My research in the Chiosis Laboratory has focused on the discovery and development of Heat Shock Protein 70 (Hsp70) inhibitors and on studying the role of heat shock proteins in cancer. I am using chemical tools designed and synthesized in the laboratory to identify proteins interacting with heat shock proteins or being affected by them in specific cancer cell settings and to elucidate mechanism associated with Hsp70 in cancers.
Recently, using 2,5’-thiodipyrimidine scaffold compounds computationally predicted by my colleagues to bind to a specific site of Hsp70, I have shown that a representative compound - YK5 - selectively interacted with Hsp70 and Hsc70, but not with the mitochondrial (Grp75) or the endoplasmic reticulum (Grp78) Hsp70 isoforms. My data indicated that YK5 inhibited Hsp70 functions in cancer cells by interfering with the oncogenic functions of the Hsp90/Hsp70 machinery. I have also shown that YK5 has no effect on HSF-1 activation, a feed-back effect thought to limit the potency of Hsp90 inhibitors. Currently, I and my colleagues are developing more potent Hsp70 inhibitors and are evaluating them in pre-clinical cancer models. Our ultimate goal is to translate these agents to clinic for the treatment of cancer patients.