Edwin Oh

We are a research group that thrives on collaboration. Through our interactions with collaborators, public health labs, and patients we have developed a research program that interrogates the following themes:

1) Wastewater genomics and COVID-19

Wastewater testing has been used for years to investigate viral infections, to study illicit drug use, and to understand the socioeconomic status of a community based on its food consumption. While tools are in place in many states to evaluate the presence of specific viral strains, the community has not needed previously to collaborate on a global scale to standardize procedures to detect and manage COVID-19 transmission. In response to this challenge, our laboratories in Arizona, Nevada, and Washington have developed collection techniques and genomic and bioinformatic approaches to harmonize and visualize the impact of SARS-CoV-2 infection and viral mutation rates in communities populated by local citizens and international tourists. Our findings will contribute to the development of best practices in sampling and processing of wastewater samples and genomic techniques to sequence viral strains, an area required for environmental surveillance of infectious diseases, and has the strong potential to improve the clinically predictive impact of the viral genotype on patient care and vaccine utility.

2) Rare neurological conditions

An association between the 16p13.2 copy number variation deletion and seizures has suggested that a) systematic suppression of each of genes in the loci might yield similar neurological phenotypes seen in the 16p13.2 deletion; and b) such genes might be strong candidates for harboring rare pathogenic point mutations. Through these studies, we discovered USP7 as a message capable of inducing abnormal neurological activity in brain organoids, cultured neurons, and loss-of-function mouse models. Together with collaborators at the Foundation for USP7-Related Diseases (www.usp7.org), our studies are centered on the mechanism by which USP7 gene dosage and rare variants can induce pathology. In addition, we have also identified other gene loci that mimic USP7-related disorders in human and animal models.

3) Ciliary biology and neurodevelopmental conditions

Large-scale studies have begun to map the genetic architecture of Schizophrenia. We now know that the genetic contribution to this condition arises from a variety of lesions that include a) rare copy number variants (CNVs) of strong effect; b) common non-coding alleles of mild effect; and c) rare coding alleles that cluster in biological modules. The challenge that has emerged from these studies is the requirement for large sample sizes to detect significant genetic signals. These findings intimate that SZ is genetically heterogeneous and manifesting potentially as a clinically heterogeneous group of phenotypes with discrete physiological drivers. To address this challenge and to complement the ongoing sequencing effort of cross-sectional SZ, we propose to sample individuals with extreme phenotypes (i.e., resistant to treatment: TRS) to potentially discover an enrichment of causal rare variants which would have otherwise not been observed or been difficult to detect in a large, random sampling of SZ. In addition, we will focus on the role of a specific biological module, the pericentriolar material (including the centrosome, basal body, and primary cilium) and how it relates to the development of the brain and behavior through the genomic and functional dissection of PCM1.

Nora Caberoy

Dr. Nora Caberoy’s research is on eye diseases. Specifically, she studies the retina (the thin, multi-layer, light-sensitive tissue that is found all the way at the back of the eye) and the role of retinal pigment epithelium phagocytosis in photoreceptor death that leads to retinal dysfunction and then blindness. By identifying factors and pathways associated with damage of the retina, she hopes to be able to develop ways to prevent or treat blindness.

In parallel with Caberoy’s work in the eye, she also identifies and characterizes factors that contribute to the development of obesity with the hope of developing therapeutic strategies to prevent or treat obesity. She explores the physiological and pathological roles of tubby protein in the development of obesity.

Grant Matick

To build a brain, the embryo must produce a spatially organized array of a vast number of neurons, then interconnect them. Our research group uses genetic and molecular approaches in mouse and chick embryos to investigate the functions of specific genes in brain development. This research has implications for the molecular therapy of neurological disease and injury, and is funded by the National Institutes of Health.

Our current research is on the migration of neurons and their axons through the developing brain. We investigate how molecular signals guide axons to migrate precisely long distances on longitudinal pathways, how cranial nerves grow out to connect to muscles, and also how neuron cell bodies settle in specific positions. Our studies focus on a system of signals, the Slit/Robo repellents and the Netrin attractants, to understand the mechanisms by which opposing signals are integrated by neurons.

Frank van Breukelen

Dr. van Breukelen is interested in the mechanisms that allow animals to survive in harsh environments.