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Louis Kunkel, Ph.D.

Professor of Pediatrics

Children's Hospital
Division of Genetics, Enders 570
320 Longwood Avenue
Boston, MA 02115
Telephone: 617-355-6729
Fax: 617- 730-0253
Email: Kunkel@enders.tch.harvard.edu
Predocs: 3 Postdocs: 6 Completed PhD's: 8

  

The muscular dystrophies are genetically heterogeneous muscle wasting disorders with at least 20 underlying genes, which can be mutated to yield dystrophy. How abnormalities in the proteins encoded by these genes causes the common pathogenesis is still emerging. The identification of many of these genes has lead to a better understanding of how normal muscle functions and the ways in which this normal function can be disturbed. This understanding has lead to viable approaches to therapy including gene and stem cell delivery of normal genes. Muscle is a regenerative tissue and contains mononuclear cells, which are capable of cell proliferation followed by fusion into new muscle myofibers. This regenerative capacity serves as the basis of stem cell therapy for the muscular dystrophies.

The muscular dystrophies are examples of monogenic traits where single genes bare mutations which are fully apparent in all individuals who inherit them. Most common human disease has, as its basis, interplay of genetics and environment. With the emergence of the complete human DNA sequence it is now possible to unravel the genetic component of disorders such as autism, heart disease and cognitive impairment. This is accomplished by the analysis of common variants found in genes which might influence gene or protein activity and such variation may predispose an individual to a particular disease. Finding such associations involves the analysis of many such variations in many normal and diseased individuals. The techniques and analysis of these association experiments are available in the laboratory.

 

References:

  • Haslett JN, Sanoudou D, Kho AT, Han M, Bennett RR, Kohane IS, Beggs AH, Kunkel LM. (2003) Gene expression profiling of Duchene muscular dystrophy skeletal muscle. Neurogenetics 4:173-171.
  • Montanaro F, Liadaki K, Volinski J, Flint A, Kunkel L. (2003) Skeletal muscle engraftment potential of adult mouse sink side population cells. PNAS 100:9336-9341.
  • Geesaman BJ, Benson E, Brewster SJ, Kunkel LM, Blance H, Thomas G, Perls TT, Daly MJ, Puca AA (2003) Haplotype based identification of a microsomal transfer protein marker associated with human lifespan. PNAS 100:14115-114120.
  • Shi W, Chen Z, Schottenfeld J, Stahl R, Kunkel L, Chan Y (2004) Specific assembly pathway of sarcoglycans is dependent on beta- and delta-sarcoglycan, Muscle Nerve 29:409-419.
  • Bachrach E, Li S, Perez AL, Schienda J, Liadaki K, Volinski J, Flint A, Chamberlain J, Kunkel LM. (2004) Systemic delivery of human microdystrophin to regenerating mouse dystrophic muscle by muscle progenitor cells. PNAS 101:3581-3586.