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Radiation and Cancer Biology
Xu Lab

Xu_LiangLiang Xu, MD, PhD:
Assistant Professor

One focus: Molecular therapy targeting cancer and cancer stem cells

Funded by multiple NIH and DOD grants, my lab is working on molecularly targeted cancer therapy and chemo/radiosensitization by modulating cell death signaling pathways. We are exploring microRNAs as novel targets for cancer and cancer stem cells. We are currently using novel nanotechnology to develop nanovectors targeting cancer cells for siRNA/miRNA-based novel cancer therapeutics. We are also developing nanovectors targeting cancer stem cells and exploring novel molecular therapy for cancer stem cells. Specifically, we have:

Two directions:

1. Novel nanovector delivery systems targeting cancer and cancer stem cells.

We have been working on the tumor-targeted delivery of molecular cancer therapeutics using novel nanotechnology. A self-assembled, virus-mimicking, non-viral nanovector for systemic p53 gene therapy has shown promise in chemo- and radiosensitization of breast, prostate, head and neck cancer, is now in Phase I clinical trial as the World’s first non-viral tumor-targeted p53 gene therapy entered clinical trial. Multiple US and International Patents are issued or pending. Currently, we are using this patented nanovector for tumor-targeted delivery of siRNA/miRNA-based therapeutics and novel small-molecule therapeutics. We are also working with University of Michigan Cancer Stem Cell Interest Group to explore next generation nanovectors for targeting cancer stem cells.

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

We have been involved in University of Michigan Drug Discovery Program to discover novel small-molecule cancer therapeutics targeting cell death pathways, especially for cancer cell radiosensitization and chemosensitization by molecular modulation of anti-apoptotic proteins. One of the first lead compounds tested in vitro and in vivo in my laboratory has entered Phase I-III clinical trials as the World’s first small-molecule inhibitor of Bcl-2/Bcl-xL/Mcl-1 approved by FDA and entered clinic trials. Multiple US and International Patents are issued or pending. Currently, we are also working on molecular cancer radiosensitization with Mcl-1 inhibitors.

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Publications

  1. Xu L, Yang D, Wang S, Tang W, Liu M, Davis M, Chen J, Rae JM, Lawrence TS and Lippman ME. (-)-Gossypol enhances response to radiation therapy and results in tumor regression of human prostate cancer. Mol Cancer Ther 2005; 4(2):197-205. (PMID: 15713891)
  2. Meng Y, Tang W, Dai Y, Wu X, Liu M, Ji Q, Ji M, Pienta K, Lawrence TS and Xu L. Natural BH3-mimetic   (-)-gossypol chemosensitizes human prostate cancer via Bcl-xL inhibition accompanied by increase of Puma and Noxa. Mol Cancer Ther 2008; 7(7):2192-2202. (PMID: 18645028)
  3. Abela RA, Qian J, Xu L, Lawrence TS and Zhang M. Radiation improves gene delivery by a novel transferrin-lipoplex nanoparticle selectively in cancer cells. Cancer Gene Ther 2008; 15(8):496-507. (PMID: 18483503)
  4. Ji Q, Hao X, Meng Y, Zhang M, DeSano J, Fan D and Xu L. Restoration of tumor suppressor miR-34 inhibits human p53-mutant gastric cancer tumorspheres. BMC Cancer 2008; 8(1):266. (Highly accessed) (PMID: 18803879)
  5. Dai Y, Liu M, Tang W, DeSano TJ, Burstein E, Pienta K, Lawrence TS and Xu L. Molecularly targeted radiosensitization of human prostate cancer by modulating IAP. Clin Cancer Res 2008; 14(23):7701-10. (PMID: 19047096)
  6. Dai Y, Lawrence TS and Xu L. Overcoming cancer therapy resistance by targeting inhibitors of apoptosis proteins and NF-kB. Am J Transl Res 2009; 1(1):1-15. (www.ajtr.org/files/AJTR810001.pdf)
  7. Jia G, Zhan Y, Wu D, Meng Y and Xu L. An improved ultrasound-assisted extraction process of gossypol acetic acid from cottonseed soapstock. AIChE J 2009; 55(3):797-806.
  8. Zhan Y, Jia G, Wu D, Xu YS and Xu L. Design and synthesis of a gossypol derivative with improved antitumor activities. Arch Pharm 2009; 342:223-229. (PMID: 19340835)
  9. Dai Y, DeSano TJ, Meng Y, Ji Q, Ljungman M, Lawrence TS and Xu L. Celastrol potentiates radiation therapy via impairment of DNA damage processing in human prostate cancer. Int J Radiat Oncol Biol Phys 2009; 74(4):1217-1225. (PMID: 19545787)
  10. Ji Q, Hao X, Zhang M, Tang W, Meng Y, Li L, Xiang D, DeSano TJ, Bommer GT, Fan D, Fearon ER, Lawrence TS and Xu L. MicroRNA miR-34 inhibits human pancreatic cancer tumor-initiating cells. PLoS One 2009; 4(8): e6816. (PMID: 19714243)
  11. Dai Y, Liu M, Tang W, Li Y, Lian J, Lawrence TS and Xu L. A Smac-mimetic sensitizes prostate cancer cells to TRAIL-induced apoptosis via modulating both IAPs and NF-kB. BMC Cancer 2009; 9:392. (PMID: 19895686)
  12. DeSano TJ and Xu L. MicroRNA regulation of cancer stem cells and therapeutic implications. AAPS J 2009; 11(4):682-692. (PMID: 19842044)
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Patents

  1. Chang EH, Xu L. and Pirollo KF. Targeted liposome gene delivery.  International Patent Application No. PCT/US98/24657, filed on 11/19/1998. United States Patent No. US 6,749,863, issued on June 15, 2004.
  2. Xu L., Huang CC, Alexander W, Tang WH and Chang EH.  Antibody fragment-targeted immunoliposomes for systemic gene delivery. European Patent No. EP 1,154,756B1, issued on Jan.3, 2007.
  3. Wang S, Yang D and Xu L. Small molecule antagonists of Bcl-2 family proteins. International Patent PCT filed on 12/05/2004. United States Patent No. US 7,432,304B2, issued on Oct.7, 2008.
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Lab Members and Family
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