Our Science – Bernal Website
Federico Bernal, Ph.D.
Our laboratory is interested in the study of the molecular interactions involved in cancer pathogenesis using designed organic molecule. Through an interdisciplinary approach that melds the fields of organic chemistry, biochemistry and pharmacology, we have developed compounds that allow us to probe pathways that are deregulated in cells.
An Exhaustive Exploration of p53 Function
Our focus has been the study of the p53 tumor suppressor pathway and its modulation with synthetic molecules. p53 function is altered in a majority of all cancers by either its degradation, sequestration, deletion or mutation. Regulation of p53 is mediated by the oncogenes HDM2 and HDMX, and through our work with the p53-derived hydrocarbon stapled peptide SAH-p53-8 we have shown how disruption of the p53-HDM2 and p53-HDMX complexes restores the activity of p53 in cancers that overexpress either HDM2 or HDMX. This compound has allowed us to establish a pharmacologic blueprint that helps determine the context in which inhibitors of the p53-HDM2 and p53-HDMX interactions can be used therapeutically. In collaboration with J.C. Marine's laboratory at the KU-Leuven in Belgium, we have demonstrated that HDMX overexpression is responsible for the resistance of metastatic melanoma to traditional chemotherapeutic agents.
SAH-p53-8 has been an extremely valuable tool that has also helped in the exploration of p53 functions that are independent of its transcriptional activation abilities. We have found that SAH-p53-8 can modulate the migration and invasion of triple negative breast cancers (TNBC) harboring p53 mutations. In order to investigate the molecular targets that drive these phenomena we are developing compounds based on SAH-p53-8 that will allow us to determine the details of the pathways that mediate migration and invasion.
Expansion of the Stapled Peptide Methodology to Unconventional Targets
We have begun investigations in several arenas to determine the applicability of the stapled peptide methodology to other molecular targets. The majority of the research in this arena has focused on the cancer field, but we have expanded its role to other phenomena and biological systems. These include the use of SAH-p63 and SAH-p73 compounds to study the factors that govern cellular differentiation and the development peptides capable of reaching targets in single cell organisms. We are also exploring the capability of stapled peptides to alter the conformational states of proteins and study the structural aspects of protein-protein interactions.
Applicants interested in postdoctoral work combining synthetic organic chemistry and cancer biology should contact Dr. Bernal by e-mail about current availability and time frames.
Postdoctoral candidates with strong experience in organic chemistry, medicinal chemistry, cell biology, and/or structural biology work should send a brief cover letter, C.V. and arrange for three letters of reference to be sent to Dr. Bernal.
We have no openings available at the time.
This page was last updated on 5/20/2013.