In-Kwon Kim , PHD

Lab homepage: https://www.inkwonkimlab.com/

In-Kwon Kim is an Associate Professor of Biochemistry with research interests in ADP-ribosylation metabolism, DNA damage response, and cancer drug discovery. After completing a B.S. degree from Seoul National University in 1998, he obtained his M.Sc (2000; Microbiology) and Ph.D. (2005; Biochemistry and Structural Biology) degree under the direction of Prof. Sa-Ouk Kang from Seoul National University. In 2006, he joined the research group of Prof. Tom Ellenberger at Washington University School of Medicine as a post-doc and was promoted into (Research) Assistant Professor. Since then, his research has been focused on the mechanistic structural biochemistry and drug discovery of key enzymes in ADP-ribosylation cycle and DNA damage responses. He also worked in the Washington University Drug Discovery Program. He joined the faculty at University of Cincinnati in 2016 and was promoted into Associate Professor with Tenure in 2022. His long-term research goal is to develop new tumor-selective therapeutics.

Ph.D.: Seoul National University (Korea), 2005 (Biochemistry and Structural Biology)

M.S.: Seoul National University (Korea), 2000 (Microbiology)

B.S.: Seoul National University (Korea), 1998 (Microbiology)

• Mechanism and pharmacological control of ADP-ribosylation cycle (ADP-ribosyl hydrolases and transferases)
• Nucleic acid enzymology in DNA damage response
• Development of new tumor-selective therapeutics
• Mechanism and phamacological control of SARS-CoV-2 RNA proofreading complex

2022 -To Present Associate Professor of Chemistry, University of Cincinnati,

2022 -To Present Chair, Division of Biochemistry, University of Cincinnati,

2016 -2022 Assistant Professor of Chemistry, University of Cincinnati, Cincinnati, OH

2015 -2016 Instructor in Medicine and Drug Discovery Program, Washington University School of Medicine, St. Louis, MO

2012 -2015 (Research) Assistant Professor of Biochemistry & Molecular Biophysics, Washington University School of Medicine, St. Louis, MO

Investigators:In-Kwon Kim 04-01-2023 -03-31-2024 CCTST Mechanism and Pharmacological Control of Coronaviral RNA Proofreading Role:PI $75,000 Active Type:Grant

Investigators:In-Kwon Kim 04-01-2022 -03-31-2024 Diana Lowenstein Fellowship Award Role:PI $5,000 Active Type:Fellowship Level:Department

Grant: #R01 GM141226 Investigators:Kim, In-Kwon 05-01-2021 -02-28-2025 National Institute of General Medical Sciences Reversal of residue-specific ADP-ribosylations by ADP-ribosyl-acceptor hydrolases Role:PI $1,348,826.00 Active Type:Grant

Grant: #133405-RSG-19-200-01-DMC Investigators:Kim, In-Kwon 01-01-2020 -12-31-2023 American Cancer Society - Research Scholar Grant (RSG) Mechanism and Control of Poly(ADP-ribose) Turnover Role:PI $792,000.00 Active Type:Grant Level:National

Grant: #V2018-025 Investigators:Kim, In-Kwon 11-01-2018 -10-31-2020 The V Foundation 2018 V Scholar Grant - Mechanism and Pharmacological Control of Human ADP-ribosyl-acceptor Hydrolase 3 Role:PI $200,000.00 Active Type:Grant Level:National

Grant: #N/A Investigators:In-Kwon Kim 09-01-2018 -02-28-2021 University of Cincinnati Cancer Institute 2018 Marlene Harris Ride Cincinnati Pilot Grant Award - Mechanism and Pharmacological Control of Human ADP-ribosyl-acceptor Hydrolase 3 Role:PI $35,000.00 Active Type:Grant Level:Local

Grant: #UH2 HL123429 Investigators:Holtzman, Michael; Kim, In-Kwon et al. 09-22-2014 -06-30-2016 NIH/NHLBI "Preclinical Development of an Anti-Mucus Drug" Role:Co-I $973,826/yr Completed Type:Grant Level:National

Grant: #R01 AI111605 Investigators:Holtzman, Michael; Kim, In-Kwon et al. 08-01-2014 -07-31-2016 NIH/NIAID "Interferon Signal Enhancers as Antiviral Therapeutics" Role:Co-I $289,137/yr Completed Type:Grant Level:National

Grant: #U19 AI070489 Investigators:Holtzman, Michael; Kim, In-Kwon et al. 08-01-2011 -07-31-2016 NIH/NIAID “Epithelial Barrier Programs in Asthma and Allergic Disease” Project 3: "Project 3 Epithelial Injury and TLR3 Role:Co-I $159,333/yr Completed Type:Grant Level:National

Peer Reviewed Publications

Pourfarjam, Y., Ma, Z., and Kim, I.K. (2022) ATP enhances the error-prone ribonucleotide incorporation by the SARS-CoV-2 RNA polymerase. Biochemical and Biophysical Research Communications. 625, 53-59

Hammel, M., Rashid, I., Sverzhinsky, A., Pourfarjam, Y., Tsai, M.S., Ellenberger, T., Pascal, J.M., Kim, I.K.¶, Tainer, J.A.¶, and Tomkinson, A.E.¶ (2021) An atypical BRCT-BRCT interaction with human DNA Ligase IIIa compacts the XRCC1 scaffold protein within a flexible DNA repair complex. Nucleic Acids Research. 49(1), 306-321, PMCID: PMC7797052 (¶: Co-corresponding author)

Yang, C.S., Jividen, K., Kamata, T., Dworak, N., Oostdyk, L., Remlein, B., Pourfarjam, Y., Kim, I.K., Du, K.P., Abbas, T., Sherman, N.E., Wotton, D., and Paschal, B.M. (2021) Androgen signaling uses a writer and a reader of ADP-ribosylation to regulate protein complex assembly. Nature Communications. 12(1), 2705.

Pourfarjam, Y., Ma, Z., Kurinov, I., Moss, J., and Kim, I.K. (2021) Structural and biochemical analysis of human ADP-ribosyl-acceptor hydrolase 3 (ARH3) reveals the basis of metal selectivity and different roles for the two Mg ions. Journal of Biological Chemistry.

Moiani, D., Link, T.M., Brosey, C.A., Katsonis, P., Lichtarg, O., Kim, Y., Joachimiak, A., Ma, Z., Kim, I.K., Ahmed, Z., Jones, D.E., Tsutakawa, S.E., Tainer, J.A. (2021) An efficient chemical screening method for structure-based inhibitors to nucleic acid enzymes targeting the DNA repair-replication interface and SARS CoV-2. Methods in Enzymology.

Kasson, S., Dharmapriya, N., and Kim, I.K. (2021) Selective monitoring of the protein-free ADP-ribose released by ADP-ribosylation reversal enzymes. PLoS One. 16(6):e0254022.

Ma, Z., Pourfarjam, Y., and Kim, I.K. (2021). Reconstitution and functional characterization of SARS-CoV-2 proofreading complex. Protein Expression and Purification.

Pourfarjam, Y., Kasson, S., Tran, L., Ho, C. and Kim, I.K. (2020) PARG has a robust endo-glycohydrolase activity that releases protein-free poly(ADP-ribose) chains. Biochemical and Biophysical Research Communications. 527(3), 818-823, PMID: 32439163.

Houl, J.H., Ye, Z., Brosey, C.A., Balapiti-Modarage, L.P.F., Namjoshi, S., Bacolla, A., Laverty, D., Walker, B.L., Pourfarjam, Y., Warden, L.S., Chinnam, N.B., Moiani, D., Stegeman, R.A., Chen, M.K., Hung, M.C., Nagel, Z.D., Ellenberger, T., Kim, I.K.#, Jones, D.E., Ahmed, Z.# and Tainer, J.A.# (2019) Selective small molecule PARG inhibitor causes replication fork stalling and cancer cell death. Nature Communications, in press. (#: Co-corresponding author)

Pourfarjam, Y., Ventura, J., Kurinov, I., Cho, A., Moss, J., and Kim, I.K. (2018). Structure of human ADP-ribosyl-acceptor hydrolase 3 bound to ADP-ribose reveals a conformational switch that enables specific substrate recognition. Journal of Biological Chemistry. 293, 12350-12359, PMCID: PMC6093245

Kim, I.K.**, Stegeman, R.A., Brosey, C.A., & Ellenberger, T.** (2015). A quantitative assay reveals ligand specificity of the DNA scaffold repair protein XRCC1 and efficient disassembly of complexes of XRCC1 and the poly(ADP-ribose) polymerase 1 by poly(ADP-ribose) glycohydrolase. J. Biol. Chem., 290, 3775-3783 (** Co-corresponding author).

Kim, I.K., Kiefer, J.R., Ho, C.M.W., Stegeman, R.A., Classen, S., Tainer, J.A., & Ellenberger, T. (2012). Structure of mammalian poly(ADP-ribose) glycohydrolase reveals a flexible tyrosine clasp as a substrate-binding element. Nat. Struct. Mol. Biol., 19, 653-656.

Invited Presentations

In-Kwon Kim (12-06-2022. ) Mechanism and pharmacological control of ADP-ribosyl-acceptor hydrolase 3 (ARH3) .BCRP/Breast Tumor Board Meeting, Level:Local

In-Kwon Kim (08-17-2022. ) Mechanism of the metal and substrate selectivity of human ADP-ribosyl-acceptor hydrolase 3 .ACS National Meeting 2022 (Chicago), Level:National

In-Kwon Kim (Co-Chair of Protein Structure and Function Session) (06-05-2022. ) Mechanism of the metal and substrate selectivity of human ADP-ribosyl-acceptor hydrolase 3 .ACS CERM 2022 (Ypsilanti), Level:Regional

In-Kwon Kim (02-21-2020. ) University of Cincinnati Chemistry Ph.D. program and Biochemistry Research .Estern Kentucky University, KY. Other Institution. . Level:Regional

In-Kwon Kim (05-2019. ) Reversal of residue-specific ADP-ribosylations by ADP-ribosyl-acceptor hydrolases .NSF CAREER workshop, Alexandria, VA. Level:National

Kim, In-Kwon (04-2018. ) Conformational changes of human ARH3 enable specific recognition and cleavage .The Cold Spring Harbor Laboratory Meeting; The PARP Family and ADP-ribosylation, Cold Spring Harbor, NY, USA. Conference. . Level:International

Kim, In-Kwon (04-2014. ) Mechanism and function of poly(ADP-ribose) turnover by mammalian poly(ADP-ribose) glycohydrolase .Cold Spring Harbor Laboratory Meeting: The PARP Family & Friends: Gene Regulation and Beyond, Cold Spring Harbor, NY.

Kim, In-Kwon (03-2014. ) Mechanism and function of poly(ADP-ribose) turnover by poly(ADP-ribose) glycohydrolase .13th Structural Cell Biology of DNA Repair Machines (SBDR) Workshop, Berkeley, CA.

Kim, In-Kwon (04-2013. ) Structure and function of mammalian poly(ADP-ribose) glycohydrolase .12th Structural Cell Biology of DNA Repair Machines (SBDR) Workshop, Berkeley, CA.

Poster Presentations

In-Kwon Kim (04-01-2022. ) Structural and biochemical basis of the metal and substrate selectivity of human ADP-ribosyl-acceptor hydrolase 3 .Cold Spring Harbor Laboratory "PARP family & ADP-ribosylation" meeting,

Samuel Kasson (03-31-2022. ) Enzymatic Coupling of a Classical Luciferase Assay for the Quantitative Monitoring of the Protein-Free ADP-ribose .ASBMB annual meeting 2022, Philadelphia. .

Yasin Pourfarjam and In-Kwon Kim (11-2018. ) Structure and Catalytic Mechanism of ADP-ribosyl-acceptor hydrolase 3 (ARH3) .Oesper symposium, UC. . Level:National

Yasin Pourfarjam, Ah-Ra Cho, and In-Kwon Kim (11-2017. ) Discovery and Characterization of Proteins Modulating Poly(ADP-ribose) Glycohydrolase (PARG) .Oesper symposium, UC. . Level:National

Yasin Pourfarjam and In-Kwon Kim (05-2017. ) Mechanism and regulation of human Poly(ADP-ribose) Glycohydrolase (PARG) .CBSB conference, UC. . Level:International

Lecture

In-Kwon Kim (12-2016. ) Mechanism and pharmacological control of poly(ADP-ribose) turnover and signaling .University of Cincinnati medical Center. UC. Level:Department

Kim, In-Kwon (10-2016. ) Mechanism and pharmacological control of poly(ADP-ribose) turnover and signaling .University of Cincinnati Medical Center. UC. Level:Department

Kim, In-Kwon (05-2013. ) Structure and function of mammalian poly(ADP-ribose) glycohydrolase .Korea. Other Institution.

Event Organized

GRW 2018

05-01-2022 -Bad Format: 20240431 Diana Lowenstein Fellowship Award $5,000 Type:Fellowship

01-2020 -12-2023 American Cancer Society - Research Scholar Grant Award $792,000 Status:Recipient Level:National Type:Grant

11-2018 -10-2020 V scholar young investigator award, V foundation, $200,000 Status:Recipient Level:National Type:Grant

09-2018 -02-2020 Marlene Harris Ride Cincinnati Pilot Grant Award $35,000 Status:Recipient Level:Local Type:Grant

Department of Chemistry (Graduate Admission Committee ) Committee Member Type:Departmental Service Level:University

Department of Chemistry (Moral Committee ) Committee Member Type:Departmental Service Level:University

Department of Chemistry Member Type:Departmental Service Level:Department

Department of Chemistry Program Operator Type:Departmental Service Level:Department

Department of Chemistry (Graduate Admission Committee ) Committee Member Type:Departmental Service Level:Department

Department of Chemistry (Moral Committee ) Committee Member Type:Departmental Service Level:Department

Department of Chemistry (Faculty Search Committee (Biochem) ) Committee Member Type:Departmental Service Level:Department

University of Cincinnati (Bioseparation faculty search committee ) Committee Member Type:Departmental Service Level:Department

UNIVERSITY OF CINCINNATI (Bioanalytical faculty search committee ) Committee Member Type:Departmental Service Level:Department

2011-2012 Staff Scientist, Washington University School of Medicine, , St. Louis, MO

2006-2011 Postdoctoral Fellow, Washington University School of Medicine, , St. Louis, MO

Member Korean-American Scientists and Engineers Association (KSEA),

-CHEM-3040 INTRO BIOCHEM Level:Undergraduate

-CHEM-3040 INTRO BIOCHEM Level:Undergraduate

-CHEM-4040 MOLECULES OF LIFE Level:Undergraduate

-CHEM-2031L SURVEY BIOCH LAB II Level:Undergraduate

Advanced Biochemistry IV Level:Graduate

Survey of Biochemistry Laboratory I Level:Undergraduate

US20220202821A1 Small Molecule PARG inhibitors and Methods of Use Thereof Ho, C., Ellenberger, T. Kim, I.K., Jones, D.E., Ahmed, Z., and Tainer, J.A., Awarded