My research interest focuses on the discovery of small molecule inhibitors by both rational drug design and by high-throughput screening of small molecule libraries followed by hit-optimization. Currently I am working on PD-1/PD-L1 inhibitors and deubiquitinase inhibitors for cancer therapy.
The ubiquitin proteasome system (UPS) is the main system for controlled protein degradation and a key regulator of fundamental cellular processes. The dependency of cancer cells on a functioning UPS has made this an attractive target for development of drugs that show selectivity for tumor cells. Deubiquitinases (DUBs, ubiquitin isopeptidases) are components of the UPS that catalyze the removal of ubiquitin moieties from target proteins or polyubiquitin chains, resulting in altered signaling or changes in protein stability. A number of DUBs regulate processes associated with cell proliferation and apoptosis, and as such represent candidate targets for cancer therapeutics. Inhibition of proteasomal cysteine DUB enzymes (i.e. USP14 and UCHL5) can be predicted to be particularly cytotoxic to cancer cells as it leads to blocking of proteasome function and accumulation of proteasomal substrates.
I started my doctoral studies in Fudan University (China) in September 2009, developing non-nucleoside inhibitors of HIV-1 reverse transcriptase, including computer-aided QSAR study, molecular design and synthesis. After receiving my PhD in 2015, I worked as a post-doctoral fellow in Prof. Changchun Wang’s group in the department of Macromolecular Science/ Laboratory of Advanced Materials (Fudan University), focusing on targeted cancer chemotherapy or combination therapy based on nanotechnology to improve drug efficiency and overcome drug resistance. In August 2018, I joined the Ovaa group in LUMC as a LEaDing Fellows laureate, working on PD-1/PD-L1 inhibitors and deubiquitinase inhibitors for cancer therapy.
Synergistic Cisplatin/Doxorubicin Combination Chemotherapy for Multidrug-Resistant Cancer via Polymeric Nanogels Targeting Delivery
Haiqiu Wu, Haojie Jin, Haoyu Ruan, Zihao Zhang, Chen Yang, Luyan Sun, Yongjing Li, Wenxin Qin,*, Changchun Wang*.
ACS Applied Materials & Interfaces, 2017, 9 (11), 9426–9436
Biodegradable Smart Nanogels: A New Platform for Targeting Drug Delivery and Biomedical Diagnostics
Haiqiu Wu, Changchun Wang*.
Langmuir, 2016, 32, 6211−6225.
Synthesis and Biological Evaluation of DAPY-DPEs Hybrids as Non-nucleoside Inhibitors of HIV-1 Reverse Transcriptase
Haiqiu Wu, Jin Yao, Qiuqin He, Erik De Clercq, Jan Balzarini, Dirk Daelemans, Christophe Pannecouque, Fener Chen*.
Bioorganic & Medicinal Chemistry, 2015, 23(3): 624-631.