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Jin-Gu Lee, PhD

Academic Title:

Assistant Professor

Primary Appointment:

Obstetrics, Gynecology and Reproductive Sciences

Location:

655 West Baltimore Street

Phone (Primary):

410-706-1214

Fax:

410-706-5747

Education and Training

1991 – 1999      B.S., Microbiology, Keimyung University in Korea

2002 - 2004      M.S., College of Medicine, Keimyung University in Korea

2004 - 2006      Ph. D., College of Medicine, Keimyung University in Korea

2006 - 2008      Post-doctoral fellow, Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University

2008 - 2013      Visiting Post-doctoral fellow, Laboratory of Molecular Biology, NIDDK, NIH

2013 - 2017      Research fellow, Laboratory of Molecular Biology, NIDDK, NIH

Biosketch

My major is biochemistry, molecular and cellular biology. Particularly, my doctoral research focused on the cellular signaling pathways of inflammatory responses mediated by phospholipases and reactive oxygen species (ROS), and my postdoctoral research has focused on protein quality control which is dedicated to the surveillance of protein misfolding errors in the cells. Dysfunction of the protein quality control system has been increasingly linked to the pathogenesis of human diseases including amyloidosis, type 2 diabetes, and neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s disease. Elimination of misfolded proteins generally involves tagging the affected substrates with ubiquitin (this is called ubiquitination), which targets modified polypeptides to proteasomes for degradation. For several years, I have been investigating molecular mechanisms underlying Apolipoprotein L1 (APOL1)-related kidney disease in humans. APOL1, an innate immune gene found in humans and some primates, offers protection against African trypanosome parasites that cause sleeping sickness. However, in individuals with recent African ancestry, two coding alleles in the APOL1 gene (termed risk alleles) significantly increase the risk of nondiabetic kidney disease. My recent work demonstrates that APOL1 risk alleles insert into the endoplasmic reticulum (ER) membrane, disrupting cellular ion homeostasis. This novel mechanism of APOL1-induced cellular toxicity has the potential to inform the development of future therapeutic strategies. 

Currently, I joined Dr. Peixin Yang's lab and will be working on maternal diabetes-induced embryonic anomalies using mouse, embryo, and cell culture models.

I have totally published 33 papers in international refereed journals, which have been cited more than 1,300 times (excluding self-citations of all authors).

Research/Clinical Keywords

Protein Quality Control, Protein trafficking, Ubiquitination, Neurodegenerative Diseases, Cellular Signalling

Highlighted Publications

1. Jin-Gu Lee, Yulong Fu, Jun-Yi Zhu, Pei Wen, Joyce van de Leemput, Patricio E Ray, Zhe Han (2023) A SNARE protective pool antagonizes APOL1 renal toxicity in Drosophila nephrocytes. Cell & Bioscience. 13(1):199

2. Jin-Gu Lee, Weiliang Huang, Hangnoh Lee, Joyce van de Leemput, Maureen A Kane, Zhe Han (2021) Characterization of SARS-CoV-2 proteins reveals Orf6 pathogenicity, subcellular localization, host interactions and attenuation by Selinexor. Cell & Bioscience 11:58

3. Jin-Gu Lee, Shokichi Takahama, Guofeng Zhang, Stanislav Tomarev, Yihong Ye (2016) Unconventional secretion of misfolded proteins adapts cells to proteasome dysfunction in mammalian cells. Nat. Cell Biol. 18(7): 765-76

4. Jin-Gu Lee, Woong Kim, Steven Gygi, Yihong Ye (2014) Characterization of the deubiquitinating activity of USP19 and its role in endoplasmic reticulum-associated degradation. J Biol Chem. 289(6): 3510-7

5. Jin-Gu Lee, Nia Soetandyo, Kheewoong Baek, Yihong Ye (2013) Reversible inactivation of deubiquitinases by reactive oxygen species in vitro and in cells. Nature Communications. 4: 1568.

Additional Publication Citations

  1. K.K. Park, S.M. Han, M.Y. Jegal, H.S. Jeong, J.G. Lee, H.C. Kim (2003) Patterns and Sites of Tumor Necrosis Factor-a and Transforming Growth Factor-b1 Expression in Human Renal Allograft Biopsies. Transplant Proc. 35:249-250
  2. Young-Mi Chae, Kwan-Kyu Park, Junji Magae, In-Seon Lee, Cheorl-Ho Kim, Hyun-Chul Kim, SaHyun Hong, Jin-Gu Lee, In-Jang Choi, Hyun-Soo Kim, Kwan-Sik Min, In-Kyu Lee, Young-Chae Chang (2004) Sp1-decoy oligodeoxynucleotide inhibits high glucose-induced mesangial cell proliferation. Biochem Biophys Res Commun. 319:550-555
  3. Jin-Gu Lee, Sung-Bae Park, Seung-Yeup Han, Eun-Ah Hwang, Kwan-Kyu Park, Jeong-Ho Lee, Hyun-Chul Kim (2004) Effect of TGF-b1 Antisense Oligodeoxynucleotides on Fibrosis of Peritoneum in Peritoneal Dialysis Animal Model and Mesothelial Cells Cultured in High Glucose Media. Keimyung Med J. 23:65-76
  4. ChuHee Lee, Dae-Weon Park, Jingu Lee, Tae-Il Lee, Young-Jo Kim, Yun-Sik Lee, Suk-Hwan Baek (2006) Secretory phospholipase A2 induces apoptosis through TNF-a and cytochrome c-mediated caspase cascade in murine macrophage RAW 264.7 cells. Eur J Pharmacol. 536:47-53
  5. ChuHee Lee*, Jingu Lee*, Young-Ae Choi, Shin-Sung Kang, Suk-Hwan Baek (2006) cAMP elevating agents suppress secretory phospholipase A2-induced matrix metalloproteinase-2 activation. Biochem Biophys Res Commun. 340: 1278-1283
    * Co-first author
  6. Eun-Jung Lim, Sun-Hye Lee, Jin-Gu Lee, Byung-Ro Chin, Yoe-Sik Bae, Jae-Ryong Kim, Chu-Hee Lee, Suk-Hwan Baek (2006) Activation of toll-like receptor-9 induces matrix metalloproteinase-9 expression through Akt and tumor necrosis factor-a signaling. FEBS Lett. 580:4533-4538
  7. 7. Jin-Gu Lee, Sun-Hye Lee, Dae-Weon Park, Yoe-Sik Bae, Sung-Su Yun, Jae-Ryong Kim, Suk-Hwan Baek (2007) Phosphatidic Acid as a Regulator of Matrix Metalloproteinase-9 Expression via the TNF-a Signaling Pathway. FEBS Lett. 581:787-793
  8. Eun-Jung Lim, Sun-Hye Lee, Jin-Gu Lee, Jae-Ryong Kim, Sung-Su Yun, Suk-Hwan Baek, Chu-Hee Lee (2007) Toll-like receptor 9 dependent activation of MAPK and NF-kB is required for the CpG ODN-induced matrix metalloproteinase-9 expression. Exp Mol Med. 39:239-245.
  9. Dae-Weon Park, Kheewoong Baek, Jin-Gu Lee, Yun-Ki Park, Jung-Hye Kim, Jae-Ryong Kim, Suk-Hwan Baek (2007) Activation of toll-like receptor 4 modulates vascular endothelial growth factor synthesis through prostacyclin-IP signaling. Biochem Biophys Res Commun. 362:1090-1095.
  10. 10. Sun-Hye Lee, Jin-Gu Lee, Jae-Ryong Kim, Suk-Hwan Baek (2007) Toll-Like Receptor 9-Mediated cytosolic Phospholipase A2 Activation Regulates Expression of Inducible Nitric Oxide Synthase. Biochem Biophys Res Commun. 364:996-1001
  11. Jin-Gu Lee, Sun-Hye Lee, Dae-Weon Park, Sang-Hoon Lee, Hong-Sik Yoon, Byung-Ro Chin, Jung-Hye Kim, Jae-Ryong Kim, Suk-Hwan Baek (2008) Toll-like Receptor 9-stimulated Monocyte Chemoattractant Protein 1 is Mediated Via JNK-cytosolic Phospholipase A2-ROS Signaling. Cellular Signalling. 20:105-111.
  12. Jin-Gu Lee, Eun-Jung Lim, Dae-Weon Park, Sun-Hye Lee, Jae-Ryong Kim, Suk-Hwan Baek (2008) A Combination of Lox-1 and Nox1 Regulates TLR9-Mediated Foam Cell Formation. Cellular Signalling. 20:2266-2275.
  13. So-Yeon Kim, Jin-Gu Lee, Woo-Sung Cho, Kyong-Hyun Cho, Jun Sakong, Jae-Ryong Kim, Byung-Rho Chin, Suk-Hwan Baek (2010) Role of NADPH oxidase-2 in lipopolysaccharide-induced matrix metalloproteinase expression and cell migration. Immunology and Cell Biology. 88:197–204.
  14. Hyung-Kyoung Lee, Seungeun Yeo, Jin-Sik Kim, Jin-Gu Lee, Yoe-Sik Bae, Chuhee Lee, Suk-Hwan Baek (2010) Protein Kinase C-η and Phospholipase D2 Pathway Regulates Foam Cell Formation via Regulator of G Protein Signaling 2. Mol Pharmacol. 78(3):478-85.
  15. Eun-Jung Lim, Dae-Weon Park, Jin-Gu Lee, Chu-Hee Lee, Yoe-Sik Bae, Young-Chul Hwang, Jae-Weon Jeong, Byung-Rho Chin, Suk-Hwan Baek (2010) Toll-like receptor 9-mediated inhibition of apoptosis occurs through suppression of FoxO3a activity and induction of FLIP expression. Experimental & Molecular Medicine. 42:712-20.
  16. Qiuyan Wang, Bidhan A. Shinkre, Jin-Gu Lee, Marc A. Weniger, Yanfen Liu, Weiping Chen, Adrian Wiestner, William C. Trenkle, Yihong Ye (2010) The ERAD Inhibitor Eeyarestatin I Is a Bifunctional Compound with a Membrane-Binding Domain and a p97/VCP Inhibitory Group. PLoS One. 5(11):e15479
  17. Yongwang Zhong, Yang Wang, Hui Yang, Petek Ballar, Jin-Gu Lee, Yihong Ye, Mervyn J. Monteiro, Shengyun Fang (2011) Importin beta interacts with the endoplasmic reticulum-associated degradation machinery and promotes ubiquitination and degradation of mutant alpha1-antitrypsin. J Biol Chem. 286(39):33921-30.
  18. Hyung-Kyoung Lee, Dae-Weon Park, Jun Ho Bae, Hyung Jun Kim, Dong-Gu Shin, Jong-Seon Park, Jin-Gu Lee, Sung Joong Lee, Yoe-Sik Bae, Suk-Hwan Baek (2012) RGS2 is a negative regulator of STAT3-mediated Nox1 expression. Cellular Signalling. 24(3):803-9.
  19. Jin-Gu Lee, Yihong Ye (2013) Bag6/Bat3/Scythe: a novel chaperone activity with diverse regulatory functions in protein biogenesis and degradation. Bioessays. 35(4):377-85.
    - This article has been selected as a highlight from this issue.
  20. Yue Xu, Yanfen Liu, Jin-Gu Lee, Yihong Ye (2013) A Ubiquitin-like Domain Recruits an Oligomeric Chaperone to a Retrotranslocation Complex in Endoplasmic Reticulum-associated Degradation. J Biol Chem. 288(25): 18068-76.
  21. Yanfen Liu, Soetandyo Nia, Jin-Gu Lee, Liping Liu, Yue Xu, William M Clemons Jr, Yihong Ye (2014) USP13 antagonizes gp78 to maintain functionality of a chaperone in ER-associated degradation. Elife. 3(0): e01369.
  22. Ji Hyo Lyu, Dae-Weon Park, Bin Huang, Su Hwan Kang, Soo Jung Lee, Chuhee Lee, Yoe-Sik Bae, Jin-Gu Lee, Suk-Hwan Baek (2015) RGS2 Suppresses Breast Cancer Cell Growth via a MCPIP1-Dependent Pathway. Journal of Cellular Biochemistry 116(2): 260-7
  23. Seo‐Yeon Lee, Yun‐Seok Choi, Eun‐Hee Kim, Hae‐Kap Cheong, Yun‐Ju Lee, JinGu Lee, Yihong Ye, Kyoung‐Seok Ryu (2018) Nonenzymatic acetylation of ubiquitin Lys side chains is modulated by their neighboring residues. The FEBS Journal 285(7):1277-1289
  24. Yue Xu, Lei Cui, Anthony Dibello, Lihui Wang, Juhyung Lee, Layla Saidi, Jin-Gu Lee, Yihong Ye (2018) DNAJC5 facilitates USP19-dependent unconventional secretion of misfolded cytosolic proteins. Cell Discovery 4:11
  25. Jun-Yi Zhu, Jin-Gu Lee, Joyce van de Leemput, Hangnoh Lee, Zhe Han (2021) Functional analysis of SARS-CoV-2 proteins in Drosophila identifies Orf6-induced pathogenic effects with Selinexor as an effective treatment. Cell & Bioscience 11:59
  26. Josephine Bock, Nathalie Kühnle, Julia D. Knopf, Nina Landscheidt, Jin-Gu Lee, Yihong Ye, Marius K. Lemberg (2022) Rhomboid protease RHBDL4 promotes retrotranslocation of aggregation-prone proteins for degradation. Cell Rep. 40(6): 111175
  27. Jun-yi Zhu, Guanglei Wang, Xiaohu Huang, Hangnoh Lee, Jin-Gu Lee, Penghua Yang, Joyce van de Leemput, Weiliang Huang, Maureen A. Kane, Peixin Yang, Zhe Han (2022) SARS-CoV-2 Nsp6 damages Drosophila heart and mouse cardiomyocytes through MGA/MAX complex-mediated increased glycolysis. Commun Biol. 5(1):1039
  28. Jun-yi Zhu, Jin-Gu Lee, Yulong Fu, Joyce van de Leemput, Patricio E Ray, Zhe Han (2023) APOL1-G2 accelerates nephrocyte cell death by inhibiting the autophagy pathway. Dis Model Mech. 16(12)
  29. Lihui Wang, Yue Xu, Tetsunari Fukushige, Layla Saidi, Xiaorong Wang, Clinton Yu, Jin-Gu Lee, Michael Krause, Lan Huang, Yihong Ye (2024) Mono-UFMylation promotes misfolding-associated secretion of α-synuclein. Science Advances. 10(11)