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Dr. Jiyeon Kim
Assistant Professor

  • PhD, Duke University
  • Postdoctoral, HHMI/UT-Southwestern Medical Center at Dallas (DeBerardinis lab)

Major Interests:
Understanding how metabolism is altered during tumorigenesis and metastasis is believed to be of significant translational potential. Metabolic reprogramming often increases the survival and proliferation of cancer cells, but can also introduce new targetable liabilities to these cells. The study of cancer metabolism has largely focused on central carbon metabolism, such as glycolysis, the pentose phosphate pathway, and the citric acid cycle. However, little attention has been given to investigating the functional roles of nitrogen metabolism in cancer biology.  The overarching goal in my lab is to study the fundamental molecular mechanisms underlying cancer metabolism, with a specific focus on nitrogen metabolism, and to identify metabolic liabilities that can be targeted therapeutically.

To this end, we focus on three key areas:

1. Investigation of metabolic liabilities associated with nitrogen handling in lung cancer.

The oncogene KRAS  and  tumor  suppressor STK11, encoding  the  kinase  LKB1, are frequently co-mutated (6-11%) in  non-small  cell lung  cancer (NSCLC), the leading cause of cancer death worldwide. Concomitant mutations of KRAS and LKB1 promote tumor progression and metastasis. In a study published in Nature, we disclosed an alteration of nitrogen metabolism in KRAS/LKB1 co-mutant cancer cells and human tumors. In these co-mutants, the urea cycle enzyme carbamoyl phosphate synthetase 1 (CPS1) enables an unconventional pathway in which nitrogen is trafficked from ammonia in the mitochondria to pyrimidines in the cytosol.  We will further investigate underlying mechanism of CPS1 dependence and nitrogen trafficking/transport.

2. Discovery of new metabolic pathways altered in KRAS/LKB1 co-mutant NSCLC.

We are seeking to uncover additional vulnerabilities related to nitrogen metabolism by a comprehensive analysis of metabolite levels in tumor/or cancer cells with mutations in one or both genes.  Additionally, with a combination of unbiased CRISPR screening, metabolomics methods and in vivo nutrient infusion, we plan to identify and understand key genes/metabolic pathways involved in tumor aggressiveness in KRAS/LKB1 co-mutant NSCLC.

3. Discovering and understanding metabolic vulnerabilities in bladder cancer.

The long-term goal is to broaden my research to examine and identify altered metabolic pathways, specifically nitrogen metabolism, in various types of cancer where mutation profiling, biomarker discovery, or targeted therapy has not been thoroughly explored, including bladder cancer. By integrating metabolomics analysis of human bladder tumors with gene expression data, we will reveal what metabolic pathway(s) are perturbed in different disease stages and investigate whether these changes impose liabilities that could be exploited therapeutically.

Selected publications:

Kim J, Hu Z, Cai L, Li K, Choi E, Faubert B, Bezwada D, Rodriguez-Canales J, Villalobos F, Lin Y-F, Ni M, Huffman KE, Girard L, Byers LA, Unsal-Kacmaz K, Peña CG, Heymach JV, Wauters E, Vansteenkiste J, Castrillon DH, Chen BP, Wistuba I, Lambrechts D, Xu J, Minna JD and DeBerardinis RJ. CPS1 maintains pyrimidine pools and DNA synthesis in KRAS/LKB1-mutant lung cancer cells. Nature, 2017, 546:168-172.
Nature, 2017, 546:168-172

Highlighted in Cancer Discovery

Huang F, Ni M, Chalishazar MD, Huffman KE, Kim J, Cai L, Shi X, Cai F, Zacharias LG, Ireland AS, Li K, Gu W, Kaushik AK, Liu X, Gazdar AF, Oliver TG, Minna JD, Hu Z and DeBerardinis RJ. Inosine Monophosphate Dehydrogenase Dependence in a Subset of Small Cell Lung Cancers. Cell Metab, 2018.
Cell Metab, 2018.

Kim HS, Mendiratta S, Kim J, Pecot CV, Larsen J, Zubovych I, Seo BY, Kim JM, Eskiocak B, Chung H,  McMillan E, Wu S, De Brabander J, Komurov K, Posner B, Brekken R, Sood A, Deberardinis RJ, Roth MG, Minna JD, White M. Systematic identification of molecular subtype-selective vulnerabilities in non-small cell lung cancer. Cell, 2013. 155:552-566.
Cell, 2013. 155:552-566


Contact

Email: jiyeonk@uic.edu
Site: View Lab Website
Office: 312-996-9545
Lab: 312-996-7664

Publications

View Publications on PubMed

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