| |
| author |
Makayla Pardo
| | title |
Identification and characterization of small molecules that reactivate mutant p53 in human cancer cells
| | abstract |
Cancer is a major global public health issue, and the second leading cause of
death in the United States. It is a group of complex diseases characterized by the
uncontrolled growth of abnormal cells, often caused by the loss of genomic integrity in
cells. Cellular genomic integrity is maintained by the tumor suppressor protein p53,
which is also known as: the "guardian of the genome". P53 prevents oncogenic
transformation by halting the cell cycle upon cellular stress, and activating protective
methods such as DNA repair or elimination of abnormal cells via apoptosis. The tumor
suppressor activity of p53 is attenuated in almost all human cancers. In 50% of cancers,
p53 is inactivated due to mutations. Most of these oncogenic mutations are missense
mutations in the DNA binding domain of the p53 protein, resulting in the loss of DNA
binding activity due to a conformational change at physiological temperature. Cancers
with mutant p53 are aggressive and often resistant to therapy, making the mutant p53 an
attractive target for drug discovery research. We have developed a cell-based reporter
gene assay to screen compounds for their ability to restore transcriptional activity of
mutant p53. Several small molecules of different chemical structures have been identified
through this method. Using conformation specific antibodies, we have also shown that
these molecules induce a conformational change in mutant p53 to that of the wild-type
protein, underlying the mechanism of reactivation.
| | school |
The College of Liberal Arts, Drew University
| | degree |
B.A. (2020)
|
| advisor |
Bimal Dasmahapatra
|
| full text | MPardo.pdf |
| |
