Research, Medical Students, and Physicians: Personal Experience Sung-Tsang Hsieh, MD, PhD Department of Anatomy and Cell Biology National Taiwan University College of Medicine Department of Neurology National Taiwan University Hospital Taipei Taiwan

Medical student Era Background: Graduation from high school in 1976 Medical student of National Taiwan University (NTU): 1976~1983 only very vague impression about “medical research” the only concept about “experiments”: laboratory courses in biology, chemistry, and physics, et al: hand-on experience on “known phenomena”

Resident Era Neurology resident in National Taiwan University Hospital (NTUH): 1985~1988 Medical care of patients: including diagnosis, medications, and rehabilitation Neurodegegenerative diseases: progressive loss of neurons at various levels of the neural axis Alzheimer disease Parkinson disease Spinocerebellar degeneration Peripheral neuropathy

Research course during Residency “Flavor” of laboratory works during Neurology residency Pathology training Radiology Training Basic science training: the gate to PhD studies Department of Pharmacology, Prof. MC Tsai (蔡明正教授) neuromuscular junction physiology with phrenic nerve/diaphragm preparation

Master Student Era Harvard School of Public Health: 1988~1989 Epidemiology Biostatistics Critical thinking and logical reasoning of research data and interpretation

PhD Student Era Johns Hopkins University Department of Neuroscience: 1989~2003 Imagination and learning techniques Thesis: neurofilaments and myelination

Postdoc Era Johns Hopkins Hospital Department of Neurology: 1993~1995 To explore the unknown world: “mission impossible” with learned techniques and logic and comprehensive designs Experimental degeneration of nerve terminals in the skin

Faculty Era National Taiwan University Medical Center: 1995~ Joined appointment Department of Anatomy and Cell Biology Department of Neurology

Researches in NTU (1) Skin biopsy for cutaneous nerve degeneration Animal models Human studies on neuropathy: peripheral nerve degeneration in diabetes, chemotherapy-induced, inflammation/autoimmune disease etc

Skin biopsy for neuropathy Dying-back neuropathology in DM and toxic length-dependent neuropathy Skin biopsy for “free nerve ending” Hsieh ST, Encyclopedia of Pain, 2007

3 mm punch skin biopsy 2 weeks later one year later 3 mm in diameter; no suture (only compression for several minutes is required) excellent wound healing within 2 weeks minimally invasive compared to standard sural nerve biopsy

Normal skin innervation Epidermis Dermis Intrapeidermal nerve fiber (IENF): varicose appearance in the epidermis; stained with anti-protein gene product 9.5 (PGP 9.5), a pan-axonal marker Quantifiable: IENF density

Researches in NTU (2) Physiology of pain: contact heat evoked potential (CHEP) Physiological signatures of pain

Researches in NTU (3) Neuroimaging of pain: functional magnetic resonance imaging (fMRI)

Interactions with Medical students Medical students: laboratory studies during summer or weekends Innervation of gastric mucosa in diabetes performed by a smart medical student of NTU: a paper published in Experimental Neurology before graduation from Medical School, currently in PhD program of Duke University

Implications of gastric mucosa innervation studies Reduced gastric mucosa innervation in diabetes: a new mechanisms for gastroparesis in diabetes pathology documentation of nerve degeneration in gastrointestinal neuropathy in diabetes

MD-PhD A bridge between laboratory works and clinical applications or experimental approaches to investigate clinical problems Endangered species (NIH): time-consuming and exhausted efforts Importance: Translation research, basic-clinical correlation, bench-to-bedside

Perspectives Research minds in clinical practice: New mechanisms through experiments New diagnostic tests New therapeutic strategies Collaborations among diverse disciplines

Thanks for your attention and Wish you a pleasant memory of trip in Taiwan