Current Research:

The recent sequencing of the human genome and proteome has led to the compilation of the complete catalog of disease-related human GPCRs (G-protein coupled receptors), and triggers this important target class to undergo a "rebirth" for the future blockbuster drugs. However, the lack of experimental 3D GPCR structures is still one of the key roadblocks in post-genomics GPCRs drug research today. In fact, very few high-resolution structures have been reported for GPCRs due to the lack of high-quality crystals suitable for X-ray crystallography studies, or uniformly isotope-labeled “native” proteins for NMR studies. To fill the gaps, Dr. Xie and his group focus on development and application of a comprehensively-combined chemical genomics-based GPCR drug design and discovery approach.
Xie group target cannabinoid receptor subtype CB2 because the human CB2 receptor is an important rhodopsin-like GPCR and is known to mediate signal transductions in the immune system, and CB2 ligands have the potential to be developed as drugs to treat a wide range of immune system disorders (such as immune-origin tumors, multiple sclerosis, chronic neuropain etc.). His research work is beyond the proof-of-principle stage since his group has already successfully identified several novel CB2 ligands with nanomolar (nM) receptor binding affinity (US patents). The methods and results developed will have a significant impact on the other GPCRs drug research in general.
Dr. Xie’s laboratory has the following research projects ongoing and the potential opening job positions are available for graduate students and post-doc fellows in the related research areas:
• Computational Chemical Genomics and In-silico Design Method Development. To develop 3D QSAR pharmacophore models, in-silico virtual screening and in-vitro bioassay validation as well as chemistry modification and medicinal chemistry syntheses approaches to identify novel CB2 drug-like molecules with new chemical scaffolds and high CB2 specificity (NIH DA011510). (See selected publications 1-4).
• Cheminformatics and Small Molecular Information Repository. To construct a Web-interfaced cannabinoid molecular information database repository to facility data-sharing and information exchange among scientific research communities (NIH R01 NLM 015417). To develop and construct in-house virtual compound libraries and structure-diverse/target-specific compound databases for virtual screening by the combined cheminformatics, 3D chemistry-space cell-based partition metrics and 2D fingerprint-based similarity calculation approaches. (See selected publications 5-6).
• Human CB2 Receptor Structural Proteomics Studies. To understand, in structural and functional terms, the molecular mechanisms of human CB2 receptor activation and G-protein cell signaling process in order to facilitate the structure-based design for novel CB2 drug-like molecules that may have potential for immune therapeutic treatments. This will involve GPCR membrane protein chemical biology, NMR biophysics and computer molecular modeling etc. (NIH R01 DA015770). (See selected publications 7-10).
• Cancer and Stem Cell Research. Dr. Xie also initiated collaborative research projects with the Cancer Institute using his expertise in computational chemical genomics in-silico drug screening and structure-based design. Currently, his group is working on screening and design small molecule chemical probes: a) to control self-renewing divisions of hematopoietic stem cells via design the P18INK4Cprotein inhibitors that disrupts the tertiary structure of the molecule or directly inhibit its association with cdk4 and cdk6 (collaborate with Dr. T Cheng); and b) to abrogate the cancel cell autophagy process via design the Atg4B-specific inhibitors (collaborate with Dr. X. M. Yin). Teaming up with cancer biochemistry research experts will lead to more productive and fruitful research work. (Pending NIH).

Bio:

Dr. Xie is a tenured Professor of Pharmaceutical Sciences/Drug Discovery Institute, University of Pittsburgh (Pitt). He is a Chair of the Distinguished Lecture Series Committee, a Chair of Graduate Admission Committee and a member of Graduate Program Council for School of Pharmacy at Pitt. He is a co-PI/core co-director of the NIH funded Pittsburgh Center for Chemical Methodologies & Library Development (P. Wipf, PI/Director). He is a member and co-PI of the Pittsburgh Molecular Library Screening Center (J. Lazo, PI/Director) previously funded by NIH Roadmap Initiative. He also holds joint faculty positions at the Departments of Computational Biology and Structural Biology, and Pitt Cancer Institute MT/DD Program. Before he joined in Pitt, he was a Professor of Medicinal Chemistry and a founding Director of Pharmacoinformatics Research Center in College of Pharmacy at University of Houston Texas. He held several joint faculty positions at the Institute for Molecular Design, Texas Learning Computing Center, and the Keck Center for Computational & Structural Biology, and served as an Advisory Committee Member for the NIH Pharmacoinformatics Training Program at Houston Gulf Coast Consortium (GCC), and a Director of the Chemistry Coordinating Unit for GCC-Chemical Genomics Screening Center. Prior to joining UH, Dr. Xie was a Director of IMS NMR Lab and a joint faculty member of the School of Pharmacy at the University of Connecticut for 10 years. Dr. Xie received his Pharmacy B. S. degree in 1982 from the Second Military Medical University in Shanghai, China, and his Ph.D. in Medicinal Chemistry from the School of Pharmacy, University of Connecticut in 1993, followed by a Post-doctoral training at M.I.T Francis Bitter National Magnet Laboratory. In addition, he received an Executive MBA degree in 2003. Dr. Xie was the recipient of numerous awards and honors including the North America China Bridge International Award (2000); CNSF Award (1999); NIH Young Investigator FIRST Award (1997), and a nominee for Outstanding Research Award (2006). He was a Member of the Board of Directors of the Chinese Association of Professionals in Science and Technology (CAPST) and a Chair of the CAPST-Biomedical & Pharmaceutical Society. He serves as NIH study section panel reviewer and many peer-reviewed scientific journals as well as consultants for pharma and biotech companies. He was invited an expert panel reviewer for Chinese Natural Science Foundation. His research awarded by three NIH grants focuses on GPCR chemical genomics, in-silico design/cheminformatics virtual screening method development, chemistry synthesis and recombinant GPCR membrane protein NMR structural biology, as well as small molecule chemical probe design for hematopoietic stem cells expansion.