Serk In Park, D.D.S, Ph.D.
Assistant Professor of Medicine (Clinical Pharmacology)
Assistant Professor of Cancer Biology
Vanderbilt University Medical Center
1225E MRB IV
Nashville, TN 37232
The primary goal of my laboratory aims to address what makes bone the most favored organ of prostate cancer spreading. Advanced-stage prostate cancer patients uniformly develop bone lesions (i.e. bone metastasis), resulting in severe pain, immobility, and ultimately death. A major hurdle to develop means of preventing or curing bone metastasis stems from the diversity of cell types constituting bone and the bone marrow, and determining how these cells may be involved. Indeed, the bone marrow is a reservoir of blood-forming cells, and also serves as a seedbed for the cancer cells spreading to bone. My laboratory endeavors to understand how exactly the bone marrow cells contribute to the development of bone metastasis, and ultimately how to suppress those cells to treat bone metastasis. Research outcomes from my laboratory will have impacts on understanding how prostate cancer exploits the bone marrow cells to colonize bone, and more importantly will help provide biological rationale and means for targeting a specific cell type in the bone marrow as a therapeutic approach for prostate cancer patients.
- D.D.S, Yonsei University, Seoul, Korea
- Ph.D. in Cancer Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX
- Research Fellowship, The University of Michigan, Ann Arbor, MI
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.
- Reddy NM, Greer JP, Morgan DS, Chen H, Park SI, Richards KL. A phase II randomized study of lenalidomide or lenalidomide and rituximab as maintenance therapy following standard chemotherapy for patients with high/high-intermediate risk diffuse large B-cell lymphoma. Leukemia [print-electronic]. 2016 Sep 9/22/2016; PMID: 27654851, PII: leu2016255, DOI: 10.1038/leu.2016.255, ISSN: 1476-5551.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/27654851.
- Whang YM, Park SI, Trenary IA, Egnatchik RA, Fessel JP, Kaufman JM, Carbone DP, Young JD. LKB1 deficiency enhances sensitivity to energetic stress induced by erlotinib treatment in non-small-cell lung cancer (NSCLC) cells. Oncogene [print-electronic]. 2016 Feb 2/18/2016; 35(7): 856-66. PMID: 26119936, PMCID: PMC4486321, PII: onc2015140, DOI: 10.1038/onc.2015.140, ISSN: 1476-5594.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/26119936.
- Park SI, Park SJ, Lee J, Kim HE, Park SJ, Sohn JW, Park YG. Inhibition of cyclic AMP response element-directed transcription by decoy oligonucleotides enhances tumor-specific radiosensitivity. Biochem. Biophys. Res. Commun [print-electronic]. 2016 Jan 1/15/2016; 469(3): 363-9. PMID: 26655813, PII: S0006-291X(15)30991-8, DOI: 10.1016/j.bbrc.2015.11.122, ISSN: 1090-2104.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/26655813.
- Soki FN, Cho SW, Kim YW, Jones JD, Park SI, Koh AJ, Entezami P, Daignault-Newton S, Pienta KJ, Roca H, McCauley LK. Bone marrow macrophages support prostate cancer growth in bone. Oncotarget. 2015 Nov 11/3/2015; 6(34): 35782-96. PMID: 26459393, PMCID: PMC4742141, PII: 6042, DOI: 10.18632/oncotarget.6042, ISSN: 1949-2553.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/26459393.
- Buenrostro D, Park SI, Sterling JA. Dissecting the role of bone marrow stromal cells on bone metastases. Biomed Res Int [print-electronic]. 2014; 2014: 875305. PMID: 25054153, PMCID: PMC4099112, DOI: 10.1155/2014/875305, ISSN: 2314-6141.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/25054153.
- 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 [print-electronic]. 2013 Nov 11/15/2013; 73(22): 6574-83. PMID: 24072746, PMCID: PMC3838921, PII: 0008-5472.CAN-12-4692, DOI: 10.1158/0008-5472.CAN-12-4692, ISSN: 1538-7445.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/24072746.
- 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 [print-electronic]. 2013; 8(4): e60983. PMID: 23577181, PMCID: PMC3618119, PII: PONE-D-12-24565, DOI: 10.1371/journal.pone.0060983, ISSN: 1932-6203.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/23577181.