Louis Kunkel, PhD

Department	Genetics
Hospital Title	Director, Genomics Program
Academic Title	Professor of Genetics and Pediatrics
Phone	617-355-6729
Fax
Email	Louis Kunkel
Location	300 Longwood Avenue CLS 15024.B Boston, MA 02115

Research Overview

The major focus of our laboratory is to study the muscular dystrophies, a series of progressive disorders of striated muscle that lead to the breakdown of muscle integrity. More recently, our research efforts have expanded to other complex genetic diseases including autism and interstitial cystitis.

Muscular Dystrophies
Since our discovery of the Duchenne-Becker muscular dystrophy gene dystrophin, we have taken two approaches to studying these diseases. The first is to unravel the normal function of the dystrophin-associated protein complex and determine how alteration of genes encoding members of this complex causes the disease. The second is to develop different lines of therapy for patients with muscular dystrophy.

These efforts include stem-cell-based therapy and drug-discovery strategies to develop pharmaceutical-based approaches. We are identifying potential drug targets by characterizing genes and microRNAs that are upregulated or downregulated in the disease, and through drug screening efforts in zebrafish deficient in the dystrophin gene.

The muscles of dystrophin-deficient zebrafish embryos appear patchy under polarized light (d), characteristic of muscle tearing.

Interstitial Cystitis
Interstitial cystitis (IC) is a complex genetic disorder affecting nearly 1 in 2,000 people in the United States. We have identified six families in which IC is segregating, and have found five different genetic loci that are significantly or suggestively linked to the disease. We are now sequencing the genes in these regions to find the causative mutations in these families. Identification of these genes should highlight potential disease pathways and might reveal insights into therapy.

For more information, click here.

Autism
Autism is a developmental disorder that most likely involves genes expressed in the brain and probably has both genetic and environmental causes. Because many genes expressed in the central nervous system are also expressed in whole blood, we reasoned that we might be able to find signatures of gene expression that would allow us to categorize patients with autism and possibly identify causative genes. We can now predict whether a gene expression profile is derived from a blood sample taken from an autistic child or from a control. We are expanding these studies to many more patients and controls, in the hopes of developing a diagnostic test for autism.

For more information, click here.

About Louis Kunkel

Dr. Kunkel received his PhD degree in biology from the Johns Hopkins University and completed postdoctoral fellowships at the University of California, San Francisco and at Children's Hospital Boston.

For the past 15 years, Dr. Kunkel has led Children's Genetics Division, which consists of more than fifty individuals. Dr. Kunkel is personally involved in each project in his own laboratory and this helps to assure the fulfillment of his scientific objectives.

Dr. Kunkel is a member of the National Academy of Sciences. He currently holds appointments as Director of the Program in Genomics at Children's Hospital Boston; Investigator, Howard Hughes Institute; Professor of Pediatrics and Genetics, Harvard Medical School, Boston; and Director of the Sequencing/Genotyping, Expression Array and FACS Sorting Core Facilities at Children's Hospital Boston.

Dr. Kunkel has authored 197 journal articles and 20 book chapters. He has received 22 awards and honors for scientific leadership and achievement including membership in the National Academy of Sciences, The Gairdner Foundation International Award 1989, Silvio O. Conte decade of Brain Award 1991, the MDS's S. Mouchly Small Scientific Achievement Award 1999, the Charles A. Dana Distinguished Research in Neuroscience Award, and the William Allan Award for distinguished service in human genetics in 2004.

Key Publications

• Arashiro P et al. Transcriptional regulation differs in affected facioscapulohumeral muscular dystrophy patients compared to asymptomatic related carriers. Proc Natl Acad Sci USA 2009 Apr 14; 106(15):6220-5.
   
• Guyon JR et al. Genetic isolation and characterization of a splicing mutant of zebrafish dystrophin. Hum Mol Genet 2009 Jan 1; 18(1):202-11.
   
• Eisenberg I et al. Distinctive patterns of microRNA expression in primary muscular disorders. Proc Natl Acad Sci USA 2007 Oct 23; 104(43):17016-21.
   
• Schienda J et al. Somitic origin of limb muscle satellite and side population cells. Proc Natl Acad Sci USA 2006 Jan 24; 103(4): 940-50.
   
• Bachrach E. et al. Muscle engraftment of myogenic progenitor cells following intraarterial transplantation. Muscle Nerve 2006 Jul; 34(1): 44-52.

For a complete list of Lou Kunkel's publications in PubMed, click here.