Dr Sung-Tsang Hsieh’s
Lab:
Neurobiology of
Degeneration and Pain
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Principle Investigator: Sung-Tsang Hsieh, MD, PhD
Attending Neurologist, Department of Neurology,
Professor,
Department of Anatomy and Cell Biology,
Department of Anatomy
and Cell Biology, RM#638, National Taiwan University College of Medicine, 1
Jen-Ai Road, Sec. 1, Taipei, 100, Taiwan
E-mail: shsieh@
ntu.edu.tw
PhD (Neuroscience), The
Master of Public Health (MPH, Environmental Health
Sciences),
MD, Department of Medicine,
Professional Experience
Professor, Department of
Anatomy and Cell Biology,
Attending physician (Neurologist), Department of
Neurology,
Fellow, Department of Neurology, The Johns Hopkins
University, School of Medicine, Baltimore, Maryland, USA
2018
Jonathan Pembroke Award,
International Peripheral Nerve Society,
2018
Outstanding Research Scholar,
Ministry of Science and Technology, Executive
2016
Fellow,
2015
Outstanding Research Scholar,
Ministry of Science and Technology, Executive
2012
Outstanding Research Award, National
Science Council, Executive
2010
Basic Research Award,
2009 Outstanding Research Award, National
Science Council, Executive
2008 Distinguished Scholars Research
Project, National Science Council, Executive
2008 Outstanding Teaching Award,
2005 Merck Sharp &
2003 Outstanding Teaching Award,
2003 Outstanding Research Award, National
Science Council, Executive
2002 Teaching Award, The Foundation of Alumni,
2001 Medical Research Award, Professor W. Chen
Foundation,
2000 Research Award,
1997 Teaching Award,
1995 Peter Lampert
Young Investigator Award, Society of Experimental Neuropathology,
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Skin innervation |
Functional MRI |
Contact heat evoked potential |
Themes of research
Neurobiology
of nerve degeneration and its consequences of neuropathic pain (peripheral and
central mechanisms)
Skin biopsy to diagnose human neuropathy affecting small-diameter
nociceptive nerves (small-fiber neuropathy, painful neuropathy)
Plasticity
in neural circuitry of neuropathic pain
Peripheral
mechanisms: peripheral sensitization after nerve injury
Central mechanisms of neuropathic pain: changes in somatosensory pathways on functional magnetic resonance
imaging (fMRI) and contact heat evoked potential (CHEP)
Diagnosis
and therapy of peripheral neuropathy
Hereditary neuropathies: Characot-Marie-tooth
disease (CMT), hereditary neuropathy with liability to pressure palsies (HNPP),
familial amyloid polyneuropathy
(FAP)
Inflammatory neuropathies: Guillain-Barre
syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), Miller Fishere
syndrome (MFS), neuropathies with anti-ganglioside
antibodies
Approaches
Our laboratory is devoted to
investigate the neurobiological aspects of nerve degeneration and its
consequences of neuroapthic pain, particularly
focusing on small myelinated and unmyelinated
nociceptive nerves (small-fibers) and their central pathways. These nerve
fibers terminate in the skin and are responsible for the transmission of
thermal and nociceptive stimuli. Previous studies were limited by their
small diameter (usually 1-2 micrometers), and usually required electron microscopic
examinations. We have developed new techniques to investigate the nerve
terminals in a global scale, and used these approaches to set up models of
nerve terminal degeneration. In addition to the loss of sensations, the
other major consequence of nerve injury is neuropathic pain. By applying
the above approaches including neuroimaging (fMRI),
physiology (CHEP), and molecular biology, we also established an integrated
system of neuropathic pain.
A
parallel focus in this laboratory is to use the previously described technique
to diagnose human neuropathies involving small-diameter nociceptive nerves
(small-fiber neuropathy). This is quite a difficult issue for
neurologists because there has been lack of objective methods to quantify the
degeneration of small-fibers. We are among the pioneers in this field to
diagnose small-fiber fiber neuropathies in patients with inflammatory
neuropathies and diabetes mellitus.
We have
extended our laboratory services to the diagnosis and therapy of human neuropathies:
(1) CMT, including peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ), and connexin
32 and (2) FAP for the genetic mutations of
transthyretin, the most common form of FAP.
Publications
1.
Chao CC, Hsueh HW, Kan
HW, Liao CH, Jiang HH, Chiang H, Lin WM, Yeh TY, Lin YH, Cheng YY et al. Skin
nerve pathology: biomarkers of premanifest and
manifest amyloid neuropathy. Ann Neurol
2019; 85:560-573.
2.
Kan HW, Hsieh JH, Chien HF, Lin YH, Yeh TY, Chao
CC, Hsieh ST. CD40-mediated HIF
3.
Kan HW, Chiang H, Lin WM, Yu I, Lin SW, Hsieh
ST. Sensory nerve degeneration in a mouse model mimicking early manifestations
of familial amyloid polyneuropathy
due to transthyretin Ala97Ser. Neuropathol Appl Neurobiol 2018; 44:673-686.
4.
5.
Wu SW, Wang YC, Hsieh PC,
6.
Chang MF, Hsieh JH, Chiang H, Kan HW, Huang CM, Chellis L, Lin BS, Miaw SC, Pan
CL, Chao CC et al. Effective gene expression in the rat dorsal root ganglia
with a non-viral vector delivered via spinal nerve injection. Sci Rep 2016; 6:35612.
7.
Chao CC, Huang CM, Chiang HH, Luo KR, Kan HW,
Yang NC-C, Chiang H, Lin WM, Lai SM, Lee MJ et al. Sudomotor
innervation in transthyretin amyloid neuropathy:
pathology and functional correlates. Ann Neurol 2015;
78:272-283.
8.
Chiang H, Ohno N,
Hsieh YL, Mahad DJ, Kikuchi S, Komuro
H, Hsieh ST, Trapp BD. Mitochondrial fission augments capsaicin-induced axonal
degeneration. Acta Neuropathol
2015; 129:81-96.
9.
Hsieh PC,
10.
11. Lin MT, Lee
LJH, Chao CC, Hsieh ST. Quality of life in polyneuropathy:
association with biomarkers of small fiber impairment. Health Qual Life Outcomes 2015; 13:169.
12. Hsieh JH, Lin
WM, Chiang H, Chang LY, Wu CT, Pu CM, Wu JT, Hsieh
ST. Patterns of target tissue reinnervation and trophic factor expression after nerve grafting. Plast Reconstr Surg 2013; 131:989-1000.
13. Tseng MT,
Chiang MC, Chao CC, Tseng WY, Hsieh ST. fMRI evidence of degeneration-induced
neuropathic pain in diabetes: enhanced limbic and striatal
activations. Hum Brain Mapp 2013; 34:2733-2746.
14. Tseng MT,
Chiang MC, Yazhuo K, Chao CC, Tseng WY, Hsieh ST.
Effect of aging on the cerebral processing of thermal pain in the human brain.
Pain 2013; 154:2120-2129.
15. Luo KR, Chao
CC, Hsieh PC, Hsieh ST. Effect of glycemic control on
sudomotor denervation in
type 2 diabetes. Diabetes Care 2012; 35:612-616.
16. Hsieh YL,
Chiang H, Lue JH, Hsieh ST. P2X3-mediated peripheral sensitization
of neuropathic pain in resiniferatoxin-induced
neuropathy. Exp Neurol 2012; 235:316-325.
17. Chao CC, Wu
VC, Tan CH, Wang YM, Li H, Tseng MT, Wu PC, Lin YH, Lin WM, Wu KD et al. Skin denervation and its clinical significance in late-stage
chronic kidney disease. Arch Neurol 2011; 68:200-206.
18. Luo KR, Chao
CC, Chen YT, Huang CM, Yang NC, Kan HW, Wang SH, Yang WS, Hsieh ST.
Quantitation of sudomotor innervation on skin
biopsies in diabetic neuropathy. J Neuropathol Exp Neurol 2011; 70:930-938.
19. Chao CC,
20. Yang NC, Lee
MJ, Chao CC, Chuang YT, Lin WM, Chang MF, Hsieh PC, Kan HW, Lin YH, Yang CC et
al. Clinical presentations and skin denervation in amyloid neuropathy due to transthyretin Ala97Ser. Neurology
2010; 75:532-538.
21. Tseng MT,
Tseng WY, Chao CC, Lin HE, Hsieh ST. Distinct and shared cerebral activations
in processing innocuous versus noxious contact heat revealed by functional
magnetic resonance imaging. Hum Brain Mapp 2010;
31:743-757.
22. Hsieh YL, Lin
WM, Lue JH, Chang MF, Hsieh ST. Effects of
4-methylcatechol on skin reinnervation: promotion of
cutaneous nerve regeneration after crushing injury. J Neuropathol
Exp Neurol 2009; 68:1269-1281.
23. Chao CC,
Hsieh SC, Tseng MT, Chang YC, Hsieh ST. Patterns of contact heat evoked
potential (CHEP) in neuropathy with skin denervation:
correlation of CHEP amplitude with intraepidermal
nerve fiber density. Clin Neurophysiol
2008; 119:653-661.
24. Chao CC, Sun
HY, Chang YC, Hsieh ST. Painful neuropathy with skin denervation
after prolonged use of linezolid. J Neurol Neurosurg Psychiatry 2008;
79:97-99.
25. Hsieh YL,
Chiang H, Tseng TJ, Hsieh ST. Enhancement of cutaneous nerve regeneration by
4-methylcatechol in resiniferatoxin-induced
neuropathy. J Neuropathol Exp Neurol
2008; 67:93-104.
26. Lin YY, Tseng
TJ, Hsieh YL, Luo KR, Lin WM, Chiang H, Hsieh ST. Depletion of peptidergic innervation in the gastric mucosa of streptozotocin-induced diabetic rats. Exp Neurol 2008; 213:388-396.
27. Tseng TJ,
Chen CC, Hsieh YL, Hsieh ST. Influences of surgical decompression on the dorsal
horn after chronic constriction injury: changes in peptidergic
and d-opioid receptor (+) nerve terminals.
Neuroscience 2008; 156:758-768.
28. Chao CC,
Hsieh ST, Chiu MJ, Tseng MT, Chang YC. Effects of aging on contact heat evoked
potentials: the physiological assessment of thermal perception. Muscle Nerve
2007; 36:30-38.
29. Tseng TJ,
Chen CC, Hsieh YL, Hsieh ST. Effects of decompression on neuropathic pain
behaviors and skin reinnervation in chronic
constriction injury. Exp Neurol 2007; 204:574-582.
30. Chao CC,
Hsieh ST, Shun CT, Hsieh SC. Skin denervation and
cutaneous vasculitis in eosinophilia-associated
neuropathy. Arch Neurol 2007; 64:959-965.
31. Chao CC,
Hsieh SC, Yang WS, Lin YH, Lin WM, Tai TY, Hsieh ST. Glycemic
control is related to the severity of impaired thermal sensations in type 2
diabetes. Diabetes Metab Res Rev 2007; 23:612-620.
32. Tseng MT,
Hsieh SC, Shun CT, Lee KL, Pan CL, Lin WM, Lin YH, Yu CL, Hsieh ST. Skin denervation and cutaneous vasculitis
in systemic lupus erythematosus. Brain 2006;
129:977-985.
33. Lin CY, Su
YN, Lee CN, Hung CC, Cheng WF, Lin WL, Chen CA, Hsieh ST. A rapid and reliable
detection system for the analysis of PMP22 gene dosage by MP/DHPLC assay. J Hum
Genet 2006; 51:227-235.
34. Chiang HY,
35. Chiang HY,
Chien HF, Shen HH, Yang JD, Chen YH, Chen JH, Hsieh ST. Reinnervation
of muscular targets by nerve regeneration through guidance conduits. J Neuropathol Exp Neurol 2005;
64:576-587.
36. Lee JE,
37. Lin YH,
38. Chang YC, Lin
WM, Hsieh ST. Effects of aging on human skin innervation. NeuroReport
2004; 15:149-153.
39.
40. Hsu SH, Lee
MJ, Hsieh SC, Scaravilli F, Hsieh ST. Cutaneous and
sympathetic denervation in neonatal rats with a
mutation in the delta subunit of the cytosolic chaperonin-containing t-complex peptide-1 (Cct4) gene. Neurobiol Dis 2004; 16:335-345.
41. Pan CL,
42. Shun CT,
Chang YC, Wu HP,
43. Pan CL, Tseng
TJ, Lin YH, Chiang MC, Lin WM, Hsieh ST. Cutaneous innervation in Guillain-Barre syndrome: pathology and clinical
correlations. Brain 2003; 126:386-397.
44. Chiang MC,
Lin YH, Pan CL, Tseng TJ, Lin WM, Hsieh ST. Cutaneous innervation in chronic
inflammatory demyelinating polyneuropathy.
Neurology 2002; 59:1094-1098.
45. Ko MH, Chen WP, Hsieh ST. Neuropathology of skin denervation in acrylamide-induced
neuropathy. Neurobiol Dis
2002; 11:155-165.
46. Chien HF,
Tseng TJ, Lin WM, Yang CC, Chang YC, Chen RC, Hsieh ST. Quantitative pathology
of cutaneous nerve terminal degeneration in the human skin. Acta
Neuropathol 2001; 102:455-461.
Book Chapter
Hsieh ST. Toxic
neuropathies. In Schmidt RF and Willis WD, editors.
Encyclopedia of Pain.
Book
Small fiber neuropathy and related syndromes: neurodegeneration and pain. Editor-in-Chief: