Molecular Signaling and Cancer Biology
Mentor / Lab:
Specific Research Area / Project:
Identifying small molecule mode of action of Hsp90 inhibitors
Wayne State University
Hsp90 is a well characterized chaperone protein with over 300 known cellular client proteins. Hsp90 assists with the assembly of client proteins involved in a multitude of cellular processes including cell cycle regulation, growth, apoptosis pathways, development, stress response and endocrine functions. Findings suggest cancer cells are highly dependent on this chaperone activity. Therefore, Hsp90 and its protein network members are very relevant drug targets. To date, three Hsp90 ATP-binding pocket inhibitors; Radicicol, Galdanamycin, and Novobiocin; have been well characterized, though none have survived in the clinical setting due to compound toxicity. Hsp90 inhibitors are a representative example of a downward trend that is currently present in the pharmaceutical industry: heavy reliance on families of proteins that are considered “druggable,” and constant targeting of the same motif within protein targets has led to limited discovery of new therapeutics. I plan to address this problem through a chemogenomics approach that will help aid the understanding of small molecule and Hsp90 protein network protein/gene interactions; contributing to the knowledge database necessary for continued drug discovery.
We hypothesize that by approaching drug target identification from a much broader view point, we will be able to offer alternative targets within the Hsp90 chaperone network or find a small molecule that acts directly on Hsp90 in a less toxic manner. Previous work in our laboratory has identified a subset of the NCI Diversity Set II that may be targeting Hsp90 and/or members of its chaperone network. We plan to explore these compounds on a genome wide scale in S. cerevisiae through a series of HIP/HOP profiling. This broad view point approach will allow more accurate target identification through exploration of multiple compounds and an entire genome of possible targets, allowing us to escape the “druggable” protein paradox and elicit the mode of action of these compounds.
My experience at Purdue has been amazing. I have encountered so many opportunities that I never would have thought were possible. In just two years here at Purdue I have been given the opportunity to gain not only lab experience but teaching and outreach experience as well. Being able to participate in programs like Science in Schools and my involvement with the Gifted Education Resource Institute (GERI) Summer Residential program has given me the opportunity to pass science on to the next generation. I’m also learning invaluable skills like curriculum development and how to teach science to students of all learning abilities. I have also been given opportunities to share my work at research conferences around the country as well as here at Purdue…and I’m only finishing my second year! My PULSe advisors have pointed me in a multitude of directions and are behind me 100% when I take on extracurriculars. It has really been an incredible journey thus far and has only just begun.
- Fultz, K., Peterson, S.M., Freeman, J.L. Synergistic toxicity of tungsten, nickel, and cobalt in embryonic zebrafish.First year poster session and awards program. Purdue University, West Lafayette, IN. 2012. Poster.
- Tsai, R.C, Fultz, K., Drendal, H., Aslam, K., Hazbun, T.R. Hsp31 is a cellular stress chaperone. Yeast genetics and molecular biology meeting. Princeton, NJ. 2012. Poster.
- Fultz,K., Hazbun, T.R. Barcode sequencing for chemogenomic profiling of small molecules. OIGP spring reception. Purdue University, West Lafayette, IN. 2013. Poster.
- Science in Schools 2011-2012, 2012-2013
- GERI/SRES: Summer course instructor “Fat dogs and Coughing Horses: bridging human and veterinary medicine,” July 2013
- Interdisciplinary Graduate Programs Student Advisory Board Member, PULSe Representative, beginning August 2013