Case Western Reserve University




Sanford Markowitz


Colon cancer, oncogenes, and suppressor genes

Office Phone: 216-368-1976
Office Fax: 216.368.8928

Primary Appointment: Hematology & Oncology
Markowitz Lab Web Page

My laboratory studies molecular abnormalities in colon cancer including studies of colon cancer suppressor genes and oncogenes, studies of the functions of positive and negative regulatory growth factors, and studies of the role of genomic instability in inherited and sporadic colon cancers. Some of our achievements to date include: identification of a group of "mutator" genes whose inactivation induces genomic instability and is responsible for many cases of inherited and sporadic colon cancer; discovery that TGF-beta is a negative regulatory growth factor in the gut and that TGF-beta receptors are tumor suppressor genes that are mutated in many colon and gastric cancers; demonstration that p53 is a colon cancer suppressor gene; identification of a casette of colon cancer suppressor genes that are silenced by aberrant methylation, and mapping of a new gene causing familial colon cancer to human chromosome 9. Ongoing interests in my lab include cloning new tumor suppressor genes and new genes causing familial colon cancer, elucidation of the TGF-\xDF signal transduction pathway, development of molecular based assays for cancer detection, and elucidation of genes involved in cancer metastases.

Selected Publications

Yan M, Rerko R, Platzer P, Dawson D, Willis J, Tong M, Lawrence E, Lutterbaugh J, Lu S, Willson J, Willson, Luo G, Hensold J, Tai, H, Wilson K, Markowitz, S. 2004. 15-Hydroxyprostaglandin Dehydrogenase, a COX-2 oncogene antagonist, is a TGF-\xDF induced suppressor of human gastrointestinal cancers. Proc Natl Acad Sci U S A 101:17468-17473. {Chosen as a "From The Cover" Article}. [PubMed]

Wiesner G., Daley D., Lewis S., Ticknor C., Platzer P., Lutterbaugh J., MacMillen M., Baliner B., Willis J., Elston R.C., Markowitz S.D., 2003. A subset of familial colorectal neoplasia kindreds linked to chromosome 9q22.2-31.2 Proc Natl Acad Sci U S A 100: 12961-65. [PubMed]

Grady W, Willis J, Guilford P, Dunbier A, Toro T, Lynch H, Wiesner G, Ferguson K, Eng C, Park JG, Kim SJ, Markowitz, S. 2000. Methylation of the CDH1 promoter as the second genetic hit in hereditary diffuse gastric cancer. Nature Genet 26:16-17. [PubMed]

Veigl ML, Kasturi L, Olechnowicz J, Ma A, Lutterbaugh JD, Periyasamy S, Li G-M, Drummond J, Modrich PL, Sedwick WD , Markowitz S. 1998. Biallelic inactivation of hMLH1 by epigenetic gene silencing, a novel mechanism causing human MSI cancers. Proc Natl Acad Sci (USA). 95:8698-8702. [PubMed]

Markowitz, Sanford, Jing Wang, Lois Myeroff, Ramon Parsons, LuZhe Sun, James Lutterbaugh, Robert Fan, Elizabeth Zborowska, Kenneth Kinzler, Bert Vogelstein, Michael Brattain, and James K. V. Willson. 1995. Inactivation of the type II TGF-ß receptor in colon cancer cells with microsatellite instability. Science 268: 1336-1338. [PubMed]

Complete list of Publications