About the Talkowski Laboratory

The Talkowski Laboratory is dedicated to the characterization of genomic variation contributing to human disease, with a focus on the relationship between genome structure and function. The lab integrates molecular and computational genomics methods to investigate the genetic architecture of neurological disorders, as well as to develop new technologies for translational applications in genetic diagnostics. We have defined the genomic landscape of chromosomal abnormalities in congenital anomalies, described the phenomenon of balanced chromothripsis in the human germline, and catalogued entirely new classes of complex structural variation that are surprisingly abundant in all human genomes. The lab has represented a hub of novel gene discovery in autism, human congenital anomalies, and neuropsychiatric disorders. A significant component of our research program is dedicated to pursuing functional genomic studies of regulatory pathways in rare Mendelian disorders. Our focus on structural variation has also led us to seek the dynamic range of consequences that result from alterations in higher-order three-dimensional nuclear architecture as a novel etiological mechanism in human disease.


Our recent studies have described the landscape of cytogenetic abnormalities at sequence resolution and the striking complexity of cryptic structural variation in the human genome, which has led to discovery of new genes and genomic disorders contributing to human disease. We have developed a molecular and computational diagnostic sequencing application with our customized large-insert jumping libraries and are currently engaged in large-scale validation studies of whole-genome sequencing in routine prenatal diagnostic practice.  Through ongoing contributions to the 1,000 Genomes Project Structural Variation Consortium, the Genome in a Bottle Consortium, and our Prenatal Diagnostic Consortium, we are also pursuing efforts to reliably detect all classes of structural changes in the human genome through reference based sequence alignments and de novo assembly efforts using existing and emerging technologies.

Psychology News
Psych Central
Science Daily



Another major component of the laboratory is functional genomic studies to characterize disease-associated genetic lesions. We are performing extensive transcriptomic and epigenomic studies in induced pluripotent stem cells (iPSCs) and interrogating methods for genome editing such as CRISPR/Cas9.  We recently conducted extensive studies to evaluate on-target efficiency and off-target effects of CRISPR/Cas9 genome editing technology with our collaborators at the Harvard Stem Cell Core, revealing minimal off-target effects from whole-genome sequencing in one study, and suggesting viable translational opportunities to prevent HIV infection.

Boston Children’s Hospital
Harvard Stem Cell Institute

In addition to our genomics laboratory at MGH and the Broad Institute, Dr. Talkowski is the founding director of the Genomics and Technology Core of MGH, which seeks to develop new technologies and provide molecular and computational genomics capabilities to the local and external research community.  We also have a large network of collaborations within the MGH, Harvard, Broad Institute, and MIT communities, as well as external collaboration throughout the US and internationally.

We welcome inquiries from highly qualified scientists at all levels from graduate students to senior staff scientists interested in joining our research team and collaborative network to study the genomics of human disease. Please see contact information here.

The Talkowski lab is funded by:

Recent Posts

XDP study published in Cell

February 22nd, 2018|0 Comments

X-linked Dystonia-Parkinsonism (XDP), is a rare Mendelian disorder predominantly observed on Panay island in the Philippines. The clinical phenotype most frequently combines features of dystonia and parkinsonism in a characteristic temporal progression. A region of […]


1910, 2015

Claire Redin at ASHG 2015

October 19th, 2015|0 Comments

Selected for a Plenary Talk, Claire presented the latest results from the DGAP study.

“By mapping the breakpoints, we were able to identify genes that were disrupted in patients with birth defects, which suggests that these genes […]