Finally, Dr. Bonadio's laboratory has developed a 
novel, in vivo gene transfer method. Along with col- 
leagues at the Hillenbrand Biomedical Engineering 
Center of Purdue University, members of the labora- 
tory have been able to transfer and express plasmid 
and retroviral DNAs directly into the cells of regen- 
erating tendon, ligament, cartilage, and bone. This 
discovery represents the first successful in vivo 
gene transfer experiment in skeletal tissues, and it 
provides the first indication that gene therapy is pos- 
sible for skeletal disorders. It will also allow the 
laboratory to explore the biological mechanisms 
that govern the tissue regeneration. 
Dr. Bonadio is also Assistant Professor of Pa- 
thology at the University of Michigan Medical 
School. 
Articles 
Biesecker, L.G., Erickson, R.P., Glover, T.W., and 
Bonadio, J. 1991. Molecular and cytologic stud- 
ies of Ehlers-Danlos syndrome type VIII. Am f 
Hum Genet 41:284-288. 
Cole, W.G., Patterson, E., Bonadio, J., Campbell, 
P.E., and Fortune, D.W. 1992. The clinicopatho- 
logical features of three babies with osteogenesis 
imperfecta resulting from the substitution of gly- 
cine by valine in the proa 1 (I) chain of type I pro- 
collagen. /Merf Genet 29:1 12-118. 
Wong, M., Lawton, T., Goetinck, P.F., Kuhn, J.L., 
Goldstein, S.A., and Bonadio, J. 1992. Aggrecan 
core protein is expressed in membranous bone of 
the chick embryo. Molecular and biomechanical 
studies of normal and nanomelia embryos. J Biol 
Chem 267:5592-5598. 
MOLECULAR STUDIES OF CALCIUM CHANNELS 
AND THE DYSTROPHIN-GLYCOPROTEIN COMPLEX 
Kevin P. Campbell, Ph.D., Investigator 
Dr. Campbell's research is aimed at understand- 
ing the structure and function of the membrane pro- 
teins involved in regulating intracellular Ca^^ in ex- 
citable cells. His laboratory has focused on the 
identification, purification, and characterization of 
the Ca^^ channels that function in muscle excita- 
tion-contraction coupling and in neuronal Ca^^ ho- 
meostasis. In addition, his laboratory has studied the 
structure and function of dystrophin and associated 
membrane glycoproteins, to develop an under- 
standing of why the absence of dystrophin results in 
muscular dystrophy. 
Intracellular Ca^^ Release Channels 
in Muscle and Neurons 
One goal of Dr. Campbell's research is to under- 
stand the structure and function of intracellular 
Ca^^ release channels. In skeletal muscle, Ca^^ re- 
lease from the sarcoplasmic reticulum (SR) initiates 
muscle contraction. Dr. Campbell's laboratory pre- 
viously showed that the purified ryanodine receptor 
from skeletal muscle is identical to the SR Ca^^ re- 
lease channel and SR "feet" structures. In the past 
year the laboratory has determined that abnormali- 
ties in the regulation of Ca^^ release that had been 
found in skeletal muscle from humans and pigs with 
malignant hyperthermia are directly due to a muta- 
tion in the ryanodine receptor. Previously the labo- 
ratory had found that tryptic digestion of SR vesicles 
produced clear and reproducible differences be- 
tween the immunostaining pattern of the malignant 
hyperthermic and normal ryanodine receptor pep- 
tides. In the past year the laboratory has shown that 
in isolated membranes the amino acid change in the 
ryanodine receptor from Arg*''^ to Cys*''' is directly 
responsible for the altered tryptic peptide map, due 
to the elimination of the Arg^'^ cleavage site. These 
results suggest that the 86- to 99-kDa domain of the 
ryanodine receptor containing residue 6 1 5 is near 
the cytoplasmic surface of the receptor and likely 
near important Ca^* channel regulatory sites. 
Dr. Campbell's research also concerns ryanodine 
receptor/Ca^* release channels in neuronal cells 
and nonexcitable cells. Previously his laboratory 
showed that the brain ryanodine receptor functions 
as an intracellular Ca^^ release channel and that it is 
the probable gating mechanism for caffeine- and 
Ca^^-sensitive Ca^^ stores in neurons. In the past 
year a release channel in sea urchin eggs has been 
identified. Immunolocalization of the Ca^"^ release 
channel reveals a cortical reticulum or "honey- 
comb" staining network that surrounds cortical 
granules and is associated with the membranes of 
the cortical endoplasmic reticulum. An ~380-kDa 
protein of sea urchin egg cortices is identified by 
immunoblot analysis with ryanodine receptor anti- 
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