s of all 4 aims were rather brief and superficial with many high-risk projects included. Little discussion and few alternatives were presented to the many barriers guaranteed to surface in translating to mouse models, not to mention to human disease. The feasibility of aim 3 (using immuno-competent mouse models) was difficult to evaluate given the lack of details, but the enlistment of Lisa Coussens as a collaborator is a strong positive step. Thus, the consensus was that the investigators focus on Aim 1 as the main translational goal while continuing the innovative reengineering of immune cells needed to accomplish this aim. While the science and progress has been stellar, the new management plan and budget are unsatisfactory. Budget justification for personnel and supplies was scant and it was not possible to determine what each person was going to do for the program. In view of the fact that the personnel and focus of the project need to change significantly, it is imperative that a new presentation of a management plan and budget justification be provided to reflect the shifting priorities. Also, successful completion of Aim 1 with the U Penn group will require more than monthly conferences and annual meetings. This plan needs to be well described to assure that research synergy can indeed be achieved despite the geographical constraints. Cross-over of lab research personnel for extended periods may blend the research more seamlessly. The plan should also indicate how specific projects will be rapidly phased out of NDC support. Some of the aims (such as aim 4) should be spun off into separate proposals for funding elsewhere. Overall, this center has performed at an outstanding level, but would need greater focus to accomplish the goals of the program. The following is a consolidated list of strengths and weaknesses compiled from specific reviewer comments. Strengths Development of novel strategies for controlling cell motility by using innovative extracel

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Development Center (PN2)
Project #
5PN2EY016546-08
Application #
8146906
Study Section
Special Emphasis Panel (ZEY1-VSN (20))
Program Officer
Fisher, Richard S
Project Start
2004-09-30
Project End
2015-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
8
Fiscal Year
2011
Total Cost
$1
Indirect Cost
Name
University of California San Francisco
Department
Pharmacology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Rupp, Levi J; Schumann, Kathrin; Roybal, Kole T et al. (2017) CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells. Sci Rep 7:737
Gordley, Russell M; Williams, Reid E; Bashor, Caleb J et al. (2016) Engineering dynamical control of cell fate switching using synthetic phospho-regulons. Proc Natl Acad Sci U S A 113:13528-13533
Roybal, Kole T; Rupp, Levi J; Morsut, Leonardo et al. (2016) Precision Tumor Recognition by T Cells With Combinatorial Antigen-Sensing Circuits. Cell 164:770-9
Gordley, Russell M; Bugaj, Lukasz J; Lim, Wendell A (2016) Modular engineering of cellular signaling proteins and networks. Curr Opin Struct Biol 39:106-114
Coyle, Scott M; Lim, Wendell A (2016) Mapping the functional versatility and fragility of Ras GTPase signaling circuits through in vitro network reconstitution. Elife 5:
Morsut, Leonardo; Roybal, Kole T; Xiong, Xin et al. (2016) Engineering Customized Cell Sensing and Response Behaviors Using Synthetic Notch Receptors. Cell 164:780-91
Schmid, Eva M; Bakalar, Matthew H; Choudhuri, Kaushik et al. (2016) Size-dependent protein segregation at membrane interfaces. Nat Phys 12:704-711
Mitchell, Amir; Wei, Ping; Lim, Wendell A (2015) Oscillatory stress stimulation uncovers an Achilles' heel of the yeast MAPK signaling network. Science 350:1379-83
Wu, Chia-Yung; Roybal, Kole T; Puchner, Elias M et al. (2015) Remote control of therapeutic T cells through a small molecule-gated chimeric receptor. Science 350:aab4077
Wu, Chia-Yung; Rupp, Levi J; Roybal, Kole T et al. (2015) Synthetic biology approaches to engineer T cells. Curr Opin Immunol 35:123-30

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