Some Fun Collaborations

We recently collaborated with the labs of Drs. Cowan, Rossi, and Musunuru of the Harvard Stem Cell Institute to characterize the off-target effects of the genome editing tool CRISPR/Cas9 in human embryonic stem cells and hematopoietic progenitor cells. The latter study was recently described in an article in Time Magazine.

Publications:
Mandal, Cell Stem Cell, 2014
Veres, Cell Stem Cell, 2014

In a collaborative study with Dr. David Jaffe, Director of Computational Research and Development at the Broad Institute, and Drs. Cristopher Bragg, Nutan Sharma, Xandra Breakefield, and others in the Department of Neurology at MGH, we are performing whole-genome de novo assemblies of the Filipino genome in the Island of Panay to determine the genetic cause of a rare disorder, X-Linked Dystonia Parkinsonism, that is indigenous to this population.

We are collaborating with Drs. Jim Gusella (MGH, HMS, Broad), Vijaya Ramesh (MGH, HMS) and their labs along with the Synodos Consortium to uncover the genetic architecture of neurofibromatosis type II (NF2), a rare genetic disorder causing benign nerve tumors, by performing genomic and transcriptomic analyses of tumor samples associated with NF2 from human and mouse.

We are collaborating with Drs. Jim Gusella (MGH, HMS, Broad), Marcy MacDonald (MGH, HMS, Broad) and their labs along with the CHDI Foundation to understand the pathogenic mechanism of Huntington’s disease.

We are collaborating with Dr. Bill Crowley (MGH, HMS) and his group in the Neuroendocrine Unit of MGH to perform genome and transcriptome analyses of discordant twin pairs to uncover the underlying molecular mechanism of Kallmann Syndrome.

We are collaborating with Drs. Anne L. Oaklander and Susan Slaugenhaupt (MGH, HMS) and their labs in exome sequencing of related individuals to identify genes associated with the neuropathic pain.

We have collaborated with the CHDI Foundation on investigating the genomes of transgenic disease models in mice, sheep, minipigs, and rhesus macaque monkeys.

Publications:
Chiang et al., 2012, Nat Genet

We are collaborating with Dr. Natalie Shaw on the discovery of causal genetic variants in an incredibly rare birth defect known as Arrhinia. We are investigating this phenotype with both whole-exome and whole-genome sequencing.

Publications:
Shaw and Brand et al., 2017, Nat Genet

The goal of DGAP is to gain insight into human congenital anomalies by mapping the breakpoints of balanced chromosomal abnormalities (BCAs) and subsequently identify the pathogenic mechanisms by which they cause human disease. The project includes four distinct parts. Dr. Talkowski directs Project 1: Annotation of the Morbid Human Genome. This is the genomics hub of the project in which we perform whole-genome sequencing of subjects with congenital anomalies and cytogenetically identified de novo BCAs. We are further seeking to understand BCAs in phenotypically normal individuals, as well as individuals with congenital anomalies and no identified cytogenetic abnormalities. Project 2: Model Organisms, is led by Dr. Eric Liao, a craniofacial surgeon at MGH who performs zebrafish modeling of craniofacial abnormalities, with Co-Investigator Dr. Cynthia Morton, who is focused on hearing abnormalities using mouse models. Project 3: Nuerodevelopmental Loci, is led by Dr. James Gusella and focused on cellular modeling of genes influencing neurodevelopmental disorders, which represents approximately 75% of DGAP cases. Dr. Talkowski’s lab closely collaborates on the functional genomics studies of Project 3, which includes genome editing in iPS models. Finally, the Coordinating Core is led by Dr. Cynthia Morton and Ms. Tammy Kammin, Genetic Counselor, is the recruitment face of DGAP, which enrolls subjects and performs all clinical assessments. For more information, please see the DGAP website: http://www.bwhpathology.org/dgap/
We are collaborating with Dr. Susan Slaugenhaupt’s laboratory to understand the functional genomic implications of aberrant splicing of the gene IKAP in familial dysautonomia, a rare genetic disorder that affects the development and survival of certain nerve cells. The effects of the IKAP splicing defect can be ameliorated by the compound kinetin, and we are investigating the regulatory consequences of kinetin on IKAP expression.