Louis Martens Kunkel

Louis Martens Kunkel

Professor of Pediatrics
Louis Martens Kunkel

The muscular dystrophies are progressive disorders of striated muscle leading to breakdown of muscle integrity. There is considerable clinical variability in the muscular dystrophies with the most common form caused by abnormalities of dystrophin and the remaining dozen Limb Girdle Dystrophies being caused by an additional 12 genes, some of which have been identified by their interaction with dystrophin at the muscle cell membrane. Despite extensive information about how muscle degenerates in the dystrophies, little is available in the form of therapy to ameliorate the symptoms. One approach taken by the laboratory has been to use the regenerative capacity of muscle stem cells prepared from normal individuals to repair damaged muscle of affected individuals and in the process contribute normal gene products. These studies are carried out in mouse models of the human disease and more recently in our newly identified zebrafish models of dystrophin deficiency. The latter models are also very useful in large scale screening of small molecule libraries to search for small molecules that might compensate for dystrophin deficiency or stabilize the muscle cell membrane in its absence.

With ever changing genetic technologies and the sequencing of the human genome it has become possible to start to unravel the genetic basis of complex human genetic traits such as autism and interstitial cystitis.

The Kunkel laboratory, in collaboration with the laboratory of Dr Issac Kohane, is currently testing the hypothesis that whole blood gene expression profiling can act as a surrogate for gene expression changes which might be occurring in the brains of patients with autism. Early work has shown that patients can be stratified based on gene expression signatures from signatures of control samples but many more samples are needed to establish if this is significant. We have also been able to ascertain several large families segregating IC as an apparent autosomal dominant disorder and have mapped at least 3 separate loci in the human genome which cause the same symptoms of IC. This suggests that IC may be caused by mutations in several different genes possibly interacting with one another much like the collagen genes in the different collagen disorders.

Rotation Projects:

1. Use a zebrafish model of muscular dystrophy to screen small molecule libraries for therapeutic agents.

2. Characterization of muscle stem cells as a potential way of introducing normal genes into diseased muscle.

3. Study the expression of miRNAs in normal and diseased tissues.

4. mRNA expression profiling in Autism spectrum disorders.

Contact Information

Boston Children's Hospital
CLS Building, 15024.B
3 Blackfan Circle
Boston, MA 02115
p: 617-355-6729

Community or Program Affiliation