In addition, the Lu Lab also identified USP13 (ubiquitin peptidase 13) as a potential target gene in human ovarian cancer. USP13 specifically deubiquitinates and thus upregulates ATP citrate lyase and oxoglutarate dehydrogenase, two key enzymes that determine mitochondrial respiration, glutaminolysis and fatty acid synthesis. The USP13 gene is co-amplified with PIK3CA in 29.3% of high-grade serous ovarian cancers and its overexpression is significantly associated with poor clinical outcome. Inhibiting USP13 remarkably suppresses ovarian tumor progression and sensitizes tumor cells to the treatment of PI3K/AKT inhibitor (Nature Communications, 2016).
Targeted therapies for human cancers with copy number variations
Developed novel nanodrugs for cancer therapy
The laboratory has been working on combined cancer treatment of chemo, photodynamic and photothermal therapies. In the process, the laboratory has developed a biomimetic hybrid nanoplatform with a eukaryotic cell-like configuration (Nature Communications, 2015). Another example is the NIR-laser activatable “nanobomb” that was developed to encapsulate small RNAs with high efficiency (~85%) for cytosolic delivery (Advanced Materials, 2015).
NIH R01CA203737: Targeting human cancers with hemizygous deletion of TP53
NIH R01CA206366: Nanotechnology enabled targeting of p53 deficiency in human cancer
NIH R21CA213535: Engineering antibody drug conjugates to target p53-defective triple negative breast cancer
NIH R21CA185742: Ubiquitin specific peptidases as redox sensor in oncogene-induced p53 signaling
IU School of Medicine Strategic Research Initiative fund
Vera Bradley Foundation fund
Han C, Yang L, Choi HH, Baddour J, Achreja A, Liu Y, Li Y, Li J, Wan G, Huang C, Zhang X, Nagrath D, Lu X (2016). Amplification of USP13 drives ovarian tumor metabolism. Nature Communications, 7:13525.
Wang H, Agarwal P, Zhao S, Yu J, Lu X, He X (2016). A near infrared laser-activatable “nanobomb” for breaking the barriers to microRNA delivery. Advanced Materials, 28(2):347-55.
Liu Y, Zhang X, Han C, Wan G, Huang X, Ivan C, Jiang D, Rodriguez-Aguayo C, Lopez-Berestein G, Rao PH, Maru DM, Pahl A, He X, Sood AK, Ellis LM, Anderl J, Lu X (2015). TP53 loss creates therapeutic vulnerability in colorectal cancer. Nature, 520(7549):697-701.
Zhang X, Wan G, Berger FG, He X, Lu X (2011). The ATM kinase induces microRNA biogenesis in the DNA damage response. Molecular Cell, 41:371-83.
Additional Research Team Members
Other research team members in the Lu Lab include Yuanzhang Fang, PhD (Post-doctoral Fellow), Yujing Li, PhD (Post-doctoral Fellow), Kevin Van der Jeught, PhD (Post-doctoral Fellow), Zhoulong Zhou, PhD (Post-doctoral Fellow), Lynn Zhang (visiting Research scholar), Hanchen Xu (visiting Research scholar) and Michael Frieden (Research Technician I, Lab Manager).