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Program Director/Principal Investigator (Last, First, Middle): Krampitz, Geoffrey, Wayne 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 Krampitz, Geoffrey Wayne Resident in General Surgery at Stanford Ph.D. Candidate in the Irving Weissman Lab eRA COMMONS USER NAME (credential, e.g., agency login) Krampitzg EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) INSTITUTION AND LOCATION Johns Hopkins University San Francisco State University Stanford School of Medicine Stanford School of Medicine Stanford Hospital and Clinics DEGREE (if applicable) MM/YY B.S. 05/99 06/04 06/09 06/14 06/17 M.D. Ph.D FIELD OF STUDY Biomedical Engineering Biomedical Sciences Medicine Stem Cell Bio & Regenerative Medicine General Surgery Residency A. Personal Statement. The goal of the proposed research is to elucidate the molecular basis for tumorigenicity, metastasis, and immune evasion to facilitate the development of novel therapeutic strategies for pancreatic neuroendocrine tumors (PNETs). Specifically, we plan to determine whether cell surface markers of tumorigenic cells are functionally significant, define the role of particular growth factors in promoting tumor metastasis, and target mechanisms used by tumors to evade immune surveillance for novel therapeutic strategies. I have the expertise, leadership and motivation necessary to successfully carry out the proposed work. I have a broad background in cancer and stem cell biology, with specific training and expertise in key research areas for this application. During my graduate work at UCSF, I described how hypoxia-inducible factor-dependent histone deacetylase activity determines stem cell fate in the placenta. During medical school at Stanford, I showed that adventitial stem cells contribute to restenosis after vascular injury in response to VEGF activation. As co-Investigator on university- and foundation-funded grants during my surgical residency, I laid the groundwork for the proposed research by identifying tumor-initiating cells in PNETs, describing the stem-like properties in these cells that contribute to tumor progression and metastasis, and targeting mechanisms for immune modulation in these tumors for therapeutic purposes. In addition, I successfully administered the project (e.g. staffing, research protections, budget), collaborated with other researchers, and produced several peer-reviewed publications from the project. As a result of these previous experiences, I am aware of the importance of frequent communication among project members and of constructing a realistic research plan, timeline, and budget. The current application builds logically on my prior work, and I have chosen co-investigators (Drs. Weissman and Norton) who provide additional expertise in the surgical and medical management of PNETs, cancer, stem cell, and molecular biology, as well as bioinformatics, genetics, and immunotherapies. In summary, I have a demonstrated record of accomplished and productive research projects in an area of high clinical relevance for cancer patients, and my expertise and experience have prepared me to lead the proposed project. B. Positions and Honors. Position and Employment 2011-2014 Graduate Student, Stanford School of Medicine, Stanford, CA 2009-2017 Surgical Residency, General Surgery, Stanford Hospital and Clinics, Stanford, CA 2004-2009 Medical Student, Stanford School of Medicine, Stanford, CA 2002-2004 Research Assistant, University of California San Francisco, San Francisco, CA 2000-2002 Application Software Engineer, @TheMoment, Inc., San Mateo, CA 1999-2000 Integration Software Engineer, gForce Systems, Inc., Cupertino, CA Other Experience and Professional Memberships 2013Member, Society of Robotic Surgery 2013Member, Society of American Gastrointestinal and Endoscopic Surgeons 2009Member, Americas Hepato Pancreato Biliary Association 0925-0001/0002 (Rev. 08/12) Page 1 Biographical Sketch Format Page 200920092004- Member, North American NeuroEndocrine Tumor Society Member, American College of Surgeons Member, American Medical Association Honors 2013 2013 2013 2012 2012 2009 2007 2007 2006 2006 2006 2005 2003 Advanced Residency Training at Stanford (ARTS) Program American College of Surgeons Resident Research Scholarship Resident Reviewer for JAMA Surgery A. P. Giannini Foundation Postdoctoral Research Fellowship Resident’s Prize Finalist at the Pacific Coast Surgical Association’s 83rd Annual Meeting Outstanding Poster/Abstract Presentation, Stanford Medical Student Research Symposium Kaiser Permanente Latino Association Scholar Award International Academy of Achievement Student Delegate American Medical Association (AMA) Minority Scholar Award Howard Hughes Medical Institute (HHMI) Research Training Fellowship for Medical Students The Paul & Daisy Soros Fellowships for New Americans Stanford Medical Scholars Award Nelson Fellowship Research Award C. Selected peer-reviewed publications (in chronological order). 1. Maltepe E, Krampitz GW, Okazaki KM, Red-Horse K, Mak W, Simon MC, Fisher SJ. Hypoxia-inducible factordependent histone deacetylase activity determines stem cell fate in the placenta. Development. 2005 Aug; 132(15): 3393-403. Cited in PubMed; PMID: 15987772. 2. Krampitz GW, Norton JA, Poultsides GA, Visser BC, Sun L, Jensen RT. Lymph nodes and survival in pancreatic neuroendocrine tumors. Arch Surg. 2012 Sep;147(9):820-7. 3. Worhunsky DJ, Krampitz GW, Poullos PD, Visser BC, Kunz PL, Fisher GA, Norton JA, Poultsides GA. Pancreatic neuroendocrine tumours: hypoenhancement on arterial phase computed tomography predicts biological aggressiveness. HPB (Oxford). 2013 Aug 29. 4. Krampitz GW, Norton JA. Pancreatic neuroendocrine tumors. Curr Probl Surg. 2013 Nov;50(11):509-45. 5. Krampitz GW, Norton JA. RET gene mutations (genotype and phenotype) of MEN and Familial MTC. Cancer (In Press) D. Other selected publications. 1. Krampitz, G.W., Norton, J.A. Current management of the zollinger-ellison syndrome. Advances in Surgery. 2013;47(1). 2. Krampitz GW and Norton JA. (2012) “Zollinger-Ellison Syndrome” In S. Cohn and and S. Brower (Eds.), Surgery: Evidence Based Practice. Shelton, CT: PMPH-USA. 3. Krampitz GW and Norton JA. (2012) “Gastrinoma (Discuss MEN I)” In J. Dimick, G. Upchurch, C. Sonnenday (Eds.), Clinical Scenarios in Surgery: Decision Making and Operative Technique. Baltimore, MD: Lippincott Williams & Wilkins. 4. Krampitz GW and Norton JA. (2012) “The Discovery of RET Gene and Its Role in MEN2” In E. Zeigler and W. Shen (Eds.), History of Endocrine Surgery. New York, NY: Rodopi Press. 5. Krampitz GW and Norton JA. “Exploration of the Gastrinoma Triangle” In P. Clavien, M. Sarr, Y. Fong (Eds.), Atlas of Upper Gastrointestinal and Hepato-Pancreato-Biliary Surgery. New York, NY: Springer. E. Research Support. Ongoing Research Support Norton, Jeffrey and Weissman, Irving (PIs) 01/01/14 – 06/30/14 Advanced Residency Training at Stanford The goal of this study is to identify and characterize tumor initiating cells in pancreatic neuroendocrine tumors and develop immune-based targeted therapies against these tumors. Role: Co-Investigator Norton, Jeffrey and Weissman, Irving (PIs) 07/01/11 – 06/30/14 Stanford Surgery Professional Development Grant The goal of this study is to identify and characterize tumor initiating cells in pancreatic neuroendocrine tumors and develop immune-based targeted therapies against these tumors. Role: Co-Investigator 0925-0001/0002 (Rev. 08/12) Page 6 Biographical Sketch Format Page Norton, Jeffrey and Weissman, Irving (PIs) 07/01/12 – 06/30/14 A. P. Giannini Foundation Postdoctoral Research Fellowship in California The goal of this study is to identify and characterize tumor initiating cells in pancreatic neuroendocrine tumors and develop immune-based targeted therapies against these tumors. Role: Co-Investigator Norton, Jeffrey and Weissman, Irving (PIs) 07/01/13 – 06/30/15 American College of Surgeons Resident Research Scholarship The goal of this study is to identify and characterize tumor initiating cells in pancreatic neuroendocrine tumors and develop immune-based targeted therapies against these tumors. Role: Co-Investigator Completed Research Support RN2-00909-1 Chang, Chin-Pin (PI) 01/01/09 – 12/30/12 California Institute of Regenerative Medicine (CIRM) Grant VEGF Signaling in Adventitial Stem Cells in Vascular Physiology and Disease. Role: Co-Investigator Chang, Chin-Pin (PI) 07/01/06 – 06/30/07 Howard Hughes Medical Institute (HHMI) Research Training Fellowship for Medical Students Adventitial stem cell VEGF signaling is critical for restenosis after vascular injury. As described above. Role: Co-Investigator Chang, Chin-Pin (PI) 07/01/06 – 06/30/07 The Paul & Daisy Soros Fellowships for New Americans Adventitial stem cell VEGF signaling is critical for restenosis after vascular injury. As described above. Role: Co-Investigator Chang, Chin-Pin (PI) 06/01/05 – 09/30/05 Stanford School of Medicine Medical Scholar Fellowship VEGF activates NFATc1 during heart valve development. Role: Co-Investigator Fisher, Susan (PI) 07/01/03 – 06/30/04 Nelson Fellowship Research Award Hypoxia-inducible factor-dependent histone deacetylase activity determines stem cell fate in the placenta. Role: Co-Investigator 0925-0001/0002 (Rev. 08/12) Page 7 Biographical Sketch Format Page