So Young Kim

Positions:

Associate 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

Gene expression programs of lactic acidosis in human cancers

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

Discovery and validation of broadly effective LpxH inhibitors as novel therapeutics against multi-drug resistant Gram-negative pathogens

Administered By
Biochemistry
Awarded By
National Institutes of Health
Role
Principal 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

Publications:

Orthogonal genome-wide screens of bat cells identify MTHFD1 as a target of broad antiviral therapy.

Bats are responsible for the zoonotic transmission of several major viral diseases, including those leading to the 2003 SARS outbreak and likely the ongoing COVID-19 pandemic. While comparative genomics studies have revealed characteristic adaptations of the bat innate immune system, functional genomic studies are urgently needed to provide a foundation for the molecular dissection of the viral tolerance in bats. Here we report the establishment of genome-wide RNA interference (RNAi) and CRISPR libraries for the screening of the model megabat, Pteropus alecto. We used the complementary RNAi and CRISPR libraries to interrogate P. alecto cells for infection with two different viruses: mumps virus and influenza A virus, respectively. Independent screening results converged on the endocytosis pathway and the protein secretory pathway as required for both viral infections. Additionally, we revealed a general dependence of the C1-tetrahydrofolate synthase gene, MTHFD1, for viral replication in bat cells and human cells. The MTHFD1 inhibitor, carolacton, potently blocked replication of several RNA viruses, including SARS-CoV-2. We also discovered that bats have lower expression levels of MTHFD1 than humans. Our studies provide a resource for systematic inquiry into the genetic underpinnings of bat biology and a potential target for developing broad-spectrum antiviral therapy.
Authors
Anderson, DE; Cui, J; Ye, Q; Huang, B; Tan, Y; Jiang, C; Zu, W; Gong, J; Liu, W; Kim, SY; Yan, BG; Sigmundsson, K; Lim, XF; Ye, F; Niu, P; Irving, AT; Zhang, H; Tang, Y; Zhou, X; Wang, Y; Tan, W; Wang, L-F; Tan, X
MLA Citation
Anderson, Danielle E., et al. “Orthogonal genome-wide screens of bat cells identify MTHFD1 as a target of broad antiviral therapy.Proc Natl Acad Sci U S A, vol. 118, no. 39, Sept. 2021. Pubmed, doi:10.1073/pnas.2104759118.
URI
https://scholars.duke.edu/individual/pub1497048
PMID
34544865
Source
pubmed
Published In
Proc Natl Acad Sci U S A
Volume
118
Published Date
DOI
10.1073/pnas.2104759118

A Precision Medicine Drug Discovery Pipeline Identifies Combined CDK2 and 9 Inhibition as a Novel Therapeutic Strategy in Colorectal Cancer.

Colorectal cancer is the third most common cancer in the United States and responsible for over 50,000 deaths each year. Therapeutic options for advanced colorectal cancer are limited, and there remains an unmet clinical need to identify new treatments for this deadly disease. To address this need, we developed a precision medicine pipeline that integrates high-throughput chemical screens with matched patient-derived cell lines and patient-derived xenografts (PDX) to identify new treatments for colorectal cancer. High-throughput screens of 2,100 compounds were performed across six low-passage, patient-derived colorectal cancer cell lines. These screens identified the CDK inhibitor drug class among the most effective cytotoxic compounds across six colorectal cancer lines. Among this class, combined targeting of CDK1, 2, and 9 was the most effective, with IC50s ranging from 110 nmol/L to 1.2 μmol/L. Knockdown of CDK9 in the presence of a CDK2 inhibitor (CVT-313) showed that CDK9 knockdown acted synergistically with CDK2 inhibition. Mechanistically, dual CDK2/9 inhibition induced significant G2-M arrest and anaphase catastrophe. Combined CDK2/9 inhibition in vivo synergistically reduced PDX tumor growth. Our precision medicine pipeline provides a robust screening and validation platform to identify promising new cancer therapies. Application of this platform to colorectal cancer pinpointed CDK2/9 dual inhibition as a novel combinatorial therapy to treat colorectal cancer.
Authors
Somarelli, JA; Roghani, RS; Moghaddam, AS; Thomas, BC; Rupprecht, G; Ware, KE; Altunel, E; Mantyh, JB; Kim, SY; McCall, SJ; Shen, X; Mantyh, CR; Hsu, DS
MLA Citation
Somarelli, Jason A., et al. “A Precision Medicine Drug Discovery Pipeline Identifies Combined CDK2 and 9 Inhibition as a Novel Therapeutic Strategy in Colorectal Cancer.Mol Cancer Ther, vol. 19, no. 12, Dec. 2020, pp. 2516–27. Pubmed, doi:10.1158/1535-7163.MCT-20-0454.
URI
https://scholars.duke.edu/individual/pub1464433
PMID
33158998
Source
pubmed
Published In
Mol Cancer Ther
Volume
19
Published Date
Start Page
2516
End Page
2527
DOI
10.1158/1535-7163.MCT-20-0454

A Comparative Oncology Drug Discovery Pipeline to Identify and Validate New Treatments for Osteosarcoma.

BACKGROUND: Osteosarcoma is a rare but aggressive bone cancer that occurs primarily in children. Like other rare cancers, treatment advances for osteosarcoma have stagnated, with little improvement in survival for the past several decades. Developing new treatments has been hampered by extensive genomic heterogeneity and limited access to patient samples to study the biology of this complex disease. METHODS: To overcome these barriers, we combined the power of comparative oncology with patient-derived models of cancer and high-throughput chemical screens in a cross-species drug discovery pipeline. RESULTS: Coupling in vitro high-throughput drug screens on low-passage and established cell lines with in vivo validation in patient-derived xenografts we identify the proteasome and CRM1 nuclear export pathways as therapeutic sensitivities in osteosarcoma, with dual inhibition of these pathways inducing synergistic cytotoxicity. CONCLUSIONS: These collective efforts provide an experimental framework and set of new tools for osteosarcoma and other rare cancers to identify and study new therapeutic vulnerabilities.
Authors
Somarelli, JA; Rupprecht, G; Altunel, E; Flamant, EM; Rao, S; Sivaraj, D; Lazarides, AL; Hoskinson, SM; Sheth, MU; Cheng, S; Kim, SY; Ware, KE; Agarwal, A; Cullen, MM; Selmic, LE; Everitt, JI; McCall, SJ; Eward, C; Eward, WC; Hsu, DS
MLA Citation
Somarelli, Jason A., et al. “A Comparative Oncology Drug Discovery Pipeline to Identify and Validate New Treatments for Osteosarcoma.Cancers (Basel), vol. 12, no. 11, Nov. 2020. Pubmed, doi:10.3390/cancers12113335.
URI
https://scholars.duke.edu/individual/pub1465119
PMID
33187254
Source
pubmed
Published In
Cancers
Volume
12
Published Date
DOI
10.3390/cancers12113335

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