BETRNet Roles: Project 1 Co-Investigator, Project 2 Principal Investigator, Project 3 Co-Principal Investigator, DRP Core Co-Leader, Basic Science Admin Core Co-Leader
Sanford (Sandy) Markowitz is the Markowitz-Ingalls Professor of Cancer Genetics, a Distinguished University Professor at Case Western Reserve University, and co-leader of the GI Cancer Genetics Program at the Case Comprehensive Cancer Center. Sandy’s national distinctions include his being an NCI Outstanding Investigator (R35) Awardee and his also being Principal Investigator of the Case GI SPORE, an NCI recognized national center of excellence for research in gastrointestinal cancers.
My research is primarily focused on the molecular biology of colon cancer, functional influence of oncogenes and suppressor genes on transformation, metastasis, and response to therapies.
- Genetic Mechanisms of GI Cancers
- Development of Diagnostics for Early Detection of GI Cancers
- Development of Drugs That Regulate Tissue Stem Cells and Tissue Regeneration
The Markowitz laboratory is recognized as a national leader in studies of the genetics and epigenetics of GI cancers, including in basic discovery of genetic targets in GI cancers and in translational studies aimed at developing new methods for early cancer detection, prevention, and treatment.
Highlights of studies from the Markowitz laboratory include: identifying TGF-beta as a key human tumor suppressor; identifying the first cancer associated mutations in the TGF-beta signaling pathway (mutations in TGF-beta type II receptors); identifying 15-prostaglandin dehydrogenase (15-PGDH), a prostaglandin degrading enzyme, as a novel effector of TGF-beta mediated tumor suppression and as a negative regulator of tissue stem’s repair of tissue injury; developing the first in-vivo active 15-PGDH inhibitor drugs and demonstrating their activity in potentiating tissue repair in multiple disease models that include potentiating healing of colitis and accelerating hematopoietic recovery following bone marrow transplantation; being part of the team that sequenced the first human cancer coding genome (the colon cancer genome); discovering key epigenetic markers of colon cancers and esophageal cancers; pioneering development of the first commercial stool DNA based test for colon cancer detection, based on aberrantly methylated DNA (ColoSure); pioneering development of the first commercial non-endoscopic DNA based tests for detecting esophageal cancers and their precursor lesions of Barrett’s esophagus (via engineering the EsoCheck esophageal sampling device and developing the EsoGuard methylated DNA panel assay).
Sandy’s translational advances have led to founding of two biotechnology companies, Rodeo Therapeutics (for development of 15-PGDH inhibitor drugs) and LucidDx (for development of non-endoscopic DNA testing for esophageal neoplasias). Sandy’s work on developing diagnostic tests for detecting esophageal neoplasia was reported as a highlight advance in the 2020 NCI Director’s report to Congress. In 2020 Sandy’s EsoGuard DNA assay was awarded breakthrough device designation by the FDA and his EsoCheck sampling device won FDA approval. More broadly, Sandy’s multiple contributions to GI Cancer genetics have been recognized by his winning the Hamdan Award for Medical Research Excellence from the Kingdom of Dubai.
More detailed description of highlight research and publications from the Markowitz laboratory is available on the Markowitz Laboratory of Genetic Colon Cancer Research website.
Markowitz S, Wang J, Myeroff L, Parsons R, Sun L, Lutterbaugh J, Fan RS, Zborowska E, Kinzler KW, Vogelstein B, Brattain M, Willson JKV. (1995). Inactivation of type II TGFß receptor in colon cancer cells with microsatellite instability. Science 268, 1336-1338.
Chen WD, Han ZJ, Skoletsky J, Olson J, Sah J, Myeroff L, Platzer P, Lu S, Dawson D, Willis J, Pretlow TP, Lutterbaugh J, Kasturi L, Willson JK, Rao JS, Shuber A, Markowitz SD. (2005). Detection in fecal DNA of colon cancer-specific methylation of the nonexpressed vimentin gene. J Natl Cancer Inst 97, 1124-1132.
Fink SP, Yamauchi M, Nishihara R, Jung S, Kuchiba A, Wu K, Cho E, Giovannucci E, Fuchs CS*, Ogino S*, Markowitz SD*, Chan AT*. (2014). Aspirin and the risk of colorectal cancer in relation to the expression of 15-hydroxyprostaglandin dehydrogenase (HPGD). Science Translational Medicine. 6(233), 233re2. PMCID: PMC4030641 (*SDM, CF, SO and ATC equal contributors; S. Fink, first author, from Markowitz laboratory).
Zhang Y, Desai A, Yang SY, Bae KB, Antczak MI, Fink SP, Tiwari S, Willis JE, Williams NS, Dawson DM, Wald D, Chen WD, Wang Z, Kasturi L, Larusch GA, He L, Cominelli F, Di Martino L, Djuric Z, Milne GL, Chance M, Sanabria J, Dealwis C, Mikkola D, Naidoo J, Wei S, Tai HH, Gerson SL, Ready JM, Posner B, Willson JK, Markowitz SD. (2015). Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration. Science. 348(6240):aaa2340. PMCID: PMC4481126.
Moinova HR, LaFramboise T, Lutterbaugh JD, Chandar AK, Dumot J, Faulx A, Brock W, Cabrera ODL, Guda K, Barnholtz-Sloan J, Iyear PG, Canto MI, Wang JS, Shaheen NJ, Thota PN, Willis JE, Chak A, Markowitz SD. (2018). Identifying DNA Methylation Biomarkers for Non-Endoscopic Detection of Barrett’s Esophagus. Science Translational Medicine. 10(424):eaao5848. PMCID: PMC5789768.