The mammalian genome contains a vast array of information, and selectively utilizing this information to give rise to distinct cell tissue types and cellular functions is a tremendous feat. To achieve the complexity required for a mammalian organism to function, the genome must be tightly regulated during development in order to give rise to many different tissue types. These tissue types are then required to hold cellular identity for the life of the organism.
Much of this regulation and memory is thought to come from chemical modifications placed on chromatin, a complex of DNA and histone proteins contained in every cell of the human body. Understanding how chromatin is regulated dynamically to allow proper development and cellular function is a critical question of modern biology. Pathologically, misregulation of chromatin has been recently demonstrated to be a driving force of cancer and other human diseases. This presents a unique opportunity for the understanding of basic biologic mechanisms to provide new insights for the treatment of human disease.
My lab studies how chromatin is dynamically regulated in the cell, allowing for varying levels of gene expression or gene silencing. Our approach to understanding chromatin biology involves the use of chemical tools to manipulate cellular events, which allows us to examine the direct activity of individual enzymes on complex substrates such as chromatin. We have created a unique tool called the Chromatin in vivo Assay (CiA) mouse, which enables us to selectively control chromatin with defined activities in living cells. Using this technology, we can examine the requirements for creating an “epigenetic state”, a stable regulatory mechanism capable of transmitting information through cellular generations.
As a member of the Center for Integrative Chemical Biology and Drug Discovery and the Lineberger Comprehensive Cancer Center, my lab is focused on the discovery of new small molecules that inhibit epigenetic pathways both for research purposes and as potential future therapeutics.
Education, Certification and Licensure
2008–2013 Stanford Medical School (Palo Alto, CA)
HHMI & Departments of Pathology and Developmental Biology
Postdoctoral Adviser: Gerald R. Crabtree, M.D.
2001–2007 Harvard University (Cambridge, MA)
Biological and Biomedical Sciences program at Harvard Medical School
PhD in Cell and Developmental Biology — November 2007 degree
Thesis Adviser: Randall W. King, MD, PhD
1996–2001 Case Western Reserve University (Cleveland, OH)
BS in Biology; BA in Chemistry and Philosophy — January 2001 degree
Undergraduate Research Adviser: Edward Stavnezer, PhD
- Hathaway NA*, Bell O*, Hodges C, Miller EL, Neel DS, Crabtree GR. Dynamics and Memory of Heterochromatin in Living Cells. Cell. 2012 Jun 22;149(7):1447-60. See Preview in Cell and Highlight in Nature Methods and Nature Reviews Genetics. Recommended by Faculty of 1000.
- Dimova N, Hathaway NA, Lee BH, Kirkpatrick DS, Berkowitz ML, Gygi SP, Finley D, King RW. APC/C-mediated multiple monoubiquitylation provides an alternative degradation signal for cyclin B1. Nat Cell Biol. 2012 Jan 29;14(2):168-76.Recommended by Faculty of 1000.
- Zeng X, Sigoillot F, Gaur S, Choi S, Pfaff KL, Oh DC, Hathaway N, Dimova N, Cuny GD, King RW. Pharmacologic inhibition of the anaphase-promoting complex induces a spindle checkpoint-dependent mitotic arrest in the absence of spindle damage. Cancer Cell. 2010 Oct 19;18(4):382-95.
- Kleijnen MF, Roelofs J, Park S, Hathaway NA, Glickman M, King RW, Finley D. Stability of the proteasome can be regulated allosterically through engagement of its proteolytic active sites. Nat Struct Mol Biol. 2007 Dec;14(12):1180-8. Recommended by Faculty of 1000.
- Crosas B, Hanna J, Kirkpatrick DS, Zhang DP, Tone Y, Hathaway NA, Buecker C, Leggett DS, Schmidt M, King RW, Gygi SP, Finley D. Ubiquitin chains are remodeled at the proteasome by opposing ubiquitin ligase and deubiquitinating activities. Cell. 2006 Dec 29;127(7):1401-13.
- Hanna J, Hathaway NA, Tone Y, Crosas B, Elsasser S, Kirkpatrick DS, Leggett DS, Gygi SP, King RW, Finley D.Deubiquitinating enzyme Ubp6 functions noncatalytically to delay proteasomal degradation. Cell. 2006 Oct 6;127(1):99-111.
- Kirkpatrick DS*, Hathaway NA*, Hanna J, Elsasser S, Rush J, Finley D, King RW, Gygi SP. Quantitative analysis of in vitro ubiquitinated cyclin B1 reveals complex chain topology. Nat Cell Biol. 2006 Jul;8(7):700-10. Recommended by Faculty of 1000.
- Hathaway NA, King RW. Dissecting cell biology with chemical scalpels. Curr Opin Cell Biol. 2005 Feb;17(1):12-9. Review.
- Bardeesy N, Sinha M, Hezel AF, Signoretti S, Hathaway NA, Sharpless NE, Loda M, Carrasco DR, DePinho RA. Loss of the Lkb1 tumour suppressor provokes intestinal polyposis but resistance to transformation. Nature. 2002 Sep 12;419(6903):162-7.