林琬琬, Wan-Wan Lin

1] Regulating mechanisms for cell death coming from death receptors, ER stress, DNA damage, and inflammasome

2] Innate immunity of TLR and NLR

3] Inflammation and Cancer

4] Novel functions of decoy receptor 3

5] TNF receptor family members

6] Signal transduction and gene regulation

We have been working on inflammation-related signaling pathways, gene regulation, and cancer development for many years. Besides exploring the molecular action mechanisms of several anti-inflammatory drugs, we demonstrated ligand-dependent and -independent action mechanisms of NOD2 in regulating TLR4 signaling and responses in macrophages. Regarding statins, which are HMG-CoA reductase inhibitors and widely used as lipid-lowering agents, we identified several novel anti-inflammatory and cell protective actions of statins, and provided valuable information to support their potential therapeutic uses in inflammatory diseases. Decoy receptor 3 (DcR3), a soluble receptor belonging to TNFR, is a biomarker of cancer progression. In our lab, we found DcR3 can exert inflammatory actions to modulate cancer progression via decoy and non-decoy action manners. Cell death is an important issue to control cellular homeostasis and biological functions. Among several types of programmed cell death, we have demonstrated the signaling cascades involved in necroptosis, parthanatos and autophagic death. In this respect, novel functions of caspase-8 in keratinocyte differentiation and autophagy induction were reported.

Publications:

1] Spleen tyrosine kinase mediates EGFR signaling to regulate keratinocyte terminal differentiation. J. Invest. Dermatol. 136:192-201. 2016. [Abstract]

2] Inhibition of AMPK through Lyn-Syk-Akt enhances FcεRI signal pathways for allergic response. J Mol. Med (Berl) 94:183-94. 2016.

[Abstract]

3] Syk is involved in NLRP3 inflammasome-mediated caspase-1 activation through adaptor ASC phosphorylation and enhanced oligomerization. J. Leuko. Biol. 2015 Jan 20. pii: jlb.3HI0814-371RR (cover page) (Spotlight on Leading Edge Research) [Abstract]

4] Syk mediates IL-17-induced CCL20 expression by targeting Act1-dependent K63-linked ubiquitination of TRAF6. J. Invest. Dermatol 135:490-498. 2015. [Abstract]

5] Beclin-1-independent autophagy positively regulates internal ribosomal entry site-dependent translation of hypoxia-inducible factor 1a under nutrient deprivation. Oncotarget 5(17):7525-7539. 2014. [Abstract]

6] The tyrosine kinase Syk differentially regulates Toll-like receptor signaling downstream of the adaptor molecules TRAF6 and TRAF3. Science Signaling 6:ra71. 2013. [Abstract]

7] Nutrient deprivation induces the Warburg effect through ROS/AMPK-dependent activation of pyruvate dehydrogenase kinase. BBA—Mol. Cell Res. 1833:1147-1156. 2013. [Abstract]

1] Death mechanisms of necroptosis, autophagic cell death, and parthanatos.

2] Functions and signaling cascades of pathogen recognition receptors TLRs and NLRs.

3] Cellular functions and action mechanisms of DcR3 in disease pathogenesis.

4] Inflammasome activation

5] Energy regulation in stress conditions

1] Bio-Rad electrophoresis-related equipment and gene pulser

2] Acugen AG-9600 and Perkin Elmer 2400 PCR machines