N4F. PILOT PROJECTS We typically aim to provide catalytic funding for two Pilot projects during each grant year. Pilot projects are funded for a period of two years at a level in the range of ~$6oK-9oK direct costs per year. The level depends on the extent of personnel and materials/supplies requirement for gaining preliminary results, and the time period permits assessment of how well the science and investigators integrate into the ongoing Projects or Core. The Pilot projects are selected by the Steering Committee from applications submitted by investigators in the MIT (and Harvard) communities, on the basis of potential for providing powerful new approaches that complement overall program aims. If deemed highly successful in collaborative integration, the Pilot investigator(s) can become regular PIs in the Projects or Core. During the previous grant period, Pilots directed by Ernest Fraenkel and Mike Hemann have done so, with results described in the Progress Report section and plans described in the Research Plans section for their corresponding Project and Core participation. The two Pilots intended for Year 6 of the grant if successfully renewed are presented below.

National Institute of Health (NIH)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZCA1)
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Massachusetts Institute of Technology
United States
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Zhao, Boyang; Hemann, Michael T; Lauffenburger, Douglas A (2014) Intratumor heterogeneity alters most effective drugs in designed combinations. Proc Natl Acad Sci U S A 111:10773-8
Bell, Eric L; Nagamori, Ippei; Williams, Eric O et al. (2014) SirT1 is required in the male germ cell for differentiation and fecundity in mice. Development 141:3495-504
Arneja, Abhinav; Johnson, Hannah; Gabrovsek, Laura et al. (2014) Qualitatively different T cell phenotypic responses to IL-2 versus IL-15 are unified by identical dependences on receptor signal strength and duration. J Immunol 192:123-35
Krueger, Andrew T; Kroll, Carsten; Sanchez, Edgar et al. (2014) Tailoring chimeric ligands for studying and biasing ErbB receptor family interactions. Angew Chem Int Ed Engl 53:2662-6
Beck, Jon R; Peterson, Laura B; Imperiali, Barbara et al. (2014) Quantification of protein kinase enzymatic activity in unfractionated cell lysates using CSox-based sensors. Curr Protoc Chem Biol 6:135-56
Niepel, Mario; Hafner, Marc; Pace, Emily A et al. (2014) Analysis of growth factor signaling in genetically diverse breast cancer lines. BMC Biol 12:20
Johnson, Hannah; White, Forest M (2014) Quantitative analysis of signaling networks across differentially embedded tumors highlights interpatient heterogeneity in human glioblastoma. J Proteome Res 13:4581-93
Hemann, Michael T (2014) From breaking bad to worse: exploiting homologous DNA repair deficiency in cancer. Cancer Discov 4:516-8
Buck, Lorenna D; Inman, S Walker; Rusyn, Ivan et al. (2014) Co-regulation of primary mouse hepatocyte viability and function by oxygen and matrix. Biotechnol Bioeng 111:1018-27
Morton, Stephen W; Lee, Michael J; Deng, Zhou J et al. (2014) A nanoparticle-based combination chemotherapy delivery system for enhanced tumor killing by dynamic rewiring of signaling pathways. Sci Signal 7:ra44

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