National Research Institute of Chinese Medicine, Ministry of Health and Welfare

Neuropsychopharmacology

Huang, Nai-Kuei
https://www.nricm.edu.tw/p/405-1000-376,c99.php?Lang=en

Research Field

Biology

Introduction

After graduating with a Ph.D., I realized that my technical limitations might prevent me from delving deeply into certain research areas in the future. Therefore, I joined the laboratory of Dr. Yi-Chuang Chen at the Institute of Biomedical Sciences, Academia Sinica, to engage in molecular biology and cellular physiology research. My research focused on using adenovirus as a vector for gene transfer in the central nervous system and investigating the signaling pathways through G-protein-coupled receptors (GPCRs) that counteract apoptosis. In apoptosis studies, I used serum deprivation models with PC12 cells, assessing cell death levels and apoptosis patterns using MTT assays, DNA fragmentation, and staining methods. The findings showed that stimulating the adenosine A2a receptor could activate PKA and PKC to reduce serum-deprivation-induced apoptosis in PC12 cells, offering a distinct mechanism from the known neurotrophic factor pathways that counteract cell death. This experiment not only highlights the diversity of biological responses to external stress but also provides a new perspective for the treatment of neurological damage or degeneration.

After leaving Academia Sinica, I worked in a biotechnology company in Taichung, involved in new drug development, focusing on screening new drugs using traditional Chinese herbs. This experience deeply made me realize the significant research potential of traditional Chinese medicine (TCM) in modern academia and its vast business opportunities for the industry. It also helped me understand the synergy between basic research and its clinical applications in medical development. After joining the Institute of Chinese Medicine, I applied this vision, not only developing new drugs but also conducting research on the use of single herbs, compound formulas, or innovative formulations for the treatment and mechanism exploration of neurodegenerative diseases such as Parkinson's disease, Huntington's disease, and type II cerebellar atrophy, with several research publications and patent outcomes.

In new drug development, I was the first to discover that Gastrodia elata could activate the adenosine A2a receptor and exhibit neuroprotective effects. In collaboration with Dr. Yun-Lian Lin and Dr. Yi-Chuang Chen, we extracted effective purified compounds and modified them for the treatment of Huntington's disease and Alzheimer's disease. The new drug is currently preparing for an IND application, and we are establishing a startup company to continue exploring the potential of Gastrodia elata-derived compounds. Additionally, I recently published findings on a small molecule (SRT1720) that can activate PGC-1α and NRF-2 to counteract the toxicity of paraquat, providing promising therapeutic targets for Parkinson's disease research. In compound formula research, I also discovered that Huanglian Jiedu Decoction and Liu Junzi Decoction could be used to treat Parkinson's disease and alleviate chemotherapy side effects, respectively. In innovative compound research, through collaboration with the Department of Traditional Chinese Medicine at Tri-Service General Hospital, I found that certain formulas could alleviate behavioral disorders in animal models of type II cerebellar atrophy, with clinical trials currently in preparation.

The goal of my laboratory is to screen the effective component(s) from Chinese herbal medicine and to study their mechanisms in treating neurodegenerations. Chinese herbal medicines could not only regard as our cultural properties but also play important roles in traditional or alternative medicines. The explorations of new drugs from Chinese herbal medicines are potentially important to the clinical medicines, basic research, and biotechnology industries. On the other hand, the incidence of neurodegenerations, such as Parkinson’s disease, Huntington’s disease, and abusive drug-induced neurotoxicity, are increasing recently, however the proper therapeutic ways are lack. Therefore, I have set different models to screen effective component(s) from Chinese herbal medicines to treat neurodegeneration. These models include Parkinson’s disease, Huntington’s disease, ischemia, and abusive drug-induced neurotoxicity.


Research Topics

Our laboratory mainly investigates the mechanisms of neurodegenerative diseases and studies how purified compounds, single herbs, or formulas of traditional Chinese medicine can be applied to the treatment of neurodegenerative diseases. These neurodegenerative diseases mainly include Huntington's disease (HD) and Parkinson's disease (PD). In the aspect of HD, our laboratory uses in vitro models and transgenic mice to conduct drug screening and mechanism research. The research found that Gastrodia elata has a good neuroprotective effect. Subsequently, in cooperation with National Taiwan University and Academia Sinica, we developed effective purified compounds and derivatives of Gastrodia elata, obtaining six patents (two in the US, one in China, and three in Taiwan), two world patents (pending), published five journal papers (three as corresponding author, two as first author), and obtained technology transfer. Additionally, in the mechanism exploration, our laboratory first proved that Gastrodia elata can regulate the ubiquitin-proteasome system, mitochondrial function, mitochondrial biogenesis, and mitochondrial morphology through the activation of adenosine A2A receptors, all of which can reduce the aggregation of mutant huntingtin. Recently, it was also discovered that Gastrodia elata can activate the biogenesis and activity of lysosomes, thereby increasing the degradation of mutant huntingtin. This discovery can be extended to the research of other neurodegenerative diseases, such as spinocerebellar ataxia.


Honor
  1. Exploring the Mechanisms and Therapeutic Potential of Traditional Chinese Medicine (TCM) Fructus Rhei in Fighting Parkinson's Disease: A Novel Strategy Focusing on Controlling Mitochondrial Morphological Changes and the Potential of Plant-Based New Drugs (MOST 106 2320 B 077 003 MY3)
  2. Exploring the Mechanism and Therapeutic Potential of Huanglian Jiedu Decoction Against Parkinson's Disease: A Novel Strategy for New Formula Development Focusing on the Autophagosome to Lysosome Pathway. (MOST 10 9 2320 B 077 005 MY3)
  3. Exploring the Protective Mechanism of Tianma Against Paraquat-Induced Parkinson's Disease: A Novel Study and Strategy Focusing on the Proteasome and Autophagy. (NSTC 113-2320-B-077-001 -)

Educational Background

Research fellow, Traditional Chinese Medicine Basic Medical Research Group, National Research Institute of Chinese Medicine, Ministry of Health and Welfare
February 2013 till now
Assistant Researcher, Traditional Chinese Medicine Basic Medical Research Group, National Research Institute of Chinese Medicine, Ministry of Health and Welfare
August 2001
Postdoctoral Researcher, Institute of Biomedical Sciences, Academia Sinica
July 1997 – July 2000
Doctorate in Life Sciences, National Defense Medical Center
August 1993 – July 1997
Master’s Degree in Physiology, National Defense Medical Center
August 1991 – July 1993
Bachelor’s Degree in Medical Engineering, Chung Yuan Christian University
September 1985 – June 1989
 


2 Vacancies

Job Description

The selected candidate will actively engage in cutting-edge research, explore new methodologies, and contribute to advancements in treating neurodegenerative diseases through innovative experimentation and collaboration.

Preferred Intern Education Level

Applicants must currently be enrolled as undergraduate or graduate students majoring in life sciences, pharmacological sciences, or a closely related discipline.

Skill sets or Qualities

Biological sciences

Life sciences

Pharmacological sciences