51LS – New strategy to treat mutant p53-expressing cancers

Status: Filled – Intern: Ben Michaels
Intern: Ben Michaels
Faculty Name: dr-le-su
UAB Department:
UAB School:
Campus Address: 601 Genome Way, Huntsville, AL 35806
Telephone Number: (256) 327-9659
Email: lsu@hudsonalpha.org or Click to Send E-Mail
For how many summers have you served as a preceptor: 1
CCC Research Area: Cancer Biology
Number of hours per week that the preceptor will personally supervise or work with the intern: 20
Other faculty, staff, or graduate students who may help to supervise the intern:
1. Christina Cooley (Research Associate)
Title of Project: 51LS – New strategy to treat mutant p53-expressing cancers
Project Description:

Mutations in the p53 gene are present in more than half of all human cancers. The majority of these genetic alterations change the p53 tumor suppressor into a driver of malignant transformation. This so-called gain-of-function (GOF) activity is dependent on the molecular interaction of mutant p53 and other proteins. A thorough understanding of the proteins that bind to p53 mutants, as well as the pathways along which p53 mutations exert the oncogenic function, would assist the development of truly effective treatments. Here, we provide exciting evidence for the existence of a novel mutant p53 transcriptional complex which can directly activate the c-MET oncogene in multiple cancer cells. Our overarching goal is to generate direct evidence for using clinically applicable c-MET inhibitors as a therapeutic option for different forms of cancer expressing p53 mutants. To this end, we will (1) screen a panel of cancer cell lines for the presence of mutant p53/c-MET signaling and (2) examine the effectiveness of c-MET inhibition in cell culture assays. We respect the fact that mutant p53 acts upstream of the c-MET pathway and maintains its activity upon c-MET inhibition to compromise the drug sensitivity. In this regard, we have discovered a dramatic synergistic effect between c-MET and histone deacetylase (HDAC) inhibitors in mutant p53-expressing synovial sarcoma cells, and will extend our study to many other cancer types. In summary, this proposal is based on a novel mechanism of mutant p53 action. This knowledge can be used to design new therapeutic approaches for the treatment of diverse human cancers associated with various p53 mutations.

Project Status: Already up and running
Location of Project: Huntsville, AL (HudsonAlpha)
Proposed Start Date: June 1, 2020
Proposed End Date: July 31, 2020
Expected work schedule for intern: Flexible, intern can largely set his or her own schedule (as for students who are instructed how to proceed and are permitted to work independently with weekly guidance) and should contribute full-time effort.
Category of Project: Laboratory Research
Cancer topic: Breast, Colon and rectum, Genetics, Liver, Lung and Bronchus, Ovary, Pancreas, Treatment, Multiple Cancer Sites
Does this project involve human subjects: No
Does this project involve animal subjects: No

Measure c-MET transcript and protein levels in a large panel of human cancer cell lines expressing wild-type and mutant p53.


Determine the effect of mutant p53 deletion on c-MET transcript and protein expression in human cancer cells.


Test the in vitro efficacy of different c-MET inhibitors in mutant p53 cancers.

Preceptor will provide intern with access to the following:
Office or desk space, Laboratory work bench space, Supplies needed to complete project, Equipment needed to complete project
Likelihood that intern will be included as an author on one or more publications
related to this summer research project:
Very likely
Areas in which the ideal candidates will have experience:
Biochemistry, Cell Biology, Genetics and Genomics, Grant Proposal Preparation, Laboratory Skills, basic knowledge, Laboratory Skills, advanced knowledge, Manuscript Preparation for Submission to a Journal, Molecular Biology, Scientific Writing Skills, (a) Functional Proteomics; (b) Gene Regulation