Rothbart
Laboratory
Chromatin Signaling in Health and Disease
The Rothbart Laboratory investigates the molecular logic of chromatin signaling. We seek to understand how cells write, erase, read and interpret epigenetic information to regulate genome function, maintain cellular identity and respond to developmental, environmental and metabolic cues.
Our research combines biochemistry, cell biology, ‘omics’ technologies and cancer models to uncover mechanisms that regulate chromatin signaling networks. We study how these networks integrate diverse molecular inputs — including histone modifications, DNA methylation and cellular metabolism — to coordinate genome regulation in normal physiology and disease.
By uncovering molecular mechanisms that regulate chromatin signaling, we seek to establish fundamental principles of epigenetic regulation and reveal new therapeutic opportunities for cancers and other diseases driven by epigenetic dysfunction.
In parallel, we develop innovative technologies and molecular tools that enable the broader scientific community to investigate chromatin signaling with greater precision and accelerate discoveries in epigenetics research.
Recent News
Learn More
Fighting to outsmart cancer: A Q&A with graduate student Yanqing Liu
Using viral mimicry to help the immune system see — and fight — cancer
Pinpointing weaknesses in cancer’s armor
Chomiak AA, Tiedemann RL, Liu Y, Kong X, Cui Y, Wiseman AK, Thurlow KE, Cornett EM, Topper MJ, Baylin SB, Rothbart SB. 2024. Select EZH2 inhibitors enhance viral mimicry effects of DNMT inhibition through a mechanism involving NFAT:AP-1 signaling. Sci Adv 10(13).
Kong X#, Chen J#, Xie W# et al. 2019. Defining UHRF1 domains that support maintenance of human colon cancer DNA methylation and oncogenic properties. Cancer Cell.
Our Impact
We’re raising thousands to save millions.
We’re turning hope into action for the millions of people around the world affected by diseases like cancer and Parkinson’s. Find out how you can help us make a difference.
- 141 peer-reviewed papers published in 2025, 74 of which were in high-impact journals
- 15 VAI-SU2C Epigenetics Dream Team clinical trials launched to date
- 10 clinical trials and related projects supported by VAI through the International Linked Clinical Trials Program
Scott Rothbart, Ph.D.
Professor, Department of Epigenetics; Director, Cancer Epigenetics Training Program
Areas of Expertise
Chromatin biochemistry, cancer epigenetics, functional proteomics
Biography
Dr. Scott Rothbart is an internationally recognized expert in the field of epigenetics, particularly in the area of chromatin regulation through histone post-translational modifications. He earned a B.S. in food science and human nutrition from the University of Florida, followed by a Ph.D. in pharmacology and toxicology from Virginia Commonwealth University in the lab of Dr. Rick Moran. Dr. Rothbart then completed a postdoctoral fellowship in Dr. Brian Strahl’s lab at the University of North Carolina at Chapel Hill. He established his lab at Van Andel Institute in 2015 and rose through the ranks to full professor in 2023. Dr. Rothbart also is a basic science investigator on the Van Andel Institute–Stand Up To Cancer® Epigenetics Dream Team and director of the VAI Cancer Epigenetics Training Program. Dr. Rothbart’s work has contributed fundamental insights into mechanisms of epigenetic regulation and has introduced new tools and methodologies to the field. He is the recipient of numerous awards and honors, including a K99/R00 career development award from the National Cancer Institute, an R35 Maximizing Investigators’ Research Award (MIRA) from the National Institute of General Medical Sciences, and a Research Scholar Award from the American Cancer Society.
Projects
Chromatin signaling enables cells to organize, interpret and transmit epigenetic information across the genome. Our laboratory studies the molecular mechanisms that govern these signaling networks and how their disruption contributes to cancer and other human diseases.
Project Area 1: Signal recognition
How do chromatin-associated proteins recognize complex combinations of epigenetic signals?
Chromatin-associated proteins interpret combinations of histone modifications, DNA methylation and other chromatin features to regulate their localization and activity. We study the molecular mechanisms that enable chromatin reader proteins to decode these signals and direct genome regulation.
Project Area 2: Signal integration
How are diverse chromatin signals coordinated to regulate genome function?
Our work examines how histone modifications, DNA methylation, chromatin-associated proteins and cellular metabolism converge into integrated signaling networks that maintain epigenetic states and enable cells to respond to developmental and environmental changes.
Project Area 3: Signal inheritance
How is chromatin information faithfully transmitted through cell division?
We study the molecular mechanisms that preserve epigenetic information during DNA replication, with a particular focus on UHRF1-dependent signaling pathways that couple histone ubiquitination to maintenance DNA methylation. These studies provide fundamental insight into how epigenetic information is inherited across cell generations.
Project Area 4: Signaling dysfunction and therapeutic opportunities
How do disrupted chromatin signaling networks drive disease?
Defects in chromatin signaling contribute to cancer and numerous other diseases. We investigate how alterations in chromatin regulatory networks create therapeutic vulnerabilities and how these mechanisms can be exploited to develop more effective epigenetic therapies.
ArrayNinja is a portable, open source and interactive application that unifies the planning, visualization, and analysis of custom microarray experiments.
ArrayNinja is distributed as a virtual machine (VM) that runs a local and private web server. Because the tools are packaged as a VM and utilize a web browser as a user interface, ArrayNinja is platform agnostic.
Download and installation
Virtual Machine
The ArrayNinja VM is built to use VirtualBox, which is a free tool for building and running virtual machines. VirtualBox must be installed before the ArrayNinja VM can be used.
To download the ArrayNinja VM, visit https://hub.docker.com/r/bradleydickson/arrayninja/.
To run ArrayNinja, unzip the VM and load the VM into virtualbox. Once the VM is running, navigate your web browser to the localhost:2080.
Docker Application
ArrayNinja can be run on linux platforms via a docker application. The docker can be found at Docker Hub and it can be installed by pulling bradleydickson/arrayninja.
The docker app should be started with command:
docker run -d -p 2080:80 bradleydickson/arrayninja
License
Academic and not-for-profit
ArrayNinja is released under GNU General Public License, version 2. This program is free software; you can redistribute it and/or modify it under the terms of the GNU General Public License as published by the Free Software Foundation; version 2 of the License.
This program is distributed in the hope that it will be useful, but WITHOUT ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the GNU General Public License for more details.
You should have received a copy of the GNU General Public License along with this program; if not, write to the Free Software Foundation, Inc., 51 Franklin Street, Fifth Floor, Boston, MA 02110-1301, USA.
Contact
For business and licensing inquiries, please contact [email protected].
For scientific inquiries, please contact [email protected].
Citations
Dickson BM, Cornett EM, Ramjan Z, Rothbart SB. 2016. ArrayNinja: An open source platform for unified planning and analysis of microarray experiments. Methods Enzymol 574:53–57.
Publications
Dickson BM, Cornett EM, Ramjan Z, Rothbart SB. 2016. ArrayNinja: An open source platform for unified planning and analysis of microarray experiments. Methods Enzymol 574:53–57.
Cornett EM, Dickson BM, Vaughan RM, Krishnan S, Trievel RC, Strahl BD, Rothbart SB. 2016. Substrate specificity profiling of histone-modifying enzymes by peptide microarray. Methods Enzymol 574:31–52.
fABMACS is a flexible adaptively biased flavor of GROMACSv5.0.5. fABMACS was developed to maximize scalability of adaptive biasing so that better efficiency can be achieved when simulation systems are distributed across a large computing infrastructure.
Download and installation
fABMACS is available for download and use. Instructions and example inputs (for the ligand-protein system in the publication) are available as well. Please visit https://github.com/BradleyDickson/fABMACS.
License
Academic and not-for-profit
fABMACS is released under GNU General Public License, version 2. This program is free software; you can redistribute it and/or modify it under the terms of the GNU General Public License as published by the Free Software Foundation; version 2 of the License.
This program is distributed in the hope that it will be useful, but WITHOUT ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the GNU General Public License for more details.
You should have received a copy of the GNU General Public License along with this program; if not, write to the Free Software Foundation, Inc., 51 Franklin Street, Fifth Floor, Boston, MA 02110-1301, USA.
Contact
For questions about fABMACS or commercial use, contact [email protected].
Citations
Dickson BM, de Waal PW, Ramjan ZH, Xu HE, Rothbart SB. In press. A fast, open source implementation of adaptive biasing potential uncovers a ligand design strategy from the chromatin regulator BRD4. J Chem Phys. Article
Access to high-quality antibodies is a necessity for the study of histones and their posttranslational modifications (PTMs). The Histone Antibody Specificity Database is an online and expanding resource that catalogs the behavior of widely used, commercially available histone antibodies by peptide microarray. This interactive web portal provides a critical resource to the biological research community that routinely uses these antibodies as detection reagents for a wide range of applications.
Contact
Citations
Rothbart SB, Dickson BM, Raab JR, Grzybowski AT, Krajewski K, Guo AH, Shanle EK, Josefowicz SZ, Fuchs SM, Allis CD, Magnuson TR, Ruthenberg AJ, Strahl BD. 2015. An interactive database for the assessment of histone antibody specificity. Molecular Cell 59(3):502–511.
Publications
Dickson BM, Cornett EM, Ramjan Z, Rothbart SB. In press. ArrayNinja: An open source platform for unified planning and analysis of microarray experiments. Methods Enzymol.
Cornett EM, Dickson BM, Vaughan RM, Krishnan S, Trievel RC, Strahl BD, Rothbart SB. In press. Substrate specificity profiling of histone-modifying enzymes by peptide microarray. Methods Enzymol.
Rothbart SB, Dickson BM, Raab JR, Grzybowski AT, Krajewski K, Guo AH, Shanle EK, Josefowicz SZ, Fuchs SM, Allis CD, Magnuson TR, Ruthenberg AJ, Strahl BD. 2015. An interactive database for the assessment of histone antibody specificity. Molecular Cell 59(3):502–511.
We are continually seeking highly motivated individuals with a strong publication record to join us in our energetic, interactive and fast-paced environment. A Ph.D. with molecular biology experience is required to apply. Additional experience in biochemistry, proteomics, microarray and/or cell biology is preferred (but not necessary) as we seek individuals with high training potential. Interested candidates should email Dr. Rothbart to inquire. Graduate students interested in joining the lab are encouraged to apply through Van Andel Institute Graduate School.
Bradley Dickson, Ph.D.
VAI Staff Scientist
Joel Hrit, Ph.D.
Research Scientist, Department of Epigenetics
Regulatory mechanisms of maintenance DNA methylation by DNMT1
Yanqing Liu, M.Sc.
Ph.D. Student, VAI Graduate School
Research Focus: Mechanisms and therapeutic vulnerabilities of DNMTi-associated epigenetic plasticity
Amy Nuffesse
Senior Administrative Assistant II, Department of Epigenetics
Tian (Devin) Qiu, M.S.
Ph.D. Student, VAI Graduate School
Research Focus: Spatial multi-omics profiling of DNMT inhibitor-treated solid tumor biopsies
Vincent Sartori
Ph.D. Student, VAI Graduate School
Research focus to be determined.
Kate Thurlow, M.Sc., M.S.
M.D./Ph.D. Student
Research Focus: Improving epigenetic cancer therapy through the utilization of metabolic phenotypes
Rochelle Tiedemann, Ph.D.
Research Scientist, Department of Epigenetics
Ashley Wiseman, M.S.
Lab Manager, Department of Epigenetics
