M. R. Kerbel
May 30, 2018
Citations
373
Influential Citations
5,337
Citations
Quality indicators
Journal
Remote & Controlled
Abstract
We recently generated new models to study the role of Tau, a key protein in the development of Alzheimer’s and neurodegenerative diseases. Over the last two years we obtained data that Tau affects the stability of DNA and the transcription of genes which provided the basis for further studies funded by a new grant from NIH. In addition, we established Drosophila as a model to investigate effects of botanicals on age-related changes like reduced locomotion and disrupted sleep. These studies are part of a collaborative effort to study the beneficial effects of botanicals using different animal models with the goal to identify plant extracts and compounds that promote resilience during aging. These studies have also recently been funded by a multidisciplinary project grant. Human disease risk represents a very complex set of interacting factors, including environmental and work-place stress and chemical exposures as well has inter-individual differences in genetic composition. One of the best-documented outcomes of stress is the production of chemi-cals that have the capacity to damage the genetic material within cells. Although all cells have defenses and DNA repair mechanisms to combat this damage, the efficiencies with which cells can respond varies between individuals and thus can modify disease risk. Over the past year, we have had several publications characterizing inter-individual differences in DNA repair and the mechanisms through which maximizing repair can lead to prolonged health. The research focus of my laboratory is on the biochemical mechanisms and regulation of DNA repair systems. The goal of this research is to translate basic science disco-veries related to cellular DNA damage response pathways into actionable clinical interventions and improved therapeutic response. We made significant advances during 2019-2020 in our understanding of a novel druggable target for acute myeloid leuke-mia (AML). AML is a complex blood cell disease in which different genomic alterations define multiple subtypes that confer significant differences in patient prognoses. We have shown that deficiencies in a DNA repair enzyme make these cancer cells more susceptible to killing by conventional chemotherapy which suggests that small mole-cule inhibitors of this enzyme may be a beneficial therapeutic approach for AML. I Improvement of Mentored Experiences in Research Train-the-Trainers Facilitating Mentoring, CIMER My research focuses on the health effect of environmental pollutants such as particulate matter. Air pollution has been confirmed as an important risk factor for global mortality and cardiovascular disease. Our current projects aim to investigate the underlying mechanisms by which air pollutants promote diabetes and cardiovascular diseases. The laboratory utilizes state-of-the-art whole body mouse exposure systems and various molecular, physiologic, immunologic, and imaging approaches to dissect the role of inflammatory regulation and lipid oxidation in air pollution-associated cardiometabolic diseases. Circadian rhythms are 24-hour cycles in physiology regulated by the brain‘s suprachiasmatic nucleus (SCN). Neuronal network activity is required for the brain‘s circadian clock‘s proper function. We used a combination of electrophysiological and long-term imaging methods to study cellular mechanisms required for circadian clock function. We demonstrated that the circadian neural network uses endocannabinoids, adeno-sine, and gamma-aminobutyric acid (GABA) as intercellular signaling between SCN neurons and astrocytes. These signaling compounds synchronize the electrical activity and the molecular circadian clocks of the SCN neurons. These findings suggest that intercellular and possibly long-range SCN GABAergic signaling is essential for behavioral rhythmicity and proper functioning of the SCN neural network. Disruptions of our internal body clocks and sleep, as often encountered by shift workers, increase the risk for disease. The goals in our laboratory are to understand how endogenous clocks in the body are synchronized, and how these regulate physiology and behavior. We use neuroendocrinology and behavior studies in mouse models and prospective and cross-sectional cohort studies to inform our approaches. Our current studies examine the mechanisms of androgen recepters and sex differences in the circadian clock. We have discovered a hormonal effect on light sensitivity and activity levels in mice. We are also examining the reproductive consequences of shift work and the gender differences in the association of sleep apnea, heart disease, and mortality. made conducting this research difficult, I pivoted to use the consequences of the pandemic on professional sports as a natural experiment to determine the impact of travel on athletic performance. These findings garnered much local and national attention, including the entire front page of the Sunday sports section of the Oregonian, Oregon’s largest newspaper, and an interview on National Public Radio’s “All Things Considered” radio show. Insufficient sleep is related to workplace safety, high risk for obesity, chronic disease, and early mortality. Long haul team truck drivers, where one driver sleeps in a moving vehicle while the other partner drives, face especially challenging sleeping conditions. Our Tech4Rest pilot study evaluated interventions to advance team drivers’ sleep, health, and well-being: (1) a therapeutic mattress system vs. a traditional coil spring mattress, and (2) then we added an active suspension seat and a behavioral healthy sleep intervention (Fit4Sleep, adapted from our effective Safety & Health Involvement For Truckers [SHIFT] program). Compared to a new coil spring mattress, the therapeutic mattress altered the prevalence of certain vibration frequencies, produced greater improvements in fatigue and sleep, and was universally preferred. The addition of the seat and behavioral program produced the largest effects on sleep outcomes, as well as new additional improvements in physical activity. My research team focuses on improving the quality of life for individuals through building a healthy and safe workplace, mainly through improving organizational safety culture and climate. Over the past two decades, I have developed and applied an interdisciplinary approach in order to ensure employees’ health, well-being and safety at work. Besides conducting scientific research, My team has also provided consulting ser-vices to the field by putting scientific approaches into practice. In addition, my lab is focusing on examining and evaluating possible interventions that could help improve workplace safety culture and climate and, in turn, promote organizational and societal well-being. We published the results of an NIEHS-funded study of Egyptian pesticide workers exposed primarily to chlorpyrifos, among the most widely-used pesticides in the world and a bioterrorism agent. We demonstrated for the first time a dose-res-ponse in a test of motor and cognitive performance based on job title (applicator, technician, engineer, control). This established that long-term exposure to chlor-pyrifos is neurotoxic in adult workers. It also suggested that the mechanism that produced the neurotoxicity was different following long-term exposures than in short-term exposures, which explained the mystery of why neurotoxic effects in many prior studies had not correlated with biomarkers of short-term exposures.