Drug discovery and development is undergoing rapid change toward an increasing dependency on academic institutions providing sources of new potential treatment. With this change, there is a growing need for academic researchers who are knowledgeable in all steps of translational research in order to progress compounds far into the drug discovery pipeline. It is my goal to become a professor focused on translational research and developing new treatments for cancer therapy. Dr. Hong-yu Li and I have devised a training plan that address my goals and provides a clear path to achieve them. The first portion of the training plan is the dissertation work already completed, which focused on developing a strong foundation in organic and medicinal chemistry. In the first project, we identified TrkA kinase inhibitors using a pyrazine based scaffold. The second project was centered on developing a library of Flt3 kinase inhibitors using novel synthetic methodology developed in the lab. Additional side projects also focused on developing new synthetic methodology to access biologically relevant molecules. The dissertation work to be completed is a comprehensive translational project aiming to develop lead compounds with dual activity against the CSF-1R and Aurora B kinases. Recently published findings suggest an indirect link between both kinases that could result in synergistic anti-cancer activity. Both kinases are validated targets for breast cancer, and developing dual inhibitors with balanced activity against both serves to unveil a novel treatment paradigm for breast cancer patients. Preliminary data has identified compounds with potent activity against CSF-1R, Aurora B, and c-Kit kinases. The proposed work aims to develop compounds optimized to have selectivity for CSF-1R and Aurora B over c-Kit. The postdoctoral research direction is focused on continuing to develop lead compounds through in vivo efficacy studies. In line with this work, cell based assays will be utilized to study the biological interplay of dual CSF-1R and Aurora B inhibition. Additionally, new projects will be pursued to develop additional skills in cancer biology and immunotherapy. The work described in this proposal highlights the steps for technical and career skill development I plan to take to achieve my goal of becoming an academic independent investigator and helping cancer patients in need.

Public Health Relevance

My ultimate career goal is to develop new treatments for cancer patients in need. I plan to achieve this by becoming an academic independent investigator focused on translational research for new cancer therapies. The steps I have taken and plan to take towards this goal will help progress cancer research and identify new compounds capable of being developed into new therapeutic options for cancer patients.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Project #
1F99CA212480-01
Application #
9230077
Study Section
Special Emphasis Panel (ZCA1-RTRB-R (A1))
Program Officer
Mcguirl, Michele
Project Start
2016-09-21
Project End
2018-08-31
Budget Start
2016-09-21
Budget End
2017-08-31
Support Year
1
Fiscal Year
2016
Total Cost
$45,076
Indirect Cost
Name
University of Arizona
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
806345617
City
Tucson
State
AZ
Country
United States
Zip Code
85721