PHS 398 (Rev. 11/07), Biographical Sketch Format Page s2

Program Director/Principal Investigator (Last, First, Middle):

BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES.

NAME POSITION TITLE Brendan D. Manning Associate Professor of Genetics & Complex eRA COMMONS USER NAME Diseases BMANNING1 EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) DEGREE INSTITUTION AND LOCATION YEAR(s) FIELD OF STUDY (if applicable) U. of Massachusetts, Amherst, MA BS 1993 Microbiology Yale University, New Haven, CT Molecular, Cellular, & PhD 2000 Developmental Biology

A. Positions and Honors. Positions and Employment 2000 – 2004 Postdoctoral Research Fellow, Department of Systems Biology, Harvard Medical School; Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 2004 – 2009 Assistant Professor, Department of Genetics & Complex Diseases, Harvard University, School of Public Health, Boston, MA Associate Professor, Department of Genetics & Complex Diseases, Harvard University, School of Public Health, Boston, MA

Honors/Awards/Memberships 2000 John Spangler Nicholas Prize for Best Dissertation, Yale University. 2001-2004 American Cancer Society Research Fellow 2002 Co-recipient, Tuberous Sclerosis Alliance’s Rothberg Award for Courage in Research 2003- Grant Review Committee, Tuberous Sclerosis Alliance 2004-2007 Leukemia & Lymphoma Society, Special Fellow Career Development Award PI/Member, Kidney Cancer Program, Dana-Farber/Harvard Cancer Center 2006- Scientific Advisory Board, The LAM Foundation 2006-2008 American Diabetes Association, Junior Faculty Career Development Award 2007- International Scientific Advisory Board, The Tuberous Sclerosis Alliance 2007 Keynote Speaker, The Frye-Halloran Symposium on Neuro-oncology, Mass Gen Hospital 2008 Keynote Speaker, mTOR signaling: From Cancer to CNS Function, NIH-NINDS 2008 Keynote Speaker, TSC International Research Conference, Brighton, UK 2009- Research Advisory Board, The Children’s Tumor Foundation 2009- Faculty Member, Cell Signaling Section, Faculty of 1000 Biology 2009- PI/Member, Cancer Cell Biology Program, Dana-Farber/Harvard Cancer Center 2009 Keynote Speaker, Society for the Study of Behavioral Phenotypes, U of Cambridge, UK 2010 Conference Chair, Gordon Conference on Phosphorylation & G-Protein Signaling Networks

B. Selected publications (in chronological order). Lessie TG, Hendrickson W, Manning BD, Devereux R. Genomic complexity and plasticity of Burkholderia cepacia. FEMS Microbiol Lett 1996; 144:117-28. Manning BD, Padmanabha R, Snyder M. The Rho-GEF Rom2p localizes to sites of polarized cell growth and participates in cytoskeletal functions in Saccharomyces cerevisiae. Mol Biol Cell 1997; 8:1829-44. Manning BD, Barrett JG, Wallace JA, Granok H, Snyder M. Differential regulation of the Kar3p kinesin-related protein by two associated proteins, Cik1p and Vik1p. J Cell Biol 1999; 144:1219-33. Barrett JG, Manning BD, Snyder M. The Kar3p kinesin-related protein forms a novel heterodimeric structure with its associated protein Cik1p. Mol Biol Cell 2000; 11:2373-85.

PHS 398/2590 (Rev. 11/07) Page Biographical Sketch Format Page Program Director/Principal Investigator (Last, First, Middle): Manning BD, Snyder M. Drivers and passengers wanted! the role of kinesin-associated proteins. Trends Cell Biol 2000; 10:281-9. Manning BD, Tee AR, Logsdon MN, Blenis J, Cantley LC. Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway. Mol Cell 2002; 10:151-62. Manning BD, Cantley LC. Hitting the target: emerging technologies in the search for kinase substrates. Science STKE 2002; PE49. Tee AR, Fingar DC, Manning BD, Kwiatkowski DJ, Cantley LC, Blenis J. Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling. Proc Natl Acad Sci USA 2002; 99:13571-6. Luo J, Manning BD, Cantley LC. Targeting the PI3K-Akt pathway in human cancer: rationale and promise. Cancer Cell 2003; 4:257-62. Manning BD, Cantley LC. Rheb fills a GAP between TSC and TOR. Trends Biochem Sci 2003;28:573-6. Manning BD, Cantley LC. United at last: the tuberous sclerosis complex gene products connect the phosphoinositide 3-kinase/Akt pathway to mammalian target of rapamycin (mTOR) signalling. Biochem Soc Trans 2003; 31:573-8. Tee AR, Manning BD, Roux PP, Cantley LC, Blenis J. Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb. Curr Biol 2003; 13:1259-68. Brugarolas J, Lei K, Hurley RL, Manning BD, Reiling JH, Hafen E, Witters LA, Ellisen LW, Kaelin WG, Jr. Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. Genes Dev 2004; 18:2893-904. Manning BD. Balancing Akt with S6K: implications for both metabolic diseases and tumorigenesis. J Cell Biol 2004; 167:399-403. Shaw RJ, Bardeesy N, Manning BD, Lopez L, Kosmatka M, DePinho RA, Cantley LC. The LKB1 tumor suppressor negatively regulates mTOR signaling. Cancer Cell 2004; 6:91-9. Manning BD, Logsdon MN, Lipovsky AI, Abbott D, Kwiatkowski DJ, Cantley LC. Feedback inhibition of Akt signaling limits the growth of tumors lacking Tsc2. Genes Dev 2005; 19: 1773-8. Kwiatkowski DJ, Manning BD. Tuberous sclerosis: a GAP at the crossroads of multiple signaling pathways. Hum Mol Genet 2005; 15: R251-8. Sodhi A, Chaisuparat R, Hu J, Ramsdell AK, Manning BD, Sausville EA, Sawai ET, Molinolo A, Gutkind JS, Montaner S. The TSC2/mTOR pathway drives endothelial cell transformation induced by the Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor. Cancer Cell 2006; 10:133-43. Zhang HH, Lipovsky AI, Dibble CC, Sahin M, Manning BD. S6K1 regulates GSK3 under conditions of mTOR-dependent feedback inhibition of Akt. Mol Cell 2006; 24:185-97. Manning BD, Cantley LC. AKT/PKB signaling: navigating downstream. Cell 2007; 129:1261-74. Ozcan U, Ozcan L, Yilmaz E, Duvel K, Sahin M, Manning BD, and Hotamisligil GS. Loss of the tuberous sclerosis complex tumor suppressors triggers the unfolded protein response to regulate insulin signaling and apoptosis. Mol Cell 2008; 29:541-51. Huang J and Manning BD. The TSC1-TSC2 complex: a molecular switchboard controlling cell growth. Biochem J 2008; 412:179-90. Huang J, Dibble CC, Matsuzaki M, and Manning BD. The TSC1-TSC2 complex is required for proper activation of mTOR complex 2. Mol Cell Biol 2008; 28:4104-15. Chakrabarti P, Anno T, Manning BD, Luo Z, and Kandror KV. The mammalian target of rapamycin complex 1 regulates leptin biosynthesis in adipocytes at the level of translation. Mol Endocrinol 2008; 22:2260-7. Huang J and Manning BD. A complex interplay between Akt, TSC2, and the two mTOR complexes. Biochem Soc Trans 2009; 37:217-22. Manning BD. Challenges and opportunities in defining the essential cancer kinome. Science Signaling 2009; 2:pe15. James MF, Han S, Polizzano C, Plotkin SR, Manning BD, Stemmer-Rachamimov AO, Gusella JF, and Ramesh V. NF2/Merlin is a novel negative regulator of mTOR complex 1 and activation of mTORC1 is associated with meningioma and schwannoma growth. Mol Cell Biol 2009; 29:4250-61. Zhang HH, Huang J, Duvel K, Boback B, Wu S, Squillace RM, Wu CL, and Manning BD. Insulin stimulates adipogenesis through the Akt-TSC2-mTORC1 pathway. PLoS One 2009; 4:e6189.

PHS 398/2590 (Rev. 11/07) Page Biographical Sketch Format Page Program Director/Principal Investigator (Last, First, Middle): Huang J, Wu S, Wu CL, and Manning BD. Signaling events downstream of mTOR complex 2 are attenuated in cells and tumors deficient for the tuberous sclerosis complex tumor suppressors. Cancer Res 2009; 69:6107-14. Dibble CC and Manning BD. A molecular link between Akt regulation and chemotherapeutic response. Cancer Cell 2009; 16:178-80. Dibble CC, Asara J, and Manning BD. Characterization of Rictor phosphorylation sites reveals direct regulation of mTOR complex 2 by S6K1. Mol Cell Biol 2009; 29:5657-70. Menon S and Manning BD. Common corruption of the mTOR signaling network in human tumors. Oncogene 2009; 27:S43-51. Yecies JL and Manning BD. Chewing the fat on tumor cell metabolism. Cell 2010; 140: 28-30. Duvel K, Yecies JL, Menon S, Raman P, Lipovsky, AI, Souza AL, Triantafellow E, Ma Q, Gorski R, Cleaver S, Vander Heiden MG, MacKeigan JP, Finan PM, Clish CB, Murphy LO, and Manning BD. Activation of a metabolic gene regulatory network downstream of mTOR complex 1. Mol Cell 2010; 39: 171-183. Manning, BD. Insulin Signaling: Inositol phosphates get into the Akt. Cell 2010; 143:861-63.

PHS 398/2590 (Rev. 11/07) Page Biographical Sketch Format Page