The Vilar Laboratory pursues cutting-edge translational research focused on the genetics of premalignant intestinal lesions (polyps/adenomas) and colorectal cancers, as well as drug development for prevention and treatment of premalignant intestinal polyps and colorectal cancers. This research is divided into the following major areas:
Annotation of the Genomic and Transcriptomic landscape of premalignant polyps in FAP and Lynch Syndrome
A detailed understanding of the genomic and transcriptomic make-up of premalignant lesions is essential in order to proceed further with targeted chemopreventive drug development. A detailed description of the genome and gene expression signatures displayed by premalignant polyps of the small and large intestine has not yet been accomplished. We are currently using next-generation sequencing to undertake this challenge in both Familial Adenomatous Polyposis(FAP) and Lynch Syndrome patients. This line of research is developed in close collaboration with Dr. Paul Scheet’s group that provides with the bioinformatic support to perform the analysis. These projects are supported by Research Initiation Funds provided by MD Anderson to the Vilar Laboratory and by philanthropic funding generously donated by the Feinberg Family Fund.
Discovering New Targets for Chemoprevention in Familial Adenomatous Polyposis
It has been shown that chemopreventive strategies involving nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors (COXibs) reduce the polyp burden in the colorectum of patients with FAP. However, these drugs are not extensively used in the clinical setting due to safety concerns. Therefore, prophylactic surgery continues being the main risk-reducing strategy for colorectal cancer in FAP families. Our overarching goal is to discover and develop new chemopreventive therapies for patients with FAP. These projects are funded by the NCI (R03 CA176788-01A1) and the Duncan Family Institute.
Co-Clinical trials in genetically engineered mouse models.
The Vilar Lab has several mouse models that recapitulate the biology of FAP (APCMin/+ and APC1638) and Lynch Syndrome (VilCreMSH2LoxP). These models are essential to perform cross-species comparisons between human and murine lesions (comparisons of premalignant polyps and normal mucosa). In addition, any potential targeted therapy suggested by findings of our two other projects needs to be validated first in mouse models prior to proceed with clinical trial design. We are currently treating several cohort of mice with novel chemopreventive approaches.