I am a trained medicinal chemist currently working in the laboratory of Dr. Gabriela Chiosis at Memorial Sloan Kettering Cancer Center as a research faculty. During the past nine years, I have been working to develop novel therapeutics targeting heat shock proteins, such as Hsp90, Hsp70 and Grp94, involved in cell stress and survival which may play a critical role in the development of cancer and potentially other diseases. We take a chemical biology approach to investigate heat shock proteins with the ultimate goal of translating agents into the clinic for the treatment of human diseases. In this regard, my expertise in designing and synthesizing small-molecule inhibitors as well as biological probes for these targets has been critical to the successful outcomes of our research projects. I have an extensive knowledge of chemistry and an understanding of its proper application for establishing structure activity relationships (SAR) as well as a keen understanding of what is required to transform a molecule into a drug. I have also acquired knowledge of cancer biology and a belief that it is the biology which drives the successful development of any drug discovery program. I feel that my qualifications and experience to date put me in a position to uniquely impact the field and to potentially provide cures to cancer.
In an effort to better understand HSP tumor biology with the ultimate purpose of clinical translation of these agents, my research has focused on the design and synthesis of small-molecule inhibitors and chemical tools useful for detailed biological studies. Efforts thus far have resulted in one agent, PU-H71, a potent inhibitor of Hsp90, to enter into clinical trials in patients with advanced solid tumors, lymphoma and myeloproliferative disorders. Additionally, we have developed an assay utilizing a radiolabeled version of the clinical agent referred to as PU-PET, which is intended as a companion diagnostic for Hsp90 inhibition therapy. This agent, 124I-PU-H71, has also entered into clinical trials as a non-invasive means to determine tumor pharmacokinetics and intra-tumoral concentration through PET imaging. PU-PET has the potential to determine those patients which might benefit from Hsp90 inhibitor therapy and therefore offers a powerful tool for successful clinical outcomes.
My direct association with the development of these clinical trials has given me a more profound understanding of the term “bench to bedside”. My research has also contributed towards the discovery and optimization of a Grp94-selective inhibitor and a novel class of small-molecule Hsp70 inhibitors which are currently undergoing evaluation for efficacy in pre-clinical models of cancer. During this period I have also been involved in a multitude of collaborative efforts. I have provided our collaborators with mg to gram amounts of small molecule inhibitors for which I have developed suitable scale-up synthetic methods, formulations for their proper in vivo use and have established conditions for their proper use and storage.