The objective of the Weng lab is to investigate and manipulate the innate immune systems using chemical biology, and to develop lead compounds and protein drugs against inflammatory disorders. The immune systems defend us against external infection and internal damage. Dysregulated equilibrium between activation and tolerance of immune responses is the key causal element to numerous disorders, including cancers, autoimmune diseases, and ageing. Innate immune disorders can be treated with small molecules (e.g. NSAIDs) and protein drugs (e.g. TNF blocker). Yet, many inflammatory diseases are still hard to treat. We see major opportunity to modulate immune equilibrium and restore homeostasis by targeting the innate immune inhibitory pathways, starting with the anti-inflammatory hepatokine GDF15.

Colchicine is one of the popular medicines with around three million prescriptions per year in the US. It treats acute inflammation and provides life-long protection in the autoinflammatory disease FMF. Interest of colchicine has grown steadily in the last decade thanks to repurposing trials in cardiology, dermatology and other diseases where myeloid cells drive inflammation. How does colchicine treat inflammation? Colchicine concentrates in the liver. We proved that it acts selectively in the liver hepatocytes.

We have discovered a novel axis of liver-myeloid cell communication and identified the colchicine-triggered, anti-inflammatory hepatokine GDF15. We characterized the molecular pathways by which GDF15 is induced in liver, and by which it inhibits activation of myeloid cells.

Positions Held

• 2021 – present   Assistant Research Fellow, Institute of Biological Chemistry, Academia Sinica
• 2014 – 2021   Postdoctoral Fellow, Department of Systems Biology, Harvard Medical School
• 2014     Distinguished Academia Sinica Postdoctoral Scholar

Degrees

• 2006 – 2013   Ph.D., Biochemistry and Molecular Biology, Yang-Ming University
• 2003 – 2005   M.S., Institute of Biochemical Sciences, Taiwan University

1. Pan YJ, Tong SK, Hsu CW, (Weng JH), Chung BC  (2022-04)  Frontiers in cell and developmental biology  10, 866267  "Zebrafish Establish Female Germ Cell Identity by Advancing Cell Proliferation and Meiosis."
   
2. Shi J, (Weng JH), Mitchison TJ  (2021-11)  eLife  10, e73673  "Immunomodulatory drug discovery from herbal medicines: Insights from organ-specific activity and xenobiotic defenses."
   
3. (Weng JH)*, Koch PD, Luan HH, Tu HC, Shimada K, Ngan I, Ventura R, Jiang R, Mitchison TJ*  (2021-04)  Nature metabolism  3(4), 513-522  "Colchicine acts selectively in the liver to induce hepatokines that inhibit myeloid cell activation."
   
4. Tang HW, (Weng JH), Lee WX, Hu Y, Gu L, Cho S, Lee G, Binari R, Li C, Cheng ME, Kim AR, Xu J, Shen Z, Xu C, Asara JM, Blenis J, Perrimon N  (2021-03)  Proceedings of the National Academy of Sciences of the United States of America  118(10), e2021945118  "mTORC1-chaperonin CCT signaling regulates m(6)A RNA methylation to suppress autophagy."
   
5. Chen YH, Hsu HY, Yeh MT, Chen CC, Huang CY, Chung YH, Chang ZF, Kuo WC, Chan NL, (Weng JH), Chung BC, Chen YJ, Jian CB, Shen CC, Tai HC, Sheu SY, Fang JM  (2016-11)  Journal of medicinal chemistry  59(21), 9906-9918  "Chemical Inhibition of Human Thymidylate Kinase and Structural Insights into the Phosphate Binding Loop and Ligand-Induced Degradation."
   
6. (Weng JH), Chung BC  (2016-07)  Steroids  111, 54-59  "Nongenomic actions of neurosteroid pregnenolone and its metabolites."
   
7. (Weng JH), Liang MR, Chen CH, Tong SK, Huang TC, Lee SP, Chen YR, Chen CT, Chung BC  (2013-10)  Nature chemical biology  9(10), 636-642  "Pregnenolone activates CLIP-170 to promote microtubule growth and cell migration."
   
8. Chen WY, (Weng JH), Huang CC, Chung BC  (2007-10)  Molecular and cellular biology  27(20), 7284-7290  "Histone deacetylase inhibitors reduce steroidogenesis through SCF-mediated ubiquitination and degradation of steroidogenic factor 1 (NR5A1)."