Dr. Chao-Yie Yang is a 2014 recipient of an AA&MDSIF research grant award for his project titled: Discovery of small molecule complement inhibitors as the treatment for PNH.
Dr. Chao-Yie Yang is a chemist specialized in computer-aided drug design and a hematology/oncology researcher who earned his PhD in Chemistry. He is currently a research assistant professor in the Hem/Onc division of Internal Medicine at the University of Michigan. He has contributed to a drug development team at U of M led by Dr. Shaomeng Wang to develop anti-cancer therapy agents targeting key proteins that prevent programmed cell death in cancer cells. One compound, AT-406, is currently entering a phase 2 clinical trial for advanced solid tumors and lymphomas. Recently, Dr. Yang started to develop his independent translational cancer research program.
Dr. Yang is interested in developing small molecule inhibitors to interrogate the contribution of dysfunctional proteins to diseases. Reasons that these proteins are dysfunctional include overproduction and amino acid mutations. Consequently, in cancer, they interact with other partners to promote proliferation, resistance to chemotherapy, and metastasis. We use these small molecule inhibitors to block the functions of these proteins and to prove the significant roles of the targets to drive tumor development in laboratory systems. They can then serve as leads and be developed, with time, into oral drugs.
Dr. Yang specializes in using various computational methods to design the small molecule inhibitors to improve their potencies and to make them orally available. In many projects, structures of the protein and the inhibitors guide the design ideas and expedite the optimization process as opposed to trial-and-error modifications of compounds. One of Dr. Yang’s current focuses is to develop compounds for treating hematological cancers. The projects include a discovery of compounds for alleviating graft-versus-host diseases (GvHD) for treating patients receiving hematopoietic stem cell transplantation with a collaborator at Indiana University.
The goal of this research is to develop small molecule inhibitors that target two different proteins contributing to PNH disease development. Although antibody-based therapy is available for PNH, oral drugs would benefit patients even more because of cost reduction, ease of administration and for patients acquired resistance to antibody therapy. Dr. Yang was excited by the opportunity the PNH Research and Support Foundation provided him to connect with researchers at the Cleveland Clinic to access PNH patient samples and to develop oral drugs for PNH patients as a team. He will publish his works to share with the PNH research community in near future.