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.

Donald Price

A major theme in my research is to understand how species adapt to diverse environmental and biological factors and diverge into new species. The evolutionary changes that permit species to survive and reproduce across a wide range of environments has resulted in a remarkable range of biological complexity.

My research group studies the interplay of behavior, ecology, genetics, and physiology to determine how species adapt to environmental changes and how diversification of populations leads eventually to the formation of new species. One focus of my group is the amazing Hawaiian Drosophila, which boasts up to 1,000 species in several taxonomic groups. Using genome sequencing and gene expression analyses coupled with detailed behavioral and physiological measurements we have identified genes that are involved in temperature adaptation between two species and between two populations within one species along an environmental gradient. We have also identified genes and epicuticular hydrocarbons that are involved in behavioral reproductive isolation and hybrid sterility between species. Initial studies have begun on the interaction with microbes, (bacteria and yeasts) that are important for food, internal parasites/symbionts, and possibly host-plant associations. In collaboration with others, we are also investigating the genetics of Hawaiian bats and birds, Drosophila melanogaster, the invasive Drosophila suzukii, and Hawaiian Metrosideros trees.

Helen J. Wing

Helen J. Wing is an Associate Professor of Molecular Microbiology in the School of Life Sciences at the University of Nevada, Las Vegas. She obtained her Ph.D. in Biochemistry from the University of Birmingham (UK) in 1997, where she studied transcriptional gene regulation in Escherichia coli. She worked with both Prof. Stephen J.W. Busby and Prof. John R. Guest in her first post-doctoral position, where she employed biochemical approaches to study transcription. In 2000, Helen moved to the U.S. to take a post-doctoral position with Marcia B. Goldberg M.D. at Harvard Medical School and Massachusetts General Hospital. It was here that she became interested in the transcriptional regulation of Shigella virulence genes and antimicrobial peptides. She joined the faculty at the University of Nevada, Las Vegas in 2005.
The primary focus of my research laboratory is virulence gene expression in the bacterial pathogen Shigella flexneri, the causal agent of bacillary dysentery, which is estimated to kill over 1 million people each year. All four species of Shigella harbor a large virulence plasmid, which carries most of the genes required to cause disease in the human host, including those required for invasion, type III secretion and actin-based motility, a process that allows bacteria to spread from one human cell to another. We are interested in the environmental cues, the timing and the molecular events that trigger the expression of virulence genes. We are particularly interested in the complex interplay between nucleoid structuring proteins, proteins that facilitate the packaging of DNA into tiny cells, and the transcriptional regulators of virulence in Shigella VirF and VirB.

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.

Jeffery Shen

Dr. Shen’s research focuses on development of databases and bioinformatics tools for genome analyses and gene annotations, predictions of genes responsive to environmental/developmental cues, and predictions of gene functions (subcellular localization, and protein motifs). Another focus of my research is the molecular mechanism controlling plant responses to abiotic stresses, seed dormancy and germination. He is also interested in the mechanism underlying tissue-specific and developmentally-regulated gene expression.

The recent accomplishment in sequencing the genomes of thousands of organisms, including human being and important crops such as rice, is leading to a revolution in scientific research, medicine discovery, and improvement of the quality of our food. His lab is interested in developing (adopting, modifying, and inventing) bioinformatics tools for genome analyses and gene ontology studies. Gene ontology addresses: Biological Process (Why is this, such as cell enlargement, being done?), Molecular Function (What kind of molecule is this? Enzymes or transcription factors?), and Cellular Component (Where is this located? Nuclei or Mitochondria?).