While the human genome is often considered simply a linear sequence of protein coding genes, all this genetic information is stored in 2 meter long chromosomes that must be folded and packaged into a 10 micron nucleus. To ensure normal development, homeostasis, and health, this 3D genome folding must allow accurate regulation of gene expression, repair after damage, and copying and segregation of the genome during cell division.
Recent research in has shown that the mammalian genome is packaged in a hierarchical organization, from small scale loops bringing enhancers in contact with gene promoters to large scale chromosome territories. Disruption of 3D genome structure occurs in cancer, developmental disorders, premature aging disorders, and other diseases, but the fundamental principles and building blocks of genome structure remain uncharacterized.
Our research goals are to:
- Learn basic features and building blocks of the 3D genome structure by disrupting the structure in vitro with physical perturbations
- Investigate how the 3D genome structure responds or maintains its robustness during biologically relevant physical stress or disruption
- Find new ways to observe and measure aspects of 3D genome structure with imaging and molecular methods
- Find new statistical and modeling approaches to interpret 3D interaction data, integrating this data with other large genomic datasets
Our research tools include:
- Chromosome conformation capture (Hi-C): using high throughput sequencing to identify physical interactions between regions of the genome
- Confocal microscopy with photoconvertible fluorophores and CRISPR targeted imaging
- Genome wide profiling of chromatin states (ATAC-Seq, ChIP-Seq, RNA-Seq)
- Computational data analysis, integration and modeling
Home Page: https://rpmlab.wordpress.com/
Ph.D. Biophysics, Harvard University
Crane E*, Bian Q*, McCord RP*, Lajoie BR*, Wheeler BS, Ralston EJ, Uzawa S, Dekker J, Meyer BJ. (2015) Condensin-driven remodelling of X chromosome topology during dosage compensation. Nature 523(7559):240-4.
McCord RP, Nazario-Toole A, Zhang H, Chines PS, Zhan Y, Erdos MR, Collins FS, Dekker J, Cao K. (2013) Correlated alterations in genome organization, histone methylation, and DNA-lamin A/C interactions in Hutchinson-Gilford progeria syndrome. Genome Res. 23(2):260-9
Belton JM, McCord RP, Gibcus JH, Naumova N, Zhan Y, Dekker J. (2012) Hi-C: a comprehensive technique to capture the conformation of genomes. Methods 58(3):268-76.
Zhang Y*, McCord RP*, Ho YJ, Lajoie BR, Hildebrand DG, Simon AC, Becker MS, Alt FW, Dekker J. (2012) Spatial organization of the mouse genome and its role in recurrent chromosomal translocations. Cell 148(5):908-21.
Imakaev M, Fudenberg G, McCord RP, Naumova N, Goloborodko A, Lajoie BR, Dekker J, Mirny LA. (2012) Iterative correction of Hi-C data reveals hallmarks of chromosome organization. Nat Methods. 9(10):999-1003.
McCord RP, Zhou VW, Yuh T, Bulyk ML. Distant cis-regulatory elements in human skeletal muscle differentiation. Genomics 98(6):401-11.