Immunology Faculty Member - Kate Jeffrey, PhD

Kate Jeffrey, PhD

Massachusetts General Hospital
Department of Medicine

50 Blossom St, Thier340
Boston, MA 02114
Tel: 617-643-5887
Email: KJeffrey@mgh.harvard.edu
Visit my lab page here.



Epigenomic regulation of innate immunity

At the core of every immune response is a signal-, cell lineage-specific and kinetically precise gene expression program. It is becoming increasingly clear that the epigenome is critical for generating such precise transcriptional responses in diverse innate immune cell types. To this end, post-translational modifications on histones control the accessibility of DNA to transcription factors and serve as docking sites for epigenetic "reader" proteins that aid assembly of transcriptional machinery complexes. Dysregulation of many epigenome regulators is a recurrent and sentinel event in multiple diseases, including some immune disorders. Hence, proteins and that "write", "erase" or "read" the epigenome are some of the most promising and intently pursued targets in drug discovery today. BET inhibitors are an exciting and novel class of epigenetic therapy that disrupt binding of "reader" proteins Brd2, Brd3 and Brd4 to modified histones. Work during my postdoctoral studies was integral to the development of these novel agents as anti-inflammatory therapies. These drugs have now entered clinical trials as novel anti-cancer and anti-inflammatory drugs. Based on this promise, my laboratory at MGH is now exploring novel epigenome reader proteins that dictate innate immune cell function. We are also investigating the potential of other small molecules targeting epigenetic machinery as a way to boost or subdue the innate immune response in disease. Furthermore, we are understanding how pathogens have hijacked the immune cell epigenome for their benefit and the consequence of mutated epigenetic enzymes for immune driven disorders.







































Last Update: 8/31/2017



Publications


Kate L. Jeffrey, Tilman Brummer, Michael S. Rolph, Sue M. Liu, Nuria A.Callejas, Raelene J. Grumont, Corine Gillieron, Fabienne Mackay, Shane Grey, Montserrat Camps, Christian Rommel, Steve Gerondakis & Charles R. Mackay (2006). Positive regulation of immune cell function and inflammatory responses by phosphatase PAC-1. Nature Immunology 7, 274-282. f1000.com/1031133. PMID:16474395.

Edwige Nicodeme*, Kate L. Jeffrey*, Uwe Schaefer, Soren Beinke, Scott Dewell, Chun-wa Chung, Rohit Chandwani, Ivan Marazzi, Paul Wilson, Herve Coste, Julia White, Jorge Kirilovsky, Charles M. Rice, Jose M. Lora, Rab K. Prinjha, Kevin Lee and Alexander Tarakhovsky (2010). Suppression of inflammation by a synthetic histone mimic. Nature, Dec 23;468(7327):1119-23. *Contributed equally. f1000.com/7111956. PMID: 21068722.

Ivan Marazzi, Jessica Ho, Jaehoon Kim, Balaji Manicassamy, Scott Dewell, Randy A. Albrecht, Rab K. Prinjha, Kate L. Jeffrey, Kevin Lee, Adolfo Garcia-Sastre, Robert Roeder and Alexander Tarakhovsky (2012). Suppression of the antiviral response by an influenza “histone mimic”. Nature, Mar 14;483(7390):428-33. PMID: 22419161.

Stuti Mehta and Kate L. Jeffrey (2015). Beyond receptors and signaling: epigenetic factors in the regulation of innate immunity. Nature Immunology and Cell Biology Jan 6. doi: 10.1038/icb.2014.101. PMID: 25559622

Bandyopadhaya A, Tsurumi A, Maura D, Jeffrey KL, Rahme LG. A quorum sensing signal promotes host tolerance training through HDAC1-mediated epigenetic reprograming. Nature Microbiology. Oct 3 2016. Doi:10.1038/ NMICROBIOL.2016.1743

Yang Li, Megha Basavappa, Jinfeng Lu, Shu-Wei Dong, D. Alexander Cronkite, John T. Prior, Hans-Christian Reinecker, Paul Hertzog, Yanhong Han, Wan-Xiang Li, Sihem Cheloufi, Fedor V. Karginov, Shou-Wei Ding, Kate L. Jeffrey. Induction and suppression of antiviral RNA interference by influenza A virus in mammalian cells. Nature Microbiology 2016 Dec 5, 2:16250. Doi: 10.1038/nmicrobiol.2016.250. PMID: 27918527
 
Stuti Mehta, D. Alexander Cronkite, Megha Basavappa, Tahnee L. Saunders, Fatemeh Adiliaghdam, Hajera Amatullah, Sara A. Morrison, Jose D. Pagan, Robert M. Anthony, Pierre Tonnerre, Georg M. Lauer, James C. Lee, Sreehaas Digumarthi, Lorena Pantano, Shannan J. Ho Sui, Fei Ji, Ruslan Sadreyev, Chan Zhou, Alan C. Mullen, Vinod Kumar, Yang Li, Cisca Wijmenga, Ramnik J. Xavier, Terry K. Means, Kate L. Jeffrey. Maintenance of macrophage transcriptional programs and intestinal homeostasis by epigenetic reader SP140. Science Immunology. 2016 March 3 Vol. 2, Issue 9, DOI: 10.1126/sciimmunol.aag3160



© 2016 President and Fellows
of Harvard College