Entrevistas ImunoFoz2011 - Jonathan Powell

SBlogI entrevista:

Dr. Jonathan Powell
Jonhs Hopkins Medical Institute, EUA

SBlogI - What is the theme of your lecture at ImunoFoz 2011?

Powell, J. - The mammalian Target of Rapamycin (mTOR) plays a central role in regulating T cell differentiation, activation and tolerance.

SBlogI - What is the main finding or conclusion that will be emphasized?

Powell, J. - Our studies have revealed that mTOR plays a critical and central role in regulating Th1, Th2, Th17 and T reg differentiation. Further for CD8+ T cells we are able to demonstrate specific roles for mTOR signaling in regulating the generation of CD8 effector and memory cells.

SBlogI - What is the significance of this finding?

Powell, J. - By dissecting the specific pathways downstream of mTOR we have identified new targets for the regulation of immunity to infectious diseases, autoimmunity and tumor immunity. For example, knocking out mTORC1 signaling leads to resistance to the mouse model of Multiple Sclerosis (EAE). Alternatively, selectively knocking out pathways downstream of mTORC2 leads to resistance to asthma. Alternatively, by enhancing mTOR activity we have created T cells that demonstrate superior ability to kill tumors. Likewise, we are currently investigating models of viral and parasitic infections.

SBlogI - What are the future perspectives in this area?

Powell, J. - Our studies are revealing important insight in terms of the pathways by which mTOR regulates T cell differentiation and function. By continuing to dissect these pathways we are identifying novel targets to manipulate the immune response. In as much as mTOR regulates the cellular metabolic machinery, these studies are revealing the importance of metabolism in regulating T cells.

SBlogI - What are the challenges in this area? Are there controversies? Opponent hypotheses?

Powell, J. - The exciting challenge ahead is to specifically define the downstream targets of mTOR responsible for regulating T cells. Molecules such as Akt, S6K1, the FOXO’s, STAT’s, SOCS, KLF2 appear to be involved but undoubtedly more downstream targets of mTOR will be revealed.

SBlogI - Any suggestions for background reading?

Powell, J. -

Delgoffe GM, Pollizzi KN, Waickman AT, Heikamp E, Meyers DJ, Horton MR, Xiao

B, Worley PF, Powell JD. The kinase mTOR regulates the differentiation of helper

T cells through the selective activation of signaling by mTORC1 and mTORC2. Nat

Immunol. 2011 Apr;12(4):295-303. Epub 2011 Feb 27. PubMed PMID: 21358638; PubMed

Central PMCID: PMC3077821.

Lee K, Gudapati P, Dragovic S, Spencer C, Joyce S, Killeen N, Magnuson MA,

Boothby M. Mammalian target of rapamycin protein complex 2 regulates

differentiation of Th1 and Th2 cell subsets via distinct signaling pathways.

Immunity. 2010 Jun 25;32(6):743-53. PubMed PMID: 20620941; PubMed Central PMCID:

PMC2911434.

Powell JD, Delgoffe GM. The mammalian target of rapamycin: linking T cell

differentiation, function, and metabolism. Immunity. 2010 Sep 24;33(3):301-11.

Review. PubMed PMID: 20870173; PubMed Central PMCID: PMC2962404.