Kyle Siebenthall

Joined Program: 2006
Prior Training: B.A. Biological Sciences, Cornell University
Trask Lab
kts6 [ a t ] u.washington.edu

Research:
My overall research interests are nuclear architecture (the three-dimensional structure of the genome in the cell nucleus, and how this impacts gene regulation) and epigenetics. Both of these interests led me to study facioscapulohumeral dystrophy (FSHD) in the Trask lab. FSHD is the third most common muscular dystrophy and is caused by the contraction of a repeat array in the subtelomere of the long arm of chromosome 4 (4q35). We do not currently understand why this causes the disease, nor do we understand why contractions of the array are only pathogenic on one of nine haplotypes in this region. Contractions of a highly homologous repeat array on chromosome 10 are also not pathogenic.

We endeavor to understand this disease at three different levels: genomic sequence & structure, epigenetic state and nuclear organization. Working with data generated in the Eichler Lab and using DNA from various sources, we aim to increase the sequence coverage of the different 4q35 haplotypes to look for variation in sequence and structure that may play a role in the disease. Understanding the epigenetic state of 4q35 is part of the Trask Lab’s larger goal of interrogating the state of subtelomeric regions throughout the genome. I am currently examining the role of nuclear organization in FSHD using circular chromosome conformation capture (4C) in one-year pilot project funded by the Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center.

The FSHD work in the Trask Lab is carried out in collaboration with Drs. Stephen Tapscott and Galina Filippova at the FHCRC, Dr. Dan Miller at UW and Dr. Silvere van der Maarel at Leiden University, The Netherlands.