The Talkowski Lab is focused on understanding the genetic etiology of complex developmental and neuropsychiatric disorders. Collectively, our efforts revolve around a cycle that traverses from discovery of genomic variation across global populations to disease association, mechanistic modeling, and translation to diagnostic interpretation in the emerging era of genomic medicine.
Our group integrates molecular and computational genomics approaches to understand the functional consequences of genomic variation, with a particular interest in the relationship between genome structure and function. Our program has been recognized for its impact in introducing sequence-based genomics into the field of cytogenetics and prenatal diagnostics, performing the first large-scale sequencing studies of chromosomal abnormalities in neurodevelopmental disorders, and characterizing novel classes of complex chromosomal rearrangements that occur in the human germline.
We are actively leading studies to explore the genetic architecture of autism, including the large-scale whole-genome sequencing studies in autism families. We have also performed a series of functional genomic studies using genome editing techniques and iPSC technologies to investigate loss-of-function mutations associated with autism and rare Mendelian disorders such as congenital arhinia and X-linked dystonia parkinsonism. These studies have also defined long-range positional effects resulting from alteration to three-dimensional regulatory structures encompassing genes critical to neurodevelopment. We are also deeply engaged in determining the implications of emerging genomics technologies in diagnostic screening. We are a part of the Center for Genomic Medicine at Massachusetts General Hospital and have primary affiliations with Harvard Medical School and the Broad Institute of MIT and Harvard.