Investigators

Dave Gilbert, Ph.D.

Professor
Genome Structure & Function

Research Focus

Our goal is to understand how mammalian chromosomes are organized within the nucleus to carry out their functions. DNA replication provides and excellent forum in which to study chromosome structure and function. Structural and functional units of chromosomes replicate coordinately, often through the synchronous firing of clusters of replication origins that encompass domains of approximately 0.5 Mb. Each of these replication domains is programmed to replicate at a specific time during S-phase. In general, transcriptionally active (euchromatin) domains replicate early in S-phase, and transcriptionally silent (heterochromatin) domains replicate late. Programmed changes in replication timing accompany key stages of animal development and are often coupled to changes in gene expression.

Our working hypothesis is that structural, functional, and replication domains share topographical boundaries and represent basic units of chromosome organization. We would like to understand what regulates where and when replication begins, how developmental cues communicate with the cell-cycle machinery to elicit changes in the program for replication, and how that program is disrupted in cancer.

We have recently initiated a new approach to cancer research that addresses a longstanding need to understand why some cancers respond to treatment and others do not. We are hopeful this new approach will allow us to diagnose which molecular pathways are disrupted in cancers that defy treatment. In brief, cancer is a disease of DNA. The DNA of cancers contain unique “signatures” of re-arrangements that have occurred in the sequence of DNA. We propose that this history contains a code that can tell us which pathways have been disrupted, if we can crack the code. Together with a team of leaders in diverse aspects of cancer research, we have shown that we can create different patterns of DNA re-arrangements by perturbing different cancer-relevant pathways using easily manipulable cells in culture. By cataloging the DNA re-arrangements that results from perturbing various pathways, and comparing them to thousands of actual human cancers whose DNA has been sequenced, we intend to match pathways to signatures.

More on Dr. Gilbert’s research and lab can be found here.


Education

Ph.D. in DNA Replication, Stanford University, 1989
B.A. in Biochemistry/Cell Biology with a minor in Philosophy, University of California, San Diego, 1982


Professional Experience

2021 – Present, Professor, San Diego BioMed
2015 – 2018 Co-Founder of the Center for Genomics and Personalized Medicine
2006 – 2020 J.H. Taylor Distinguished Professor of Molecular Biology, Florida State University
2003 – 2006 Full Professor, SUNY Upstate Medical University
1998 – 2003 Associate Professor, SUNY Upstate Medical University
1994 – 1998 Assistant Professor, SUNY Health Science Center at Syracuse


Honors and Awards

Florida State University Graduate Faculty Mentorship Award, 2016
Florida State University Distinguished Research Professor Award, 2015
FSU Biology Pfeiffer Endowed Professorship for Cancer Research, 2015 – 2018
NIH Career Enhancement Award for Stem Cell Research, 2004 – 2005
SUNY Upstate President’s Award for Excellence in Research for a Young Professor, 2002


Professional Activities

Co-Chair and Chair, Gordon Research Conference on Genome Architecture, 2017 and 2019
Chair of the NIH 4D Nucleome Consortium Cell Lines and Samples WG Phase 1 and 2, 2016 – Present
Member of NIH 4-Dimensional Nucleome (4DN) Consortium, 2011 – Present
Member, International Society for Stem Cell Research, 2014 – Present
Elected member, American Society for Hematology, 2013 – Present
Member of NIH ENCODE2, ENDOCE3, and mouseENCODE constoria, 2011 – 2018
Elected Council Delegate of the AAAS, section on Biological Sciences, 2010 – 2013
Elected Fellow of the AAAS, 2008 – Present
Editorial Board, Journal of Cell Biology, 2008 – 2021
Board Member, Epigenetics Society, 2008 – Present
Board Member, SouthEast Stem Cell Consortium (SESCC), 2008 – 2018
Peer Review, American Cancer Society, 1996 – 2004
Peer Review, NIH, 1997 – Present
Peer Review, US Army Reserve Medical Corps Breast Cancer Program, 1995 – 1998
Roache Post-Doctoral Fellowship, 1991 – 1994
Eur. Mol. Biol. Org Post-Doctoral Fellowship, 1989 – 1991

Select Publications

Daniel A. Bartlett, Vishnu Dileep, Steve Henikoff, David M. Gilbert. High throughput genome-wide single cell protein:DNA binding site mapping by targeted insertion of promoters (TIP-seq). bioRxiv 2021.03.17.435909; doi: https://doi.org/10.1101/2021.03.17.435909.

Daniel Emerson, Peiyao A. Zhao, Kyle Klein, Chunmin Ge, Linda Zhou, Takayo Sasaki, Liyan Yang, Sergey V. Venvev, Johan H. Gibcus, Job Dekker, David M. Gilbert, Jennifer E. Phillips-Cremins. (2022) Cohesin-mediated loop anchors confine the location of human replication origins. NATURE, in press

Weitao Wang, Kyle Klein, Karel Proesmans, Hongbo Yang, Claire Marchal, Xiaopeng Zhu, Tyler Borman, Alex Hastie, Zhiping Weng, John Bechhoefer, Chun-Long Chen, David M. Gilbert, Nicholas Rhind. Genome-Wide Identification of Early-Firing Human Replication Origins by Optical Replication Mapping. MOLECULAR CELL, 81:2975-2988. (PMID: 34157308)

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Kyle N. Klein, Peiyao A. Zhao, Xiaowen Lyu, Daniel A. Bartlett, Amar Singh, Ipek Tasan, Lotte P. Watts, Shin-ichiro Hiraga, Toyoaki Natsume, Xuemeng Zhou, Danny Leung, Masato T. Kanemaki, Anne D. Donaldson, Huimin Zhao, Stephen Dalton, Victor G. Corces, David M. Gilbert. Replication timing maintains the global epigenetic state in human cells SCIENCE, 2021 April 23;372(6540): 371-378. doi: 10.1126/science.aba5545. Epub 2021 Apr 22. PMID: 33888635.

Sarni, D., Sasaki, T., Miron, K., Tur-Sinai, M.I., Rivera-Mulia, J.C., Magnuson, B., Jjungman, M., Gilbert D.M. and Karem, B. (2020) 3D genome organization contributes to genome instability at fragile sites. NAT. COMM., 11(1):3613 (PMID: 32680994).

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Zhao, PA, Sasaki, T., Gilbert, D.M. (2020) High Resolution Repli-Seq defines the temporal choreography of initiation, elongation and termination of replication in mammalian cells. GENOME BIOL. 21: 76 (PMID: 32209126)

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Rivera-Mulia, JC, Sasaki, T., Trevilla-Garcia, C., Nakemichi, N., Knapp, DJHF, Hammond, C., Chang, B., Tyner, J.W., Devidas, M., Zimmerman, J., Klein, K.K., Somasundaram, V., Druker, B., Gruber, T., Koren, A., Eaves, C.J., Gilbert, D.M. (2019) Replication timing alterations in leukemia affect clinically relevant chromosome domains. BLOOD ADV. 3: 3201-3213 (PMID: 31698451)

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Marchal C., Sima J., Gilbert D.M. (2019) Control of DNA replication timing in the 4D genome. NATURE REV. MOL. CELL. BIOL., 20:721-737 (PMID: 31477886)

Dileep, V., Wilson, KA, Marchal, C, Lyu, X, Zhao, PA, Li, B., Poulet, A., Bartlett, D.A., Rivera-Mulia, JC, Qin, Z., Robins, A.J., Schulz, T.C., Kulik, M.J., Dalton S., Corces, V.G., Gilbert, D.M. (2019) Early differentiation of human embryonic stem cells is accompanied by rapid transcriptional re-programming and discordance between replication timing and chromatin compartment. STEM CELL REPORTS 13:193-206 (PMID: 31231024)

Sima J, Chakraborty A, Dileep V, Michalski M, Klein K.N., Holcomb N.P., Turner J.L., Paulsen M.T., Rivera-Mulia JC, Trevilla-Garcia C, Bartlett DA, Zhao PA, Washburn BK, Nora EP, Kraft K, Mundlos S, Bruneau BG, Ljungman M, Fraser P, Ay F, Gilbert DM. (2019) Identifying cis-Elements for Spatiotemporal Control of Mammalian DNA Replication. CELL 176:816-830 (PMID 30595451)

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Complete list of Dr. Gilbert’s published work.

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Our research programs are funded primarily by grants from the National Institutes of Health (NIH). Private donations help to accelerate the progress of research through the purchase of laboratory supplies and equipment or the recruitment of additional laboratory personnel. Thank you!

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