Dr. Xiongbin Lu

The Vera Bradley Foundation Chair in Breast Cancer Innovation

Professor of Medical and Molecular Genetics - IUPUI

Strategic Research Initiative Distinguished Investigator

• BS, Biological Sciences & Technology, Zhejiang University, Zhejiang, China
• Ph.D, Biochemistry, Shanghai Institute of Biochemistry, Chinese Acadamy of Science

Cancer Genomics and Targeted Therapy

Genomic instability is one of the most pervasive characteristics of cancer cells. In my laboratory, we have been studying DNA damage response and cancer genomic alterations, (translocation, amplification, and deletion).  My recent work revealed that frequent homozygous deletion of the p53 gene often encompasses a neighboring essential gene, POLR2A, rendering cancer cells vulnerable to further suppression of POLR2A (Liu Y et al., Nature 2015, profiled by Nature Rev Cancer, Nature Rev Clin Oncol, and Cancer Discov). In collaboration with physician scientists and bio-engineering scientists, we are now developing antibody-drug conjugates that specifically target human cancers with hemizygous loss of p53/POLR2A.

Non-coding RNAs and DNA Damage Response

I have also been very interested in the roles of non-coding RNAs in the DNA damage response and human tumorigenesis. I was the first to identify a RNA-binding protein (RBP), KSRP, as a key player that translates DNA damage signaling to microRNA biogenesis, (Zhang X, et al, Mol Cell 2011; Wan G et al., Trends Biochem Sci, Wan G et al, Cell Reports 2013). Given a higher level of complexity on the sequences and structures of pri-miRNAs, the processing specificity of miRNAs is primarily attributed to the Drosha complex in miRNA maturation. Regulatory RBPs in the Drosha complex are the key factors that determine the expression of specific miRNAs. In my laboratory, we have identified several important RBPs that recruit specific pri-miRNA for processing. For example, DDX1 promotes the expression of a subset of miRNAs that are associated with ovarian cancer progression and metastasis, (Han C et al., Cell Reports 2014). We have also investigated a number of novel noncoding RNAs in the epigenetic regulation of gene expression, (Wan G, et al., EMBO J, 2013).

Nanodrugs for Cancer Therapy

My laboratory has been collaborating with biomedical engineering scientists to develop nanoscale biomaterials to safely and effectively deliver one or more small and macromolecules including hydrophilic/hydrophobic anticancer drugs, proteins/peptides, and siRNAs/miRNAs. For example, we have synthesized dual (temperature and pH) responsive polymeric nanoparticles with a core-shell morphology to co-encapsulate both hydrophilic and hydrophilic drugs for targeting tumors and the drug resistance mechanisms of cancer (Zhang W et al., ACS Nano 2010; Rao W et al.,  ACS Nano 2015). Moreover, we have been working on combined cancer treatment of chemo, photodynamic, and photothermal therapies. We have developed a biomimetic hybrid nanoplatform with a eukaryotic cell-like configuration (Eukacell) and a NIR-laser activatable “nanobomb” for controlled release of small RNAs (Wang H et al., Nature Communications 2015; Wang H et al, Advanced Materials 2016).

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My laboratory will continue these efforts in understanding cancer biology, identifying novel drug targets and therapies, and developing new cancer drugs using innovative nanoscale biomaterials.

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