Dr. Huang is an University Associate Professor in Ph.D. Program in Medical Neuroscience at Taipei Medical University. After she graduated from Taipei Medical University, she got the pharmacist license and involved in the research about the pharmacology and molecular mechanism of cervical cancer during her master and Ph. D. research in National Cheng-Kung University. In her postdoctoral fellow in Academia Sinica, she was interested in neurodegenerative diseases, and focused on studying the pathological protein TDP-43 in both frontotemporal lobar degeneration (FTLD) with ubiquitin inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS). Now she is an associate professor in Taipei Medical University, and she continues her interest in exploring more molecular mechanism of TDP-43 in neural-related diseases. 

Our previous studies focused on identifying the physiological function and neuropathies of the neurodegenerative disease-related pathological TDP-43. Also, we endeavor to explore potential therapeutic strategy specifically targeting on ameliorating TDP-43-related proteinopathies. Unrevealing these underlying mechanism is thus essential to provide more comprehensive understanding about TDP-43 neuropathies.

TDP-43: TDP-43 is identified as the major component of the ubiquitin positive inclusion in the frontotemporal lobar degeneration (FTLD-U) and amyotrophic lateral sclerosis (ALS) neurodegenerative diseases, suggesting the mismetabolism of TDP-43 protein is the major cause for the pathological TDP-43 aggregates formation. However, the comprehensive picture of the metabolism and mis-metabolism of TDP-43 protein itself in normal cells remains unclear. We provide a comprehensive model of the metabolism and mismetabolism of TDP-43 in relation to these findings is presented in J. Cell. Sci. 2014. In addition, we also discovered the impact of loss-of-function of TDP-43 on autophagy regulation which contributes to the development of TDP-43 proteinopathies. Our works was presented in J. Biol. Chem. 2011. We also explore the detailed therapeutic mechanism of traditional herb medicine berberine on TDP-43 proteinopathy which provides an candidate drug targeting with less side effect potentially developed as an alternative therapy for TDP-43-related neuropathology in FTLD and ALS (J Biomed Sci, 2016) (104-2320-B-038-054-MY3). Moreover, we have identified Znf179 as an E3 ubiquitin ligase for TDP-43 and demonstrated the ZNF-179-mediated regulatory mechanism in TDP-43 metabolism and TDP-43-related proteinopathies. A better understanding of the function of the novel E3 ligase, Znf179, and the correlation between Znf179 and TDP-43 will provide a new therapeutic avenue for the ALS and FTLD-U patients in the future (J Biomed Sci, 2018)(104-2320-B-038-054-MY3). In clinical trial, we have demonstrated the elevation of plasma TDP-43 in the exosome may develop as a potential biomarker for the diagnosis of ALS patients (J. Neurol. Sci. 2020). Moreover, in our phase II clinical trial, we found that the add-on therapy of tamoxifen mildly attenuates the disease progression in the first 6 months, implicating the benefit role of tamoxifen for the early disease onset ALS patients (Medicine, 2020). Not only in FTLD and ALS, we discovered that TDP-43 also plays a role in ischemia stroke and involved in rapamycin-mediated therapeutic effect in ischemia stoke disease model (Int J Mol Sci. 2022)(110-2320-B-038-067-MY3).  To explore the specific way to target TDP-43 for proteasome degradation, we dedicated to unravel the role of TNKS-mediated ADP-ribosylation of TDP-43 and TNKS-PI31 signaling cascade for the activity regulation and axonal transportation of 20S proteasome under normal condition and TDP-43-related neuropathies (Manuscript is in preparation) (110-2320-B-038-067-MY3). Overall speaking. we provide a better understanding of the TDP-43 proteinopathies and open a new therapeutic avenue for ALS and FTLD-U patients.

1. Jayarama Krishnan Bose, Chi-Chen Huang and *C.-K. James Shen, Regulation of autophagy by the neuropathological protein TDP-43. J. Biol. Chem. (2011) Dec. 286:44441-8
2. Chi-Chen Huang*, Jayarama Krishnan Bose, Pritha Majumder, Kuen-Haur Lee, Jen-Tse Joseph Huang, Jeffrey K. Huang, Che-Kun James Shen*, 2014, Metabolism and Mis-Metabolism of the Neuropathological Signature Protein TDP-43. J. Cell Sci., (2014) May127: 3024-3038. (* Co-corresponding author)
3. Yi-Chao Lee#, Wan-Chen Huang#, Jiann-Her Lin#, Tzu-Jen Kao, Hui-Ching Lin, Kuen-Haur Lee, Hsin-Chuan Lin, Che-Kun James Shen, Wen-Chang Chang, Chi-Chen Huang *. Znf179 E3 ligase-mediated TDP-43 polyubiquitination is involved in TDP-43- ubiquitinated inclusions (UBI) (+)- related neurodegenerative pathology. J. Biomed. Sci. (2018) Nov., 5: 76-92. (#These authors are co-first authors). (本人為通訊作者) (SCI; 2021，5-year IF: 10.802; Ranking in MEDICINE, RESEARCH & EXPERIMENTAL : 7.9 %)
4. Po-Chih Chen, Yi-Chen Hsieh, Chi-Chen Huang & Chaur-Jong Hu*. Tamoxifen for amyotrophic lateral sclerosis: A randomized double-blind clinical trial. Medicine. (2020) May. 99: e20423- e20429. (SCI; 2021 5-year IF: 2.227; Ranking in MEDICINE, GENERAL & INTERNAL : 70.9 %)
5. Po-Chih Chen, Dean Wu, Chaur-Jong Hu, Hsin-Yi Chen, Yi-Chen Hsieh* & Chi-Chen Huang*.  Exosomal TAR DNA-binding protein-43 and neurofilaments in plasma of amyotrophic lateral sclerosis patients: A longitudinal follow-up study. J. Neurol. Sci. (2020) July, 418: 117070-117076. (* Co-corresponding author) (本人為共同通訊作者) (SCI; 2021 5-year IF: 3.861; Ranking in CLINICAL NEUROLOGY : 33.5 %)
6. Yi-Syue Tsou# , Jing-Huei Lai#, Kai-Yun Chen, Cheng-Fu Chang, Chi-Chen Huang*. Therapeutic Effect of Rapamycin on TDP-43-Related Pathogenesis in Ischemic Stroke. Int. J. Mol. Sci. (2022) Dec., 24: 676-697. (# These authors contributed equally to this work.) (# These authors contributed equally to this work.) (本人為通訊作者) (SCI; 2021 5-year IF: 6.628; Ranking in BIOCHEMISTRY & MOLECULAR BIOLOGY : 23.3 %)