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Po-Wu GeanProfessor
E - Mail
powu@mail.ncku.edu.tw
Office Phone
(06) 235-3535 ext 5507
Laboratory Phone
Highest Education
Brief Biography
- Associate Professor, National Cheng Kung University (Aug 1, 1988 – Jul 31, 1991)
- Professor, National Cheng Kung University (Aug 1, 1991 – present)
- Visiting Professor, University of Texas, USA (Feb 1, 1995 – Jan 31, 1996)
- Director, Institute of Pharmacology, National Cheng Kung University (Aug 1, 1996 – Jul 31, 2002)
- Director, Pharmacy Department, National Cheng Kung University Hospital (Aug 1, 1999 – Jul 31, 2003)
- Board Director, ScinoPharm Taiwan Ltd., appointed by Executive Yuan Development Fund (Aug 2002 – present)
- Professor and Dean, College of Pharmacy, China Medical University (secondment) (Oct 1, 2003 – Jul 31, 2005)
- Convener, Pharmacy and Chinese Medicine Division, National Science Council (Jan 2005 – Dec 2007)
- Vice Dean, College of Medicine, National Cheng Kung University (Aug 1, 2007 – Jul 31, 2009)
- Dean, College of Bioscience and Biotechnology, National Cheng Kung University
Research Areas
Treatment strategies for post-traumatic stress disorder (PTSD) and prevention of relapse
In the past decade, we have integrated biochemical, physiological, pharmacological, and behavioral experimental approaches to investigate the mechanisms of memory formation. Recently, we studied a phenomenon in which, for example, when parents repeatedly tell children not to do certain things, the children may initially refrain from doing them superficially. However, over time, even if they strongly desire to do so, they may no longer dare to act. This resembles a form of “brainwashing,” suggesting that repeated reinforcement is effective.
In animal studies, for instance, when a light stimulus is initially paired with a shock, mice develop fear. When the light is later presented without shock, a new memory is formed. These two types of memory represent competing cognitive processes, and the original memory may still re-emerge due to this competition. Similarly, a child who wants to play outside but is repeatedly told not to do so experiences competing motivations; initially, occasional instructions are insufficient to suppress the behavior. However, with long-term repeated inhibition, the desire gradually diminishes and the behavior is eventually suppressed.
This illustrates the concept of conditioning and how cognitive states can be modified. Our early experiments using repeated light–no-shock conditioning often failed due to relapse. We therefore extended the conditioning from 30 trials to 120 repeated trials of light–no-shock pairing. We found that although there was still an increase in response after 30 trials, the effect gradually decreased after 75 trials, and after 90 trials, the original excitatory trace disappeared.
This provides an important lesson that conditioning can be modified, and how to achieve complete and stable modification is a key future research direction. The main goal of this study is to provide therapeutic strategies and relapse prevention approaches for PTSD patients through physiological and pharmacological analyses.
Investigation of Alzheimer’s disease and development of anti-dementia drugs
Dementia is a severe neurodegenerative disorder that affects cognition and memory. Alzheimer’s disease is the most common form of dementia. We will use two transgenic mouse models of Alzheimer’s disease to investigate cellular and molecular mechanisms that exacerbate or prevent disease progression.
Specific Aim 1: To examine whether neurotrophic factors can improve disease progression and whether their inhibitors accelerate deterioration. Whole-cell patch-clamp recordings will be used to analyze cellular mechanisms underlying dementia progression caused by social isolation.
Specific Aim 2: To investigate the relationship between Cdk5 and dementia progression induced by social isolation. The underlying mechanisms may involve synaptic receptors such as AMPA receptors, NMDA receptors, and PSD-95. We will test whether Cdk5 inhibitors can prevent disease progression.
Specific Aim 3: To screen potential therapeutic drugs for dementia, including N-acetylcysteine (NAC), protein dephosphorylation modulators, and ugonin K. The ultimate goal is to identify effective pharmacological agents to prevent dementia through physiological and pharmacological studies.
Development of therapeutics for malignant glioma
Glioma is the most common type of brain tumor, and malignant gliomas have extremely high mortality rates. Current treatment options, including surgery, radiotherapy, and chemotherapy, remain largely ineffective. Therefore, developing new therapeutic strategies is urgent.
We recently found that minocycline can inhibit glioma growth via autophagic cell death. This effect is associated with the accumulation of acidic vesicular organelles, as detected by acridine orange and monodansylcadaverine staining, and the conversion of LC3-I to LC3-II, indicating autophagosome formation.
We also found that HL66 inhibits the proliferation of malignant glioma cells. Flow cytometry analysis showed that HL66 induces cell cycle arrest at the G2/M phase followed by cell death. Immunofluorescence staining revealed the formation of multinucleated giant cells.
In addition, Western blot analysis indicated that HL66 induces mitotic catastrophe accompanied by activation of cysteine proteases and increased cyclin B1 expression. In vivo studies further confirmed that HL66 suppresses the growth of human malignant glioma tumors. Future studies will focus on elucidating the detailed molecular mechanisms of HL66-induced mitotic catastrophe in malignant glioma cells.
In the past decade, we have integrated biochemical, physiological, pharmacological, and behavioral experimental approaches to investigate the mechanisms of memory formation. Recently, we studied a phenomenon in which, for example, when parents repeatedly tell children not to do certain things, the children may initially refrain from doing them superficially. However, over time, even if they strongly desire to do so, they may no longer dare to act. This resembles a form of “brainwashing,” suggesting that repeated reinforcement is effective.
In animal studies, for instance, when a light stimulus is initially paired with a shock, mice develop fear. When the light is later presented without shock, a new memory is formed. These two types of memory represent competing cognitive processes, and the original memory may still re-emerge due to this competition. Similarly, a child who wants to play outside but is repeatedly told not to do so experiences competing motivations; initially, occasional instructions are insufficient to suppress the behavior. However, with long-term repeated inhibition, the desire gradually diminishes and the behavior is eventually suppressed.
This illustrates the concept of conditioning and how cognitive states can be modified. Our early experiments using repeated light–no-shock conditioning often failed due to relapse. We therefore extended the conditioning from 30 trials to 120 repeated trials of light–no-shock pairing. We found that although there was still an increase in response after 30 trials, the effect gradually decreased after 75 trials, and after 90 trials, the original excitatory trace disappeared.
This provides an important lesson that conditioning can be modified, and how to achieve complete and stable modification is a key future research direction. The main goal of this study is to provide therapeutic strategies and relapse prevention approaches for PTSD patients through physiological and pharmacological analyses.
Investigation of Alzheimer’s disease and development of anti-dementia drugs
Dementia is a severe neurodegenerative disorder that affects cognition and memory. Alzheimer’s disease is the most common form of dementia. We will use two transgenic mouse models of Alzheimer’s disease to investigate cellular and molecular mechanisms that exacerbate or prevent disease progression.
Specific Aim 1: To examine whether neurotrophic factors can improve disease progression and whether their inhibitors accelerate deterioration. Whole-cell patch-clamp recordings will be used to analyze cellular mechanisms underlying dementia progression caused by social isolation.
Specific Aim 2: To investigate the relationship between Cdk5 and dementia progression induced by social isolation. The underlying mechanisms may involve synaptic receptors such as AMPA receptors, NMDA receptors, and PSD-95. We will test whether Cdk5 inhibitors can prevent disease progression.
Specific Aim 3: To screen potential therapeutic drugs for dementia, including N-acetylcysteine (NAC), protein dephosphorylation modulators, and ugonin K. The ultimate goal is to identify effective pharmacological agents to prevent dementia through physiological and pharmacological studies.
Development of therapeutics for malignant glioma
Glioma is the most common type of brain tumor, and malignant gliomas have extremely high mortality rates. Current treatment options, including surgery, radiotherapy, and chemotherapy, remain largely ineffective. Therefore, developing new therapeutic strategies is urgent.
We recently found that minocycline can inhibit glioma growth via autophagic cell death. This effect is associated with the accumulation of acidic vesicular organelles, as detected by acridine orange and monodansylcadaverine staining, and the conversion of LC3-I to LC3-II, indicating autophagosome formation.
We also found that HL66 inhibits the proliferation of malignant glioma cells. Flow cytometry analysis showed that HL66 induces cell cycle arrest at the G2/M phase followed by cell death. Immunofluorescence staining revealed the formation of multinucleated giant cells.
In addition, Western blot analysis indicated that HL66 induces mitotic catastrophe accompanied by activation of cysteine proteases and increased cyclin B1 expression. In vivo studies further confirmed that HL66 suppresses the growth of human malignant glioma tumors. Future studies will focus on elucidating the detailed molecular mechanisms of HL66-induced mitotic catastrophe in malignant glioma cells.
Awards
- 1992 – Excellent Paper Award, Chinese Pharmacological Society
- 1995–1996 – Outstanding Research Award, National Science Council (NSC)
- 1997–1998 – Outstanding Research Award, National Science Council (NSC)
- 1999–2000 – Outstanding Research Award, National Science Council (NSC)
- 1998 – Best Basic Research Paper Award, College of Medicine, National Cheng Kung University
- 1998 – Outstanding Research Award, Wang Shih-Chun (Academician) Award, Society of Basic Neuroscience, Taiwan
- 2001 – Best Basic Research Paper Award, College of Medicine, National Cheng Kung University
- 2002–2004 – Distinguished Professor, National Cheng Kung University
- 2005–2007 – Distinguished Professor, National Cheng Kung University
- 2002–2004 – Distinguished Research Fellow, National Science Council (NSC)
- 2005–2007 – Distinguished Research Fellow, National Science Council (NSC)
- 2006 – Academic Award, Ministry of Education, Taiwan
- 2007 – 17th Wang Ming-Ning Award for Outstanding Contribution to Public Health
- 2007 – Chair Professor, National Cheng Kung University
- 2008 – Distinguished Research Fellow, National Science Council (NSC)
- 2009 – Selected among Top 50 Scientific Achievements, National Science Council (NSC)
- 2010 – Outstanding Alumni, Department of Pharmacy, National Taiwan University
- 2011 – National Chair Professor, Ministry of Education, Taiwan
- 2013 – 9th Yung Shin–Lee Tian-Te Pharmaceutical Science and Technology Award