BBS Faculty Member - Scott Kennedy

Scott Kennedy

Department of Genetics

Harvard Medical School
Genetics - NRB 266
77 Avenue Louis Pasteur
Boston, MA 02115
Tel: 617-432-0094
Fax: 617-432-7663
Email: kennedy@genetics.med.harvard.edu



Organisms possess a blueprint for life, which they transmit to their progeny. DNA (genetic information) is a major constituent of life’s blueprint. It is now known that epigenetic information can also be inherited. A major focus of my lab is to understand the molecular mechanism(s) by which epigenetic information is inherited.

We are using genetic, molecular, and biochemical approaches in the model organism C. elegans to understand the how and why of epigenetic inheritance. To date, we have shown that one mechanism by which epigenetic information can be inherited is via a nuclear RNA interference (RNAi) pathway that uses non-coding RNAs as informational vectors to drive the multi-generational transfer of gene silencing information. Heritable gene silencing by small regulatory RNA occurs via chromatin modification and RNA Polymerase II inhibition. Interestingly, we have shown that heritable gene regulation by non-coding RNA is necessary to maintain the immortal nature of germ cells. These observations have led us to propose that animals may use the nuclear RNAi machinery to transmit epigenetic information, accrued by past generations, into future generations to regulate important biological processes.

In the future, my lab will continue to explore the how and why of epigenetic inheritance. In particular, we will be interested in understanding the mechanism(s) by which multi-generational epigenetic memories are initiated and maintained, identifying genes subjected to multi-generational regulation during the normal course of growth and reproduction, determining if the epigenetic inheritance factors we identify in C. elegans play analogous roles in mammals, and asking if environmental experiences can alter heritable epigenetic states. We hope that insights from our research will prove to be globally applicable to our understanding of gene regulation and epigenetic inheritance in all animals, and that our work might make it possible to influence heritable epigenetic processes in mammals with the long-term goal of mitigating human disease.



Last Update: 8/15/2014



Publications

Guang S, Bochner A, Pavelec D, Burkhart K, Harding S, Lachowiec J, Kennedy S (2008) An Argonaute transportsa siRNAs from the cytoplasm to the nucleus. Science 321:537-541

Guang S, Bochner AF, Burkhart KB, Burton N, Pavelec DM, Kennedy S (2010) Small regulatory RNAs inhibit RNA polymerase II during the elongation phase of transcription.
Nature 465(7301): 1097-1101

Burton NO, Burkhart KB, Kennedy S (2011) Nuclear RNAi maintains heritable gene silencing in Caenorhabditis elegans.
Proc Natl Acad Sci USA 108(49):19683-19688

Buckley B, Burkhart K, Gu SG, Spracklin G, Kerschner A, Fritz H, Kimble J, Fire A, Kennedy S (2012) A nuclear Argonaute promotes multigenerational epigenetic inheritance and germline immortality.
Nature 489:447-451

Juang B, Gu S, Starnes L, Palladino F, Goga A, Kennedy S, L’Etoile ND. (2013) Endogenous nuclear RNAi mediates behavioral adaptation to odor.
Cell 154, 1010-22.



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