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.

Maryam Raeeszadeh-Sarmazdeh

Maryam Raeeszadeh-Sarmazdeh joined the University of Nevada, Reno in July 2019 as an assistant professor. Dr. Sarmazdeh was a senior research fellow in the Department of Cancer Biology at Mayo Clinic, Florida from 2017 to 2019 at Dr. Radisky’s lab, during which her work was focused on engineering novel protein-based therapeutics based on natural enzyme inhibitors. Prior to her appointment at Mayo Clinic, she was a postdoctoral scholar at the Chemical and Biomolecular Engineering Department at the University of Delaware at Prof. Wilfred Chen’s lab for 2.5 years. Dr. Sarmazdeh earned her Ph.D. in Chemical and Biomolecular Engineering from the University of Tennessee at Knoxville under Prof. Eric Boder’s supervision. There, her research was focused on generating site-specific protein immobilization on the surface and protein engineering using yeast surface display and directed evolution.

Heather Burkin

Dr. Heath Burkin’s research is focused on signaling pathways in the pregnant uterus. She has been involved in a variety of research topics related to understanding fertility and fetal, infant and child health problems at the molecular level during a career spanning approximately 10 years. This topic is extremely relevant today when 12.8% of births in the United States are premature. Since preterm birth is the leading cause of infant morbidity and mortality, it is distressing that this number is so much higher than in other developed countries.

Her research is focused on signaling pathways activated by stretch in human myometrium. An estimated 10% of preterm births can be attributed to abnormal uterine distension and mechanical forces regulate myometrial gene expression, cell growth, and contractility. Further defining the signaling pathways that regulate stretch-induced activation of the human myometrium will have important implications for the treatment of preterm labor.