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Myoung Sook Kim, PhD

Academic Title:

Assistant Professor

Primary Appointment:

Pathology

Additional Title:

Assistant Professor

Location:

655 W Baltimore Street, BRB 11-056 Baltimore, MD 21201

Phone (Primary):

410-706-1347

Fax:

410-328-6559

Education and Training

Education

1993   B.S., Pusan National University School of Pharmacy
          Major: Pharmaceutical Science

1996   M.S., Pusan National University School of Pharmacy
          Major: Pharmaceutical Science

2000   Ph.D., Natural Science, Pusan National University, South Korea
          Major: Cellular and Molecular Biology

Adviser: Kyu-Won Kim, Ph.D.

Title of thesis - Functional Studies of Histone Deacetylase Inhibitors and Multidrug

Resistance-Reversing Compounds as Novel Angiogenesis Inhibitors

Post Graduate Education and Training    

2001 – 2002   Post-Doctoral Fellow, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine (Cancer Biology)

2002 – 2003   Post-Doctoral Fellow, Department of Biomedical Engineering, Johns Hopkins, University (Stem Cell Engineering)

2003 – 2007   Post-Doctoral Fellow, Department of Otolaryngology– Head and Neck Cancer, Research Division, Johns Hopkins University School of Medicine (Cancer Epigenetics)

Biosketch

Thus far, my research career has been devoted to the field of cancer research and the area of tumor metabolism has been of particular interest. From my previous work, I have been aware of the role of RUNX2 in cancer because my research topic during my training included stem cell engineering and osteogenic differentiation, which is dependent on RUNX2 (ref, 3). Since I was appointed to the faculty in the Department of Pathology, I have expanded my research to RUNX2-mediated tumor metabolism in breast cancer. 

1. Kim MS, Chang X, LeBron C, et al. Neurofilament heavy polypeptide regulates the Akt-beta-catenin pathway in human esophageal squamous cell carcinoma.PLoS One. 2010; 5(2):e9003.

2. Kim MS, Huang Y, Lee J, et al. Cellular transformation by cigarette smoke extract involves alteration of glycolysis and mitochondrial function in esophageal epithelial cells. Int J Cancer. 2010; 127(2):269-81.

3. Kim MS, Hwang NS, Lee J, et al. Musculoskeletal differentiation of cells derived from human embryonic germ cells. Stem Cells. 2005; 23(1):113-23.

4. Choe M, Brusgard JL, Chumsri S, et al. The RUNX2 Transcription Factor Negatively Regulates SIRT6 Expression to Alter Glucose Metabolism in Breast Cancer Cells. J Cell Biochem. 2015; 116(10):2210-26. (Co-author).

Tumor metabolism,  a shift to dependence on glycolysis from mitochondrial oxidative phosphorylation

Aerobic glycolysis and mitochondrial dysfunction are common features of aggressive cancer growth. Neurofilament heavy chain polypeptide (NEFH) was one of the TSGs that I identified. A few years ago, I reported promoter methylation and loss of expression of the NEFH in primary esophageal cancer that were of a high tumor grade and advanced stage. Loss of NEFH resulted in up-regulation of pyruvate kinase-M2 type and down-regulation of pyruvate dehydrogenase (PDH) via activation of the Akt/beta-catenin pathway, resulting in enhanced aerobic glycolysis and mitochondrial dysfunction. In addition, I found that chronic exposure of nonmalignant esophageal epithelial cells to cigarette smoke extract causes alterations in cellular phenotypes, leading to acquisition of tumorigenic characteristics. The underlying mechanism of cigarette smoke extract-induced glycolysis and mitochondrial dysfunction involves upregulation of glycolytic enzymes and reciprocally downregulation of mitochondrial genes.  Most recently, this expertise was important for the results and publication of the research focusing on how RUNX2 promotes glycolytic switching in breast cancer cells by increasing expression of genes involved in glycolysis and inhibition of mitochondrial function.

 

1. Kim MS, Chang X, LeBron C, et al. Neurofilament heavy polypeptide regulates the Akt-beta-catenin pathway in human esophageal squamous cell carcinoma.PLoS One. 2010; 5(2):e9003.

2. Kim MS, Huang Y, Lee J, et al. Cellular transformation by cigarette smoke extract involves alteration of glycolysis and mitochondrial function in esophageal epithelial cells. Int J Cancer. 2010; 127(2):269-81.

3. Choe M, Brusgard JL, Chumsri S, et al. The RUNX2 Transcription Factor Negatively Regulates SIRT6 Expression to Alter Glucose Metabolism in Breast Cancer Cells. J Cell Biochem. 2015; 116(10):2210-26 (Co-author).

 

Identification of novel tumor suppressor genes and tumor biomarkers

My areas of expertise include the identification and elucidation of cancer biomarkers and epigenetic alterations (both DNA methylation and histone modifications) of tumor suppressor genes (TSGs). I have identified novel TSGs regulated by cancer epigenetic mechanisms and developed biomarkers with clinical significance. I examined epigenetic alterations, specifically promoter hypermethylation patterns, in various human malignancies, including breast cancer, using epigenetic and pharmacological approaches. So far, I have identified more than 10 novel tumor suppressors as potential biomarkers in colon, gastric, esophageal, and breast cancer.

 

1. Kim MS, Lebron C, Nagpal JK, et al. Aberrant hypermethylation in the DFNA5 gene promoter increases risk of lymph node metastasis in human breast cancer. Biochem Biophys Res Commun. 2008; 370(1):38-43.

2. Kim MS, Louwagie J, Carvalho B, et al. Promoter DNA methylation survey of colon cancer identifies a novel diagnostic and therapeutic markers. PLoS ONE. 2009; 4(8):e6555.

3. Brait M, Ling S,  Nagpal JK, et al. Cysteine dioxygenase 1 is a tumor suppressor gene silenced by promoter methylation in multiple human cancers. PLoS One. 2012; 7(9):e44951 (Corresponding author).

4. Kim MS, Chang X, LeBron C, et al. Neurofilament heavy polypeptide regulates the Akt-beta-catenin pathway in human esophageal squamous cell carcinoma.PLoS One. 2010; 5(2):e9003.

Histone deacetylase inhibitors as novel angiogenic inhibitors

During my PhD program, I examined the role of histone deacetylases (HDAC) in the regulation of p53 and hypoxia-inducible factor-1a in tumor angiogenesis. Significantly, this study discovered the potential of HDAC inhibitors to be applied to anticancer therapy. For my first post-doctoral training, I studied the combination of HDAC inhibitors with various anticancer drugs targeting DNA such as etoposide. I found that loosening-up the chromatin structure by histone acetylation by HDAC inhibitors could increase the efficacy of these anticancer drugs.

1. Kim MS, Kwon HJ, Lee YM, et al. Histone deacetylases induce angiogenesis by negative regulation of tumor suppressor genes. Nat. Med. 2001; 7(4):437-43.

2. Kim MS, Blake M, Baek JH, et al. Inhibition of histone deacetylase increases cytotoxicity to anticancer drugs targeting DNA. Cancer Res. 2003: 63(21):7291-300.

3. Kim MS, Baek JH, Chakravarty D, et al. Sensitization to UV-induced apoptosis by the histone deacetylase inhibitor Trichostatin A (TSA). Exp. Cell Res. 2005; 306:94-102.

Research/Clinical Keywords

RUNX2 and breast cancer research Tumor metabolism - glycolysis and mitochondrial oxidative phosphorylation Drug resistance - taxane chemotherapy and resistance tumor suppressor genes and tumor biomarkers

Highlighted Publications

  1. Myoung Sook Kim, Ho Jeong Kwon, You Mie Lee, Jin Hyen Baek, Jae-Eun Jang, Sae-Won Lee, Eun-Joung Moon, Hye-Sun Kim, Seok-Ki Lee, Hae Young Chung, Chul-Woo Kim, Kyu-Won Kim.Histone Deacetylases Induce Angiogenesis by Negative Regulation of Tumor Suppressor Genes. Nat. Med., 7 (4), 437-443 (Apr, 2001).
  2. Myoung Sook Kim, Keishi Yamashita, Jin Hyen Baek, Hannah Lui Park, Andre Lopes Carvalho, Motonobu Osada, Mohammad Obaidul Hoque, Sunil Upadhyay, Masaki Mori, Chul-so Moon, David Sidransky. NMDA Receptor Type 2B, at 12p12, is epigenetically inactivated and exhibits tumor suppressive activity in human esophageal cancer. Cancer Res., 66(7): 3409-3418 (April, 2006).
  3. Mohammad Obaidul Hoque*, Myoung Sook Kim *, Kimberly Laskie Ostrow*, Junwei Liu*, G. Bea A. Wisman, Hannah Lui Park, Luana Poeta, Carmen Jeronimo, Rui Henerique, Ágnes Lendvai, Ed Schuuring, Shahnaz Begum, Eli Rosenbaum, Maté Ongenaert, Keshi Yamashita, Joseph Califano, William Westra,  Ate G.J. van der Zee,Wim Van Criekinge, and David Sidransky. Genome-wide Promoter Analysis Uncovers Portions of the Cancer Methylome. Cancer Research, 68(8):2661-70 (Apr, 2008).  *, Equal contribution.
  4. Myoung Sook Kim, Joost Louwagie, Beatriz Carvalho, Jochim S. Terhaar sive Droste, Hannah Lui Park,  Keishi Yamashita, Junwei Liu, Kimberly Laskie Ostrow, Shizhang Ling, Rafael Guerrero-Preston, Semra Demokan, Zubeyde Yalniz, Nejat Dalay,Gerrit A Meijer, Wim Van Criekinge, David Sidransky. Promoter DNA methylation survey of colon cancer identifies a novel diagnostic and therapeutic markers. PLoS ONE, 4(8):e6555 (Aug, 2009).
  5. Myoung Sook Kim, Yiping Huang, Juna Lee, Xiaoli Zhong, Wei-Wen Jiang, Edward A. Ratovitski and David Sidransky. Cellular transformation by cigarette smoke extract involves alteration of glycolysis and mitochondrial function in esophageal epithelial cells. Int J Cancer. 127(2):2 69-81 (Jul, 2010). *Featured in *MDLinx.com on Feb. 4, 2010, assigned to the specialty of Oncology (http://www.mdlinx.com/oncology/medical-news-article/2010/02/04/cellular-transformation/3036906). *, The world's most up to date index of articles that matter in the daily lives of physicians and other healthcare professionals.
  6. Jun Okamura, Yiping Huang, David Moon, Mariana Brait, Xiaofei Chang, Myoung Sook Kim#. Down-regulation of insulin-like growth factor-binding protein 7 in cisplatin-resistant non-small cell lung cancer. Cancer Biol Ther. 13(3):148-55 (Feb, 2012).
  7. Mariana Brait, Shizhang Ling, Jatin K. Nagpal, Xiaofei Chang, Hannah Lui Park, Juna Lee, Jun Okamura, Keishi Yamashita, David Sidransky, and Myoung Sook Kim#. Cysteine dioxygenase 1 is a tumor suppressor gene silenced by promoter methylation in multiple human cancers. PLoS One. 2012;7(9):e44951.

Additional Publication Citations

  1. Kim JS, Shim KH, Kim MS, Kim KW, Lee KY and Chung HY. Study on The Antioxidative Activity of Human Milk. J. Korean Soc. Food Nutr. 1995 Oct;24:651-657.

  2. Myoung Sook Kim, Kyeng Mi Jung, Jung-Won Kim, Hyun-Kyung Kang, Kyu-Won Kim, Kyung-Hee Lee, Sung-Cheul Hong, and Hae-Young Chung. Interaction of Nitric Oxide and Superoxide in Liver Cells, Pusan Bull. Pharm. Sci. 1997 Feb;31, 35-47.

  3. Hae Young Chung, Bong Sook Baek, Myoung Sook Kim, Jung Im Huh, Kyung Hee Shim, Kyu-Won Kim and Kyung Hee Lee, Xanthine Dehydrogenase/Xanthine Oxidase and Oxidative Stress. AGE. 1997;20:127-139.

  4. Moon-Kyoung Bae, Yoo-Wook Kwon, Myoung Sook Kim, Soo-Kyung Bae, Myung-Ho Bae, You Mie Lee, Yung-Jin Kim, and Kyu-Won Kim, Identification of Genes Differentially Expressed by hypoxia in Hepatocellular Carcinoma Cells. Biochem. Biophys. Res. Commun. 1998 Feb:243(1): 158-162.

  5. Hyun-Kyung Kang, Myoung Sook Kim, Nam-Deuk Kim, Mi-Ae Yoo, Kyu-Won Kim, Jong Kim, Yuji Ikeno, Byung-Pal Yu, and Hae-Young Chung. Downregulation of Telomerase in Rat during the Aging Process. Mol. Cells. 1999 Jun:9(3):286-291.

  6. Myoung Sook Kim, You Mie Lee, Eun Joung Moon, Se Eun Kim, Jung Joon Lee, and Kyu-Won Kim, Anti-Angiogenic activity of Torilin, a Sesquiterpene Compound isolated from Torilis japonica. Int. J. Cancer, 87 (2), 269-275 (July, 2000).

  7. Hae Young Chung, Takako Yokozawa, Myoung Sook Kim, Kyoung Hee Lee, Kyu Won Kim, Ryung Yang, and Jin Ho Choi. The mechanism of nitric oxide and/or superoxide cytotoxicity in endothelial cells. Exp. Toxicol Pathol., 52 (3), 227-233 (June, 2000).

  8. Myoung Sook Kim, Jin Hyen Baek, Moon-Taek Park, Tae-Kwon Sohn, Se Eun Kim, Jung Joon Lee and Kyu-Won Kim. Anti-invasive Activity of Torilin, a Sesquiterpene Compound isolated from Torilis japonica. Oncol. Rep., 8 (2), 359-364 (Mar-Apr, 2001).

  9. Myoung Sook Kim, Jin Hyen Baek, Moon-Kyoung Bae,and Kyu-Won Kim. Human rad21 gene, hHR21SP, is downregulated by Hypoxia in human tumor cells. Biochem. Biophys. Res. Commun., 281 (5), 1106-1112 (Mar, 2001).

  10. Myoung Sook Kim, Ho Jeong Kwon, You Mie Lee, Jin Hyen Baek, Jae-Eun Jang, Sae-Won Lee, Eun-Joung Moon, Hye-Sun Kim, Seok-Ki Lee, Hae Young Chung, Chul-Woo Kim, Kyu-Won Kim.Histone Deacetylases Induce Angiogenesis by Negative Regulation of Tumor Suppressor Genes. Nat. Med., 7 (4), 437-443 (Apr, 2001).

  11. Mi-Sook Lee, Eun-Joung Moon, Sae-Won Lee, Myoung Sook Kim, Kyu-Won Kim, Yung-Jin Kim. Angiogenic activity of pyruvic acid in in vivo and in vitro Angiogenesis models. Cancer Res., 61 (8), 3290-3293 (Apr 15, 2001).

  12. Sun-Hee Park, Kyu-Won Kim, Yong Su Lee, Jin Hyen Baek, Myoung Sook Kim, You Mie Lee, Mi-Sook Lee, Yung-Jin Kim. Hypoglycemia-induced VEGF expression is mediated by intracellular Ca2+ and protein kinase C signaling pathway in HepG2 human hepatoblastoma cells. Int. J. Mol. Med., 7 (1), 91-96 (Jan, 2001).

  13. Ho Jeong Kwon, Myoung Sook Kim, Min Jung Kim, Hidenori Nakajima, Kyu-Won Kim. Histone deacetylase inhibitor FK228 inhibits tumor angiogenesis. Int. J. Cancer, 97 (3), 290-296 (Jan 20, 2002).

  14.  Myoung Sook Kim , Mellissa Blake, Jin Hyen Baek, Glenda Kohlhagen, Yves Pommier, and France Carrier. Inhibition of histone deacetylase increases cytotoxicity to anticancer drugs targeting DNA. Cancer Res., 63 (21), 7291-7300 (Nov, 2003).

  15. Myoung Sook Kim, Nathaniel S. Hwang, Lee J, Tae-Kyun Kim, Leong K, Michael J Shamblott, John Gearhart, Jennifer Elisseeff. Musculoskeletal differentiation of cells derived from human embryonic germ cells. Stem Cells, 23 (1), 113-123 (Jan, 2005).

  16. Myoung Sook Kim, Jin Hyen Baek, Devulapalli Chakravarty, David Sidransky and France Carrier. Sensitization to UV-induced apoptosis by the histone deacetylase inhibitor Trichostatin A (TSA). Exp. Cell Res. 306, 94-102 (March, 2005).

  17. Diana L. Mandelker, Keishi Yamashita, Yutaka Tokumaru, Koshi Mimori, David L. Howard, Andre Lopes Carvalho, Wei-Wen Jiang, Hannah Lui Park, Myoung Sook Kim, Motonobu Osada, Masaki Mori, David Sidransky. PGP9.5 promoter methylation is an independent prognostic factor for esophageal squamous cell carcinoma. Cancer Res., 65 (11), 4963-4968 (June, 2005).

  18. Myoung Sook Kim, Jin Hyen Baek, Jeong Ae park, Bang Yeon Hwang, Se Eun Kim, Jung Joon Lee and Kyu-Won Kim. Wilfoside K1N isolated from Cynanchum wilfordii inhibits angiogenesis and tumor cell invasion. Int. J. Oncol., 26 (6), 1533-1539 (June, 2005).

  19. Motonobu Osada, Yuichi Nagakawa, Hannah Lui Park, Keishi Yamashita, Guojun Wu, Myoung Sook Kim, Alexey Fomenkov, Barry Trink and David Sidransky. p63-specific activation of the BPAG-1e promoter. J. Investigative Dermatol, 125 (1), 52-60, (July, 2005).

  20. Motonobu Osada, Hannah Lui Park, Yuichi Nagakawa, Keishi Yamashita, Alexey Fomenkov, Myoung Sook Kim, Guojun Wu, Shuji Nomoto, Barry Trink and David Sidransky. Differential recognition of response elements determines target gene specificity for p53 and p63. Mol. Cell. Biol., 25 (14) 6077-7089 (July, 2005).

  21. Nathaniel S. Hwang, Myoung Sook Kim, Somponnat Sampattavanich, Jin Hyen Baek, Zijun Zhang and Jennifer Elisseeff. The effects of three dimensional culture and growth factors on the chondrogenic differentiation of murine embryonic stem cells. Stem Cells, 24(2):284-291 (Feb, 2006).

  22. Motonobu Osada, Hannah Lui Park, Yuichi Nagakawa, Begum S, Keishi Yamashita, Guojun Wu, Myoung Sook Kim, Barry Trink and David Sidransky. A novel response element confers p63-and p73-specific activation of the WNT4 promoter. Biochem. Biophys. Res Commun., 339(4):1120-1128 (Jan, 2006).

  23. Keishi Yamashita, Hannah Lui Park, Myoung Sook Kim, Yutaka Tokumaru, Motonobu Osada, Hiroshi Inoue, Masaki Mori, David Sidransky. PGP9.5 methylation in diffuse type gastric cancer. Cancer Res., 66(7); 3921-3927 (April, 2006).

  24. Myoung Sook Kim, Keishi Yamashita, Jin Hyen Baek, Hannah Lui Park, Andre Lopes Carvalho, Motonobu Osada, Mohammad Obaidul Hoque, Sunil Upadhyay, Masaki Mori, Chul-so Moon, David Sidransky. NMDA Receptor Type 2B, at 12p12, is epigenetically inactivated and exhibits tumor suppressive activity in human esophageal cancer. Cancer Res., 66(7): 3409-3418 (April, 2006).

  25. Sunil Upadhyay, Chunyan Liu, Russell Finley, Aditi Chatterjee, Elizabeth Mambo, Mohammad O. Hoque, Myoung Sook Kim, James Engles, Uwe Schlattner, D Neumann, Edward Ratovitski, David Sidransky. LKB1/STK11 suppresses COX-2 induction and cellular invasion through PEA3. Cancer Res,, 66(16):7870-7879 (Aug, 2006).

  26. Guojun Wu, Zhongmin Guo, Aditi Chatterjee, Xin Huang, Ethel Rubin, Feng Wu, Elizabeth Mambo, Xiaofei Chang, Myoung Sook Kim, Chulso Moon, Joseph A. Califano, Edward A. Ratovitski, Susanne M. Gollin, Saraswati Sukumar, David Sidransky and Barry Trink. Overexpression of glycosylphosphatidylinositol (GPI) transamidase phosphatidylinositol glycan class T and/or GPI anchor attachment 1 induces tumorigenesis and contributes to invasion in human breast cancer. Cancer Res., 66(20):9829-9836 (Oct, 2006).

  27. Guojun Wu, Zhongmin Guo, Xiaofei Chang, Myoung Sook Kim, Jatin K. Nagpal, Junwei Liu, Joni M. Maki, Kari I. Kivirikko, Stephen P Ethier, Barry Trink,, David Sidransky. LOXL1 and LOXL4 are epigenetically silenced and can inhibit RAS/ERK signaling pathway in human bladder cancer. Cancer Res., 67(9):4123-4129 (May, 2007).

  28. Junwei Liu, Myoung Sook Kim, Jatin Nagpal,  Keishi Yamashita, Luana Poeta, Xiaofei Chang, Juna Lee, Hannah Lui Park, Carmen Jeronimo, William H. Westra, Masaki Mori, Chulso Moon, Barry TrinkDavid Sidransky. Quantitative hypermethylation of NMDAR2B in human gastric cancer. Int J Cancer, 121(9):1994-2000 (Jul, 2007).

  29. Myoung Sook Kim, Keishi Yamashita, Young Kwang Chae, Yutaka Tokumaru, Xiaofei Chang, Marianna Zahurak, Motonobu Osada, Hannah Lui Park, Alice Chuang , Joseph A. Califano, and David Sidransky. NMDA receptor 2B promoter methylation predicts poor prognosis in esophageal squamous cell carcinoma. Clin Cancer Res., 13(22):6658-65 (Nov, 2007).

  30. Keishi Yamashita, Myoung Sook Kim, Hannah L. Park, Yutaka Tokumaru, Motonobu Osada, Hiroshi Inoue, Masaki Mori, David Sidransky. HOP/OB1/NECC1 promoter DNA is frequently hypermethylated and involved in tumorigenic ability in esophageal squamous cell carcinoma. Mol Cancer Res., 6(1):31-41 (Jan, 2008).

  31. Jong Chul Park, Young Kwang Chae, Choon Hee Son, Myoung Sook Kim, Juna Lee, Kimberly Ostrow, David Sidransky, Mohammad Obaidul Hoque, and Chulso Moon. Epigenetic silencing of human T (brachyury homologue) gene in non-small-cell lung cancer. Biochem Biophys Res Commun., 365(2):221-6 (Jan, 2008).

  32. Jang-Hee Woo, Young Kwang Chae, Se Jin Jang, Myoung Sook Kim, Jin Hyen Baek, Jongchul Park, Barry Trink, Edward Ratovitski, Taekyeol Lee, Beom Park, Minjoo Park, Ji Hye Kang, Jean-Charles Soria, Juna Lee, Joseph Califano, David Sidransky, Chulso Moon. Membrane trafficking of AQP5 and cAMP dependent phosphorylation in bronchial epithelium. Biochem Biophys Res Commun., 366(2):321-7 (Feb, 2008).

  33. Jun-Wei Liu, Jatin K. Nagpal, Carmen Jeronimo, Ji Eun Lee, Rui Henrique, Myoung Sook Kim, Kimberly L Ostrow, Keishi Yamashita, Vim van Criekinge, Guojun Wu, Chulso Moon, Barry Trink, David Sidransky. Hypermethylation of MCAM gene is associated with advanced tumor stage in prostate cancer. Prostate. 68(4):418-26 (Mar, 2008).

  34. Jang-Hee Woo, Juna Lee, Myoung Sook Kim, Se Jin Jang, David Sidransky, Chulso Moon. The effect of aquaporin 5 overexpression on the Ras signaling pathway. Biochem Biophys Res Commun., 367(2):291-8 (Mar, 2008).

  35. Hannah Lui Park, Myoung Sook Kim, Keishi Yamashita, William Westra, Andre Lopes Carvalho, Juna Lee, Wei-Wen Jiang, Jin Hyen Baek, Junwei Liu, Motonobu Osada, Chulso Moon, Joseph A. Califano, Masaki Mori, and David Sidransky. DCC promoter hypermethylation in esophageal squamous cell carcinoma. Int J Cancer, 122(11):2498-2502 (Feb, 2008).

  36. Myoung Sook Kim, Xiaofei Chang, Jatin K. Nagpal, Keishi Yamashita, Jin Hyen Baek, Santanu Daspguta, Guojun Wu, Jang-Hee Woo, Motonobu Osada, William H. Westra, Barry Trink, Edward A. Ratovitski, Chulso Moon and David Sidransky. The N-Methyl-D-Aspartate Receptor Type 2A Promoter is frequently methylated in human colorectal carcinoma and suppresses cell growth. Oncogene, 27(14):2045-54 (Mar, 2008).                                                                                                                     

  37. Mohammad Obaidul Hoque*, Myoung Sook Kim *, Kimberly Laskie Ostrow*, Junwei Liu*, G. Bea A. Wisman, Hannah Lui Park, Luana Poeta, Carmen Jeronimo, Rui Henerique, Ágnes Lendvai, Ed Schuuring, Shahnaz Begum, Eli Rosenbaum, Maté Ongenaert, Keshi Yamashita, Joseph Califano, William Westra,  Ate G.J. van der Zee,Wim Van Criekinge, and David Sidransky. Genome-wide Promoter Analysis Uncovers Portions of the Cancer Methylome. Cancer Research, 68(8):2661-70 (Apr, 2008).  *, Equal contribution.     

  38. Jang-Hee Woo, Juna Lee, Young Kwang Chae, Myoung Sook Kim, Jin Hyen Baek, Jong Chul Park, Minjoo Park, Ian M. Smith, Barry Trink, Edward Ratovitski, Taekyeol Lee, Beom Park, Se Jin Jang, Jean-Charles Soria, Joseph Califano, David Sidransky, Chulso Moon. Overexpression of AQP5, a putative oncogene, promotes cell growth and transformation. Cancer Lett. 264(1):54-62 (Jun, 2008).

  39. Myoung Sook Kim, Cynthia Lebron, Jatin K. Nagpal, Young Kwang Chae, Xiaofei Chang, Yiping Huang, Tony Chuang, Keishi Yamashita, Barry Trink, Edward A. Ratovitski, Joseph A. Califano, David Sidransky. Aberrant hypermethylation in the DFNA5 gene promoter increases risk of lymph node metastasis in human breast cancer. Biochem Biophys Res Commun. 370(1):38-43 (May, 2008).

  40. Young Kwang Chae, Janghee Woo, Mi-Jung Kim, Sung Koo Kang, Myoung Sook Kim, Juna Lee, Seung Koo Lee, Gyungyub Gong, Yong Hee Kim, Jean Charles Soria, Se Jin Jang, David Sidransky, and Chulso Moon. Expression of aquaporin 5 (AQP5) promotes tumor invasion in human non-small cell lung cancer. PLoS ONE. 3(5):e2162 (May, 2008).

  41. Yutaka Tokumaru, Keishi Yamashita, Myoung Sook Kim, Hannah L. Park, Motonobu Osada, Masaki Mori, and David Sidransky. The role of PGP9.5 as a Tumor Suppressor Gene in Human Cancer. Int J Cancer, 123, 753–759 (May, 2008).

  42. Myoung Sook Kim, Xiaofei Chang , Keishi Yamashita , Jatin Nagpal , Jin Hyen Baek , Guojun Wu, Barry Trink, Edward Ratovitski, Masaki Mori, and David sidransky. Aberrant promoter methylation and tumor suppressive activity of the DFNA5 gene in colorectal carcinoma. Oncogene, 27(25):3624-34 (Jun, 2008).

  43. Jun-Wei Liu, Jatin K. Nagpal, Wenyue Sun, Ji Eun Lee, Myoung Sook Kim, Kimberly L Ostrow, , Shaoyu Zhou,  Carmen Jeronimo, Rui Henrique, Vim van Criekinge, Chulso Moon, Joseph A. Califano, Barry Trink, David Sidransky. SSBP2 is frequently hypermethylated and suppresses growth through cell cycle inhibition in human prostate cancer. Clin Cancer Res, 14(12):3754-60 (Jun, 2008).

  44. Sung Koo Kang, Young Kwang Chae, Janghee Woo, Myoung Sook Kim, Jong Chul Park, Juna Lee, Jean-Charles Soria, Se Jin Chang, David Sidransky, Chulso Moon. Role of human aquaporin 5 in colorectal carcinogenesis. American Journal of Pathology 173(2):518-25 (Jun, 2008).

  45. Young Kwang Chae, Sung Koo Kang, Myoung Sook Kim, Janghee Woo, Juna Lee, Steven Chang, Dong-Wook Kim, Myungshin Kim, Seonyang Park, Inho Kim, Bhumsuk Keam, Jiyoung Rhee, Nam Hee Koo, Gyeongsin Park, Soo-Hyun Kim, Se-Eun Jang, Il-Young Kweon, David Sidransky, and Chulso Moon. Human AQP5 plays a role in the progression of chronic myelogenous leukemia (CML). PLoS ONE 3(7):e2594 (Jul, 2008).

  46. Kimberly Laskie Ostrow, Hannah Lui Park, Mohammad Hoque, Myoung Sook Kim, Junwei Liu, Pedram Argani, William Westra, Wim Van Criekinge, David Sidransky. Pharmacologic unmasking of epigenetically silenced genes on breast cancer. Clin Cancer Res 15(4):1184-91 (Feb, 2009).

  47. Myoung Sook Kim, Joost Louwagie, Beatriz Carvalho, Jochim S. Terhaar sive Droste, Hannah Lui Park,  Keishi Yamashita, Junwei Liu, Kimberly Laskie Ostrow, Shizhang Ling, Rafael Guerrero-Preston, Semra Demokan, Zubeyde Yalniz, Nejat Dalay,Gerrit A Meijer, Wim Van Criekinge, David Sidransky. Promoter DNA methylation survey of colon cancer identifies a novel diagnostic and therapeutic markers. PLoS ONE, 4(8):e6555 (Aug, 2009).

  48. Chonglin Yang, Myoung Sook Kim, Devulapalli Chakravarty, Fred E. Indig and France Carrier. Nucleolin Binds to the Proliferating Cell Nuclear Antigen and Inhibits Nucleotide Excision Repair. Mol Cell Pharmacol 1(3):130-137 (Aug, 2009).

  49. Huang Y, Myoung Sook Kim, Ratovitski E Midkine promotes tetraspanin-integrin interaction and induces FAK-Stat1alpha pathway contributing to migration/invasiveness of human head and neck squamous cell carcinoma cells. Biochem Biophys Res Commun 377(2):474-478 (Dec, 2008).

  50. Myriam Loyo, Rafael Guerrero-Preston, Mariana Brait, Mohmammad O. Hoque, Alice Chuang, Myoung Sook Kim, Rajni Sharma, Nanette J. Liégeois, Wayne M. Koch, Joseph A. Califano, William H. Westra, David Sidransky. Quantitative detection of Merkel Cell Virus in human tissues and possible mode of transmission. International Journal of Cancer 126(12):2991-6 (Jun, 2010).

  51. Myoung Sook Kim, Juna Lee and David Sidransky. DNA methylation markers in colorectal cancer (Review) Cancer and Metastasis Reviews 29(1):181-206 (Mar, 2010). Review.

  52. Myoung Sook Kim, Xiaofei Chang, Cynthia Lebron, Jatin K. Nagpal, Juna Lee, Yiping Huang, Keishi Yamashita, Barry Trink, Edward A. Ratovitski and David Sidransky. Neurofilament heavy polypeptide regulates the Akt-b-catenin pathway in human esophageal squamous cell carcinoma. PLoS ONE 5(2):e9003 (Feb, 2010).

  53. Xiaofei Chang, Constance Monitto, Semra Demokan, Myoung Sook Kim, Charles M. Rudin, Joseph A. Califano and David Sidransky. Identification of hypermethylated genes associated with cisplatin resistance in human cancers. Cancer Research 70(7):2870-9 (Apr, 2010).

  54. Ooki A, Yamashita K, Kikuchi S, Sakuramoto S, Katada N, Kokubo K, Kobayashi H, Kim MS, Sidransky D, Watanabe M. Potential utility of HOP homeobox gene promoter methylation as a marker of aggressiveness in gastric cancer. Oncogene 29(22):3263-75 (Jun, 2010).

  55. Myriam Loyo, Mariana Brait, Myoung Sook Kim, Kimberly L. Ostrow, Chunfa C. Jie, Alice Y. Chuang, Joseph A. Califano, Nanette J. Liégeois, Shahnaz Begum, William H. Westra, Mohammad O. Hoque, Qian Tao, David Sidransky. A survey of methylated candidate tumor suppressor genes in nasopharyngeal carcinoma. Int J Cancer. 128(6):1393-403 (Mar, 2011).

  56. Myoung Sook Kim, Yiping Huang, Juna Lee, Xiaoli Zhong, Wei-Wen Jiang, Edward A. Ratovitski and David Sidransky. Cellular transformation by cigarette smoke extract involves alteration of glycolysis and mitochondrial function in esophageal epithelial cells. Int J Cancer. 127(2):2 69-81 (Jul, 2010). *Featured in *MDLinx.com on Feb. 4, 2010, assigned to the specialty of Oncology (http://www.mdlinx.com/oncology/medical-news-article/2010/02/04/cellular-transformation/3036906). *, The world's most up to date index of articles that matter in the daily lives of physicians and other healthcare professionals.

  57. Yiping Huang, Xiaofei Chang, Yong Gu Cho, Juna Lee, Xiaoli Zhong, Il-Seok Park, Jun-Wei Liu, Joseph A. Califano, Edward A. Ratovitski and David Sidransky, Myoung Sook Kim#. Cigarette smoke induces promoter methylation of single-stranded DNA-binding protein 2 in human esophageal squamous cell carcinoma. International Journal of Cancer 128(10):2261-73 (May, 2011).

  58. Xiaofei Chang, Keishi Yamashita, David Sidransky, and Myoung Sook Kim#. Aberrant promoter methylation of heat shock protein 2 in human esophageal cancer. Int J Oncol. 38(4):1129-35 (2011 Apr).

  59. Yong Gu Cho, Xiaofei Chang, Il-Seok Park, Keishi Yamashita, Chunbo Shao, Patrick Ha, Sara I. Pai, David Sidransky, and Myoung Sook Kim#. Promoter methylation of leukemia inhibitory factor receptor gene in colorectal carcinoma. Int J Oncol. 39(2):337-44 (Aug, 2011).

  60. Il-Seok Park, Xiaofei Chang, Myriam Loyo, Gaosong Wu, Alice Chuang,  Myoung Sook Kim, Young Kwang Chae, Sofia Lyford-Pike, William H. Westra, John R. Saunders, David Sidransky, and Sara Isabel Pai. Characterization of the methylation patterns in human papillomavirus type 16 viral DNA in head and neck cancers. Cancer Prev Res (Phila). 4(2):207-17 (Feb, 2011).

  61. Jun Okamura, Yiping Huang, David Moon, Mariana Brait, Xiaofei Chang, Myoung Sook Kim#. Down-regulation of insulin-like growth factor-binding protein 7 in cisplatin-resistant non-small cell lung cancer. Cancer Biol Ther. 13(3):148-55 (Feb, 2012).

  62. Mariana Brait, Shizhang Ling, Jatin K. Nagpal, Xiaofei Chang, Hannah Lui Park, Juna Lee, Jun Okamura, Keishi Yamashita, David Sidransky, and Myoung Sook Kim#. Cysteine dioxygenase 1 is a tumor suppressor gene silenced by promoter methylation in multiple human cancers. PLoS One. 2012;7(9):e44951.

  63. Huang Y, Bell LN, Okamura J, Kim MS, Mohney RP, Guerrero-Preston R, Ratovitski EA. Phospho-ΔNp63α/SREBF1 protein interactions: Bridging cell metabolism and cisplatin chemoresistance.  Cell Cycle. 2012 Oct 15;11(20):3810-27

  64. Huang Y, Jeong JS, Okamura J, Myoung Sook Kim, Zhu H, Guerrero-Preston R, Ratovitski EA. Global tumor protein p53/p63 interactome: making a case for cisplatin chemoresistance. Cell Cycle. 2012 Jun 15;11(12):2367-79.

  65. Chunbo Shao, Marietta Tan,  Justin A. Bishop, Jia Liu, Weiliang Bai, Daria A. Gaykalova, Takenori Ogawa, Ami R. Vikani, Yuri Agrawal, Ryan J. Li, Myoung Sook Kim,  William H. Westra, David Sidransky; Joseph A. Califano, and Patrick K Ha. Suprabasin is hypomethylated and associated with metastasis in salivary adenoid cystic carcinoma. PLoS One. 2012;7(11):e48582.

  66. Chang X, Izumchenko E, Solis LM, Kim MS, Chatterjee A, Ling S, Monitto CL, Harari PM, Hidalgo M, Goodman SN, Wistuba II, Bedi A, Sidransky D. The Relative Expression of Mig6 and EGFR Is Associated with Resistance to EGFR Kinase Inhibitors. PLoS One. 2013;8(70):e68966.

  67. Michailidi C, Soudry E, Brait M, Maldonado L, Jaffe A, Ili-Gangas C, Brebi-Mieville P, Perez J, Kim MS, Zhong X, Yang Q, Valle B, Meltzer SJ, Torbenson M, Esteller M, Sidransky D, Guerrero-Preston R. Genome-wide and gene-specific epigenomic platforms for hepatocellular carcinoma biomarker development trials. Gastroenterol Res Pract. 2014;2014:597164.

  68. Yamashita K, Waraya M, Kim MS, Sidransky D, Katada N, Sato T, Nakamura T, Watanabe M. Detection of Methylated CDO1 in Plasma of Colorectal Cancer; A PCR Study. PLoS One. 2014; 9(12):e113546.

  69. Choe M, Brusgard JL, Chumsri S, Bhandary L, Zhao XF, Lu S, Goloubeva OG, Polster BM, Fiskum GM, Girnun GD, Kim MS, Passaniti A. The RUNX2 Transcription Factor Negatively Regulates SIRT6 Expression to Alter Glucose Metabolism in Breast Cancer Cells. J Cell Biochem. J Cell Biochem. 2015;116(10):2210-26.

  70. Juna Lee, Piotr T. Wysocki, Ozlem Topaloglu, Leonel Maldonado, Mariana Brait, Shahnaz Begum, David Moon, Myoung Sook Kim, Joseph A. Califano, David Sidransky, Mohammad O. Hoque, and Chulso Moon. Epigenetic silencing of S100A2 in bladder and head and neck cancers. Oncoscience. 2015 Mar 16;2(4):410-8. eCollection 2015.

Research Interests

Tumor metabolism

Drug Resistance

Development of Cancer Biomakers  

Awards and Affiliations

 

Honors And Awards

2002                            Women in Cancer Research, Brigid G. Leventhal Scholar-in-Training Award,                                                         American Association for Cancer Research

2007 – 2012                Young Clinical Scientist Award, Flight Attendant Medical Research Institutions             (FAMRI)

2012 – 2013                Young Investigator Award, Elsa U. Pardee Foundation

 

National Service       

2008 – Present            Ad Hoc Reviewer, International Journal of Cancer, Journal of Cell Biology, Cancer             Biology and Therapy, Molecular Cancer Therapeutics, PLOS ONE, Journal of             Cellular Biochemistry

 

 

 

Grants and Contracts

Ongoing Research Support

NIH/NCI P30 CA134274-04, Cullen (PI)                                                                                 10/01/11 to 09/30/16

NCI Cancer Center Support Grant (CCSG)

As a member of the Hormone Responsive Cancers Program, this grant provides the resources for our laboratory to facilitate the coordination of collaborations across a broad spectrum of research from basic laboratory research to clinical investigation and population science.

Role: Co-Investigator

 

UMGCC Pilot Grant, Passaniti (PI)                                                                                       10/01/15 to 06/30/16

Transcriptional targeting as a therapeutic strategy to restrain breast cancer progression.                                                        This pilot project from the Greenebaum Cancer Center focuses on inhibiting the biological activity of RUNX2 using novel transcriptional inhibitors. 

Role: Co-Investigator

VA Merit Review I01 BX002205A, Passaniti (PI)                                                                     10/1/13 to 6/30/17

Transcriptional regulation of  tumor growth                                                                                                                                                   

This competitive renewal project focuses on the role of the RUNX2 transcription factor in regulating BC cell metabolism and epithelial de-differentiation.  Targeted inhibition of RUNX2 using Vitamin D3 will be used therapeutically to alter cell metabolism and promote differentiation.

Role: Collaborator

 

Completed Research Support

Flight Attendant Medical Research Institutions (FAMRI), Kim (PI)                            07/01/2007- 06/30/2012

Title: Epigenetic Alterations in Progression of Esophageal Squamous Cell Carcinoma by Tobacco Smoking.

The major goal of this study is to develop strategies for early detection and treatment of human esophageal cancer.

Role: Principal Investigator

 

NIH R37 (5R37DE012588-10), Sidransky (PI)                                                             04/01/1998 - 02/28/2012

Title: Molecular progression model for HNSCC

The major goal of this study is to validate microRNAs as potential biomarkers in serum samples from a cohort     of patients with longitudinal follow-up and a subset of normal subjects’ samples.

Role: Co-investigator

 

Elsa U. Pardee Foundation, Kim (PI)                                                                               06/01/2012- 05/31/2013

Title: In vitro and in vivo characterization of miR-675 in esophageal squamous cell carcinoma

Goal of the project: To develop miR-675 as a novel regulator in esophageal carcinogenesis

Role: Principal Investigator

 

Pending Grant Support

NIH NCI 1R03 CA208216-01 Passaniti (PI)                                                                           7/1/2016 - 6/30/2018

Breast cancer mechanistic models to define angiogenic and metastatic potential

The goals of this NCI Small Grants Program for Cancer Research proposal are to identify the MMP requirements for RUNX2/TAZ-mediated production of sE.Cad, which promotes metastasis in BC cells and to develop a functional assay to test BC cell angiogenic and metastatic potential (AMP) mediated by RUNX2/TAZ and MMP expression. 

Role on project: Co-investigator

 

NIH R01 1R01 CA215170-01 (Passaniti)                                                                            12/1/2016 - 11/30/2021

Targeting RUNX2-regulated Hippo signaling for breast cancer therapy

Agency: National Institutes of Health (NCI)

The focus and goal of this proposal are to determine the significance and requirement of RUNX2 in inactivating the Hippo tumor suppressor and to explore the mechanisms regulating Hippo signaling crosstalk and oncogenic function.

Role on project: Co-investigator.

Community Service

2008 – Present            Ad Hoc Reviewer, International Journal of Cancer, Journal of Cell Biology, Cancer             Biology and Therapy, Molecular Cancer Therapeutics, PLOS ONE, Journal of             Cellular Biochemistry