Jae-Kyun (James) Ko

Since the successful debut of recombinant human insulin, recombinant DNA technology has played a critical role in developing and producing biopharmaceuticals. Based on innovative site-directed mutagenesis (SDM) and directed evolution technologies, I have pursued constructing a novel platform to create the next generation of biopharmaceuticals with optimized drug properties, novel biological functions, and beneficial traits during production. My current interests are tailoring and investigating a drug-candidate MG53 protein for the treatment of tissue injury by application of genetic engineering and computational approaches to manipulate its structure and function.

Fields: Molecular & cell biology, oncology, biochemistry, biotechnology

Research interests: Apoptosis, autophagy and muscle aging

Expertise:

• In vitro high-throughput gene manipulation
• Site-directed mutagenesis, directed evolution
• Protein structure analysis
• Vector design for protein expression and purification
• Manipulation of cell lines and mouse lines by using CRISPR/Cas9 gene editing
• Confocal microscopy and biochemical analysis
• RNA-seq, microarray data analysis

Establishing and managing laboratories

• Mutagenex Inc (www.mutagenex.com)
• Molecular Biology Core, Wexner Medical Center, OSU (https://medicine.osu.edu/departments/surgery/research/molecular-biology)

• 2011: Invited Seminar, Ko JK, (2014), Topic: Current Applications of Site-Directed Mutagenesis and Directed Evolution, KAIST, Daejeon, South Korea
• 2006-present: American Association for Cancer Research (AACR)
• 2005-present: Biophysical Society (BPS)
• 2019: Establish Molecular Biology Core lab and open services (URL: https://medicine.osu.edu/departments/surgery/research/molecular-biology)
• 2020-present: Membership of the Comprehensive Cancer Center (https://cancer.osu.edu/)
• Journal editorial reviewer:

- International Journal of Pharmacy and Chemistry (http://www.ijopc.com)

- The Journal of Thoracic and Cardiovascular Surgery (https://www.jtcvs.org/)

- The Annals of Thoracic Surgery (https://www.annalsthoracicsurgery.org/)

• Venture Capital ($300K) funded from Korean Community in Central New Jersey, 2006
• Research start funding from Department of Surgery, the College of Medicine, OSU (PI) 08/01/2018 – 07/31/2023
• R01- EY030621 (Co-Investigator)

9/01/2019 – 07/31/2023

National Eye Institute (NEI)

"Preservation of Limbal Stem Cell Function in Corneal Injury"

• R01- DK123475 (Co- Investigator)

01/13/2020 – 11/30/2024

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

“Preservation of DCD Allograft Integrity for Liver Transplantation”

• R01- HL153876 ( Co-Investigator)

07/01/2020 - 06/30/2024

National Heart, Lung, and Blood Inst (NHLBI)

“Inhibiting Cell Death for Protecting Cardiac Injury”

Complete List of Published Works


25 publications with more than 1750 citations since 2003




Research articles

1. Membrane-delimited signaling and cytosolic action of MG53 preserve hepatocyte integrity during drug-induced liver injury. Han, Y., Black, S., Gong Z., Ko, JK ., et al. J Hepatol. 2021, Nov 1:S0168-8278(21)02154-1.

2. Geng BC, Choi KH, Wang SZ, Chen P, Pan XD, Dong NG, Ko JK , Zhu H. A simple, quick, and efficient CRISPR/Cas9 genome editing method for human induced pluripotent stem cells. Acta Pharmacol Sin 41, 1427–1432 (2020).

( Co-corresponding author )

3. Choi S, Cui C, Luo Y, Kim SH, Ko JK , Huo X, Ma J, Fu LW, Souza RF, Korichneva I, Pan Z: Selective inhibitory effects of zinc on cell proliferation in esophageal squamous cell carcinoma through Orai1. FASEB J . 2018, 32: 404-416. Epub 2017 Sep 19.

4. Cai C, Lin P, Zhu H, Ko JK , Hwang M, Tan T, Pan Z, Korichneva I, Ma J: Zinc Binding to MG53 Protein Facilitates Repair of Injury to Cell Membranes. J Biol Chem . 2015, 290: 13830-13839. Epub 2015 Apr 13.

5. De G, Ko JK , Tan T, Zhu H, Li H, Ma J: Amphipathic tail-anchoring peptide is a promising therapeutic agent for prostate cancer treatment. Oncotarget . 2014, 5: 7734-7747.

6. Ko JK , Choi KH, Zhao X, Komazaki S, Pan Z, Weisleder N, Ma J: A versatile single-plasmid system for tissue-specific and inducible control of gene expression in transgenic mice. FASEB J 2011, 25: 2638-2649. Epub 2011 Apr 25.

7. Ko JK , Choi KH, Peng J, He F, Zhang Z, Weisleder N, Lin J, Ma J: Amphipathic tail-anchoring peptide and Bcl-2 homology domain-3 (BH3) peptides from Bcl-2 family proteins induce apoptosis through different mechanisms. J Biol Chem 2011, 286: 9038-9048. Epub 2010 Dec 28 (Selected as a Paper of the Week) .

Reviewer's commentarty: A New Weapon in the Fight against Cancer

8. Tjondrokoesoemo A, Park KH, Ferrante C, Komazaki S, Lesniak S, Brotto M, Ko JK , Zhou J, Weisleder N, Ma J: Disrupted membrane structure and intracellular Ca²+ signaling in adult skeletal muscle with acute knockdown of Bin1. PLoS One 2011, 6(9):e25740. Epub 2011 Sep 30.

9. Hwang M, Ko JK , Weisleder N, Takeshima H, Ma J: Redox-dependent oligomerization through a leucine zipper motif is essential for MG53-mediated cell membrane repair. Am J Physiol Cell Physiol 2011, 301: C106-114. Epub 2011 Apr 27.

10. Zhao X, Min CK, Ko JK , Parness J, Kim do H, Weisleder N, Ma J: Increased store-operated Ca2+ entry in skeletal muscle with reduced calsequestrin-1 expression. Biophys J 2010, 99:1556-1564.

11. Woo JS, Hwang JH, Ko JK , Weisleder N, Kim do H, Ma J, Lee EH: S165F mutation of junctophilin 2 affects Ca2+ signaling in skeletal muscle. Biochem J 2009, 427:125-134.

12. Woo JS, Hwang JH, Ko JK , Kim do H, Ma J, Lee EH: Glutamate at position 227 of junctophilin-2 is involved in binding to TRPC3. Mol Cell Biochem 2009, 328:25-32.

13. Cai C, Weisleder N, Ko JK , Komazaki S, Sunada Y, Nishi M, Takeshima H, Ma J: Membrane repair defects in muscular dystrophy are linked to altered interaction between MG53, caveolin-3, and dysferlin. J Biol Chem 2009, 284:15894-15902.

14. Cai C, Masumiya H, Weisleder N, Matsuda N, Nishi M, Hwang M, Ko JK , Lin P, Thornton A, Zhao X, et al.: MG53 nucleates assembly of cell membrane repair machinery. Nat Cell Biol 2009, 11:56-64.

15. Landstrom AP, Weisleder N, Batalden KB, Bos JM, Tester DJ, Ommen SR, Wehrens XH, Claycomb WC, Ko JK , Hwang M, et al.: Mutations in JPH2-encoded junctophilin-2 associated with hypertrophic cardiomyopathy in humans. J Mol Cell Cardiol 2007, 42:1026-1035.

16. Ko JK , Choi KH, Pan Z, Lin P, Weisleder N, Kim CW, Ma J: The tail-anchoring domain of Bfl1 and HCCS1 targets mitochondrial membrane permeability to induce apoptosis. J Cell Sci 2007, 120:2912-2923 ( Editor's highlighted paper) .

Reviewer's commentarty: Lethal sting in a Bcl2 tail

17. Yang WS, Ko JK , Park SO, Choi HY, Kim YN, Kim CW: C-terminal region of Bfl-1 induces cell death that accompanies caspase activation when fused with GFP. J Cell Biochem 2005, 94:1234-1247.

18. Qin L, Li X, Ko JK , Partridge NC: Parathyroid hormone uses multiple mechanisms to arrest the cell cycle progression of osteoblastic cells from G1 to S phase. J Biol Chem 2005, 280:3104-3111.

19. Ko JK , Ma J: A rapid and efficient PCR-based mutagenesis method applicable to cell physiology study. Am J Physiol Cell Physiol 2005, 288: C1273-1278.

20. Cho JA, Yeo DJ, Son HY, Kim HW, Jung DS, Ko JK , Koh JS, Kim YN, Kim CW: Exosomes: a new delivery system for tumor antigens in cancer immunotherapy. Int J Cancer 2005, 114:613-622.

21. Choi KH, Choi HY, Ko JK , Park SS, Kim YN, Kim CW: Transcriptional regulation of TNF family receptors and Bcl-2 family by chemotherapeutic agents in murine CT26 cells. J Cell Biochem 2004, 91:410-422.

22. Kwon GY, Jeong J, Woo JK, Choi HY, Lee MJ, Ko JK , Shim YH, Kim CW: Co-expression of bfl-1 enhances host response in the herpes simplex virus-thymidine kinase/ganciclovir gene therapy system. Biochem Biophys Res Commun 2003, 303:756-763.

23. Ko JK , Lee MJ, Cho SH, Cho JA, Lee BY, Koh JS, Lee SS, Shim YH, Kim CW: Bfl-1S, a novel alternative splice variant of Bfl-1, localizes in the nucleus via its C-terminus and prevents cell death. Oncogene 2003, 22:2457-2465.

24. Ko JK , Choi KH, Kim HJ, Choi HY, Yeo DJ, Park SO, Yang WS, Kim YN, Kim CW: Conversion of Bfl-1, an anti-apoptotic Bcl-2 family protein, to a potent pro-apoptotic protein by fusion with green fluorescent protein (GFP). FEBS Lett 2003, 551:29-36.

25. Ko JK , Choi KH, Kim IS, Jung EK, Park DH: Inducible RGS2 is a cross-talk regulator for parathyroid hormone signaling in rat osteoblast-like UMR106 cells. Biochem Biophys Res Commun 2001, 287:1025-1033




Book & chapter

· Ko JK , Ma J: Efficient PCR-based mutagenesis method applicable to diverse mutagenesis strategies using type IIs restriction enzymes. In PCR: Methods Express. Scion Publishing Ltd. (2007) 217-228.

· Kang KW, Hong SJ, Kim DR, Jung HI, Ko JK , Kim YH, Choi KH (1995) Animal being forgotten - Leech. Academy Press, Korea

1. (WO/2008/060776)

ATAP peptides, nucleic acids encoding the same and associated methods of use

Ma J, Ko JK , Kim CW, Weisleder N (2008). Application No.: PCT/US2007/080307

2. (WO/2004/110474)

A pharmaceutical composition for inducing apoptosis comprising a fusion protein of Bfl-1 and green fluorescent protein or a gene encoding same. Kim CW, Ko JK , Yang WS (2004). Application No.: PCT/KR2004/001324

3. (WO/2004/014954)

Exosome containing exogenous antigen through gene transfection and method for utilizing the same. Kim CW, Ko JK , Cho JA (2003). Application No.: PCT/KR2003/001575

• 26th Annual Department of Surgery Research Conference, MG53-mediated control of REDD2 plays important roles in exercise-mediated activation of autophagy in skeletal muscle, and compromised MG53/REDD2 signaling contributes to age-related decline of muscle function. Choi KH, Cho JH, Kim J, Lee KE, Zhu H, Ko JK and Ma J, May 13, 2021.Oral presentation.
• 2021 NHLBI Long Non-coding (lnc) RNAs Symposium: From Basic Mechanism to Human Disease, Long non-coding RNA Camirt plays a sentinel role in aging-related heart failure via interaction with Phb2 to modulate mitophagy signaling in the heart. Wang X, Li X, Ko JK , Sun N, Miano J, Ma J and Cai C, March 11-12, 2021, Oral presentation.
• The Experimental Biology 2019 Meeting, Exogenous MG53 Protects Adult Mouse Cardiomyocytes by Preventing Mitochondria Damage in Response to Oxidative Stress, Gumpper KN, Ko JK , Xu L, Han R, Zhou H, Lin PH, Ma J, The FASEB Journal, Volume33, Issue S1, Experimental Biology 2019 Meeting Abstracts, April 2019, p833.3
• Invited Seminar, Ko JK , (2014), Current Applications of Site-Directed Mutagenesis and Directed Evolution, KAIST, Daejeon, South Korea
• Ko JK , Peng J, Choi KH, Zhang Z, Zong WX, Weisleder N, Lin J, Ma J (2010) Amphipathic tail-anchoring peptide and BH3 peptide induced mitochondrial permeabilization and apoptosis are mechanistically distinct Biophysical Society 54th annual meeting, San Francisco, CA, USA.
• Min CK, Zhao X, Ko JK , Pan Z, Parness J, Kim DH, Weisleder N, Ma J. (2009) Increased store-operated Ca2+ entry in skeletal muscle with knockdown of calsequestrin. Biophysical Society 53rd annual meeting, Boston, MA, USA.
• Woo JS, Hwang JH, Ko JK , Weisleder N, Kim DH, Ma J, Lee EH. (2009) S165F mutation in junctophilin-2 affects phosphorylation and Ca2+ signaling in skeletal muscle. Biophysical Society 53rd annual meeting, Boston, MA, USA.
• Cai C, Masumiya H, Weisleder N, Matsuda N, Nishi M, Hwang M, Ko JK , Lin P, Thornton A, Zhao X, Pan Z, Komazaki S, Brotto M, Takeshima H, Ma J. (2009) MG53 nucleates assembly of cell membrane repair machinery. Biophysical Society 53rd annual meeting, Boston, MA, USA.
• Cai C, Masumiya H, Weisleder N, Matsuda N, Nishi M, Hwang M, Ko JK , Lin P, Thornton A, Zhao X, Pan Z, Komazaki S, Brotto M, Takeshima H, Ma J. (2008) MG53 is an essential component of the acute membrane repair machinery. Biophysical Society 52nd annual meeting, Long Beach, CA, USA.
• Ko JK , Peng J, Lin, J., Ma, J. (2008) ATAP perturbs mitochondria membrane permeability to induce apoptosis independent of Bcl-2 protein function. Biophysical Society 52nd annual meeting, Long Beach, CA, USA.
• Ko JK , Choi KH, Pan Z, Lin P, Kim CW and Ma J. (2006) Tail-anchoring domain of Bfl-1 targets mitochondria and induces apoptosis by its amphipathic property. American Association for Cancer Research (AACR) annual meeting, Washington DC, MD, USA.
• Ko JK , Choi KH, Pan Z, Lin P, Kim CW and Ma J. (2005) Apoptosis induction by targeting amphipathic peptide of Bfl-1 tail-anchor domain to mitochondria. Biophysical J. 49th annual meeting, Long Beach, CA, USA.
• Ko JK , Lee MJ, Cho SH, Cho JA, Koh JS, Shim YH, Kim CW. (2002) Bfl-1S, a novel alternative splice variant of Bfl-1, localizes in the nucleus via its C-terminus and prevents cell death, Cell Death and Differentiation Conference 2002, October, Italy.
• Ko JK , Cho SH, Lee BY, Cho JA, Lee MJ, Koh JS, Shim YH, Kim CW. (2001) Cloning and molecular characterization of a novel Bfl-1s, an alternative mRNA splicing product of BFL-1gene, The 7th Korean Japanese Lymphoreticular Workshop, Seoul, Korea.
• Kang KW, Hong SJ, Kim DR, Jung HI, Lee CY, Ko JK , Kim YH, Choi KH, and Kang SS. (1996) Screening and Medical Applications of Protease Inhibitors from Lower Animal, Leech. The 1st APEC Symposium on Biodiversity and its Bioconversion., Seoul, Korea.