The relationship between humans and robots is full of feedback loops: how our brain processes what we see, feel, and act affects how the intelligent machine reacts and vice versa. Understanding this feedback loop will enable us to design better day-to-day automated systems. For instance, operations performed with surgical robots are guided with the surgeon’s movement. My research in the UW BioRobotics Laboratory investigates how the human brain adapts to technology. I programmed a haptic paddle to apply timed forces on human subjects to investigate how uncertainty, in the form of a disturbance, affects response over time. Understanding how human behavior changes is crucial for improving automated systems that can be simulated by the haptic paddle such as cable-driven surgical robots. We apply the haptic paddle to model forces a surgeon may experience during surgery, such as tough tissues or other disturbances, while operating a robotic surgical device. As we measure the participant’s learning curve over longer periods and more trials, the participant builds a better understanding of how to react relative to their force exerted on to the paddle. By increasing our understanding of how the human brain works, we can begin to improve precision of surgical operation.

After neurologic injuries like stroke, users must relearn how to interact with devices to achieve different tasks. However, hand dominance before and after neurologic injury could affect motor learning and recovery. Understanding a) whether hand dominance plays an effect on motor learning and adaptation of predictive (i.e. feedforward) and reactive (i.e. feedback) controllers and b) how motor learning is impacted by which side was affected by stroke is crucial for personalizing rehabilitation techniques. We are currently investigating the effect of hand dominance on motor learning during continuous tasks for users without motor impairments. 10 participants were asked to play a simple trajectory-tracking game, first with their non-dominant hand and then with their dominant hand. We found that participants’ feedback controllers improved with practice for their non-dominant hand (p=0.005), but their feedforward controllers were unchanged (p=0.88). Furthermore, the participants transferred their feedback controller from their non-dominant hand to their dominant hand (p=0.33). This suggests that the non-dominant hand may be more specialized for error correction and impedance control, and that rehabilitation for users who had a right-hemisphere stroke should focus on improving reactive control.

The mobility of autonomous walking robots is an essential characteristic in their operation. Due to currently imposed constraints in battery technology, the optimization of robotic locomotion for energy efficiency is paramount. Previously, elastic payload suspension has been employed to reduce the cost of transportation in a hexapedal robot. Prior results suggest that the optimal load suspension characteristics are a function of robot morphology and locomotion strategy. A payload suspension system that can be easily adjusted would allow for the accommodation of a variety of these morphologies and locomotion strategies. We have designed a tunable suspension system that will allow for experimentally determining optimal suspension characteristics in a cost-effective manner. The design enables continuous adjustment of the suspension stiffness and damping, so optimal parameters can be determined through hardware experimentation. This hardware experimentation allows for the creation of a numerical model for an oscillating payload’s behavior, which can be compared to simulations. We have completed calculations and design of this hardware, and anticipate seeing that the data collected from its usage will verify the utilization of a haptic testing system in robotics development and allow us to determine methods for calculating the best parameters for elastic payload suspension. This verification of simulated data will allow for further research in developing more efficient methods of payload attachment to legged robots, examination of locomotion when carrying payloads, and design of payload management methods.

Though renewed efforts in tuberculosis (TB) research have facilitated massive strides in treating Mycobacterium tuberculosis (Mtb), TB remains a global health problem with an estimated 10 million infections and 1.5 million deaths in 2018. The ability of the pathogen to sequester itself inside a granuloma, a mass of immune cells whose precise mechanism of regulation is unknown, prevents the simple study of Mtb pathogenesis and subsequent treatment discovery. Current in vivo models have been established to study TB infection using animal models or tissues, limiting biological relevance of human disease while current in vitro models lack components of the complex lung microenvironment during infection. We present the creation of a novel microscale infection model, which uses open and suspended microfluidic principles to enable spatial and temporal manipulation of cultures in suspended hydrogel plugs. Utilizing the ‘stacking’ feature of the device, we demonstrate the ability of a model granuloma consisting of M.bovis BCG (Mycobacterium bovis bacille Calmette-Guérin) and monocyte-derived macrophages to interact with a model vasculature layer consisting of endothelial cells. Analysis of soluble factors for proinflammatory cytokines and characterization of infection-dependent angiogenesis in the vasculature layer are used to verify crosstalk between cultures. In the future, we envision this model expanding to contain multiple immune cell types and to incorporate additional aspects of the lung anatomy to approach a more accurate pathophysiological model as a tool for other researchers’ studies.

Adolescents with newly diagnosed T1D are at risk for poor physical and psychosocial outcomes. We explored associations between glycemic control (A1C) with diabetes-distress, resilience, and psychosocial comorbidities (e.g., depression) over the first five years of diagnosis. Adolescents, aged 10-17, with newly diagnosed T1D completed validated diabetes-distress and resilience scales one-year post-diagnosis. Psychosocial comorbidities and A1C were extracted from patient charts for 5-years from diagnosis, and A1C values were averaged per year. Regression analyses were used to investigate associations between resilience, diabetes-distress and psychosocial comorbidities with A1C. A1C was assessed annually up to five years post-diagnosis. At one-year post-diagnosis, N=60 adolescents (M=13.22±2.09 years) completed distress (M=27.97±7.01) and resilience scales (M=40.35±17.10). Average A1C at 1-year was 7.73± 1.57 and at 5-years was 8.78 ±1.92. 14% of the sample had at least one psychosocial comorbidity at diagnosis. Between years 1-5 post diagnosis, 28.6% of the sample had at least one comorbidity. The most common comorbidities were depression and anxiety. Diabetes-distress was associated with average A1C in the second year (F(1,29)=4.397, p=.045, R2=.132), third year, (F(1,27)=6.596, p=.016, R2=.196), fourth year, (F(1,24)=10.196, p=.004, R2=.298), and fifth year post-diagnosis (F(1,19)=10.665, p=.004, R2=.360). Resilience was associated with average A1C in the second year (F(1,29)=6.848, p=.014, R2=.191) and fifth years (F(1,19)=4.790, p=.041, R2=.201) post-diagnosis. Total psychosocial comorbidities at diagnosis was associated with average A1C in the second year (F(1,49)=2.209, p<.01), third year (F(1,45)=7.925, p<.01), and fifth year (F(1,28)=7.919, p<.01) post diagnosis. The first year of diagnosis for adolescents with T1D is crucial for detecting patients who are at a higher risk for developing poorer health outcomes. Adolescents who present with psychosocial comorbidities at diagnosis and report poor resilience and high distress one year later are at risk for subsequent poor glycemic control. 

Understanding complex population dynamics between species is key for guiding environmental and wildlife management decisions. Accurately identifying the diet of various predator species across northeastern Washington (NEWA) and central Washington (CWA) can provide comprehensive insight into these relationships in terms of predator-predator and predator-prey dynamics. DNA metabarcoding can identify species-specific DNA within a sample and presents an ideal way to perform diet analysis in this context. In a previous NEWA study, the diet profiles of a range of predators were fully resolved, but for the American black bear (Ursus americanus), approximately 80% of its diet composition was undetermined. For increased understanding of the black bear’s diet in Washington, prey species must be identified across a range of geographic areas. This study compares the prey components of the black bear’s diet in both NEWA and CWA in order to provide a comprehensive analysis of its role in the predator-prey community. DNA samples used for analysis were from scat collected by detection dogs during a 2015-2016 NEWA and 2018 CWA field term. Of the 12 bear samples from CWA,9 samples had identified prey and of the 15 bear samples from NEWA, 6 had identified prey. These results add valuable information about prey species composition in a key predator’s diet across a wide geographic region, as well as seasonal shifts in diet composition in relation to other carnivores in the NEWA community. Future research will be conducted on the plant portion of the black bear’s omnivorous seasonal diet. Data collected from this project will provide valuable information that must be considered for further studies on the Washington black bear population and the food groups it consumes.

Over the last decade, wolves have been naturally returning to Washington state. Mapping the population growth and reproductive activity of wolves across Washington is key to understanding their recovery and to assisting wildlife conservation management. Accurate identification of the number of pregnant wolves per pack during the breeding season could help. Progesterone levels excreted in feces provide a reliable index of pregnancy in most mammals; progesterone rises post-ovulation but only remains elevated above a “pregnancy-threshold” among females that become pregnant. Unfortunately, this pregnancy-threshold metric is less reliable in canids because progesterone levels often remain above this threshold during the typical gestation period among all post-ovulatory females, regardless of whether the females become pregnant. Since gut microbiome diversity has also been shown to differ between pregnant and non-pregnant mammals, this study examined whether the combination of progesterone levels and gut microbiome diversity can refine pregnancy diagnosis in free-ranging wolves. Five high progesterone and five low progesterone fecal samples from ten unique female wolves were provided by the Center for Conservation Biology from the 2015-2017 study in Northeast Washington. Gut microbiome profiles were generated by sequencing the V4 16S rRNA gene region in each sample and analyzed using Qiime 2 and R with the Silva reference database for microbial taxonomy classification. Principal coordinates analysis of Bray-Curtis distance between samples at the microbiome phylum level showed separate clusters among high versus low progesterone samples, with one exception. The microbiome community of one high progesterone sample clustered with the low progesterone samples. This sample also had the lowest progesterone concentration among the high progesterone samples and may thus be from a non-pregnant post-ovulatory female. These initial findings suggest that the combination of progesterone levels and microbiome diversity show promise as a pregnancy diagnostic tool that may be able to distinguish pregnant from non-pregnant wolves.

Prostate cancer (PCa) is the most commonly diagnosed and second most deadly cancer in men. Almost all of these deaths are the result of a very progressed form called metastatic, castration-resistant prostate cancer (mCRPC), which currently has no cure and is incompletely understood. Cancer-related mutations in the untranslated regions (UTRs) of mRNA transcripts have been found to contain various sequence or structural motifs that contribute to the regulation of these cancer-causing genes. These regions are extremely dynamic in their control over gene expression affecting mRNA stability and translation efficiency which have both been previously implicated in prostate cancer. However, the degree to which these mutations in the UTRs functionally contribute to prostate cancer remains poorly understood – especially in the 3’ untranslated region (3’UTR). A candidate gene list to investigate was constructed from an analysis of patient tumor sequencing data from a broad cohort of 230 localized and metastatic prostate cancer patients. I Gibson cloned wild type (WT) and mutant 3’UTRs from the candidate genes into luciferase plasmid constructs. Subsequent dual luciferase assay data revealed significant changes in protein expression between WT and mutant constructs most notably in the genes NCL and CLEC18B. Nucleolin (NCL) is a protein involved in the synthesis and maturation of ribosomes and is oncogenic in many cancers when overexpressed, while CLEC18B is largely unstudied. Given this existing functional evidence and my preliminary data, further investigation into the differential expression of NCL and the cellular mechanism through which it is achieved is warranted. My project focuses on elucidating the effects of 3’UTR somatic mutations on translational regulatory regions of the human genome, so that we may uncover new patterns in the progression of prostate cancer and subsequently elicit possible novel therapeutic targets with which to better treat these patients.

Spinal cord injury (SCI) affects the lives of over 294,000 individuals in the United States alone. Therefore, there is an urgency for development of therapies for SCI. We are exploring the role of environmental enrichment in promoting motor recovery from chronic cervical SCI that produces partial to complete forelimb paralysis in adult rats. Novelty, a major component of our environmental enrichment, has been associated with memory consolidation which could be related to the release of plasticity-related products (PRPs). PRPs are a key component of lasting plasticity changes in vitro, which could prove to be vital to motor learning after spinal cord injury. Throughout a 6-week therapy period during which the rats are exposed to environmental enrichment, motor function of the impaired forelimb is assessed using behavioral scores on a reach-and-grasp pellet-retrieval task. Our project will utilize environmental enrichment to enhance the effectiveness of our physical training paradigm. Environmental enrichment will include access to toys that provide opportunities for physical exercise, socialization, and social learning. The toys will be changed each week to promote novelty. We predict that environmental enrichment will have an additive effect in promoting recovery of the impaired forelimb when combined with physical therapy. We hope these results will help inform how neural plasticity can be deployed for design of effective therapies for promoting motor recovery after chronic SCI.

Motor injuries, such as stroke and spinal cord injury, are some of the leading causes of long-term disability and death worldwide. Patients are often left behind with debilitating consequences, such as paralysis or severe motor impairments, creating an urgent need for new therapies to be developed. A treatment option that is gaining momentum is the use of electrical stimulation to strengthen neural pathways for improving motor function of affected individuals. Towards this goal, I have investigated a novel electrical-stimulation paradigm called movement-triggered theta-burst stimulation (MT-TBS) to modulate neuronal connectivity in the motor cortex of macaque monkeys. To implement MT-TBS, a monkey is trained to perform a target-tracking task that activates wrist muscles involved in flexion and extension. While the monkey performs the task, sites in the motor cortex associated with wrist flexion or extension simultaneously receive theta burst stimulation; hence the movement triggers stimulation of cortical sites in this closed-loop system. After receiving MT-TBS, monkeys continue to perform the same target-tracking task on the days following conditioning. Early results show that 50% larger gains in cortical connectivity can be achieved on the same day of conditioning with open-loop TBS. This may indicate that MT-TBS may be an even better method for strengthening connections in the motor cortex. For my research project, I investigated the effects of MT-TBS on changes in the strength of neuronal connections in the motor cortex when coupled with repetition of the conditioned movement in the days following stimulation. In a series of experiments, MT-TBS was delivered during flexion, extension and with the muscle at rest. If successful, pairing MT-TBS with physical rehabilitation will serve as an effective strategy for aiding individuals with motor impairments.

Pain catastrophizing (PC) and pain-related self-efficacy (PSE) have both been shown to be associated with patient function in individuals with chronic pain, but the extent to which they may contribute independent variance to the prediction of pain and pain interference has been rarely examined. We conducted a secondary analysis of baseline data from a randomized controlled clinical trial with 177 individuals with chronic low back pain and/ or chronic pain associated with multiple sclerosis, muscular dystrophy, acquired amputation, and/ or spinal cord injury. We hypothesized PSE and PC would each be associated with pain interference (BPI), over and above the variance they share with each other and with a measure of pain intensity (0-10 NRS). Linear regression analyses revealed PC and PSE were each uniquely associated with BPI, after accounting for their shared variance and NRS. PC and PSE together accounted for substantial variance in BPI, over and above pain intensity, ΔR² = .20, F(1,170) = 59.74, p < .001, PC (B = 0.35, p < .001) and PSE (B = -0.20, p < .01). The findings indicate PSE and PC may play unique roles in adjustment to chronic pain, although PC may have larger effects. Conclusions regarding the causal role of PSE and PC on patient function cannot be determined from this cross-section study. However, future research should evaluate temporal and possible causal associations between PC, PSE, and subsequent changes in BPI and other important pain-related domains. Findings from such research would inform the potential importance of targeting these variables to maximize treatment benefits in individuals with chronic pain.