Liang Xu, Ph.D.

Molecular therapy targeting cancer and cancer stem cells, via novel nanovectors and rational drug design.

1) Novel small-molecule cancer therapeutics - Drug discovery and molecular cancer therapy.

My lab has been working on drug discovery for novel small molecule cancer therapeutics targeting cell signaling pathways, especially for cancer cell chemo/radiosensitization by molecular modulation of apoptosis/autophagy/necroptosis. One of the first lead compounds tested in vitro and in vivo in my lab has completed Phase I-IIb clinical trials, as the World’s first pan-Bcl-2/Bcl-xL/Mcl-1 inhibitor entered clinic trials. Another XIAP inhibitor is also in clinical trials.

Currently, I am working on molecular cancer drug discovery, using structure-based rational drug design for novel small molecule inhibitors targeting Musashi-1/2 and HuR, the RNA-binding proteins so far believed “undruggable”. Through high-throughput screening and lead optimization, we obtained nanomolar to submicromolar lead compounds, and two provisional patents were filed in 2014. One new R01 was funded in 2014; one R01 scored 20, percentile 3%, started in 2015. Our long-term goal is for further lead optimization to obtain more potent and specific, drug like leads for development as first-in-class Musashi-1/2 or HuR inhibitors as whole new therapy for cancer.

2) Novel nanovector delivery systems targeting cancer and cancer stem cells - Drug/gene delivery.

Funded by multiple NIH and DOD grants, my lab works on the tumor-targeted delivery of molecular cancer therapeutics using novel nanotechnology. A self-assembled, virus-mimicking, non-viral nanovector for non-viral tumor-targeted, systemic p53 gene therapy has shown promise in chemo/radiosensitization of breast, prostate, head and neck cancer, just completed a first-in-human Phase I clinical trial, now in multi-center Phase II Trials. Multiple US and International Patents are issued or pending.

Currently, I am exploring next generation nanovectors for tumor-targeted delivery of siRNA/miRNA/CRISPR-based therapeutics for targeting cancer and cancer stem cells. In 2014, I have 7 papers published on nanoparticles for cancer targeting and molecular imaging. Imaging-based nano-drug delivery for cancer targeted therapy will be my focus.