So Young Kim

Positions:

Assistant Research Professor in Molecular Genetics and Microbiology

Molecular Genetics and Microbiology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2002

State University of New York at Stony Brook

Grants:

Characterization of NYP Peptides in Prostate Cancer

Administered By
Pathology
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Identification of Therapeutic Interventions in Ataxia-Telangiectasia Using a Novel Model of Metabolic Stress

Administered By
Pharmacology & Cancer Biology
Awarded By
University of Pennsylvania
Role
Collaborator
Start Date
End Date

Interferon-inducible cell-intrinsic host defense against Chlamydia trachomatis

Administered By
Molecular Genetics and Microbiology
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Compound library reformatting

Administered By
Molecular Genetics and Microbiology
Role
Principal Investigator
Start Date
End Date

Interferon-driven ubiquitin response targets Chlamydia inclusions in human cells

Administered By
Molecular Genetics and Microbiology
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Publications:

The whole-genome landscape of Burkitt lymphoma subtypes.

Burkitt lymphoma (BL) is an aggressive, MYC-driven lymphoma comprising 3 distinct clinical subtypes: sporadic BLs that occur worldwide, endemic BLs that occur predominantly in sub-Saharan Africa, and immunodeficiency-associated BLs that occur primarily in the setting of HIV. In this study, we comprehensively delineated the genomic basis of BL through whole-genome sequencing (WGS) of 101 tumors representing all 3 subtypes of BL to identify 72 driver genes. These data were additionally informed by CRISPR screens in BL cell lines to functionally annotate the role of oncogenic drivers. Nearly every driver gene was found to have both coding and non-coding mutations, highlighting the importance of WGS for identifying driver events. Our data implicate coding and non-coding mutations in IGLL5, BACH2, SIN3A, and DNMT1. Epstein-Barr virus (EBV) infection was associated with higher mutation load, with type 1 EBV showing a higher mutational burden than type 2 EBV. Although sporadic and immunodeficiency-associated BLs had similar genetic profiles, endemic BLs manifested more frequent mutations in BCL7A and BCL6 and fewer genetic alterations in DNMT1, SNTB2, and CTCF. Silencing mutations in ID3 were a common feature of all 3 subtypes of BL. In vitro, mass spectrometry-based proteomics demonstrated that the ID3 protein binds primarily to TCF3 and TCF4. In vivo knockout of ID3 potentiated the effects of MYC, leading to rapid tumorigenesis and tumor phenotypes consistent with those observed in the human disease.
Authors
Panea, RI; Love, CL; Shingleton, JR; Reddy, A; Bailey, JA; Moormann, AM; Otieno, JA; Ong'echa, JM; Oduor, CI; Schroeder, KMS; Masalu, N; Chao, NJ; Agajanian, M; Major, MB; Fedoriw, Y; Richards, KL; Rymkiewicz, G; Miles, RR; Alobeid, B; Bhagat, G; Flowers, CR; Ondrejka, SL; Hsi, ED; Choi, WWL; Au-Yeung, RKH; Hartmann, W; Lenz, G; Meyerson, H; Lin, Y-Y; Zhuang, Y; Luftig, MA; Waldrop, A; Dave, T; Thakkar, D; Sahay, H; Li, G; Palus, BC; Seshadri, V; Kim, SY; Gascoyne, RD; Levy, S; Mukhopadyay, M; Dunson, DB; Dave, SS
MLA Citation
Panea, Razvan I., et al. “The whole-genome landscape of Burkitt lymphoma subtypes..” Blood, vol. 134, no. 19, Nov. 2019, pp. 1598–607. Pubmed, doi:10.1182/blood.2019001880.
URI
https://scholars.duke.edu/individual/pub1415067
PMID
31558468
Source
pubmed
Published In
Blood
Volume
134
Published Date
Start Page
1598
End Page
1607
DOI
10.1182/blood.2019001880

Genome-wide CRISPR Screen to Identify Genes that Suppress Transformation in the Presence of Endogenous KrasG12D.

Cooperating gene mutations are typically required to transform normal cells enabling growth in soft agar or in immunodeficient mice. For example, mutations in Kras and transformation-related protein 53 (Trp53) are known to transform a variety of mesenchymal and epithelial cells in vitro and in vivo. Identifying other genes that can cooperate with oncogenic Kras and substitute for Trp53 mutation has the potential to lead to new insights into mechanisms of carcinogenesis. Here, we applied a genome-wide CRISPR/Cas9 knockout screen in KrasG12D immortalized mouse embryonic fibroblasts (MEFs) to search for genes that when mutated cooperate with oncogenic Kras to induce transformation. We also tested if mutation of the identified candidate genes could cooperate with KrasG12D to generate primary sarcomas in mice. In addition to identifying the well-known tumor suppressor cyclin dependent kinase inhibitor 2A (Cdkn2a), whose alternative reading frame product p19 activates Trp53, we also identified other putative tumor suppressors, such as F-box/WD repeat-containing protein 7 (Fbxw7) and solute carrier family 9 member 3 (Slc9a3). Remarkably, the TCGA database indicates that both FBXW7 and SLC9A3 are commonly co-mutated with KRAS in human cancers. However, we found that only mutation of Trp53 or Cdkn2a, but not Fbxw7 or Slc9a3 can cooperate with KrasG12D to generate primary sarcomas in mice. These results show that mutations in oncogenic Kras and either Fbxw7 or Slc9a3 are sufficient for transformation in vitro, but not for in vivo sarcomagenesis.
Authors
Huang, J; Chen, M; Xu, ES; Luo, L; Ma, Y; Huang, W; Floyd, W; Klann, TS; Kim, SY; Gersbach, CA; Cardona, DM; Kirsch, DG
MLA Citation
Huang, Jianguo, et al. “Genome-wide CRISPR Screen to Identify Genes that Suppress Transformation in the Presence of Endogenous KrasG12D..” Sci Rep, vol. 9, no. 1, Nov. 2019. Pubmed, doi:10.1038/s41598-019-53572-w.
URI
https://scholars.duke.edu/individual/pub1421434
PMID
31748650
Source
pubmed
Published In
Scientific Reports
Volume
9
Published Date
Start Page
17220
DOI
10.1038/s41598-019-53572-w

Functional genomics approach for the identification of human host factors supporting dengue viral propagation.

Dengue virus (DENV) is endemic throughout tropical regions of the world and there are no approved treatments or anti-transmission agents currently available. Consequently, there exists an enormous unmet need to treat the human diseases caused by DENV and block viral transmission by the mosquito vector. RNAi screening represents an efficient method to expand the pool of known host factors that could become viable targets for treatments or provide rationale to consider available drugs as anti-DENV treatments. We developed a high-throughput siRNA-based screening protocol that can identify human DENV host factors. The protocol herein describes the materials and the procedures necessary to screen a human cell line in order to identify genes which are either necessary for or restrict DENV propagation at any stage in the viral life cycle.
Authors
Barrows, NJ; Jamison, SF; Bradrick, SS; Le Sommer, C; Kim, SY; Pearson, J; Garcia-Blanco, MA
MLA Citation
Barrows, Nicholas J., et al. “Functional genomics approach for the identification of human host factors supporting dengue viral propagation..” Methods Mol Biol, vol. 1138, 2014, pp. 285–99. Pubmed, doi:10.1007/978-1-4939-0348-1_18.
URI
https://scholars.duke.edu/individual/pub1026091
PMID
24696344
Source
pubmed
Published In
Methods Mol Biol
Volume
1138
Published Date
Start Page
285
End Page
299
DOI
10.1007/978-1-4939-0348-1_18

Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells.

An alternative to therapeutic targeting of oncogenes is to perform "synthetic lethality" screens for genes that are essential only in the context of specific cancer-causing mutations. We used high-throughput RNA interference (RNAi) to identify synthetic lethal interactions in cancer cells harboring mutant KRAS, the most commonly mutated human oncogene. We find that cells that are dependent on mutant KRAS exhibit sensitivity to suppression of the serine/threonine kinase STK33 irrespective of tissue origin, whereas STK33 is not required by KRAS-independent cells. STK33 promotes cancer cell viability in a kinase activity-dependent manner by regulating the suppression of mitochondrial apoptosis mediated through S6K1-induced inactivation of the death agonist BAD selectively in mutant KRAS-dependent cells. These observations identify STK33 as a target for treatment of mutant KRAS-driven cancers and demonstrate the potential of RNAi screens for discovering functional dependencies created by oncogenic mutations that may enable therapeutic intervention for cancers with "undruggable" genetic alterations.
Authors
Scholl, C; Fröhling, S; Dunn, IF; Schinzel, AC; Barbie, DA; Kim, SY; Silver, SJ; Tamayo, P; Wadlow, RC; Ramaswamy, S; Döhner, K; Bullinger, L; Sandy, P; Boehm, JS; Root, DE; Jacks, T; Hahn, WC; Gilliland, DG
MLA Citation
Scholl, Claudia, et al. “Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells..” Cell, vol. 137, no. 5, May 2009, pp. 821–34. Pubmed, doi:10.1016/j.cell.2009.03.017.
URI
https://scholars.duke.edu/individual/pub780648
PMID
19490892
Source
pubmed
Published In
Cell
Volume
137
Published Date
Start Page
821
End Page
834
DOI
10.1016/j.cell.2009.03.017

Identification of Novel Mast Cell Activators Using Cell-Based High-Throughput Screening.

Mast cells (MCs) are known to regulate innate and adaptive immunity. MC activators have recently been described as safe and effective vaccine adjuvants. Many currently known MC activators are inadequate for in vivo applications, however, and research on identifying novel MC activators is limited. In this study, we identified novel MC activators by using high-throughput screening (HTS) assays using approximately 55,000 small molecules. Data sets obtained by the primary HTS assays were statistically evaluated using quality control rules and the B-score calculation, and compounds with B-scores of >3.0 were chosen as mast cell activators (hits). These hits were re-evaluated with secondary and tertiary HTS assays, followed by further statistical analysis. From these hits, we selected 15 compounds that caused degranulation in murine and human MCs, with potential for flexible chemical modification for further study. Among these 15 compounds, ST101036, ST029248, and ST026567 exhibited higher degranulation potency than other hit compounds in both human and mouse MCs. In addition, the 15 compounds identified promote de novo synthesis of cytokines and induce the release of eicosanoids from human and mouse MCs. HTS enabled us to identify small-molecule MC activators with unique properties that may be useful as vaccine adjuvants.
Authors
Choi, HW; Chan, C; Shterev, ID; Lynch, HE; Robinette, TJ; Johnson-Weaver, BT; Shi, J; Sempowski, GD; Kim, SY; Dickson, JK; Gooden, DM; Abraham, SN; Staats, HF
MLA Citation
Choi, Hae Woong, et al. “Identification of Novel Mast Cell Activators Using Cell-Based High-Throughput Screening..” Slas Discov, vol. 24, no. 6, July 2019, pp. 628–40. Pubmed, doi:10.1177/2472555219834699.
URI
https://scholars.duke.edu/individual/pub1379583
PMID
30917061
Source
pubmed
Published In
Slas Discov
Volume
24
Published Date
Start Page
628
End Page
640
DOI
10.1177/2472555219834699