The two objectives of this application are to support training of a physician as a medical scientist and to contribute to the basis understanding of human cancer. Dr. Simons aspires to take a clinical education from this medical residency at Massachusetts General Hospital and fellowship in medical oncology at John Hopkins into a career of independent scholarship in oncology. Towards these ends, Dr. Simons will train as a post-doctoral fellow in the Laboratory of Molecular Genetics of the John Hopkins Oncology Center under the tutelage of Dr. Bert Vogelstein, the award sponsor. Colorectal cancer is chosen for inquiry in part because it is the second most common cause of cancer deaths in the United States. A long range goal of Dr. Vogelstein's laboratory program is to locate, clone, sequence, and characterize the function of putative colorectal tumor suppressor genes. Deletions of putative tumor suppressor genes on chromosome 17 and 18 are observed in over 70% of human colorectal carcinomas. Dr. Simon's research will focus on cloning a putative colorectal tumor suppressor gene in phase I. Restriction length polymorphism analysis has allowed identification of a relatively small region within chromosome 18 alpha that encompasses the putative suppressor gene. Chromosome walking techniques will be used to identify expressed sequences within this region. cDNA libraries will be screened to isolate candidate suppressor genes containing expressed sequences. The wide range of molecular genetic techniques necessary to conduct these studies will guarantee a rigorous education in molecular biology. Successful implementation of these studies should provide a fertile area of research for phase II. Phase I of the award will also encompass a didactic program in molecular biology. A faculty advisory committee of four senior basic scientists, chaired by the sponsor, will review a written research progress report and seminar presented every four months. Dr. Simons will also attend eight formal graduate courses with the Department of Molecular Biology and Genetics at the Johns Hopkins University School of Medicine. Having satisfactorily completed phase I, Dr. Simons will assume a faculty position to pursue these studies further in phase II.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Physician Scientist Award (K11)
Project #
5K11CA001495-04
Application #
3085859
Study Section
Cancer Institutional Fellowship Review Committee (CT)
Project Start
1990-02-01
Project End
1995-01-31
Budget Start
1993-02-01
Budget End
1994-01-31
Support Year
4
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Sanda, M G; Restifo, N P; Walsh, J C et al. (1995) Molecular characterization of defective antigen processing in human prostate cancer. J Natl Cancer Inst 87:280-5
Twillie, D A; Eisenberger, M A; Carducci, M A et al. (1995) Interleukin-6: a candidate mediator of human prostate cancer morbidity. Urology 45:542-9
Nelson, J B; Hedican, S P; George, D J et al. (1995) Identification of endothelin-1 in the pathophysiology of metastatic adenocarcinoma of the prostate. Nat Med 1:944-9
Cho, K R; Oliner, J D; Simons, J W et al. (1994) The DCC gene: structural analysis and mutations in colorectal carcinomas. Genomics 19:525-31
Sanda, M G; Ayyagari, S R; Jaffee, E M et al. (1994) Demonstration of a rational strategy for human prostate cancer gene therapy. J Urol 151:622-8
Simons, J W; Oliner, J D; Cho, K R et al. (1992) SAM 1.1 and JOSH 4.4: two RFLPs within the human DCC gene. Hum Mol Genet 1:352
Shah, K V; Daniel, R W; Simons, J W et al. (1992) Investigation of colon cancers for human papillomavirus genomic sequences by polymerase chain reaction. J Surg Oncol 51:5-7