Research

The Advanced Center for Translational and Genetic Medicine (ACT-GeM) utilizes biological and bioinformatic tools to identify and interpret human genetic variation; to understand the fundamental pathomechanisms of human genetic disease; and to develop novel therapeutic modalities. Grounded on two decades of experience using in vivo and in vitro assays to model human genetic phenomena, we employ cell, zebrafish and mouse models with scalable cutting-edge tools. To date, we have modeled variants in >800 genes, with aspirations of saturating our knowledge of the morbid human genome. 

We have used our toolkit to support the candidacy of novel contributors to rare and common disease; to measure the effect of genetic variation in cell- and tissue-specific contexts; to understand genetic architecture in terms of cis- and trans-compensatory events; to dissect biochemical pathways; and to develop new therapeutic targets. Although our studies fall under three broadly defined thematic areas, these are subject to substantial crosstalk, reflective of the overlapping interests of our faculty and of the multidisciplinary nature of ACT-GeM.

Publications

Please find a selection of the papers to which our Center has contributed below. More publications can be found on the Google Scholar pages for Dr. Nico Katsanis and Dr. Erica Davis.

Oligogenic Effects of 16p11.2 Copy-Number Variation on Craniofacial Development. (PMID: 31553903)

SSBP1 mutations cause mtDNA depletion underlying a complex optic atrophy disorder.(PMID: 31550240)

Germline-Activating RRAS2 Mutations Cause Noonan Syndrome. (PMID: 31130285)

Bi-allelic Variants in DYNC1I2 Cause Syndromic Microcephaly with Intellectual Disability, Cerebral Malformations, and Dysmorphic Facial Features. (PMID: 31079899)

Mutations in NCAPG2 Cause a Severe Neurodevelopmental Syndrome that Expands the Phenotypic Spectrum of Condensinopathies. (PMID: 30609410)

Kctd13-deficient mice display short-term memory impairment and sex-dependent genetic interactions. (PMID: 30590535)

Small molecule inhibition of RAS/MAPK signaling ameliorates developmental pathologies of Kabuki Syndrome. (PMID: 30018450)

Dual Molecular Effects of Dominant RORA Mutations Cause Two Variants of Syndromic Intellectual Disability with Either Autism or Cerebellar Ataxia. (PMID: 29656859)

Transcriptome-wide association study of schizophrenia and chromatin activity yields mechanistic disease insights. (PMID: 29632383)

Temperature-activated ion channels in neural crest cells confer maternal fever-associated birth defects. (PMID: 29018170)

Exome-wide Association Study Identifies GREB1L Mutations in Congenital Kidney Malformations. (PMID: 29220675)

Gene expression elucidates functional impact of polygenic risk for schizophrenia. (PMID: 27668389)

Copy-Number Variation Contributes to the Mutational Load of Bardet-Biedl Syndrome. (PMID:27486776)

Identification of cis-suppression of human disease mutations by comparative genomics. (PMID:26123021)

Loss of δ-catenin function in severe autism. (PMID: 25807484)