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, 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
Awarded By
Perlara
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:

Development of a precision medicine pipeline to identify personalized treatments for colorectal cancer.

BACKGROUND: Metastatic colorectal cancer (CRC) continues to be a major health problem, and current treatments are primarily for disease control and palliation of symptoms. In this study, we developed a precision medicine strategy to discover novel therapeutics for patients with CRC. METHODS: Six matched low-passage cell lines and patient-derived xenografts (PDX) were established from CRC patients undergoing resection of their cancer. High-throughput drug screens using a 119 FDA-approved oncology drug library were performed on these cell lines, which were then validated in vivo in matched PDXs. RNA-Seq analysis was then performed to identify predictors of response. RESULTS: Our study revealed marked differences in response to standard-of-care agents across patients and pinpointed druggable pathways to treat CRC. Among these pathways co-targeting of fibroblast growth factor receptor (FGFR), SRC, platelet derived growth factor receptor (PDGFR), or vascular endothelial growth factor receptor (VEGFR) signaling was found to be an effective strategy. Molecular analyses revealed potential predictors of response to these druggable pathways. CONCLUSIONS: Our data suggests that the use of matched low-passage cell lines and PDXs is a promising strategy to identify new therapies and pathways to treat metastatic CRC.
Authors
Altunel, E; Roghani, RS; Chen, K-Y; Kim, SY; McCall, S; Ware, KE; Shen, X; Somarelli, JA; Hsu, DS
MLA Citation
Altunel, Erdem, et al. “Development of a precision medicine pipeline to identify personalized treatments for colorectal cancer.Bmc Cancer, vol. 20, no. 1, June 2020, p. 592. Pubmed, doi:10.1186/s12885-020-07090-y.
URI
https://scholars.duke.edu/individual/pub1448846
PMID
32580713
Source
pubmed
Published In
Bmc Cancer
Volume
20
Published Date
Start Page
592
DOI
10.1186/s12885-020-07090-y

Discovery of endogenous ligands and the function of OR51E2 in prostate cancer

Authors
Abaffy, T; Bain, J; Muehlbauer, M; Spasojevic, I; Lodha, S; Bruguera, E; O'Neal, S; Kim, SY; Matsunami, H
MLA Citation
Abaffy, Tatjana, et al. “Discovery of endogenous ligands and the function of OR51E2 in prostate cancer.” Chemical Senses, vol. 45, no. 2, 2020, pp. 130–130.
URI
https://scholars.duke.edu/individual/pub1447801
Source
wos-lite
Published In
Chemical Senses
Volume
45
Published Date
Start Page
130
End Page
130

From the Clinic to the Bench and Back Again in One Dog Year: How a Cross-Species Pipeline to Identify New Treatments for Sarcoma Illuminates the Path Forward in Precision Medicine.

Cancer drug discovery is an inefficient process, with more than 90% of newly-discovered therapies failing to gain regulatory approval. Patient-derived models of cancer offer a promising new approach to identify new treatments; however, for rare cancers, such as sarcomas, access to patient samples is limited, which precludes development of patient-derived models. To address the limited access to patient samples, we have turned to pet dogs with naturally-occurring sarcomas. Although sarcomas make up <1% of all human cancers, sarcomas represent 15% of cancers in dogs. Because dogs have similar immune systems, an accelerated pace of cancer progression, and a shared environment with humans, studying pet dogs with cancer is ideal for bridging gaps between mouse models and human cancers. Here, we present our cross-species personalized medicine pipeline to identify new therapies for sarcomas. We explore this process through the focused study of a pet dog, Teddy, who presented with six synchronous leiomyosarcomas. Using our pipeline we identified proteasome inhibitors as a potential therapy for Teddy. Teddy was treated with bortezomib and showed a varied response across tumors. Whole exome sequencing revealed substantial genetic heterogeneity across Teddy's recurrent tumors and metastases, suggesting that intra-patient heterogeneity and tumoral adaptation were responsible for the heterogeneous clinical response. Ubiquitin proteomics coupled with exome sequencing revealed multiple candidate driver mutations in proteins related to the proteasome pathway. Together, our results demonstrate how the comparative study of canine sarcomas offers important insights into the development of personalized medicine approaches that can lead to new treatments for sarcomas in both humans and canines.
Authors
Rao, SR; Somarelli, JA; Altunel, E; Selmic, LE; Byrum, M; Sheth, MU; Cheng, S; Ware, KE; Kim, SY; Prinz, JA; Devos, N; Corcoran, DL; Moseley, A; Soderblom, E; Hsu, SD; Eward, WC
URI
https://scholars.duke.edu/individual/pub1434058
PMID
32117764
Source
pubmed
Published In
Frontiers in Oncology
Volume
10
Published Date
Start Page
117
DOI
10.3389/fonc.2020.00117

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, p. 17220. 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

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