Biomedical Research Education & Training
Faculty Member

Park, Serk In, D.D.S., Ph.D.
Assistant Professor of Medicine
Assistant Professor of Cancer Biology

Lab Url: http://www.mc.vanderbilt.edu/root/vumc.php?site=CenterForBoneBiology

Phone Number: 615-936-7607

Email Address: serkin.park@vanderbilt.edu

Park, Serk In's picture
Academic history
D.D.S., Yonsei University, Seoul, Korea
Ph.D., The University of Texas M. D. Anderson Cancer Center, Houston, TX
Research Fellowship, The University of Michigan, Ann Arbor, MI
N/A

Office Address   Mailing Address

1225E MRB IV

2215B Garland Avenue 37232-0575


Research Keywords
Prostate cancer, Metastasis, Bone, Tumor microenvironment, Bone marrow-derived cells, Src family kinase, Mouse models,Cancer,Endocrinology,Kinase,Knockout,Mouse,Pathology

Research Specialty
Bone marrow-derived cells in the prostate cancer microenvironment

Research Description
The tumor microenvironment is comprised of primary cancer cells mixed with multiple types of stromal cells, of which a significant fraction originates in the bone marrow. For this reason, bone is an essential partner for tumor progression. However, it is unclear how tumor cells co-opt the bone and/or bone marrow to facilitate a favorable tumor microenvironment.

Among those bone marrow-derived cells in the tumor microenvironment, a subset of myeloid lineage cells, myeloid-derived suppressor cells (MDSCs), has been shown to correlate significantly with tumor progression. MDSCs suppress the host immune response and infiltrate tumor tissue to promote tumor growth and angiogenesis. Beyond these critical roles, little is known about the regulation of MDSCs within bone by distant primary tumor cells, not to mention therapeutic approaches targeting MDSCs.

The Park Laboratory aims to address how tumor cells stimulate the bone microenvironment to regulate MDSCs, contributing to tumor growth, angiogenesis and/or metastasis.

For this aim, prostate cancer takes a unique position, not only because of disastrous mortality and morbidity, but also because of preferential metastasis to the skeleton. Accordingly, prostate cancer cells secrete numerous important bone-modulating cytokines, leading to osteoblastic/osteolytic reactions that stimulate the adjacent bone marrow cells.

We will investigate the molecular mechanism of MDSC activation, expansion, and/or mobilization within the bone marrow of prostate tumor hosts. Additionally, we will examine the therapeutic approaches targeting MDSCs in pre-clinical models with investigational drugs. The potential research outcomes will promote understanding of the vicious partnership between cancer and bone.

Publications
Cho, SW, Soki, FN, Koh, AJ, Eber, MR, Entezami, P, Park, SI, van Rooijen, N, McCauley, LK. Osteal macrophages support physiologic skeletal remodeling and anabolic actions of parathyroid hormone in bone. Proc Natl Acad Sci U S A, 111(4), 1545-50, 2014

Ding, X, Park, SI, McCauley, LK, Wang, CY. Signaling between transforming growth factor ?? (TGF-??) and transcription factor SNAI2 represses expression of microRNA miR-203 to promote epithelial-mesenchymal transition and tumor metastasis. J Biol Chem, 288(15), 10241-53, 2013

Jin, R, Sterling, JA, Edwards, JR, DeGraff, DJ, Lee, C, Park, SI, Matusik, RJ. Activation of NF-kappa B signaling promotes growth of prostate cancer cells in bone. PLoS One, 8(4), e60983, 2013

Park, SI, Lee, C, Sadler, WD, Koh, AJ, Jones, J, Seo, JW, Soki, FN, Cho, SW, Daignault, SD, McCauley, LK. Parathyroid hormone-related protein drives a CD11b+Gr1+ cell-mediated positive feedback loop to support prostate cancer growth. Cancer Res, 73(22), 6574-83, 2013

Zhang, H, Yu, C, Dai, J, Keller, JM, Hua, A, Sottnik, JL, Shelley, G, Hall, CL, Park, SI, Yao, Z, Zhang, J, McCauley, LK, Keller, ET. Parathyroid hormone-related protein inhibits DKK1 expression through c-Jun-mediated inhibition of ??-catenin activation of the DKK1 promoter in prostate cancer. Oncogene, 2013

Jung, Y, Shiozawa, Y, Wang, J, McGregor, N, Dai, J, Park, SI, Berry, JE, Havens, AM, Joseph, J, Kim, JK, Patel, L, Carmeliet, P, Daignault, S, Keller, ET, McCauley, LK, Pienta, KJ, Taichman, RS. Prevalence of prostate cancer metastases after intravenous inoculation provides clues into the molecular basis of dormancy in the bone marrow microenvironment. Neoplasia, 14(5), 429-39, 2012 PMCID:3384430

Park, SI, Liao, J, Berry, JE, Li, X, Koh, AJ, Michalski, ME, Eber, MR, Soki, FN, Sadler, D, Sud, S, Tisdelle, S, Daignault, SD, Nemeth, JA, Snyder, LA, Wronski, TJ, Pienta, KJ, McCauley, LK. Cyclophosphamide creates a receptive microenvironment for prostate cancer skeletal metastasis. Cancer Res, 72(10), 2522-32, 2012 PMCID:3384430

Park, SI, McCauley, LK. Nuclear localization of parathyroid hormone-related peptide confers resistance to anoikis in prostate cancer cells. Endocr Relat Cancer, 19(3), 243-54, 2012 PMCID:3384430

Soki, FN, Park, SI, McCauley, LK. The multifaceted actions of PTHrP in skeletal metastasis. Future Oncol, 8(7), 803-17, 2012

Li, X, Koh, AJ, Wang, Z, Soki, FN, Park, SI, Pienta, KJ, McCauley, LK. Inhibitory effects of megakaryocytic cells in prostate cancer skeletal metastasis. J Bone Miner Res, 26(1), 125-34, 2011 PMCID:3179321

Li, X, Liao, J, Park, SI, Koh, AJ, Sadler, WD, Pienta, KJ, Rosol, TJ, McCauley, LK. Drugs which inhibit osteoclast function suppress tumor growth through calcium reduction in bone. Bone, 48(6), 1354-61, 2011 PMCID:3072580

Park, SI, Soki, FN, McCauley, LK. Roles of bone marrow cells in skeletal metastases: no longer bystanders. Cancer Microenviron, 4(3), 237-46, 2011 PMCID:3234319

Park, SI, Kim, SJ, McCauley, LK, Gallick, GE. Pre-clinical mouse models of human prostate cancer and their utility in drug discovery. Curr Protoc Pharmacol, Chapter 14, Unit 14.15, 2010 PMCID:3072580

Kopetz, S, Lesslie, DP, Dallas, NA, Park, SI, Johnson, M, Parikh, NU, Kim, MP, Abbruzzese, JL, Ellis, LM, Chandra, J, Gallick, GE. Synergistic activity of the SRC family kinase inhibitor dasatinib and oxaliplatin in colon carcinoma cells is mediated by oxidative stress. Cancer Res, 69(9), 3842-9, 2009

Park, SI, Zhang, J, Phillips, KA, Araujo, JC, Najjar, AM, Volgin, AY, Gelovani, JG, Kim, SJ, Wang, Z, Gallick, GE. Targeting SRC family kinases inhibits growth and lymph node metastases of prostate cancer in an orthotopic nude mouse model. Cancer Res, 68(9), 3323-33, 2008 PMCID:3179321

Park, SI, Shah, AN, Zhang, J, Gallick, GE. Regulation of angiogenesis and vascular permeability by Src family kinases: opportunities for therapeutic treatment of solid tumors. Expert Opin Ther Targets, 11(9), 1207-17, 2007 PMCID:1978423

Shah, AN, Summy, JM, Zhang, J, Park, SI, Parikh, NU, Gallick, GE. Development and characterization of gemcitabine-resistant pancreatic tumor cells. Ann Surg Oncol, 14(12), 3629-37, 2007 PMCID:3179321

Zhang, J, Park, SI, Artime, MC, Summy, JM, Shah, AN, Bomser, JA, Dorfleutner, A, Flynn, DC, Gallick, GE. AFAP-110 is overexpressed in prostate cancer and contributes to tumorigenic growth by regulating focal contacts. J Clin Invest, 117(10), 2962-73, 2007 PMCID:1978423


Postdoctoral Position Available
No

Postdoctoral Position Details
N/A

Updated Date
02/25/2014