Xin Lu John M. and Mary Jo Boler Assistant Professor

Molecular Understanding and Immunotherapy of Metastatic Cancer
Xin Lu

Research Interests:

Understanding and targeting the tumor microenvironment is at the forefront of current basic and translational cancer research. Targeting tumor microenvironment is closely related to tumor immunology and immunotherapy, one of the most exciting and rapidly evolving areas of cancer research. An intense focus of research in our lab is to investigate the molecular and cellular mechanisms underlying the cancer ─ tumor microenvironment crosstalk, in particular interactions between cancer cells and the myeloid compartment, in both primary tumors and metastases to bone and other organs. We hypothesize that the efficacy of immune checkpoint blockade drugs (e.g. anti-CTLA4, anti-PD1 antibodies) on refractory metastatic cancer can be potently enhanced when combined with other therapy modalities, including targeted therapy that specifically antagonize immunosuppressive activities yet preserve T cell functions in the tumor microenvironment.

We are equally interested in the most prevalent cancer types that men and women suffer from (prostate cancer and breast cancer), as well as rare cancer types such as penile cancer and sarcoma. As part of the Center for Rare and Neglected Diseases (CRND), our mission is to understand and eliminate cancer as a disease in the near future through bench-to-bedside translational research and partnership with drug discovery powerhouses. To achieve this goal, we use integrated approaches centered at cancer genome mining and validation as well as sophisticated inducible transgenic mouse modeling.

 

Biography:

  • John M. and Mary Jo Boler Assistant Professor, University of Notre Dame, IN 2017-Present
  • Instructor, Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 2014-2016
  • HHMI/Jane Coffin Childs Postdoctoral Fellow. Department of Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 2011-2014
  • HHMI/Jane Coffin Childs Postdoctoral Fellow. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 2010-2011
  • Ph.D. (Molecular Biology), Princeton University, Princeton, NJ 2004-2010
  • B.S. (Biological Sciences), Tsinghua University, Beijing, China 2000-2004

 

Recent Papers:

  • Lu, X., J. W. Horner, E. Paul, X. Shang, P. Troncoso, P. Deng, S. Jiang, Q. Chang, D. J. Spring, P. Sharma, J. A. Zebala, D. Y. Maeda, Y. A. Wang and R. A. DePinho Effective Combinatorial Immunotherapy for Castration Resistant Prostate Cancer. Nature. 2017; In press.
  • Zhao, D., Lu, X., Wang, G., Lan, Z., Liao, W., Li, J., Liang, X., Chen, J.R., Shah, S., Tang, M., et al. (2017). Synthetic essentiality of chromatin remodeling factor CHD1 in PTEN deficient cancer. Nature. 2017; In press.
  • Hu B, Wang Q, Wang YA, Hua S, Sauvé CG, Ong D, Lan ZD, Chang Q, Ho YW, Monasterio MM, Lu X, Zhong Y, Zhang J, Deng P, Tan Z, Wang G, Liao WT, Corley LJ, Yan H, Zhang J, You Y, Liu N, Cai L, Finocchiaro G, Phillips JJ, Berger MS, Spring DJ, Hu J, Sulman EP, Fuller GN, Chin L, Verhaak RG, DePinho RA. Epigenetic Activation of WNT5A Drives Glioblastoma Stem Cell Differentiation and Invasive Growth. Cell. 2016; 167(5):1281-1295
  • Wang G*, Lu X*, Dey P, Deng P, Wu C, Jiang S, Fang Z, Zhao K, Konaparthi R, Hua S, Zhang J, Tapia E,Kapoor A, Wu C, Patel N, Guo Z, Ramamoorthy V, Tieu T, Heffernan T, Zhao D, Shang X, Khadka S, Hou P, Hu B, Jin E, Yao W, Pan X, Ding Z, Shi Y, Li L, Chang Q, Troncoso P, Logothetis C, McArthur M, Chin L, Wang YA, DePinho RA. Targeting YAP-dependent MDSC infiltration impairs tumor progression. Cancer Discovery. 2016 Jan;6(1):80-95. (*Co-first authors with equal contribution)
  • Wan L, Lu X, Yuan S, Wei Y, Guo F, Shen M, Yuan M, Chakrabarti R, Hua Y, Smith HA, Blanco MA, Chekmareva M, Wu H, Bronson RT, Haffty BG, Xin Y, Kang Y. MTDH-SND1 Interaction Is Crucial for Expansion and Activity of Tumor-Initiating Cells in Diverse Oncogene- and Carcinogen-Induced Mammary Tumors. Cancer Cell. 2014: 26(1):92-105
  • Lu X*, Agasti S*, Vinegoni C, Waterman P, DePinho RA, Weissleder R. Optochemogenetics (OCG) allows more precise control of genetic engineering in mice with CreER regulators. Bioconjugate Chemistry. 2012: 23(9):1945-51. (*Co-first author)
  • Ding Z, Wu CJ, Jaskelioff M, Ivanova E, Kost-Alimova M, Protopopov A, Chu GC, Wang G, Lu X, Labrot ES, Hu J, Wang W, Xiao Y, Zhang H, Zhang J, Zhang J, Gan B, Perry SR, Jiang S, Li L, Horner JW, Wang YA, Chin L, DePinho RA. Telomerase reactivation following telomere dysfunction yields murine prostate tumors with bone metastases. Cell. 2012; 148:896-907.
  • Lu X, Mu E, Wei Y, Riethdorf S, Yang Q, Yuan M, Yan J, Hua Y, Tiede B, Lu X, Haffty B, Pantel K, Massagué J, and Kang Y. VCAM-1 promotes osteolytic expansion of indolent bone micrometastasis of breast cancer by engaging α4β1-positive osteoclast progenitors. Cancer Cell. 2011; 20:701-714. (Featured Article)
  • Lu X, Yan C, Yuan M, Wei Y, Hu G, and Kang Y. In vivo dynamics and distinct functions of hypoxia in primary tumor growth and organotropic metastasis of breast cancer. Cancer Res. 2010; 70: 3905-3914
  • Lu X, Lu X, and Kang Y. Organ-specific enhancement of metastasis by spontaneous ploidy duplication and cell size enlargement. Cell Res. 2010; 20:1012–1022.
  • Lu X, Wang Q, Hu G, Van Poznak C, Fleisher M, Reiss M, Massagué J, and Kang Y. ADAMTS1 and MMP1 proteolytically engage EGF-like ligands in an osteolytic signaling cascade for bone metastasis. Genes & Dev. 2009; 23:1882-1894. (Cover highlight)
  • Lu X, and Kang Y. Efficient acquisition of dual metastasis organotropism to bone and lung through stable spontaneous fusion between MDA-MB-231 variants. Proc. Natl. Acad. Sci. 2009; 106:9385-9390
  • Lu X, and Kang Y. Chemokine (C-C Motif) ligand 2 engages CCR2+ stromal cells of monocytic origin to promote breast cancer metastasis to lung and bone. J. Biol. Chem. 2009; 284: 29087-29096.
  • Lu X, and Kang Y. Cell fusion as a hidden force in tumor progression. Cancer Res. 2009; 69: 8536-8539.