research

Mapping rare variants to function using clinical and population-scale multi-omics

We develop computational and statistical tools to uncover pathogenic coding and non-coding variants across undiagnosed rare diseases. We work with multi-disciplinary researchers, patients and families to provide diagnostic discoveries within the Genomic Answers for Kids program at Children's Mercy Hospital, with a focus on regulatory variation and rare complex diseases such as congenital heart defects. 

To enable this, our research integrates genomic, functional and phenotypic resources from across the spectrum of human diseases in both differentiated and pluripotent cellular contexts. These insights - from patient to population-scale - allow us to develop generalizable methods to pinpoint causal disease genes, pathways, and cis- and trans-regulatory mechanisms underlying complex rare disease phenotypes, enabling expanded patient genome assessment and the potential for gene-based therapeutic targeting. 

Lab news

• Nov 2022: we are delighted to welcome Cas LeMaster to the lab! Cas joins us as a Bioinformatics Scientist. Welcome!

• Sep 2022: NoA received from NIGMS for our R35 MIRA grant on the genomics of non-Mendelian pediatric rare diseases

• Aug 2022: NoA received from NHGRI for our R21 grant on novel approaches for relating genetic variation to function and disease

• May 2022: lab news in the press! genomeweb, "Polygenic Risk Score Performance Improved With Expression-Related Rare Variant Insights" 

• May 2022: our paper on identifying large-effect rare coding and non-coding variants in complex disease using outlier gene expression is published in AJHG - congrats to all co-authors!

• Oct 2021: Craig is selected as a 2021 Marion Merrell Dow/Ed Connolly Research Scholar - an endowment funding pediatric genomic research to find answers, better treatments, and cures for childhood illness and disease

• May 2021: we are delighted to welcome Marissa Keever (current doctoral candidate at University of Illinois at Urbana-Champaign), who will join the lab as a Postdoctoral Research Scholar this summer - welcome Marissa!

• Mar 2021: lab news in the press! Nature Reviews Genetics, "Stem cells root out genetic variants"

• Mar 2021: our i2QTL Consortium iPSC manuscript is now published in Nature Genetics - congrats to all co-authors!

• Oct 2020: the Smail Lab has officially opened within the Genomic Medicine Center at the new Children's Mercy Research Institute, Kansas City, MO