Research Interests:
Dr. Kennedy is applying immunohistochemistry, confocal microscopy,
and computer processing to quantify nerves in human skin and gastrointestinal
tract. The objective is for earlier diagnosis of neuropathy, nerve
injury and evaluation of therapeutic trials. Evaluation of diabetic
patients after pancreas and islet transplantation is a special interest.
The work has expanded into investigation of the microbiology of
wound healing and trophic factors on regeneration of wounds and
their reinervation.
The Kennedy lab research investigates unmyelinated nerves in the
skin and internal organs using immunohistochemical staining and
confocal microscopic techniques with diabetes as the main clinical
disease of interest. Analysis of nerves in skin biopsies are used
for early diagnosis of diabetic neuropathy, particularly, in diabetic
patients undergoing pancreas transplantation or recently islet transplantation
to cure their diabetes. Our evaluation of the patient includes neurological
examination, quantitative sensory examination, nerve conduction
tests and skin biopsy/blister. Another major interest is neuropathy
of the enteric nervous system in diabetes, Hirschsprung’s disease,
Barrett’s esophagus,gastric reflux disease and other disorders
in which unmyelinated nerves undergo previously unrecognized degeneration.
We have also developed minimally invasive micro methods to study
unmyelinated nociceptors regeneration after micro mechanical and
chemical (capsaicin) wounds on mice, pigs, human volunteers and
patients. The work requires close cooperation with neurologists,
surgeons, internists and pathologists.
The goals of our research team are:
| I. Study epidermal nerves: |
1. In skin of patients with peripheral neuropathies of
different types with emphasis on diabetic patients undergoing
pancreas or Islet transplantation. Nerves are stained by
immunohistochemistry, imaged with confocal microscopy, and
quantified with computer method.
2. In models of denervation (blisters, capsaicin) to understand
nerve regeneration.
3. In patients with autonomic neuropathy (e.g. Riley-Day
(Familial Dysautonomia), Friedreich ataxia)
4. In animal models, e.g. mouse model of nerve regeneration.
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| II. Study nerves of the gastrointestinal (GI) tract. |
1. In stomach, duodenum and jejunum of diabetic patients.
2. In animal models of GI denervation (e.g. pig).
3. Hirschsprung’s agangliosis
4. Infantile constipation
5. Barrett’s esophagus
6. Gastric reflux
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| III. Study of nerves in the urinary bladder. |
1. In diabetic patients receiving a pancreas transplant.
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The work includes study of the influences on regenerating cutaneous
nerves, trophic factors and capillary permeability on healing of
mechanical, chemical, and thermal skin wounds in normal and diabetic
patients and in pig and mouse models. For this purpose, we developed
non-traumatic micro methods to perform nerve regeneration studies
on human volunteers and patients. For example we devised the method
described in paper #11 "A skin blister method to study epidermal
nerves in peripheral nerve disease".
Patients are studied by electrophysiology, clinical motor and sensory
tests. Nerves removed in skin biopsies and skin blisters are visualized
by immunohistochemistry and imaged by confocal microscopy before
computer quantitation. Two recent studies, references 10 and 12
which describe the effects of intradermal and topical capsaicin
on structure and regeneration of epidermal nerves in humans, exemplify
our goal to combine basic research with topics of clinical importance.
The work on the GI tract is relatively new and unpublished. We
are at the brink of describing changes of GI innervation for the
first time in several diseases (see above).
Selected Publications:
Selim MM, Wabner KA, Wendelschafer-Crabb G, Kennedy WR. Stimulated growth of human and pig epidermal nerve fibers by tape stripping. Arch Dermatol Res. 2007 Dec;299(10):513-6.
Walk D, Wendelschafer-Crabb G, Davey C, Kennedy WR. Concordance between epidermal nerve fiber density and sensory examination in patients with symptoms of idiopathic small fiber neuropathy. J Neurol Sci. 2007 Apr 15;255(1-2):23-6.
Vulchanova L, Casey MA, Crabb GW, Kennedy WR, Brown DR. Anatomical evidence for enteric neuroimmune interactions in Peyer's patches. J Neuroimmunol. 2007 Apr;185(1-2):64-74.
Davis MD, Weenig RH, Genebriera J, Wendelschafer-Crabb G, Kennedy WR, Sandroni P. Histopathologic findings in primary erythromelalgia are nonspecific: special studies show a decrease in small nerve fiber density. J Am Acad Dermatol. 2006 Sep;55(3):519-22.
Wendelschafer-Crabb G, Kennedy WR, Walk D. Morphological features of nerves in skin biopsies. J Neurol Sci. 2006 Mar 15;242(1-2):15-21.
Recent Post-Docs
Nidal Khalili M.D. 1998-1999
Mona Selim M.D., Ph.D. 1999-2000
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