The Cremins lab aims to understand how chromatin works through long-range physical folding mechanisms to encode neuronal specification and long-term synaptic plasticity in healthy and diseased neural circuits. We pursue a multi-disciplinary approach integrating data across biological scales in the brain, including molecular Chromosome-Conformation-Capture sequencing technologies, single-cell imaging, optogenetics, genome engineering, induced pluripotent stem cell differentiation to neurons/organoids, and in vitro and in vivo electrophysiological measurements.
Our long-term scientific goal is to dissect the fundamental mechanisms by which chromatin architecture causally governs genome function and, ultimately, long-term synaptic plasticity and neural circuit features in healthy mammalian brains as well as during the onset and progression of neurodegenerative and neurodevelopmental disease states
Our long-term mentorship goal is to develop a diverse cohort of next-generation scientific thinkers and leaders cross-trained in molecular and computational approaches. We seek to create a positive, high-energy environment with open and honest communication to empower individuals to discover and refine their purpose and grow into the best versions of themselves.
Just like the digital codes of replicating life held within DNA, the brain’s fundamental secret will be laid open one day. But even when it has, the wonder will remain, that mere wet stuff can make this bright inward cinema of thought, of sight and sound and touch bound into a vivid illusion of an instantaneous present, with a self, another brightly wrought illusion, hovering like a ghost at its centre. Could it ever be explained, how matter became conscious? –Ian McEwan, Saturday (Jonathan Cape, 2005), pp. 254-255
James H. Sun, Linda Zhou, Daniel J. Emerson, Sai A. Phyo, Katelyn R. Titus, Wanfeng Gong, Thomas G. Gilgenast, Jonathan A. Beagan, Beverly L. Davidson, Flora Tassone, Jennifer E. Phillips-Cremins, Disease-associated short tandem repeats co-localize to chromatin domain boundaries, Cell, 175: 1-15, 2018. *Authors contributed equally to this work
Linda Zhou, Chunmin Ge, Thomas Malachowski, Ji Hun Kim, Keerthivasan Raanin Chandradoss, Chuanbin Su, Hao Wu, Alejandro Rojas, Owen Wallace, Katelyn R. Titus, Wanfeng Gong, Jennifer E Phillips-Cremins, Spatially coordinated heterochromatinization of distal short tandem repeats in fragile X syndrome, BioRxiv 441217 [Preprint]. Available from: https://doi.org/10.1101/2021.04.23.441217
Kiran Girdhar, Gabriel E. Hoffman, Jaroslav Bendl, Samir Rahman, Pengfei Dong, Will Liao, Leanne Brown, Olivia Devillers, Bibi S. Kassim, Jennifer R Wiseman, Royce Park, Elizabeth Zharovsky, Rivky Jacobov, Elie Flatow, Alexey Kozlenkov, Thomas Gilgenast, Jessica S. Johnson, Lizette Couto, Mette A. Peters, Jennifer E. Phillips-Cremins, Chang-Gyu Hahn, Raquel E. Gur, Carol A. Tamminga, David A. Lewis, Vahram Haroutunian, Psychencode Consortium, Stella Dracheva, Barbara K. Lipska, Stefano Marenco, Marija Kundakovic, John F. Fullard, Yan Jiang, Panos Roussos, Schahram Akbarian, Acetylated Chromatin Domains Link Chromosomal Organization to Cell- and Circuit-level Dysfunction in Schizophrenia and Bipolar Disorder, BioRxiv 446728 [Preprint]. Available from: https://doi.org/10.1101/2021.06.02.446728.
Jonathan A. Beagan, Thomas G. Gilgenast, Jesi Kim, Zachary Plona, Heidi K. Norton, Gui Hu, Sarah C. Hsu, Emily J. Shields, Xiaowen Lyu, Effie Apostolou, Konrad Hochedlinger, Victor G. Corces, Job Dekker, and Jennifer E. Phillips-Cremins, Local Genome Topology Can Exhibit an Incompletely Rewired 3D-Folding State during Somatic Cell Reprogramming, Cell Stem Cell, 18:611-624, 2016.
Jonathan A. Beagan, Michael T. Duong, Katelyn R. Titus, Linda Zhou, Zhendong Cao, Jingjing Ma, Caroline V. Lachanski, Daniel R. Gillis, Jennifer E. Phillips-Cremins, CTCF and YY1 coordinate a 3D genome looping switch during early neurodevelopment, Genome Research, 27:1139-1152, 2017.
Ji Hun Kim, Mayuri Rege, Jacqueline Valeri, Margaret C. Dunagin, Aryeh Metzger, Katelyn R. Titus, Thomas G. Gilgenast, Wanfeng Gong, Jonathan A. Beagan, Arjun Raj, Jennifer E. Phillips-Cremins, LADL: Light-activated dynamic looping for endogenous gene expression control, Nature Methods, 16(7): 633-639, 2019.
Di Zhang, Thomas G. Gilgenast, Jennifer E. Phillips-Cremins, Ross C. Hardison, Gerd A. Blobel, Alteration of genome folding via contact domain boundary insertion, Nature Genetics, in press, DOI: 10.1038/s41588-020-0680-8, 2020.
Ji Hun Kim, Katelyn R. Titus, Wanfeng Gong, Jonathan A. Beagan, Zhendong Cao, Jennifer E. Phillips-Cremins, 5C-ID: Increased resolution Chromosome-Conformation-Capture-Carbon-Copy with in situ 3C and double alternating primer design, Methods, 142: 39-46, 2018. *Authors contributed equally to this work
Heidi K. Norton, Daniel J. Emerson, Jesi Kim, Katelyn R. Titus, Shi Gu, Danielle S. Bassett, Jennifer E. Phillips-Cremins, Detecting the 3D chromatin domain hierarchy with network modularity, Nature Methods, 15(2): 119-122, 2018. *Authors contributed equally to this work
Thomas G. Gilgenast and Jennifer E. Phillips-Cremins, Systematic comparison of statistical methods for identifying looping interactions in 5C data. Cell Systems, 8: 197-211, 2019.
Lindsey R. Fernandez, Thomas G. Gilgenast, and Jennifer E. Phillips-Cremins, 3DeFDR: statistical methods for identifying cell type-specific looping interactions in 5C and Hi-C data , Genome Biology, 21:219, 2020.
Jonathan A. Beagan, Elissa D. Pastuzyn, Lindsey R. Fernandez, Michael H. Guo, Kelly Feng, Katelyn R. Titus, Harshini Chandrashekar, Jason D. Shepherd and Jennifer E. Phillips-Cremins, Three-dimensional genome restructuring across timescales of activity-induced neuronal gene expression, Nature Neuroscience, 23: 707-717, 2020.
Lesly Calderon, Felix D Weiss, Jonathan A Beagan, Marta S Oliveira, Yi-Fang Wang, Thomas Carroll, Gopuraja Dharmalingam, Wanfeng Gong, Kyoko Tossell, Vincenzo de Paola, Chad Whilding, Mark A Ungless, Amanda G Fisher, Jennifer E Phillips-Cremins, Matthias Merkenschlager, Activity-induced gene expression and long-range enhancer-promoter contacts in cohesin-deficient neurons, BioRxiv 432639 [Preprint]. Available from: https://doi.org/10.1101/2021.02.24.432639.
Daniel J. Emerson, 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, Cohesin-mediated loop anchors confine the location of human replication origins, BioRxiv 425437 [Preprint]. Available from: https://doi.org/10.1101/2021.01.05.425437.
Haoyue Zhang, Daniel J. Emerson, Thomas G. Gilgenast, Katelyn R. Titus, Yemin Lan, Peng Huang, Di Zhang, Hongxin Wang, Cheryl A. Keller, Belinda Giardine, Ross C. Hardison, Jennifer E. Phillips-Cremins, Gerd A. Blobel, Chromatin Structure Dynamics During the Mitosis to G1-Phase Transition, Nature, 576: 158-162, 2019. *Co-corresponding last author.
Sarah C. Hsu, Thomas G. Gilgenast, Caroline R. Bartman, Christopher R. Edwards, Aaron J. Stonestrom, Peng Huang, Daniel J. Emerson, Perry Evans, Michael T. Werner, Cheryl A. Keller, Belinda Giardine, Ross C. Hardison, Arjun Raj, Jennifer E. Phillips-Cremins, Gerd A. Blobel, The BET protein BRD2 cooperates with CTCF to enforce transcriptional and architectural boundaries, Molecular Cell, 66(1): 102-116, 2017. *Co-corresponding last author
Jennifer E. Phillips-Cremins, Michael E. Sauria, Amartya Sanyal, Tatiana Gerasimova, Bryan Lajoie, Joshua Bell, Chintong Ong, Tracy Hookway, Changying Guo, Yuhua Sun, Michael Bland, William Wagstaff, Stephen Dalton, Todd McDevitt, Ranjan Sen, Job Dekker, James Taylor, and Victor G. Corces, Architectural protein subclasses shape 3-D organization of genomes during lineage commitment, Cell, 153(6): 1281-1295, 2013.
Our work is supported by the New York Stem Cell Foundation, the Alfred P. Sloan Foundation, the National Science Foundation, the National Institute of Mental Health, the National Institute of Neural Disorders and Stroke, NIH Common fund initiatives, the Friedreich’s Ataxia Research Alliance, the Chan Zuckerberg Initiative, and the NIH 4D Nucleome Common Fund Initiative.