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.

Cory Rusinek

Professor Rusinek is interested in electroanalytical chemistry, sensor development, and materials technology. This includes development in both biological and environmental sensing where applications in neurochemical detection, wearable sensors, and environmental monitoring coalesce for tangible impact on society. Prof. Rusinek is also interested in electrochemical methods for fundamental understanding of molten salt chemistry. In Prof. Rusinek’s group, students are exposed to a multi-disciplinary environment, pulling from knowledge in chemistry, electrochemistry, chemical engineering, and materials science.

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.

Iain Buxton

The Buxton lab is exploring contraction-relaxation coupling in the uterine myometrium in order to better understand and develop treatments for the problem of preterm labor. Preterm delivery of an underdeveloped fetus is a global problem. Babies delivered prior to full development at term have multiple medical problems that plague these individuals throughout their lifetime. Prematurity explains 75% of all fetal morbidity and mortality. Thus, beyond the tragic and costly fact of their prematurity, is the major impact on individuals and societies long-term. There are no effective (or FDA-approved) medications that prevent contractions of the uterus in patients who enter labor preterm (PTL). What is used is ineffective at allowing the fetus to remain in the womb until term. Drugs employed to prevent PTL (tocolytics) are only evaluated for an ability to prevent labor for 48 hours, a time during which treatments can ready the fetus to breath air. PTL leads to preterm delivery (PTD) in over 50% of cases. Spontaneous PTL (sPTL, no explanation such as infection) accounts for the majority of PTL.

The approach to sPTL we are pursuing is based on the non-canonical pathway by which NO relaxes myometrium. Our approach hypothesizes specific S-nitrosation differences in the protein fingerprint of sPTL compared with laboring myometrium. What is needed to investigate sPTL is to know the specific proteins that are post-translationally S-nitrosated and their abundance and/or unique presence and the impact of their S-nitrosation in pregnancy, labor and sPTL.

We have discovered particular unique proteins that are deferentially S-nitrosated and are pursuing their role in mediating relaxation on pregnancy and labor. One such protein is a channel called TREK-1. This channel is stretch-activated. We discovered genetic variants of the channel associated with PTL in women. Electrophysiological measurement of these gene variant channels suggests that their expression in women may constitute a mechanism to explain PTL in these patients. Drug discovery is in process to generate therapeutics to treat this form of PTL.

In a second thrust, the Buxton lab is looking for therapeutic targets in breast cancer. Tumor cells migrate to distant sites in the body before they are capable of forming aggressive metastases and thus remain dormant. We do not know the cellular behavior of disease we label latent but attracting a blood supply may be an early property that precedes and is required for those lesions that become malignant in women. Breast cancer specific mortality is almost exclusively a function of metastasis. Growth of tumor cells as metastases dictates that tumor cells must first develop a capillary blood supply or risk necrosis. Metastatic tumor cells have already attracted a blood supply, a hallmark of cancer. What activates dormant cells at metastatic sites to move from a quiescent to aggressive phenotype is not known. It is critical to determine the effect of a kinase we discovered to be released from cancer cells because every indication is that it produces a blood supply for cells that can later become malignant, an event that cannot take place unless a blood supply is available. Our current experiments are focused on the actions of the kinase that permit intravasation and extravasation of tumor cells that permit their passage to distant sites in the body where they can lodge and remain undetected for years. We have developed an inhibitor of the kinase and hope to demonstrate its potential a breast cancer prophylactic.

Pradip Bhowmik

My interests focus on organic and polymer synthesis in general. More specifically, we are interested in developing novel light-emitting and liquid-crystalline polymers for their multitude applications in modern technology including biosensors. In another project, we are developing ionic liquids based on the concept of green chemistry, and liquid-crystalline and light-emitting organic salts to make them functional materials. Carbon nanotube-based composite materials based on ionic polymers are of significant interest in our group. In recent years, we are also actively pursuing for the development of cisplatin analogs for the development cancer therapy.

Dustin Hines

The brain operates as a complex orchestration that involves many different cellular players. Dr. Dustin Hines’ research is aimed at understanding the role that glial cells play under normal and pathological conditions, which include neuropsychiatric disorders (depression), traumatic brain injury, stroke and Alzheimer disease. In particular, Dr. Hines researches how astrocytes and microglia cells both talk and listen to neurons. Dr. Hines employs molecular genetics, biochemistry, confocal and two photon microscopy, electrophysiology and behavioral assessments in mouse models to gain understanding of how glia cells impact brain signaling, circuitry and behavior. Dr. Hines’ research ultimately is directed towards understanding how all of the cells of the brain are orchestrated into the precise symphony that we call behavior.

Yu Kuang

Dr Kuang is currently the Lincy Endowed Assistant Professor and American Board Radiology board certified therapeutic medical physicist in the CAMPEP accredited Medical Physics Program at the University of Nevada, Las Vegas (UNLV). He obtained his Ph.D. in Biomedical Engineering from Case Western Reserve University in 2009 and completed my medical physics postdoctoral training at the University of Michigan in 2010 and Stanford University in 2012. His clinical emphasis is on the routine external beam radiotherapy physics practice and SBRT techniques. His research focuses on the development and clinical integration of novel medical imaging devices with medical linear accelerator and proton therapy device; real-time image guided and adaptive radiation therapy; combining biological- and imaging- biomarkers for early detection of cancers and cancer Interventions; nanotechnology and its application in imaging and therapeutics; molecular imaging for radiation biology and clinical applications.

Brendan Morris

research in computationally efficient intelligent systems. The lab combines computer vision, machine learning, and pattern recognition to develop “real” solutions. Intelligent systems are those that are able to observe the world, learn from these observations, and understand the environment. The real-time systems are designed to operate continuously and robustly through all operating modes.

Research areas of interest include traffic monitoring and pedestrian safety, activity analysis and assessment, visual object recognition, self-driving cars.

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.

Amber Howerton

Dr. Howerton is an Assistant Professor of Chemistry at Nevada State College.  Dr. Howerton is actively involved in undergraduate research both as independent studies during the school year and as a mentor in summer NSF-INBRE.  Her research centers around sporulating bacteria (Bacillus anthracis, Bacillus cereus, Clostridium difficile).  Her students have studied germination kinetics to identify activation and inhibition compounds, synthesized potential spore germination inhibitors and studied the inflammation response initiated by these bacterial toxins and spore proteins. Also, as a researcher of C. diff,  she is interested in the microbiome of the intestine before and after antibiotic use.  Her students have studied bile salt hydrolases and their expression before and after rodents are treated with antibiotics. It is possible these enzymes play some role in the observable different susceptibility of rodents to C.diff.  She is always up for new adventures if students present me with a workable research proposal!