T. (2003) Maintenance of stable heterochromatin domains by dynamic HP1 binding. SCIENCE 299: 721-725.
44. Li, F., Chen, J. Solessio, E., and Gilbert, D.M. (2003) Spatial distribution and specification of
mammalian replication origins during G1-phase. J. CELL BIOL. 161:257-266.
45. McNairn, A.J. and Gilbert, D.M. (2003) Epigenomic Replication: linking epigenetics to DNA replication.
BIOESSAYS 25(7): 647-56.
46. Okuno, Y., Hahn, P.J. and Gilbert, D.M. (2004) Structure of a Palindromic Amplicon Junction Implicates
Microhomology-Mediated End Joining as a Mechanism of Sister Chromatid Fusion During Gene Amplification. NUCL. ACIDS RES. 32: 749-756.
47. Bettinger, B., Gilbert, D.M. and Amberg, D.C. (2004) Actin Up in the Nucleus., NATURE REV. MOL.
CELL BIOL. 5: 410-415.
48. Gilbert, D.M. (2004) The Future of Human Embryonic Stem Cell Research: Addressing Ethical
flict with Responsible Scientific Research. MED. SCI. MON. 10: 99-103.
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49. Kourmouli, N., Jeppesen, P., Mahadevhiah, S., Burgoyne, P., Wu, R., Gilbert, D.M., Bongiorni, S.,
Prantera, G., Fanti, L., Pimpinelli, S., Shi, W., Fundele, R. and Singh, P.B. (2004) Heterochromatin and trimethylated lysine 20 of histone H4 in animals. J. CELL SCI. 117: 2491-2501.
50. Angus, S.P, Mayhew, C.N., Solomon, D.A., Markey, M.P., Okuno, Y., Bartek, J., Cardoso, M.C., Gilbert,
D.M and Knudsen E.S. (2004) RB reversibly inhibits DNA replication via two temporally distinct mechanisms. MOL. CELL. BIOL. 24: 5404-5420.
51. Gilbert, D.M. (2004) In Search of the Holy Replicator NATURE REV. MOL. CELL BIOL. 5:1-8.
52. Hiratani, I., Leskovar, A., Gilbert D.M. (2004) Differentiation-Induced Replication Timing Changes are Restricted to AT/LINE-rich Isochores. PROC. NAT. ACAD. SCI. 101: 16861-6.
53. Panning, M.M. and Gilbert, D.M. (2005) Spatio-temporal organization of DNA replication in murine embryonic stem, primary, and immortalized cells. J. CELL. BIOCHEM. 95: 74-82.
54. Wu, R., Terry, A.V., Singh, P.B., and Gilbert, D.M. (2005) Differential Sub-nuclear Localization and Replication Timing of Histone H3 Lysine 9 Methylation Sites. MOL. BIOL. of the CELL 16: 2872-2881.
55. McNairn, A.J., Okuno, Y.O., Misteli, T. and Gilbert, D.M. (2005) Chinese Hamster ORC Subunits Dynamically Associate With Chromatin Throughout the Cell Cycle. EXP. CELL RES. 308:345-56.
56. McNairn, A.J. and Gilbert, D.M. (2005) Over-expression of ORC Subunits and Increased ORC-Chromatin
Association in Transformed Mammalian Cells. J. CELL. BIOCHEM. 96: 879-887
57. Gilbert, D.M. (2005) Origins Go Plastic, MOL. CELL 20:657-658.
58. Wu, R., Terry, A. and Gilbert, D.M. (2006) Observing Nuclear Structure/Chromatin Changes with
rescently labeled Antibodies. METHODS IN MOL. BIOL. 325:139-148
Fluo-
59. Takayo Sasaki, Sunita Ramanathan, Yukiko Okuno, Chiharu Kumagai, Seemab S. Shaikh and Gilbert,
D.M. (2006) The Chinese Hamster DHFR Replication Origin Decision Point Follows Activation of Transcription and Confines Initiation to the Intergenic Region, MOL. CELL. BIOL. 26:1051-1062.
60. Gilbert, D.M. and Gasser, S.M. (2006) Nuclear Structure and DNA Replication. In: DNA replication and
human disease. CSH Press (ed. M. L. DePamphilis), Cold Spring Harbor Laboratory Press, Cold Spring
Harbor, New York: 175-196
61. Wu, R., Singh, P.B. and Gilbert, D.M. (2006) Uncoupling Global and Fine-Tuning Replication Timing Determinants for Mouse Peri-Centric Heterochromatin. J. CELL BIOL., 174: 185-194.
62. Gilbert, D.M. (2007) Replication Origin Plasticity, Taylor-Made: inhibition vs. recruitment of new origins under conditions of replication stress. CHROMOSOMA, 116: 341-347.
63. Sasaki, T. and Gilbert, D.M. (2007) The Many Faces of the Origin Recognition complex. CURR. OPIN.
CELL BIOL., 19:337-343.
64. Gilbert, D.M. and Zink, D. (2007) Nuclear Structure of Normal and Cancer Cells. GENOME BIOLOGY
8:312.
65. Lu J, Gilbert DM. (2007) Proliferation-Dependent and Cell-Cycle Regulated Transcription of Mouse Pericentric Heterochromatin. J. CELL BIOL. 179: 411-421.
66. Yokochi, T. and Gilbert, D.M. (2007) Methods for Visualizing Replication Origins in Mammalian Cells.
CURRENT PROTOCOLS IN CELL BIOLOGY 22.20.1.22.10.14 (PMC2636809)
67. Lu J. and Gilbert, D.M. (2008) Cell Cycle Regulated Transcription of Heterochromatin in Mammals vs. Fission Yeast: functional conservation or coincidence? CELL CYCLE 7: 1907-1910 (PMC2710769
68. Hiratani, I, Ryba, T, Itoh, M. Yokochi, T., Schwaiger, M., Chang, C-W, Lyou, Y. Townes, T.M., Schubeler,
D. and Gilbert, D.M. (2008) Global Re-organization of Replication Domains During Embryonic Stem Cell
Differentiation PLoS BIOLOGY 6: e25. (PMC2561079)
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69. Weddington, N., Stuy, A., Hiratani, I. Ryba, T., Yokochi, T. and Gilbert, D.M. (2008) ReplicationDomain: a
visualization tool and comparative database for genome-wide replication timing data. BMC Bioinformatics, 9:530 (PMC2636809)
70. Gilbert, D.M. (2009) Establishment of a Spatial and Temporal Program for Mammalian Chromosome Replication. PROTEIN, NUCLEIC ACID AND ENZYME 54: 320-326. (PMC3057877).
71. Hiratani, I. and Gilbert, D.M. (2009) Replication Timing as a Novel Epigenetic Mark. EPIGENETICS, 4: 9397. (PMC2688700)
72. Hiratani, I., Takebayashi, S., Lu, J. and Gilbert, D.M. (2009) Replication timing and transcriptional control:
beyond cause and effect. Part II. CURR. OPIN. GEN. DEV. 19: 142-149 (PMC2677117)
73. Yokochi, T, Poduch, K., Ryba, T, Lu, J., Hiratani, I., Tachibana, M., Shinkai, Y. and Gilbert, D.M. (2009)
G9a Selectively Represses a Class of Late-Replicating Genes at the Nuclear Periphery. PNAS 106:1936319368. (PMC2780741)
74. Hiratani, I., Ryba, T., Itoh, M., Rathjen, J., Kulik, M., Papp, B., Fussner, E., Bazett-Jones, D.P., Plath, K.,
Dalton, S., Rathjen, P.D., Gilbert, D.M. (2010) Genome-Wide Dynamics of Replication Timing Revealed by
In Vitro Models of Mouse Embryogenesis, GENOME RESEARCH, 20:155-169 (PMC2813472)
75. Pope, BD, Hiratani, I and Gilbert, D.M. (2010) Domain-wide regulation of DNA replication timing during
mammalian development, CHROMOSOME RESEARCH, 18:127-136 (PMC2827620)
76. Hiratani, I. and Gilbert, D.M. (2010) Autosomal Lyonization of Replication Domains During Early Mammalian Development. In: The Cell Biology of Stem Cells (ed. E. Meshorer and K. Plath) Landes Biosciences,
Austin, Texas. ADV. EXP. MED BIOL. 695: 41-58 (PMID: 21222198)
77. Ryba, T., Hiratani, I., Lu, J., Itoh, M., Kulik, M., Zhang, J., Dalton, S. and Gilbert, D.M. (2010) Evolutionarily
conserved replication timing profiles predict long range chromatin interactions and distinguish closely related cell types. GENOME RESEARCH 20:761-770 (PMC2877573).
78. Lu, J., Li, F., Murphy, C.S., Davidson, M.W. and Gilbert, D.M. (2010) G2-Phase Chromatin Lacks Determinants of Replication Timing. J. CELL BIOLOGY, 89 955-965 (PMC2886351)
79. Pombo, A. and Gilbert D.M. (2010) Nucleus and Gene Expression: the structure function conundrum.
CURR. OPIN. CELL BIOL. 22: 269-270
80. Gilbert, D. M. (2010) Evaluating genome-scale approaches to eukaryotic DNA replication. NATURE REVIEWS GENETICS 11(10): 673-684 (PMC2962615)
81. Gilbert, D.M., Takebayashi, S., Ryba, T, Lu, J., Pope B.D., Wilson, K.A., and Hiratani, I. (2010) Space and
Time in the Nucleus: Developmental Control of Replication Timing and Chromosome Architecture. COLD
SPRING HARBOR SYMP. QUANT. BIOL., LXXV, ePub ahead of print. (PMID: 21139067)
82. Gilbert, D.M. (2010) Cell fate transitions and the replication timing decision point. J. CELL BIOL. 191: 899903. (PMC2995162)
83. Lubelsky, Y, Sasaki, T., Kuipers, M.A., Lucas, I., Le Beau, M.M., Carignon, S., Debatisse, M., Prinz, J.A.,
Dennis, J. H. and Gilbert, D.M. (2011) Pre-replication complex proteins assemble at regions of low nucleosome occupancy within the Chinese hamster dihydrofolate reductase initiation zone, NUCL. ACIDS RES.,
39:3141-3155 (PMC3082903)
84. Ryba, T., Battaglia, D., Pope, B.D., Hiratani, I. and Gilbert, D.M. (2011) Genome-Scale Analysis of Replication Timing: from Bench to Bioinformatics. NATURE PROTOCOLS, 6:870-895 (PMC3111951)
85. Kuipers, M.A., Stasevich, T.J., Sasaki, T., Wilson, K.A., Hazelwood, K.L., McNally, J.G., Davidson, M.W.
and Gilbert, D.M. (2011) Highly stable loading of Mcm proteins onto chromatin in living cells requires replication to unload. J CELL BIOL. 192:29-41. (PMC3019549)
86. Shirley, J.W., Ty, S., Takebayashi, S., Liu, X. and Gilbert, D.M. (2011) FISH Finder: A High-Throughput
Tool for Analyzing FISH Images. BIOINFORMATICS. 27:933-938. (PMC3065689)
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87. Gilbert, D.M. and Wallrath, L.L. (2011) Chromatin and chromosomes. MOL BIOL CELL. 22:717
(PMC3057689)
88. Ryba, T., Hiratani, I., Sasaki,T., Battaglia, D., Kulik, M., Zhang, J., Dalton, S., Gilbert, D.M. (2011) Replication Timing: A Fingerprint for Cell Identity and Pluripotency. PLoS COMPUTATIONAL BIOL e1002225
(PMC3197641)
89. Sasaki, T., Li, A., Gillespie, P., Blow, J.J., Gilbert, D.M. (2011) Evidence For a Mammalian Late-G1 Phase
Inhibitor of Replication Licensing Distinct From Geminin or Cdk Activity. NUCLEUS 2: 455-464
(PMC332585)
90. Pope, B.D., Tsumagari, K., Battaglia, D., Ryba, T., Hiratani, I., Ehrlich, M., Gilbert, D.M. (2011) DNA Replication Timing is Maintained Genome-wide in Primary Human Myoblasts Independent of D4Z4 Contraction
in FSH Muscular Dystrophy. PLoS ONE 6:e27413 (PMC3214052)
91. Wang, X., Takebayashi, SI, Bernardin, E., Gilbert, DM, Chella, R., Guan, J. (2012) Microfluidic extraction
and stretching of chromosomal DNA from single cell nuclei for DNA fluorescence in situ hybridization. BIOMED MICRODEVICES 14: 443-451 (PMC3425352)
92. Wu, X., Robotham, J.M., Lee, E., Dalton, S., Kneteman, N.M, Gilbert, D.M., Tang, H. (2012) Productive
Hepatitis C Virus Infection of Stem Cell-Derived Hepatocytes Reveals a Critical Transition to Viral Permissiveness during Differentiation PLoS PATHOGENS 8: e1002617 (PMC3320597).
93. Ryba, T., Battaglia, D, Chang, B.H., Shirley, J.W., Buckley, Q., Pope, B.D., Devidas, M., Druker, B.J., Gilbert, D.M. (2012) Abnormal Developmental Control of Replication Timing Domains in Pediatric Acute Lymphoblastic Leukemia. GENOME RESEARCH, 22: 1833-1844. (PMC3460179).
94. Pope, B.D., Chandra, T., Buckley, Q., Hoare, M., Ryba, T., Wiseman, F.K., Kuta, A., Wilson, M.D., Odom,
D.T., Gilbert, D.M. (2012) Replication-timing boundaries facilitate cell-type and species-specific regulation
of a rearranged human chromosome in mouse. HUMAN MOL. GEN., 21: 4162-4170. (PMC3441118).
95. Dileep, V., Didier, R., Gilbert, D.M. (2012) Genome-wide Analysis of Replication Timing In Mammalian
Cells: troubleshooting problems encountered when comparing different cell types. METHODS, A Companion to Methods In Enzymology, 52: 165-169. (PMC3432148).
96. Rhind, N. and Gilbert, D.M. (2012) Replication Timing. In: DNA replication and human disease. CSH
Press (ed. M. L. DePamphilis and M. Mechali), Cold Spring Harbor Laboratory Press, Cold Spring Harbor,
New York, in press.
97. Takebayashi, S., Dileep, V., Ryba, T., Dennis, J.H. and Gilbert, D.M. (2012) Chromatin-interaction compartment switch at developmentally regulated chromosomal domains reveals an unusual principle of chromatin folding. PNAS 109:12574-12579 (PMC3411983).
98. Mouse ENCODE Project Consortium [86 total authors] (2012) An Encyclopedia of Mouse DNA Elements
(Mouse ENCODE). GENOME BIOL. 13:418 (PMC3491367).
99. Gilbert, D.M. (2012) “Human Reproduction in the 21st Century”, Haden-McNeil, LLC (course text book)
100. Chandra, T. et. al., [26 additional authors], Gilbert, D.M. and Narita, M. (2012) Independence of Repressive Histone Marks and Chromatin Compaction During Senescent Heterochromatic Layer Formation.
MOL. CELL 47:203-214 (PMID:22795131). PMC Journal – In Process
101. Gilbert, D.M. (2012) Replication Origins Run (Ultra) Deep. NAT. STR. MOL. BIOL. 19:740-742 (PMID:
22864361)
102. Cornacchia, D., Dileep, V., Quivy, J.P., Foti R., Tili, F., Almouzni, G., Gilbert, D.M. and Buonomo, S.B.C.
(2012) Mouse Rif1 is a key regulator of the replication-timing program in mammalian cells. EMBO J., 31:
3678-3690. (PMC3442270)
103. Takebayashi, S., Ryba, T., Gilbert, D.M. (2012) Developmental control of replication timing defines a new
breed of chromosomal domains with a novel mechanism of chromatin unfolding. NUCLEUS 3: 500-507.
(PMC3515532)
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104. Liu, J., Kirkland, B, Shirley, J., Wang, Z., Zhang, P., Stembridge, J., Wong, W., Takebayashi, S., Gilbert,
D.M., Lenhert, S. and Guan J. (2013) Development of single-cell array for large-scale DNA fluorescence in
situ hybridization. LAB ON A CHIP 13:1316-1324. (PMC3594524)
105. Pope BD, Aparicio OM, Gilbert D.M. (2013) SnapShot: Replication timing. Cell 152: 1390.e1. doi:
10.1016/j.cell.2013.02.038. (PMID: 23498945) PMC Journal – In Process
106. Pope BD, Gilbert D.M. (2013) The Replication Domain Model: Regulating Replicon Firing in the Context
of Large-Scale Chromosome Architecture. J MOL. BIOL. doi:pii: S0022-2836(13)00245-3.
10.1016/j.jmb.2013.04.014. [Epub ahead of print] (NIHMSID #479317)
107. Kirkland B, Wang Z, Zhang P, Takebayashi S, Lenhert S, Gilbert DM, Guan J. (2013) Low-cost fabrication
of centimetre-scale periodic arrays of single plasmid DNA molecules. LAB ON A CHIP 13(17):3367-72. doi:
10.1039/c3lc50562f. (NIHMS #501676)
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D. Research Support
Ongoing Research Support
R01 GM083337-05
Gilbert (PI)
2/13/12 - 12/31/15
"cis-Acting Elements regulating developmental control of replication timing”
This proposal focuses on the identification of cis-acting DNA/chromatin elements that delineate units of replication timing using chromosome engineering methods developed in mouse ES cells.
P01 GM085354
Dalton (PI)
8/1/08 – 1/31/14
“Understanding Mechanisms of hESC Self-Renewal and Cell Fate Commitment”
Principle Investigator: Stephen Dalton, PhD
Agency: NIH
My subproject of this PPG, entitled “Replication Domain Organization during hESC Differentiation”, investigates replication timing during human embryonic stem cell differentiation to determine aspects of the replication program that are conserved between mouse and human.
Role: Co-PI (PI of subproject)
R21 CA161666-01A1
Gilbert (PI)
12/7/12-11/31/14
“Replication Profiling as a diagnostic tool in B-cell Acute Lymphoblastic Leukemia”
We propose to link unique features of the replication-timing program to ALL patient outcome by analyzing replication-timing profiles from patient cohorts with known outcomes that lack strong prognostic features.
Research Support Completed During the Last Three Years
PO1 GM085354-02S1
Gilbert (PI)
9/30/09 - 8/31/11
Administrative Supplement for Human Embryonic Stem Cell Biology
This supplement explored the structure of the human embryonic stem cell cycle.
R01 GM083337
Gilbert (PI)
9/30/07 - 2/12/12
"Genome Plasticity During ES Cell Differentiation to Neural Lineages”
The major goal of this project was to investigate mechanisms and significance of replication timing changes
during mouse ES neural differentiation.
Technology Transfer Feasibility (TTF), Bankhead-Coley Cancer Research Program
Gilbert (PI)
11/01/11-10/31/12
“Replication Profiling as a diagnostic tool in B-cell Acute Lymphoblastic Leukemia
This award investigated the feasibility of translating unique features of replication timing in leukemia cells into a
commercially viable diagnostic kit for replication timing as biomarkers (i.e. developed the FISH-based assay
proposed in Aim2 of this application).
Bridge grant, Bankhead-Coley Cancer Research Program
Gilbert (PI)
9/1/11-8/31/12
“Replication Profiling as a diagnostic tool in B-cell Acute Lymphoblastic Leukemia”
The goal of this pilot grant is to generate sufficient preliminary replication timing data with patient samples to
submit a proposal for federal funding (resulting in R21 CA161666-01A1).
Role: PI
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