Xiaowei Zhang

Lead a group to investigate cancer drug efficacies using cell-based methods and mouse models. 1. Use PDX and CDX tumor models for pharmacology studies 2. Generate primary cancer cells lines and drug resistant cell lines for cancer biology and pharmacology studies. 3. Test small molecule drug responses using 2D and 3D culture.

DNA/RNA technology will make all disease-related genes targetable. I used anti-sense DNA and siRNA drugs to silence gene expression for immunotherapy and target therapy. I also screened small molecules for combination therapy with anti-sense therapy. 1. Designed CpG-conjugated anti-STAT3 oligonucleotides to silence its expression while activate immune response in prostate cancer. 2. Found GSK3 as a novel target in prostate cancer (Molecular Therapy, 2017) 3. Discovered the mechanism for siRNA/miRNA/oligonucleotides transportation in cells (PNAS, 2018)

Studied molecular pathogenesis of prostate cancer using cell 3D sphere culture and mouse models 1. Cloned and purified lentivirus constructs expressing oncogenes AKT, AR, c-Myc, K-RAS, etc 2. Implanted NOD-SCID mice with prostate stem cells transformed with oncogene lentivirus to study pathogenesis of prostate cancer 3. 3D Cultured prostate stem cell spheres to study the development of prostate tissues

Acute promyelocytic leukemia is the most successful cancer treatment. Without treatment, average survival after diagnosis was only one month; Arsenic trioxide has cured the leukemia (now 10-year survival > 95%). Using this model, I studied the mechanisms underlying leukemogenesis and drug response. 1. In a Science paper as the first author, Reported the molecular target of arsenic trioxide: PML-RARa oncoprotein (Science, 2010) 2. Used proteomics techniques (2D electrophoresis + mass spectrometry) and gene arrays to understand drug response at molecular levels 3. Identified DNMT3A mutation in myeloid leukemia using exome sequencing (Nature Genetics, 2011)

As a clinical oncologist and research scientist, I treated patients, performed clinical trials with adoptive T cell therapy, and studies cancer cell vaccines using lung cancer mouse models.