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2015 Scientific Report

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Van Andel Research

Van Andel Research Institute | Scientific Report 2015 Xiaohong Li, Ph.D. Laboratory of Tumor Microenvironment and Metastasis Dr. Li received her Ph.D. from the Institute of Zoology, Chinese Academy of Sciences in Beijing in 2001, and since 2000 has pursued postdoctoral training in the laboratories of David Ong and Neil Bhowmick at Vanderbilt University in Nashville, Tennessee. She was a research assistant professor in the Department of Cancer Biology from 2009 to 2012, mentored by Lynn Matrisian. Dr. Li joined VARI as an Assistant Professor in September 2012. From left: Ganguly, Li, Lewis, Vander Ark, Meng Staff Sourik Ganguly, Ph.D. Priscilla Lee, B.S. Diana Lewis, A.S. Xiangqi (Neil) Meng, Ph.D. Alexandra Vander Ark, M.S. Students Samuel Ameh Yiqing Dong Rebecca Emery Peter Hsueh, B.S. Julienne Louters, B.S. Demarcus Williams 16

Li Research Interests Our laboratory is committed to understanding cancer metastases, particularly bone metastases. Most people who die of cancer have metastases somewhere in their body, but metastases of certain cancers (such as breast, prostate, and lung) are more likely to be found in bone. Once in the bone, cancer cells induce either osteolytic (bone resorption) or osteoblastic (abnormal bone formation) lesions, which cause fractures, spinal cord compression, hypercalcemia, and extreme bone pain. Current treatments for bone-metastasis patients reduce some symptoms such as pain but do not increase survival time. In order to develop early diagnostic and targeted therapeutic strategies, our long-term goal is to determine the mechanisms through which different cancers cause distinct types of bone lesions. To achieve this goal, we study the cancer cells and the microenvironments of both the primary site and the bone-metastasis site. The microenvironment of the bone is a rich reservoir of growth factors and cytokines, such as transforming growth factor (TGF)- and hepatocyte growth factor (HGF). These factors play crucial roles in both cancerous and healthy bone. More importantly, their effects are highly context-dependent spatially and temporally. Our short-term goal is to delineate the context-dependent effects of the important factors in bone metastases. Our current projects are as follows. 1) Determine the influence of the primary microenvironment on the development of prostate cancer osteoblastic bone lesions. The objectives are to determine how TGF- from the prostate contributes to bone lesion development, to identify the cytokines induced by the loss of TGF- signaling that mediate prostate cancer bone metastasis, and to determine the prognostic and therapeutic value of the identified cytokines for bone metastases. The Prostate Cancer Research Program of the Department of Defense has funded this project from 2012 until 2016. 2) Identify the cell-specific effects of TGF- signaling from the bone microenvironment on bone metastases. Using genetically engineered mouse models, we have been able to knock out TGF- signaling in certain bone cells. Context-dependent TGF- effects on osteolytic or osteoblastic bone metastases from different types of cancers will be investigated. 3) Establish animal models of osteoblastic bone metastasis and identify the signaling pathway that drives this process, in collaboration with VARI’s Cindy Miranti. 4) Determine the stromal HGF signaling effect on heterogenous cancer cell bone metastasis, in collaboration with VARI’s George Vande Woude. 5) Test new applications of bone-tropic and tumor-specific agents in early detection of and drug delivery for cancer bone metastasis, in collaboration with VARI’s Anthony Chang. 6) Screen new lymphangiogeneis factors as potential therapeutic targets of cancer metastases, in collaboration with Dr. Miles Qian, Sun Yat-sen University, China. Recent Publication Banerjee, J., R. Mishra, X. Li, R.S. Jackson II, A. Sharma, and N.A. Bhowmick. 2014. A reciprocal role of prostate cancer on stromal DNA damage. Oncogene 33(41): 4924–4931. 17

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