Markowitz laboratory studies the genetics of colon
Key questions that we study are:
1. What genes contribute to the growth of colon cancers?
2. What genes cause colon cancer to occur in certain
3. How can we detect and diagnose colon cancer while it
is in its early, curable stages?
Among the observations we have made are:
• TGF-beta receptors are colon cancer suppressor genes
that are mutated in one-third of human colon cancers.
• One novel effector of the TGF-beta pathway in the gut
is 15-PGDH, an enzymatic antagonist of COX2, that acts
by degrading prostaglandins, and that shows tumor
• In individuals with Hereditary Diffuse Gastric Cancer
who inherit one mutant E-Cadherin allele, the second hit
leading to cancer development is often aberrant
methylation of the promoter of the remaining wild-type
• Aberrant methylation of both maternal and paternal
hMLH1 DNA repair genes is the pathogenetic event
accounting for initiation of 15% of non-familial colon
cancers that show loss of mismatch repair (so called
microsatellite instability cancers).
• Two novel genes that are methylated and inactivated in
approximately half of human colon cancers are a nuclear
helicase, HLTF, and a membrane transporter for butyrate,
• Aberrantly methylated DNAs can be detected in the
serum of some patients with colon cancer, as a tumor
• Chromsome 9q likely harbors a novel familial colon
Projects we are currently working on are:
o The identification of the familial colon cancer gene
on chromosome 9q.
o The further elucidation of the PGDH tumor suppressor
o The further elucidation of the tumor suppressor
pathways mediated by HLTF and SLC5A8.
o The discovery of new genes that are methylated in
o The discovery of novel secreted proteins that could be
used for early detection and diagnosis of colon cancer.
o The identification of genes important in the
development of metastatic colon cancer.