Lindsey Barske, PhD

The Barske lab studies how embryonic patterning genes control the composition and architecture of the developing skull and pharynx. The lab's recent identification shows an essential role for the gene Pou3f3 and its associated non-coding regulatory sequences in determining the number and type of skeletal appendages that protect and promote the flow of oxygenated water over the gills of aquatic vertebrates. Though these appendages are now vestigial in terrestrial vertebrates like us, the initial stages of their development are highly conserved. Importantly, aberrant development of these structures in humans can result in clinically significant and infection-prone branchial cleft cysts or fistulae in the neck. Their work reveals a novel potential congenital cause of these anomalies and could improve future screening and intervention measures.

Matthew S. Hestand, PhD

Short-read DNA sequencing dominates molecular diagnostics, yet long-read single-molecule sequencing technologies, such as those provided by PacBio and Oxford Nanopore, can more accurately identify variants in repetitive regions, low-frequency mutations, structural variants, and phasing of variants. Along with international collaborators, Matthew Hestand, PhD, helped educate the medical genomics community on these improvements through multiple reviews (PMID 30115375, 30621217, 29401301), and as a guest editor for a special edition of the Journal Genes focusing on these technologies. With collaborators, he is now utilizing PacBio sequencing to improve characterization of complex structural rearrangements in multiple Cincinnati Children's patients with neurological diseases and is in the process of bringing nanopore-based sequencing in-house for more accurate and cost-effective pharmacogenomics testing.

Yaping Liu, PhD

A recently established important biomarker for cancer diagnosis and prognosis are circulating cell-free DNA (cfDNA) in blood plasma. It still not yet clear whether or not genome-wide cfDNA fragmentation pattern is useable as a potential universal biomarker, and therefore understand genome-wide association studies (GWAS) non-coding SNPs in common complex diseases. Yaping Liu, Phd, and his team, established the experimental and computational platform to study cfDNA fragmentation across different GWAS diseases and are applying these to many common complex disorders.

Willaim C. Nichols PhD

In collaboration with Regeneron, the Nichols lab and collaborators generated whole exome sequence data on 2572 Group 1 pulmonary arterial hypertension (PAH) patients enrolled in the PAH Biobank. This is the world’s largest collection of whole exome/whole genome sequence data for patients with this disease. Their association analysis identified two novel genes (KLK1 and GGCX) in our cohort as well as replicated two novel genes (BMP9 and AQP1) identified by UK collaborators in a cohort of 1,000 idiopathic PAH patients. For the first time their studies include genetic analysis of patients with associated PAH as well as drugs and toxins PAH.

Ying Sun, PhD

To develop a treatment for neuronopathic Gaucher disease (nGD) that has no effective therapy available, the Sun laboratory established a non-invasive neural stem cell approach by intravenous infusion of neural precursor cells (NPC) expresses Integrin α4β1, Very Late Antigen-4 that facilitates NPC entry into the brain. Their studies demonstrate the potential efficacy of iPSC-derived NPC therapy for nGD, and provide a framework for personalized medicine using iPSC-derived NPCs as a specific, effective, non-invasive, and autologous cell therapy. Human Molecular Genetics accepted this work for publication and a patent application submitted.