Dr. Yen, Jeffrey J.Y. 's publons link picture

Dr. Yen, Jeffrey J.Y.

Adjunct Research Fellow
  • 02-27899017 (Lab) (Room No: N237)
  • 02-27829142 (Fax)

  • Cytokine Receptor Biology
  • Mouse Disease Model/Phenotyping
  • GVHD/SJS Therapy

Education and Positions:
  • Ph.D. Baylor College of Medicine

1) Epithelial Barrier Integrity and Skin Microbiota in Kojak Mice


Atopic dermatitis (AD) is prevalent in modern society, especially in infant and child, and causes a long-term effect in life, development and learning. AD is a complex chronic inflammatory skin disorder that results from intimate interactions among genetic predisposition, host environment, skin barrier defects, and immunological factors. However, a clear genetic roadmap leading to atopic dermatitis remains to be fully explored. From a genome-wide mutagenesis screen, deficiency of ZDHHC13, a palmitoylacyl transferase, has previously been shown to be associated with skin and multitissue inflammatory phenotypes. Genetic and immunological studies revealed that this dermatitis is a keratinocyte-cell autonomous disorder, and is not caused by adaptive immunity, nor by TNF-a, nor IL-1b. To clarify the importance of palmitoylation enzyme activity and its substrates, we generated knock-in mice to destroy the enzymatic site of ZDHHC13 protein and the results suggested that knock-in mice phenocopy the knock-out mice. Further quantitative tandem mass spectra revealed that multiple pathways are regulated by ZDHHC13, including filaggrin degradation and hydrolysis pathways. On the other hand, to study how skin microbiota cross-talk with the defective barrier, we established a cleaner SPF room that can prevent skin inflammation of Kojak mice, like in Germ-free room, and currently is studying the bacterial dysbiosis. Our future goal will include identification of dysbiosis and microbiota functional composition responsible for skin inflammation. Seeking for the underlying mechanism of dysbiosis-associated skin inflammation and development of innovative therapeutics to treat human atopic dermatitis are our final goals.


1. Song IW, Li WR, Chen LY, Shen LF, Liu KM, Yen JJ, Chen YJ, Chen YJ, Kraus VB, Wu JY, Lee MT, Chen YT. Palmitoyl acyltransferase, Zdhhc13, facilitates bone mass acquisition by regulating postnatal epiphyseal development and endochondral ossification: a mouse model. PLoS One. 2014 Mar 17;9(3):e92194. doi:10.1371/journal. pone. 0092194.

2. Liu KM, Chen YJ, Shen LF, Haddad AN, Song IW, Chen LY, Chen YJ, Wu JY, Yen JJ, Chen YT. Cyclic Alopecia and Abnormal Epidermal Cornification in Zdhhc13- Deficient Mice Reveal the Importance of Palmitoylation in Hair and Skin Differentiation. J Invest Dermatol. 2015 Nov;135(11):2603-10. doi: 10.1038/jid. 2015.240. 

3. Shen LF, Chen YJ, Liu KM, Haddad ANS, Song IW, Roan HY, Chen LY, Yen JJY, Chen YJ, Wu JY, Chen YT. Role of S-Palmitoylation by ZDHHC13 in Mitochondrial function and Metabolism in Liver. Sci Rep. 2017 May 19;7(1):2182. doi: 10.1038/s41598-017-02159-4.

4. Chen LY, Yang-Yen HF, Tsai CC, Thio CL, Chuang HL, Yang LT, Shen LF, Song IW, Liu KM, Huang YT, Liu FT, Chang YJ, Chen YT, Yen JJ. Protein Palmitoylation by ZDHHC13 Protects Skin against Microbial-Driven Dermatitis. J Invest Dermatol. 2017 Apr;137(4):894-904. doi: 10.1016/j.jid.2016.12.011. Epub 2016 Dec 23. 



2) CBAP acts as a novel oncoprotein in human T cell acute lymphoblastic leukemia


A relative high frequency of relapse remains a clinical enigma for cure of T-cell acute lymphoblastic leukemia (T-ALL) patients, which has recently been implicated with heterogeneous dysregulated signaling profiles. Recently, we demonstrated that GM-CSF/IL-3/IL-5 receptor common b-chain-associated protein (CBAP) is highly expressed in many human T-ALL cell lines and is required to bolster leukemia cell in vitro proliferation and in vivo leukemogenesis in xenograft mouse model. Down-regulation of CBAP markedly restrains expansion of leukemia cells and alleviates disease aggravation of leukemic mice. Transcriptomic profiling and biochemical analyses reveal that CBAP acts as a key regulator of Raf-MEK-ERK and Akt-mTORC1 signaling pathways to control leukemia cell growth. Here we further found that CBAP physically associates with Akt and TSC2 through independent domains, and serves as a scaffold protein to facilitate Akt-dependent TSC2 phosphorylation, leading to elevated Rheb-GTP loading and subsequent activation of mTORC1 signaling. Disruption of this tripartite complex through ectopic expression of N-terminal 26 residues of CBAP shows a relieve of Akt-mediated TSC2 phosphorylation, resulting in suppression of leukemia cell growth. Taken together, our findings uncover CBAP a novel oncogenic contribution to T-ALL leukemogenesis and a functional role in regulation of Akt-TSC2-mTORC1 signaling for leukemia cell proliferation, and may provide a therapeutic strategy to suppress many types of Akt-TSC2-mediated cancers.


1. Chiang YJ, Ho KC, Liao WT, Liu CS, Chen YG, Ho CL, Huang SF, Shih LY, Yang-Yen HF, Yen JJ. CBAP regulates the Rheb-GAP activity of TSC2 complexes by promoting Akt-dependent TSC2 phosphorylation and TSC1 displacement. 2017. In revision.

Our Team
Team photo

Journal 43 Book 3

  1. Chen LY, Lin KR, Chen YJ, Chiang YJ, Ho KC, Shen LF, Song IW, Liu KM, Yang-Yen HF, Chen YJ, Chen YT, Liu FT, (Yen JJY)*. Palmitoyl Acyltransferase Activity of ZDHHC13 Regulates Skin Barrier Development Partly by Controlling PADi3 and TGM1 Protein Stability JOURNAL OF INVESTIGATIVE DERMATOLOGY 140(5),959- (2020-05) [JCR] [WOS]
  2. Yun-Jung Chiang, Wei-Ting Liao, Kun-Chin Ho, Shih-Hao Wang, Yu-Guang Chen, Ching-Liang Ho, Shiu-Feng Huang, Lee-Yung Shih, Hsin-Fang Yang-Yen & Jeffrey Jong-Young Yen CBAP modulates Akt-dependent TSC2 phosphorylation to promote Rheb-mTORC1 signaling and growth of T-cell acute lymphoblastic leukemia. ONCOGENE 38(9), 1432-1447 (2019) [JCR] [WOS]
  3. Liu CS, Yang-Yen HF, Suen CS, Hwang MJ, Yen JJ Cbl-mediated K63-linked ubiquitination of JAK2 enhances JAK2 phosphorylation and signal transduction. Scientific reports 7(1), 4613 (2017) [JCR] [WOS]
  4. Yao L, Mustafa N, Tan EC, Poulsen A, Singh P, Duong-Thi MD, Lee JXT, Ramanujulu PM, Chng WJ, Yen JJY, Ohlson S, Dymock BW Design and Synthesis of Ligand Efficient Dual Inhibitors of Janus Kinase (JAK) and Histone Deacetylase (HDAC) Based on Ruxolitinib and Vorinostat. Journal of medicinal chemistry 60(20), 8336-8357 (2017) [JCR] [WOS]
  5. Chen LY, Yang-Yen HF, Tsai CC, Thio CL, Chuang HL, Yang LT, Shen LF, Song IW, Liu KM, Huang YT, Liu FT, Chang YJ, Chen YT, Yen JJY Protein Palmitoylation by ZDHHC13 Protects Skin against Microbial-Driven Dermatitis. The Journal of investigative dermatology 137(4), 894-904 (2017) [JCR] [WOS]
  6. Shen LF, Chen YJ, Liu KM, Haddad ANS, Song IW, Roan HY, Chen LY, Yen JJY, Chen YJ, Wu JY, Chen YT Role of S-Palmitoylation by ZDHHC13 in Mitochondrial function and Metabolism in Liver. Scientific reports 7(1), 2182 (2017) [JCR] [WOS]
  7. Wei Shu-Chen, Yang-Yen Hsin-Fang, Tsao Po-Nien, Weng Meng-Tzu, Tung Chien-Chih, Yu Linda C. H., Lai Liang-Chuan, Hsiao Jen-Hao, Chuang Eric Y., Shun Chia-Tung, Ni Yen-Hsuan, Xavier Ramnik J., Podolsky Daniel K., Yen Jeffery J. Y., Wong Jau-Min SHANK3 Regulates Intestinal Barrier Function Through Modulating ZO-1 Expression Through the PKCε-dependent Pathway Inflammatory Bowel Diseases 23(10), 1730-1740 (2017) [JCR] [WOS]
  8. Yang EG, Mustafa N, Tan EC, Poulsen A, Ramanujulu PM, Chng WJ, Yen JJ, Dymock BW Design and Synthesis of Janus Kinase 2 (JAK2) and Histone Deacetlyase (HDAC) Bispecific Inhibitors Based on Pacritinib and Evidence of Dual Pathway Inhibition in Hematological Cell Lines. Journal of medicinal chemistry 59(18), 8233-62 (2016) [JCR] [WOS]
  9. Lu CH, Wu CJ, Chan CC, Nguyen DT, Lin KR, Lin SJ, Chen LC, Yen JJ, Kuo ML DNA Methyltransferase Inhibitor Promotes Human CD4+CD25hFOXP3+ Regulatory T Lymphocyte Induction under Suboptimal TCR Stimulation. Frontiers in immunology 7, 488 (2016) [JCR] [WOS]
  10. Lin KR, Yang-Yen HF, Lien HW, Liao WH, Huang CJ, Lin LI, Li CL, Yen JJ Murine tribbles homolog 2 deficiency affects erythroid progenitor development and confers macrocytic anemia on mice. Scientific reports 6, 31444 (2016) [JCR] [WOS]