Assistant Professor 

Department of Genetics, Cell Biology and Anatomy 985805 Nebraska Medical Center Omaha, NE 68198-5805 402-836-9794 Email

Education:
BS, Brigham Young University, Provo, UT, 2002 - 2008
PhD, University of Michigan, Ann Arbor, MI, 2009 - 2014
Emory University, Atlanta, GA, 2015 - 2019

Honors and Awards:
K99/R00 Pathway to Independence Award, NIGMS, 2018 - 2022

Research: Principles of 3D Chromatin Organization Chromatin is deliberately arranged in the 3D nucleus so that genomic loci can influence each other long-range. The organization of chromatin is altered during development, in response to hormonal signaling, and after heat shock, indicating that the nucleus is a dynamic environment. Abnormal 3D chromatin organization is implicated in diseases such as aberrant limb formation, cancer, and embryonic lethality. My overall goal is to discover mechanisms driving the establishment and dynamics of 3D chromatin organization. Specifically, I aim to elucidate how looping, insulation, and transvection occur.
1. How are chromatin loops formed? CTCF loops are a prominent feature of mammalian chromatin organization and are thought to alter enhancer – promoter interactions. The current model is that loops are formed via cohesion-mediated extrusion that is blocked by CTCF. How mammalian CTCF is able to block extrusion is unknown. Interestingly, Hi-C maps in Drosophila melanogaster do not display CTCF loops despite nearly identical DNA binding of the CTCF protein. Understanding why these differences occur will be a major focus of the lab.
2. How do architectural proteins contribute to pairing and transvection? Transvection occurs via pairing of homologous chromosomes enabling enhancers on one chromosome to affect the expression of genes on the homologue. In Drosophila, homologous pairing of chromosomes occurs throughout interphase and is an important part of nuclear organization. Transvection is broadly affected by the presence or absence of architectural proteins, although it is unknown how. Pairing has been typically examined using low resolution FISH, but during my post-doctoral work I developed a method to examine homologous pairing at high resolution (~250 bp) using Hi-C data. I found that pairing occurs in “buttons” only a few kb in size, called hd-pairing sites. While condensin II was known to broadly inhibit pairing, I discovered that condensin II binds to hd-pairing sites partially unpairing them. By genome-wide analysis of hd-pairing sites, I also found that clustering of architectural proteins correlates with homologue pairing. My lab is interested in how these proteins affect pairing and/or transvection.
3. Predicting 3D chromatin organization As we gain an understanding of 3D chromatin organization, my lab will use that data to improve algorithms to predict Hi-C maps from other data types. This will be useful to form new hypotheses on regions that fail prediction in wild-type cells, but also could be used to predict changes in the 3D chromatin landscape in response to various treatments.

Publications listed in PubMed

Publications:

1. Cummings CT, Rowley MJ. Implications of Dosage Deficiencies in CTCF and Cohesin on Genome Organization, Gene Expression, and Human Neurodevelopment. Genes, 2022. PMID: 35456389. 
2. Rocks D, Shukla M, Ouldibbat L, Finneman SC, Kalluchi A, Rowley MJ, Kundakovic M. Sex-specific multi-level 3D genome dynamics in the mouse brain. Nature Communications. 2022 PMID: 35705546. 
3. Mirza S, Saleem I, Kalluchi A, Raza M, Pal D, Mohapatra B, Lele S, Qiu F, Yu L, Zheng Z, Zhang Y, Alsaleem MA, Rakha EA, Band H, Rowley MJ, Band V. Ecdysoneless protein regulates viral and cellular mRNA splicing to promote cervical oncogenesis. Mol Cancer Res 2022 (co-corresponding author). PMID 34670863 
4. Engstrom AK, Walker AC, Moudgal RA, Myrick DA, Kyle SM, Bai Y, Rowley MJ, Katz DJ. The inhibition of LSD1 via sequestration contributes to tau-mediated neurodegeneration. PNAS 2020. PMID 33139560.
5. Rowley MJ, Poulet A, Nichols MH, Bixler BJ, Sanborn AL, Brouhard EA, Hermetz K, Linsenbaum H, Csankovszki G, Lieberman Aiden E, Coreces VG. Analysis of Hi-C data using SIP effectively identifies loops in organisms from C. elegans to mammals. Genome Research. 2020 PMID: 32127418.
6. Gutierrez-Perez I, Rowley MJ, Lyu X, Valadez-Graham V, Vallejo DM, Ballesta-Illan E, Lopez-Atalaya JP, Kremsky I, Caparros E, Corces VG, Dominguez M. Ecdysone-Induced 3D Chromatin Reorganization Involves Active Enhancers Bound by Pipsqueak and Polycomb. Cell Rep. 2019 PMID: 31484080.
7. Rowley MJ, Lyu X, Rana V, Ando-Kuri M, Karns R, Bosco G, Corces VG. Condensin II counters cohesin and RNA Polymerase II in the establishment of 3D chromatin organization. Cell Reports. 2019; PubMed PMID: 30865881 
8. Jung YH, Kremsky I, Gold HB, Rowley MJ, Punyawai K, Buonanotte A, Lyu X, Bixler BJ, Chan AWS, Corces VG. Maintenance of CTCF– and Transcription Factor-Mediated Interactions from the Gametes to the Early Mouse Embryo. Mol Cell. 2019; PubMed PMID: 31056445
9. Rowley MJ, Corces VG. Organizational principles of 3D genome architecture. Nat Rev Genet. 2018; PubMed PMID: 30367165 
10. Lyu X, Rowley MJ, Corces VG. Architectural proteins and pluripotency factors cooperate to orchestrate the transcriptional response to hESCs to temperature stress. Mol Cell. 2018; PubMed PMID: 30122536.
11. Rowley MJ, Nichols M, Lyu X, Ando-Kuri M, Rivera S, Hermetz K, Wang P, Ruan Y, Corces VG. Evolutionarily conserved principles predict 3D chromatin organization. Mol Cell. 2017; PubMed PMID: 28826674. Cover article.
12. Rowley MJ, Rothi MH, Böhmdorfer G, Kucinski J, Wierzbicki AT. Long-range control of gene expression via RNA-directed DNA methylation. PLoS Genet. 2017; PubMed PMID: 28475589 
13. Cubenas-Potts C, Rowey MJ, Lyu X, Li G, Lei EP, et al. Different enhancer classes in Drosophila bind distinct architectural proteins and mediate unique chromatin interactions and 3D architecture. Nucleic Acids Res. 2016;  PubMed PMID: 27899590
14. Rowley MJ, Corces VG. The three-dimensional genome: principles and roles of long-distance interactions. Curr Opin Cell Biol. 2016; Review. PubMed PMID: 26852111
15. Rowley MJ, Böhmdorfer G, Wierzbicki AT. Analysis of long non-coding RNAs produced by a specialized RNA polymerase in Arabidopsis thaliana. Methods. 2013; PubMed PMID: 23707621