Our Research
Our laboratory aims to understand normal cell division mechanisms and to discover the consequences of common cell division errors in cancer cells. We take a range of approaches including genetics, functional genomics, biochemistry, live cell imaging and single cell genomics.
Our past accomplishments include: (1) the co-discovery of formin-dependent actin assembly and a mechanism for positioning mitotic spindles within asymmetrically dividing cells; (2) discoveries showing that whole genome duplication alters cell physiology, can promote evolutionary adaptation, and can drive tumor development; (3) the discovery of a mechanism explaining chromothripsis, a mutational process that generates rapid karyotype evolution in cancer and congenital disease.
We are currently addressing the mechanisms of normal nuclear envelope assembly and how defects in nuclear architecture and integrity alter the genome. Cancer-specific aberrations in nuclear architecture (cancer “nuclear atypia”) were described more than 100 years ago and are routinely used to assign tumor grade and predict patient prognosis. Yet the biological consequences of nuclear architecture defects are only starting to be understood.
We and others have determined that abnormal structures of the cell’s nucleus can trigger catastrophic mutational processes that extensively alter the genome in a single step (e.g., chromothripsis, chromosome breakage-fusion-bridge cycles, and whole genome duplication). We are taking a systematic approach to identify the mechanistic details of these mutational processes. Some questions of current interest are: Why are chromosomes fragmented if suddenly exposed to the interphase cytoplasm? How do aberrations in nuclear architecture affect transcription and the epigenetic state of chromatin? How does mitosis impact the mechanism and fidelity of DNA replication?
Our past accomplishments include: (1) the co-discovery of formin-dependent actin assembly and a mechanism for positioning mitotic spindles within asymmetrically dividing cells; (2) discoveries showing that whole genome duplication alters cell physiology, can promote evolutionary adaptation, and can drive tumor development; (3) the discovery of a mechanism explaining chromothripsis, a mutational process that generates rapid karyotype evolution in cancer and congenital disease.
We are currently addressing the mechanisms of normal nuclear envelope assembly and how defects in nuclear architecture and integrity alter the genome. Cancer-specific aberrations in nuclear architecture (cancer “nuclear atypia”) were described more than 100 years ago and are routinely used to assign tumor grade and predict patient prognosis. Yet the biological consequences of nuclear architecture defects are only starting to be understood.
We and others have determined that abnormal structures of the cell’s nucleus can trigger catastrophic mutational processes that extensively alter the genome in a single step (e.g., chromothripsis, chromosome breakage-fusion-bridge cycles, and whole genome duplication). We are taking a systematic approach to identify the mechanistic details of these mutational processes. Some questions of current interest are: Why are chromosomes fragmented if suddenly exposed to the interphase cytoplasm? How do aberrations in nuclear architecture affect transcription and the epigenetic state of chromatin? How does mitosis impact the mechanism and fidelity of DNA replication?