Personal Statement
I am a basic science investigator, primarily involved in laboratory research. My professional expertise addresses neuroendocrine mechanisms, i.e., how the brain controls hormones and how hormones control the brain.
My lab currently uses rat models to investigate mechanisms contributing to excessive alcohol drinking, mechanisms mediating resilience or vulnerability to developing PTSD after traumatic stress, and interactions between stress and alcohol drinking. Our main methods include a range of behavioral models, pharmacologic and hormonal interventions, gene expression analyses within microdissected brain areas, analyses of hormonal responses, and use of selectively-bred rat strains. Most of our current studies have immediate translational utility – informing and in some cases derived from clinical studies by our collaborators.
The organization of our current studies reflects the grants that support them. The studies in the first (NIH R01, Noradrenergic Agents As Potential New Pharmacotherapies for Alcohol Drinking) all use the selectively-bred alcohol-preferring (P) rats to address: [1] optimal prazosin dosing parameters, specificity; [2] use of prazosin alone or in combination with naltrexone; [3] phases of the alcohol addiction/relapse process sensitive to prazosin; [4] gender effects; [5] responses to other adrenergic agents; [6] effects on alcohol seeking vs alcohol consumption; and [7] initial studies of mechanisms. A recent high impact finding from these studies is that combinations of drugs addressing different mechanisms mediating excessive alcohol drinking can be much more effective than either of the individual drugs (e.g., prazosin + naltrexone, prazosin + propranolol). Studies in the second (DoD, Stress and PTSD Mechanisms as Targets for Pharmacotherapy of Alcohol Abuse, Addiction and Relapse) use an outbred rat model to address: [1] whether anxiety behavior and/or acoustic startle response can predict which subjects will develop high levels of alcohol drinking when provided intermittent repeated opportunities to drink, which subjects will progress to compulsive alcohol drinking, and if prazosin will be effective in reducing this alcohol drinking once it is established; [2] whether anxiety behavior and/or startle response can predict the effectiveness of prazosin in blocking initial development of high levels of alcohol drinking; [3] whether prazosin will block stress-induced increases in alcohol drinking; [4] whether alcohol dependence increases vulnerability to developing a PTSD-like condition after experiencing a traumatic stress; [5] whether hyperexcitability and/or anxiety associated with development of a PTSD-like condition can predict how effective prazosin will be in reducing associated alcohol drinking; and [6] whether administration of prazosin at the time of traumatic stress will prevent subsequent development of a PTSD-like condition and increased alcohol drinking.
Personal Statement
My research interests cover two main areas:
1) development and use of novel radioligands for positron emission tomography (PET) in CNS disorders
2) cannabinoid pharmacology, and cannabis use disorder and comorbid neuropsychiatric disorders
My VA Career Development Award (VA equivalent of an NIH K-award) focuses on the translational development of imaging neuroinflammation with PET following repetitive blast mild traumatic brain injury (mTBI). In collaboration with David Cook’s lab, imaging neuroinflammation in a mouse model of repetitive mTBI provides an opportunity to compare imaging outcomes directly with histopathology in brain tissue, which is not possible in humans. In collaboration with Elaine Peskind, imaging neuroinflammation in Veterans with mTBI and persistent post-concussive symptoms provides neuroanatomical specificity to ongoing neuroinflammation, which to date has been informed using cerebrospinal fluid and serum biomarkers. To accomplish this, my laboratory evaluates and develops established and novel PET radioligands for biomarkers of neuroinflammation. Additionally, I am interested in developing novel radioligands for druggable targets for which there are no current, suitable radioligands available. I have several ongoing collaborations with other investigators at UW and VA in which I provide support with PET imaging.
As a clinician and researcher, I am interested in how patients use cannabis for perceived therapeutic effect, and the risks and adverse outcomes resulting from substantial or chronic cannabis use. These clinical patterns can now be placed into context with a better understanding of the endocannabinoid system (ECS), which provide opportunity for more selective and safer therapeutic drug development. Due in part to the recentness of discovery of the ECS, one of my goals is to educate clinical providers on the preclinical and evidenced based research conducted to date on cannabis use and the ECS so they are better informed when discussing cannabis use with patients, and better prepared for understanding mechanisms of anticipated ECS-based medications currently under development. A second goal is to conduct research on cannabis use disorder and comorbid conditions, and identification of therapies that might better address a patient’s desired outcome from cannabis use, thereby reducing the likelihood of its associated risks.
Personal Statement
Over the last 25 years, my work has focused on relationships between stress and health in several risk groups (spouse caregivers of persons with Alzheimer’s disease, medical students, psychiatric/medical outpatients/inpatients, air traffic controllers, and camp counselors). We have developed and/or revised measures of medical student stress, caregiver burden, patient anger/dyscontrol, process coping, appraisal, neuropsychological function and physician awareness of patient problems. These measures have been used by university researchers, insurance companies, pharmaceutical companies in clinical trials, prisons, nursing homes/long term care, rehabilitation facilities, and public health organizations. These psychosocial and behavioral measures have been shown to predict and be predicted by physiological and cognitive measures. We have also focused on moderators of such relationships, such as gender, personality, and co-morbidities. We have used primarily multicohort long-term studies that allow for interactions between exposures to stressors, hard-wired vulnerabilities, and more temporal resources. We attempted to identify mechanisms that can be potentially altered to have long-term public health significance in persons under chronic stress. I have also attempted to isolate groups that are at high risk for negative outcomes. In a perfect world, interventions should be used to help all persons who have deleterious responses to stress, but society cannot afford this. For this reason, the identification of high risk groups is imperative for maximizing the effect of interventions.
My research program’s long range goal is to better understand the mechanisms by which chronic stress translates into physical, mental, or cognitive health problems. We are examining caregivers of spouses with AD and demographically-similar spouse non-caregivers across time and assessing the degree to which elevated depression, stress hormones, inflammation, and insulin resistance in caregivers predict cognitive decline in caregivers relative to non-caregivers. We are also attempting to replicate our earlier work that showed that chronic stress and chronic disease moderate each other’s physiological risks. For example, physiological dysregulation that is specific to a disease (e.g., metabolic syndrome with CHD, blood pressure reactivity with hypertension, and immune function with cancer history, HbA1c with diabetes) is exacerbated in caregivers with a chronic disease relative to non-caregivers with a chronic disease, but no such differences occur in caregivers versus non-caregivers without a chronic disease. Finally, we are examining a large cohort of older adults sampled from various U.S. communities in order to assess the influence of life stressors on long term cognitive function and potential mediators of such changes.
Personal Statement
I am clinical psychologist and a Professor of Psychiatry and Pediatrics, and a clinical researcher specializing in ADHD throughout the lifespan. I direct the PEARL Clinic (Program to enhance attention, regulation, and learning) at Seattle Children’s. The PEARL Clinic is based on a multidisciplinary and collaborative care model which works closely with PCP’s who refer families to PEARL for evaluation and access to our behavioral group treatment programs and treatment recommendations. The PEARL clinic also provided multidisciplinary training for psychologists, psychiatrists, pediatricians, family medicine physicians, and medical students. The majority of my clinical work involves diagnostic evaluations and consultations for the parents, referring physician, and schools.
My research emphasis is on personalizing ADHD treatment, and determining how best to combine and sequence interventions throughout the lifespan for individuals with ADHD. I have assisted in the development of several stimulant and non stimulant medications, and participated in many clinical trials. Currently, we are conducting a study for parents with ADHD who have young children with ADHD symptoms where we are treating the parent with medication and behavioral parent training or behavior parent training. I am also investigating the relationship between genetic factors and ADHD treatment response.
Other areas of interest include sleep problems and overlap with ADHD, and novel treatments such as Trigeminal Nerve Stimulation (TNS) and augmentation strategies such as mindfulness and physical exercise or activity level.
Personal Statement
I am a basic neuroscientist, a board-certified practicing psychiatrist, and an Assistant Professor of Psychiatry and Behavioral Sciences at the University of Washington Medical School. The goal of my research is to investigate the neural circuitry of cognitive, emotional and memory processing, particularly as it relates to the cerebellum, and illnesses affecting cerebellum including cognitive disorders, PTSD, TBI and dementia through the implementation of techniques in mouse behavioral genetics. In my clinical practice, I primarily see veterans with PTSD, mild cognitive impairment, and various forms of dementia in an outpatient clinic at the VAMC Puget Sound Geriatric Research, Education, and Clinical Center (GRECC) in Seattle. I have over 15 years of experience in basic science research with most of that time dedicated to the use of mouse models of neuropsychiatric disorders.
Throughout my training prior to and during graduate school, I gained background in many contemporary molecular and biochemical lab techniques, such as molecular cloning, protein biochemistry, protein crystal production, fluorometric measurement of protein kinetics, in vivo NMR spectroscopy, gene targeting, microarray genomics, immunohistochemistry, and mammalian cell culture. I have a foundation in mouse genetics, neural development, and behavior which I developed in Michael Georgieff’s lab by investigating the role of iron in developing pyramidal neurons of the mouse hippocampus. During graduate training, I also received cross-training in child psychological development. In graduate school, I developed two mouse models of nonanemic neuron specific iron deficiency: 1) a conditional knockout of the Slc11a2 gene, encoding the iron transporter DMT-1 in forebrain neurons, including hippocampal pyramidal neurons, and 2) a transgenic mouse with a reversibly inducible dominant negative (nonfunctional) form of the transferrin receptor expressed only in hippocampal pyramidal neurons. I utilized and implemented different versions of the Morris Water Maze to study learning deficits in these mouse models of perinatal brain iron deficiency, a condition that is often a consequence of diabetes during pregnancy.
During my residency training, I expanded my knowledge of neuropsychiatric disorders by directly evaluating and treating patients with neuropsychiatric disorders including PTSD, schizophrenia, Alzheimer’s disease, autism, major depression, substance abuse disorders, and personality disorders. I learned numerous pharmacological, neuromodulatory, and psychotherapeutic interventions and participated in the internally funded Neuroscience Research Track. I then received a NIMH career development award (K08) mentored by Larry Zweifel, Ph.D. In that position, I investigated interactions between catecholamines and the cerebellum in decision making, emotional and cognitive processing. In the 5 years I was in Dr. Zweifel’s lab, I learned many additional new techniques including use of viral vectors, in vivo electrophysiology, and several operant- and threat-based behaviors, and moved forward in my goal of becoming a physician scientist isolating important circuits underlying etiology of specific domains of behavioral function. This work culminated in my receiving an RO1 independent investigator award, without any gap in funding.
My current research utilizes mouse behavior, in vivo electrophysiological recordings, gene targeting, viral vectors, translational profiling, chemo- and optogenetic tools, site-specific intracranial viral vector injection, and protein chemistry. I am now forging my path as an independent investigator, and my primary goal is to understand cerebellar circuits as they relate to psychiatric and neurodegenerative illnesses and utilize this knowledge to inform and improve current and novel psychiatric illnesses, primarily in cognitive and emotional domains. As such, I am pursuing a multidisciplinary approach combining genetic, electrophysiological, pharmacological, and behavioral techniques.
Personal Statement
My research program focuses on understanding brain circuitry involved in mood regulation, including models of depression and anxiety, and also circuits related to substance abuse. Our experiments are conducted in mice that have been genetically engineered to disrupt the function of certain brain regions, or to allow the manipulation of brain activity with pulses of light, a method called “optogenetics.” Our studies uses neuroanatomical methods, electrophysiology, and behavioral assays to understand the the outcome of these genetic and optogenetic manipulations. Of current interest in the lab is the function of a poorly understood brain region called the habenula. Historically my laboratory has also focused on brain development and the role of regulatory molecules called transcription factors in determining the identity of specific kinds of neurons. We are continuing to study developmental gene regulation in the context of craniofacial development and birth defects. Our research is funded by grants from the NIH institutes NIMH and NIDA.
Personal Statement
Over the past 20 years, my research has focused on the genetics of schizophrenia and neurodegenerative disorders, particularly on the use of clinical phenotyping and innovative genomic technologies to elucidate the complex genetic architecture underlying schizophrenia and Alzheimer’s disease (AD). I served as the Director of the Geriatric Research, Education, and Clinical Center (GRECC) at the VA Puget Sound Health (VAPS) from 2011-2022, in order to focus on my research on Alzheimer’s Disease and related disorders. My current research interests are two-pronged: 1) develop machine learning models in VA’s vast electronic health records in order to assign ADRD probability scores in older Black and White Veterans; and 2) use mobile health devices to promote early diagnosis of dementia with Lewy bodies. In In these capacities, I direct multidisciplinary efforts to better understand the biology, genetics, etiology, prevention, and treatment of these disorders, and I provide clinical expertise for the differential diagnosis of neurodegenerative disorders and treatment of behavioral disturbances in dementias.
Personal Statement
My clinical interests include diagnosis and psychopharmacology of complex mood and anxiety disorders and psychosis. My research program investigates the molecular neuroscience of behavior using animal models with a focus on the involvement of the serotonin system and the neurocircuitry and plasticity involved in stress and addiction.
My lab uses rat and mouse models to investigate stress and addiction mechanisms. The lab is unusual because we pursue a very broad range of methods, including molecular, cellular, neuroanatomical, and behavioral levels of organization. We have focused on serotonin receptors historically but increasingly we are using novel molecular and genetic tools to dissect the involvement of key neural circuits in behavioral models of stress and/or addiction.
The main strategies include a range of behavioral models, intersectional transgenic and viral-mediated gene transfer manipulations of gene expression, neuropharmacology, engineered receptors (DREADDs), fiber photometry, calcium imaging, two-photon microscopy, RNAseq and RTqPCR (using RiboTag pull-down). We are trying to push the envelope in developing and using methods that allow us very precise manipulations or readouts from specific pathways such as the projections from nucleus accumbens to ventral tegmentum or lateral habenula to dorsal raphe nucleus. We are also exploring the role of microglia, the innate immune cells in the brain, during early stages of drug and alcohol withdrawal in advance of typical activation of neuroinflammation.
