Xiang-Qun (Sean) Xie, PhD, EMBA

Professor of Pharmaceutical Sciences
Associate Dean for Research Innovation
Director of CCGS & CDAR centers
University of Pittsburgh School of Pharmacy

Research Interests

Dr. Xie leads drug discovery research teams, incorporating: 1) development & application of AI machine/deep learning (ML/DL) approaches for drug target discovery and drug development; 2) medicinal chemistry for synthesis of small molecules predicted to be active toward the target protein; and 3) biological validation of predicted small molecules.  This integrated approach has been applied to a variety of studies, however Dr. Xie’s research has primarily focused on applying the innovative technology and approach to cannabinoid research, drug abuse/addiction, osteoporosis, cancer/multiple myeloma, neurodegenerative diseases, kidney fibrosis, and ex vivo expansion of hematopoietic stem cells.  Dr. Xie also has significant expertise in pharmacometrics and systems pharmacology (PSP) analysis for in silico drug evaluation for PK/PD, toxicity, and drug-drug interactions.  On a broader level, Dr. Xie also has significant expertise with “Big Data” pharmacoanalytics clinical analyses, such as: 1) determining subtle effects of drugs and drug combinations on diseases not previously known to be affected by those medications (drug repurposing) or 2)  as well as discovery of familial, epidemiological or clinical patterns associated with a disease or destructive behavior (e.g., drug abuse). Dr Xie has led AI computational drug design and experimental drug discovery technology development with a track record of over 180 publications in CELL, Nat. Comm, PNAS, JMC, etc. As such, Dr Xie has received the AAPS Award for Outstanding Research Achievements and Brenneman Scholar Award. 

Technique Expertise or Resources to share

Dr. Xie has expertise in construction and application of ML/DL technologies for drug discovery (i.e., chemical genomics or chemogenomics); construction and application of disease-specific and other chemogenomics knowledgebases (e.g., Alzheimer’s disease/neurodegenerative diseases, virus/COVID-19, cardiovascular disease, hallucinogens, apoptosis/autophagy, etc.); biophysical, molecular biological and biochemical techniques for protein purification and structural elucidation, including resolution of protein 3-dimensional structure by X-ray crystallography and cryoEM; Clinical Big Data analysis; pharmacometrics & systems pharmacology (PSP).

• Novel CB2-targeted agonists, inverse agonists and neutral antagonists with therapeutic potential (5 patents, 1 Cell, 3 JMC and 2 PNAS) and non-addictive TRPV1/CB2 ligand drugs for neuropathic pain (8 patents, AAPS J, JMC, PNAS, 3 JCIM, etc); and discovered a first negative allosteric modulator to CB2 receptor (patent)
• First-in-class p62-ZZ chemical inhibitor for neurological diseases and tumors (2 patents and Leukemia 2016, Nat Comm 2017, PNAS 2018, Autophagy 2018). The drug compound is currently under FDA IND-enabling studies towards human clinical trial in spring 2021.
• First-in-class INK4C/p18-targeted small-molecules (patent, 2015) for ex vivo expansion of murine hematopoietic stem cells (HSC) (Nat Comm 2015)
• First reported CB2-target specific small-molecules as a novel approach to reduce renal fibrosis.(Kidney Int, 2018)

Keywords

GPCRs agonist, inverse agonist, neutral antagonist, and allosteric modulator, multiple myeloma cell lines, Alzheimer’s disease, signal transduction, cannabinoid receptor 2 (CB2), X-ray crystallography, cryoEM, p62/sequestosome-1, p18/Ink4C, COVID-19, SARS-CoV-2