2016-17 Levinson Scholars

Camille is currently a senior at the University of Washington studying bioengineering and computer science. She became interested in neuroscience during her freshman year, and joined Dr. Fetz’s lab to work on a brain-computer interface project soon after. In her current research, Camille works to develop a unified, adaptable neurophysiology system based around the NeuroChip-3 in order to allow for neural engineering in the prefrontal cortex in dynamic research environments. She is also investigating the potential efficacy of the prefrontal cortex as a site for brain-computer interface control and studying cross-cortical connectivity as a function of behavioral state. After graduation, Camille plans to pursue an M.D./Ph.D. program, specifically in the field of neural engineering, and then work in translational neural engineering research for rehabilitation medicine. She would like to thank her mentor, Dr. Eberhard Fetz, for his invaluable guidance as well as Dr. and Mrs. Arthur D. Levinson for their remarkable support of undergraduate research.

Mentor: Eberhard Fetz, Physiology & Biophysics

Project Title: Using the Neurochip-3 for Brain-computer Interface and Functional Connectivity Research in the Macaque Prefrontal Cortex

Abstract: The Neurochip-3, an autonomous head-mounted electrophysiology system for primate research, will be coupled with a variety of other technologies and used to investigate cross-cortical connectivity as a function of behavior and for research concerning the use of prefrontal cortex signals for brain-computer interface (BCI) control. A head-mounted accelerometer and a Microsoft Kinect running custom movement calculation code will be integrated with the NeuroChip-3 to allow for behavioral data and neural data from multiple sites in the primate cortex to be simultaneously recorded. Analysis of neural and behavioral data collected with the NeuroChip-3 will reveal insights into how the level and type of connectivity between the prefrontal, premotor, and motor cortices change depending on the animal’s behavioral state. In addition to this, a radio frequency communication system that will allow for the NeuroChip-3 to communicate with external operant conditioning training programs will be designed and implemented; together, the NeuroChip-3 and a training program will allow for investigation of using neural signals from the prefrontal cortex for control of a BCI effector. Most BCI systems are controlled using the motor cortex, but this area could become nonviable for BCI control if it were to be damaged by a stroke or traumatic brain injury. The prefrontal cortex, which has been shown to be susceptible to operant conditioning and activated during motor planning, could be used to control a BCI instead of the motor cortex. The design of these technologies complementary to the NeuroChip-3 provides a system with which both basic neuroscience and neural engineering research can be conducted in a variety of settings and with multiple experiment types. The research that will be conducted with the overall system will yield results concerning both cross-cortical connectivity and brain-computer interface control.

Gusti Lulu Fatima is an honors candidate in Molecular, Cellular, Developmental Biology. After growing up in Indonesia, Australia and Singapore, Lulu settled in Seattle to pursue her passion in studying life sciences. Her affinity for research was honed as she joined Dr. David Gire’s Behavioral Neuroscience Lab. During the Summer of 2016, she worked at the Center for Sensorimotor and Neural Engineering as a UW fellow, where she launched her first independent research project. Now, Lulu is continuing her work on computational models of behavior. Working with both animal and human data, her project focuses on the decision-making processes of switching between memory and sensory-based behavior.
Outside of her academic endeavors, Lulu actively volunteers at Cerdas Foundation; Project Sunshine; and Nick of Time Foundation. Driven by her goal of increasing the accessibility of mental health care in rural areas, Lulu aspires to become a physician scientist.
Lulu would like to thank Dr. David Gire, her mentors, Dr. and Mrs. Levinson for their generous support. She is extremely grateful for the opportunity to continue her research, and hopes for women from developing countries to have increased participation in science and research.

Mentor: David Gire, Psychology

Project Title: Applying Control Theory to Complex Foraging Behavior: Modelling of the Decision Making Process of Rodents in Navigation

Abstract: Behavior is part of a closed-loop neural system. The subject infers environmental stimuli to generate movement, the movement which will change its environment and in turn change the subject’s perceptions. However, most natural behavior studies adopt an open-loop experimental paradigm in which the behavior of the subject is merely observed without taking into account much of the dependencies between the stimuli and behavior, and how they change one another. In contrast, experiments that attempt to make predictions about behavior tend to deconstruct the experimental tasks into sets of binary choices until it no longer resembles natural behavior. The goal of my research is to quantify complex behavior in order to make predictions on the dominant strategies used by rats in naturalistic foraging. The experiment focuses on memory and sensory perception as two distinct strategies in foraging. We hypothesize that under constant environmental conditions with consistent location of food source the rats will be memory dominant, while the rats with dynamic food location will be sensory perception dominant. However, with an introduced stimulus that resembles a predatory odor, the rats are expected to show stereotypical trajectories, with less sensory-perception cognitive load. The projected contribution of this research is a quantification of complex behavior strategies with respect to environmental dynamics without discarding the natural contextual information pertaining to the strategies.

Dianne is currently in her second year at the University of Washington majoring in Molecular, Cellular and Developmental Biology. She became interested in research during her sophomore year of high school when she competed in Science Olympiad. Her career as an undergraduate researcher kick started the summer before her freshman year as she took part of the UW GenOM Project. Dianne’s research focuses on photoperiodic flowering in plants. She is looking at how daily temperature changes affect the expression profiles of the FLOWERING LOCUS T. After graduation Dianne plans to continue doing research while working toward a Ph.D. program in Genetics. Dianne would like to thank her mentors Dr. Kubota and Dr. Imaizumi for their time, support and guidance. Fianally, Dianne would like to give a huge thanks to Dr. and Mrs. Levinson for their funding.

Mentors: Takato Imaizumi and Akane Kubota, Biology

Project Title: Effect of Daily Temperature Changes in FLOWERING LOCUS T. Expression Profiles in Nature

Abstract: An abrupt increase in Earth’s temperature due to human activity characterizes climate change today. The effect of CO2 induced climate change is forecasted to have a direct impact in agricultural productivity. To ensure the security of crop yields, we must develop a better understanding of how the flowering mechanisms in plants are affected by temperature changes. Currently, researchers studying flowering mechanisms use insufficient growth conditions that do not resemble the natural environment plants react to. Most labs studying flowering mechanisms use constant temperatures to grow plants. This project will focus on investigating the effect of daily temperature oscillation on the expression profiles of FLOWERING LOCUS T (FT) during long day conditions (16 hours light: 8 hours dark period). FT is a chief component of florigen (flower inducing substrate) which causes plants to flower. FT expression correlates with flowering time in plants, therefore it is essential to understand the environmental factors such as temperature that regulate FT expression levels. The objective of this project is to determine how and when temperature acts as a stimuli to make plants flower. Preliminary studies have demonstrated that FT is not only expressed in the evening but is also induced in the morning in plants grown outside near the summer solstice in Seattle. From these results, we hypothesized that daily temperature differences are important for recreating the double-peaked FT pattern observed in nature. This hypothesis will be tested by growing different Arabidopsis thaliana lines under simplified temperature modified lab growth conditions which will resemble the temperature changes that occur throughout the day in nature, we will then analyze FT expression profiles. The results from this project will contribute to the development of new modified lab growth conditions, and will help to gain a better understanding of the mechanism that influence morning FT peak in nature.

Chloe (Chungeun) Lee is currently a senior at the University of Washington pursuing a degree in Neurobiology with Departmental Honors. During her first quarter at UW, she took an introductory neurobiology seminar that sparked her interest in neurological disorders. Her curiosity about this field and desire to make her own contributions led her to join Dr. Weinstein’s lab in its efforts to better understand ischemic preconditioning (IPC) and stroke. The goal of Chloe’s project is to elucidate the cellular mechanisms in microglia that connect Toll-like Receptor 4 (TLR4) and Interferon-stimulated gene (ISG) expression – which are thought to be critical in skewing microglial phenotype to a more neuroprotective mode – using an in vitro model of ischemia. She hopes that results from her project could contribute to a better understanding of neuroprotective mechanisms involved in ischemic stroke and help identify possible molecular and pharmacological targets with therapeutic potential for further investigation. Upon graduation, Chloe intends to attend medical school and eventually pursue a career in academic medicine. She would like to thank her mentors, Dr. Jonathan Weinstein, Dr. Ashley McDonough, and other lab members, for their continued guidance and support throughout her research experience. She would also like to thank Dr. Levinson and Mrs. Levinson for their generous support of her research and future endeavors.

Mentor: Jonathan Weinstein, Neurology

Project Title: Ischemia-induced Interferon Signaling in Microglia

Abstract: Ischemic stroke is the 5th most common cause of death and the leading cause of serious long-term disability in the United States. Ischemic preconditioning (IPC) refers to a neuroprotective phenomenon in which a brief ischemic episode confers robust neuroprotection against subsequent prolonged ischemia. Microglia, the resident immune cells in the brain, play a central role in ischemia-induced neuroinflammation and IPC-induced neuroprotection. Previous work in the Weinstein laboratory has demonstrated that both hypoxic/hypoglycemic (ischemia-like) conditions in vitro and transient ischemia in vivo leads to robust expression of interferon stimulated genes (ISGs) in microglia that is completely dependent on expression of type 1 interferon receptor (IFNAR1). In vitro, hypoxia/hypoglycemia-induced ISG expression is also dependent on microglial expression of TLR4. We hypothesize that TLR activation by damage-associated molecular patterns (DAMPs) induces a signal transduction cascade that leads to phosphorylation of STAT1, which is also dependent on IFNAR1. Phosphorylation of STAT1 activates specific transcription factors that induce transcription of ISGs, which in turn skews the phenotype of microglia toward a neuroprotective state. My preliminary data demonstrates that we can induce STAT1 phosphorylation in microglia by stimulating with type 1 IFNs or with specific agonists for TLR3, TLR4 and TLR9. The mechanisms by which TLRs activate IFN signaling to produce ISGs are unknown. For my project, I propose to elucidate the mechanisms connecting TLRs and ISG expression. To accomplish this, I will culture primary microglia (pMG) from wild-type (WT) and IFNAR1-/- mice in the presence of TLR agonists in combination with pharmacologic inhibitors targeting specific kinases in the TLR signaling pathway. We will use the amount of phosphorylated STAT1, measured using flow cytometry, in response to a stimulus/inhibitor combination as a metric for determining engagement of the type 1 IFN pathway. We will also directly quantify the time course of hypoxia/hypoglycemia on phosphorylation of STAT1.

Guanyou is a senior undergraduate student in the Department of Bioengineering. Nanotechnology and its biomedical applications inspired him as a freshman. He has been working to develop iron oxide based nanoparticle drug delivery system for breast cancers and glioblastoma multiforme ever since. After joining Professor Miqin Zhang’s lab, he experimented on various nanoparticle bio-conjugation schemes and tested nanoparticles’ targeting and killing effects against cancer cells at both cellular and animal level. Through his publication co-authorships, Guanyou hopes to share his work with fellow researchers and facilitate the progress in anticancer nanomedicine research. With the support of Levinson Emerging Scholars program, Guanyou is currently designing a novel nanoparticle drug delivery system which combines both immune-stimulants and chemotherapeutic drugs for synergistic anti-cancer effects. Besides his research, Guanyou also actively engages in outreach events, public talks and volunteering activities to share his passion with prospective researchers and promote research within the College of Engineering. After graduating from UW, he plans to pursue a PhD degree in Bioengineering. By delving into cancer biology and drug delivery biomaterials, he is looking forward to making more discoveries in his future anti-cancer research. Guanyou would like to thank Professor Miqin Zhang and Dr. Qingxin Mu for their remarkable mentorship and support. Last but not least, he is very grateful for the generous endowment from Dr. and Mrs. Arthur D. Levinson that drives him forward in pursuing his passion.

Mentor: Miqin Zhang, Materials Science & Engineering

Project Title: Paclitaxel and Polyinosinic:Polycytidylic Acid Conjugated Iron Oxide Nanoparticle Drug Delivery System for Breast Cancer

Abstract: Breast cancer is one of the most common and aggressive cancers among women. One out of 8 women in United States have been diagnosed with breast cancer during their lifetime. After breast cancer enters late stages, the survival rate is well below 30 percent. Due to the lethality and pervasiveness of breast cancers, the need for effective treatments is dire. Conventional breast cancer treatments usually involve invasive surgical breast tumor removal, chemotherapy and radiotherapy. However, these conventional treatments usually cause severe side effects and can barely treat metastatic breast cancers. Nanomedicine is a promising solution for cancer therapy because nanoparticle drug delivery systems can efficiently inhibit tumor growth via in situ drug delivery. Nonetheless, current anticancer nanomedicine is suffering from its limitations such as over-size, non-targeting, non-biocompatible/toxic and weak potency. Recent studies have suggested that iron oxide nanoparticle is a promising platform for anticancer drug delivery because of its small size, modifiability and biocompatibility. This project’s goal is to address these limitations on nanomedicine by designing an iron oxide nanoparticle drug delivery system that can efficiently target and selectively kill breast cancer cells. Two different kinds of anticancer agents, paclitaxel and Polyinosinic:polycytidylic Acid (Poly I:C), will be conjugated onto iron oxide nanoparticles. The FDA approved chemotherapeutic drug, Paclitaxel can stabilize the microtubule assembly during cancer cell division so that cancer cells cannot complete mitosis and eventually go through apoptosis. On the other hand, Poly I:C serves as an immunotherapeutic agent because it can promote human bodies’ immune responses against breast cancer cells. Poly I:C is an important feature of our project because it can boost human body’s intrinsic immune response against cancers. With chemotherapeutic and immunotherapeutic agents both conjugated on iron oxide nanoparticle along with targeting ligands, we expect to see stronger killing profile on breast cancer cells in live experimental animals.

Mira is a current senior pursuing a degree in Microbiology. She joined the Lagunoff lab in her freshman year and was immediately immersed in their research on viral oncogenesis, specifically, how Kaposi’s sarcoma-associated herpesvirus (KSHV) alters endothelial cells to cause Kaposi’s sarcoma (KS). Mira’s research focuses on how KSHV induces an increase in peroxisomes, cellular organelles that are heavily involved in energy metabolism. She aims to identify the specific regulatory genes responsible for this peroxisome biogenesis in order to elucidate a key pathway involved KSHV pathogenesis. The ultimate goal of her project is to identify a novel target for KS treatment. Following graduation, Mira plans on spending a year doing post-baccalaureate research before applying to Ph.D. programs. In the future, she would like to work on cancer-focused translational research to combine her passions for both human health and basic science. Mira is incredibly thankful for the mentorship of Dr. Michael Lagunoff and Ph.D. candidate Zoi Sychev, and the generous support of Dr. and Mrs. Levinson in her current and future research.

Mentor: Michael Lagunoff, Microbiology

Project Title: KSHV Modulates the Expression of Genes Involved in Peroxisome Biogenesis

Abstract: Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi’s Sarcoma (KS), a cancer of endothelial cell origin that is the most common malignancy among AIDS patients worldwide. Previous research has established that the number of peroxisomes is increased during latent KSHV infection. Peroxisomes are multifunctional cellular organelles involved in a variety of metabolic pathways important to KSHV pathogenesis. I propose to evaluate the cellular mechanism by which KSHV induces peroxisome biogenesis, thereby elucidating one of the key pathways involved in KSHV latency. I hypothesized that KSHV increases the transcription of specific regulatory genes responsible for peroxisome biogenesis. After mock and KSHV infecting endothelial cells, I evaluated gene expression of a known transcription factor, peroxisome proliferator-activated receptor alpha (PPARA), that has been implicated in peroxisome biogenesis. I used real-time PCR to quantify gene expression of PPARA, in addition to other genes involved in peroxisome formation and function. My data shows upregulation of PPARA and peroxisome-associated genes, suggesting that PPARA regulates the expression of peroxisome biogenesis. To further establish the role of PPARA in peroxisome biogenesis, I intend to silence its expression using small interfering RNA (siRNA). I will then evaluate gene expression levels of peroxisome-associated genes in PPARA siRNA-transfected endothelial cells following KSHV infection. In the absence of PPARA, I expect that expression of peroxisome-associated genes will be downregulated, suggesting that PPARA regulates them at the transcriptional level. These results will establish a key mechanism in KSHV pathogenesis, and potentially contribute to the development of novel therapeutic avenues for KS treatment.

Alexander is an Honors student in the Department of Bioengineering, as well as a Physiology major. His work focuses on the response of endothelial cells to blood pressure. Specifically, he is using an in vitro model to study whether endothelial cells from veins are able to adapt to arterial pressures, as is the case in a venous bypass graft. He hopes his work will improve the science of regenerative medicine, and help create practical, lifesaving tools for doctors and patients. In the long term, Alexander is interested in understanding and reversing the deterioration associated with the aging process (senescence), specifically cardiovascular disease, which is the leading cause of death and reduced quality of life amongst the elderly. To do this, he plans to continue his studies in graduate school, and then work on translational research in biomedical industry. Alexander is also passionate about emerging technologies like 3D printing, and works to be engaged in leadership and outreach, including through writing for the undergraduate journal Denatured and through participation in the ASUW Senate. He would like to thank his mentor Dr. Ying Zheng, along with Christian Mandrycky for helping him throughout his work. Finally, he would like to thank Dr. and Mrs. Levinson for their generous contribution, and the wonderful opportunity it has provided.

Mentor: Ying Zheng, Bioengineering

Project Title: Design of Constant Pressure Flow Syringe Pump for the Study of Pressure Responses of Endothelial Cells

Abstract: Venous grafts remain an invaluable surgical tool in coronary and peripheral bypass surgery, however graft failure rate is high. Insufficient endothelial remodeling is known to correlate with graft failure. The goal of this project is to improve understanding of how endothelial cells from veins adapt to arterial pressures by providing an in vitro model of pressure-dependent endothelial remodeling. This model will consist of a syringe-pump based constant pressure system and a microvascular flow chamber seeded with venous endothelial cells. QPCR will be used to measure venous endothelial cell response to arterial pressure and compare it to a control population. In order to provide a pump system that meets our specific pressure/flow specifications and is affordable for our lab, the constant pressure source pump will be designed out of 3D printed and open source components. Per the Creative Commons license, instructions and CAD files for creating it will be made available in the public domain. The outputs of this project are a syringe pump that outputs flow which accurately emulates pressure and flow conditions in the coronary arteries and data on the role of arterial pressure in venous endothelial remodeling, which is relevant to vein bypass grafts.

Namratha is a senior in Bioengineering at the University of Washington. In her freshmen year at the University of Washington she attended the Bioengineering seminar class and was fascinated by the impact of biomedical research in global health. Motivated by her interest to impact women’s health in low resource settings, Namratha joined the Woodrow research group in spring quarter of her freshmen year in the Department of Bioengineering to research on electrospun nanofibers as an antiretroviral drug delivery platform. With the support of the Levinson Emerging Scholar Award, Namratha has been researching on the immune-modulating effects of the stiffness and porosity of nanofibers on dendritic cells to further understand the role of biomaterials in improving the immunogenicity of vaccines. Through her cultural experiences and undergraduate studies, Namratha is motivated to pursue a research-oriented medical school to focus on global health, immunoengingeering, and clinical medicine. Namratha would like to thank her research mentors Dr. Kim Woodrow and Dr. Jaehyung Park who have continuously provided guidance and encouragement for pursuing her personal and educational goals. In addition, Namratha is grateful for the generous support given by Dr. and Mrs. Arthur D. Levinson that has given her research recognition and has encouraged her to strive towards her personal and academic goals with passion.

Mentor: Kim Woodrow, Bioengineering

Project Title: Immune Modulation of Electrospun Nanofibers through Dendritic Cell Activation

Abstract: Vaccines save approximately 2.5 million lives every year, and vaccine delivery is an ongoing area of research critical to reducing the global disease burden. A vaccine is a formulation of an antigen, which is a form or fragment of a pathogen (disease-causing agent) that produces an immune response in the body. Adjuvants are recognized by antigen-presenting cells (APCs) like dendritic cells (DCs), and they are used in vaccines to enhance the body’s immune response to an antigen. Only a few adjuvants have been approved for human use worldwide due their toxicity. Multiple studies have investigated the adjuvanting effects of the chemical properties of biomaterials. However, the effects of bulk material properties like stiffness and porosity on DCs are not clearly understood, prohibiting the design of biomaterials for vaccine delivery. The goal of the project is to investigate the role of stiffness and porosity of electrospun nanofibers by observing DC activation states. It can be hypothesized that stiffer and more porous nanofiber meshes will induce higher DC activation state. This investigation will focus on Poly (vinyl alcohol) (PVA) and Chitosan (CTS) nanofibers which will be crosslinked to modulate stiffness and improve water stabilization for cell culture studies. While both PVA and CTS nanofibers will be crosslinked through thermal treatment, PVA fibers will also be treated with methanol while CTS fibers will be additionally treated with Genepin. Nanofiber porosity will be modulated through mesh thickness. Crosslinked nanofibers will be incubated with DC 2.4 cell line for cell viability studies and murine bone-marrow DCs for DC activation studies. DC activation state is measured by cytokine secretions along with CD86 and CD80 surface marker expression. The results from this study have the potential to guide design and engineering of bio-inert or immune-modulating biomaterials for vaccine delivery.

Meena Sethuraman is a junior majoring in neurobiology and molecular, cellular, and developmental biology. Early on, she was intrigued by biomedical research, and began her undergraduate research career as a freshman in Dr. David Dichek’s lab at the University of Washington studying gene therapy for atherosclerosis. Meena is fascinated by gene therapy research because of the possibilities in reversing or curing single-gene diseases, as well as in treating more complex diseases. In her project, Meena will use short regions of DNA, known as cis-regulatory modules, to enhance transgene expression of APOAI, a therapeutic gene for the protection and regression of atherosclerosis. Increasing expression levels of gene therapy vectors is important for both the efficacy and safety of gene therapy. After completing her undergraduate degree, Meena would like to use the valuable skills she has gained through research to help bridge the gap between medical research and bedside medicine. Aside from working in research, she enjoys playing the violin and is part of the UW Campus Philharmonia Orchestra. Meena would like to thank Dr. and Mrs. Arthur D. Levinson for their support in her research. She is also grateful to her mentors Dr. David Dichek and Nag Dronadula for their guidance and encouragement in her journey as a scientist.

Mentor:David Dichek, Cardiology

Project Title: Endothelial Cell-Specific Transcriptional Modules for Enhancing Transgene Expression of APOAI

Abstract: Gene therapy for atherosclerosis requires enhanced transgene expression of a therapeutic gene. This is important both for enhancing the efficacy of the transgene and for increasing the safety of gene therapy, because a higher-expressing vector can allow for lower doses to be delivered. This project aims to increase the expression of APOAI, a therapeutic gene for the protection and regression of atherosclerosis, by the use of short regions of DNA known as cis-regulatory modules. Cis-regulatory modules are enhancer regions of DNA containing transcription factor binding sites that contribute to regulation of gene expression. We used a novel in silico bioinformatics approach that identifies endothelial cell-specific enhancer elements that are enriched in an endothelial gene set and not in a randomly selected gene set. These enhancers are expected to increase transcriptional activity of APOAI, based on evolutionary conservation, co-occurrence and over-representation of transcription factor binding sites. This type of vector design is more promising than previous trial and error methods because of the selectivity of this approach in capturing regions that are vital for functional biological activity. The eleven cis-regulatory modules that we identified from this approach will each be cloned into our highest-expressing vector for APOAI. These vectors will be tested in cultured endothelial cells (in vitro model) and in rabbit carotid arteries (in vivo model) to identify the cis-regulatory modules that confer the highest transgene expression for APOAI. We hypothesize that the addition of these cis-regulatory modules into a helper-dependent adenoviral vector for APOAI will significantly improve APOAI expression, and that higher APOAI expression will more effectively prevent and reverse atherosclerosis.

Liesl has always held a fascination for the world around her, and it was this fascination that first drew her into the world of biology. During her introductory biology classes at the UW, she quickly became smitten with Darwinian evolution and the ideas and questions it posed and, as she continued through more classes, Liesl soon realized that this interest in evolutionary processes was directly applicable at the molecular level as well. Thus began her pursuit of the captivating collision of evolutionary thinking and biological processes: the field of developmental genetics. Now, as a senior studying Molecular, Cellular, and Developmental Biology, Liesl works in the Berg lab where she studies developmental genetics in the fruit fly Drosophila melanogaster. There, she is working to understand the signaling pathway involved in the cell migration that results in the formation of tubes. In addition to her role as a researcher, Liesl also serves as a teaching assistant for the Early Fall Start class CSI:Seattle, a tutor for the introductory biology series, and an Undergraduate Research Leader with the UW Undergraduate Research Program. After graduation, she hopes to pursue a PhD in genetics and, ultimately, a career that allows her to continue both research and mentorship in higher education.

Mentor: Celeste Berg, Genome Sciences

Project Title: Exploring the Role of the Novel Growth Factor Idgf6 in Drosophila Development

Abstract: From blood vessels to the small intestine to the spinal cord, tubes are an essential part of nearly all organisms. Errors in tube formation cause many of the birth defects that afflict infants today, including congenital heart defects and spina bifida, a failure to close the neural tube. Although tubular organs look different in various animals, the underlying tube-forming processes, called tubulogenesis, are highly conserved. Our lab uses the fruit fly Drosophila melanogaster as a model organism to study tube formation. Recently, we discovered that a family of genes known as Imaginal Disc Growth Factors (IDGFs) are linked to tubulogenesis in fruit flies. The mechanisms by which these genes act, however, and their involvement in the tubulogenesis pathway, remain unclear. Last year, I used a powerful new method for excising genes called CRISPR/Cas9 to investigate the function of a specific IDGF, the gene Idgf6, by deleting the gene entirely. Analysis of these knock-out mutants suggests that Idgf6 does indeed play an important role in making and shaping tubes. The next phase of my research will explore this genetic pathway by using antibody staining to first determine the mechanism of tube dysfunction in Idgf6 mutants, and later to find other genes and pathways that interact with Idgf6 to communicate with tube-forming cells during tubulogenesis. This information will expand our understanding of tubulogenesis and provide new insight into disease pathways that cause defects in newborns.

Jude, a senior at the University of Washington studying Biochemistry and Chemistry, started in research as a freshman where he worked in a wet lab. After that, he decided to try something new and different in a dry computational lab working on biomolecules. He joined the Pfaendtner Research Group in the Chemical Engineering Department. He works on a couple of projects in the lab. The first is on increasing stability of insulin protein using ionic liquid solutions. The goal being to create injectable insulin that lasts longer and acts faster in a human. Another project is on studying nanoparticle with drug molecules crossing the blood-brain barrier as a revolutionary method of drug delivery. After he graduates, Jude hopes to take a gap year to do more research at the NIH before going on to an MD/PhD program specializing in Neuroscience. He would like to thank his mentors especially Dr. Jim Pfaendtner and Dr. and Mrs. Levinson for their generosity.

Mentor: Jim Pfaendtner, Chemical Engineering

Project Title: Using Computer Simulations to Discover Molecular Mechanisms of Insulin Degradation and Stability

Abstract: Diabetes affects about 10% of the US population and is the 7th leading cause of death. Diabetes results from either a lack of insulin production (Type 1) or resistance to it (Type 2). The active form of insulin is the monomer form which regulates homeostasis of blood-glucose levels. It is crucial for insulin to be structurally sound and not degraded, especially for people using insulin pumps. However, insulin has a shelf life of about 28 days unopened and 14 days after opening the container. Efforts to improve the stability of insulin may facilitate the development of implantable pump technologies for insulin delivery and allow for longer storage of insulin. Based on a review of the literature, I hypothesize that solvation in an Ionic Liquid (IL) solution will decrease the degradation and increase the shelf-life of insulin.
To better understand the stability of the insulin protein, I compared its activity at an air-water interface to an Air-IL interface using GROMACS-simulation software. I analyzed the interfaces to optimize for the best insulin backbone stability. Simulations of insulin were performed under specified environmentally controlled parameters for temperature, pressure and potential energy. The goal is to extrapolate an ammonium or imidazolium based IL solution that will decrease aggregation of the insulin monomers. Compared to the bulk insulin form, we found that the IL-protein solution demonstrates a lower radius of gyration, an increased free energy of unfolding and a root-mean-square deviation value that levels out towards 1 Angstrom representing a stable protein. These findings suggest that insulin adopts a more stable configuration and experiences decreased degradation rates in IL solutions. The next step would be for researchers to test these computational predictions experimentally. Confirming the results would suggest that insulin in an Ionic Liquid solution will last longer in vitro than in a water-based solution.

Philip is in his fifth year as a senior in the Department of Bioengineering. After coming to the University of Washington to join its historic rowing program, Philip was drawn to research by the enthusiasm of professors he reached out to his freshman year. He started working with Dr. John Sorensen in the School of Dentistry Department of Restorative Dentistry after being exposed to how engineers can help solve clinical problems through research. Following a passion for solving healthcare problems, Philip is pursuing DDS/PhD programs with the hope of leaving a positive impact on healthcare. From there, he hopes to see patients and work in a research setting to help translate discoveries in science to innovations in patient care. After volunteering at the Seattle Union Gospel Mission Dental Clinic, Philip is particularly interested in using research discoveries to help increase access to quality dental care. After a successful rowing career, Philip has moved on to spending more time in lab along with enjoying cycling, running, and photography in his free time. He would like to recognize his mentors Dr. John Sorensen, Dr. Steve Shen, and Dr. Chris Neils for their openness and guidance in his research. Philip would also like to thank Dr. and Mrs. Levinson along with the URP staff for recognizing his work and honoring him with the opportunity to dive fully into his research project.

Mentor: John Sorensen, Restorative Dentistry

Project Title: Electromechanical Dental Implant Stability Testing Device

Abstract: Peri-implantitis is a bacterial infection of tissue supporting implants. This infection may lead to bone loss around oral implants, introducing movement to the implant system, ultimately leading to implant failure. There currently exists no device capable of quantifying bone loss in a clinical setting. It is crucial that clinicians are able to determine oral implant stability using a method that is informative, rapid, accurate, and precise. With an increasing number of oral implants being placed throughout the world, dentists must be able to decide whether an implant is healthy or not. Previous studies have found that an increase in bone loss around an implant leads to decreased natural frequency of the implant. This project proposes the use of piezoelectric drivers to measure the natural frequency of implants to determine implant stability and bone loss. It will be divided into three sections. The first section consists of showing that there is a significant natural frequency shift with increased bone loss and selecting the correct piezoelectric driver for this application. The second section involves testing the chosen piezoelectric driver in different implant conditions to determine how bone loss and other factors influence the results seen in frequency analysis of the implant. The final section will consist of designing a prototype handpiece implementing the piezoelectric driver and creating a LabView Virtual Instrument that can help clinicians assess implant stability and bone loss. Ultimately, this project has the potential to help improve the quality of implants for many dental patients worldwide.

Roujia Wang is a senior in the Department of Bioengineering at the University of Washington. Deeply impressed by the novelties as well as opportunities presented in the 3D pathology project led by the senior research scientist Dr. Ronnie Das and the principal investigator Dr. Eric J. Seibel in Human Photonics Laboratory (HPL), she joined HPL to start her research work in developing colormapping techniques for visualization in the 3D pathology project based on quantification of color information of traditional 2D microscope slides. She presented her research work on this project in the Undergraduate Research Symposium at University of Washington during last spring quarter. With the support of the Levinson Emerging Scholars Program, Roujia is currently working on her individual research project on developing surface imaging system for needle biopsy to detect its adequacy and rapid cancer lesion through milli-fluidic device. Beyond research experience, Roujia is also involved in the research community as a current undergraduate research leader assisting with the Undergraduate Research Symposium as well as outreach events with the Undergraduate Research Program. She is also serving as peer mentor for both College of Engineering and UW Honor Program as well as the Secretary of Tau Beta Pi Washington Alpha Chapter, known as the oldest and largest engineering honor society. With the passion in research, Roujia is applying for the Ph.D. programs in Bioengineering/Biomedical Engineering. Roujia would like to thank her research mentors Dr. Eric J. Seibel and Dr. Ronnie Das along with other lab members for their generous supports and guidance in her research projects. She is also grateful for the help she received from staff in the Department of Bioengineering and Mechanical Engineering and the Undergraduate Research Program. Last but not the least, she would like to thank Dr. and Mrs. Arthur D. Levinson for providing funding to her research project.

Mentor: Eric Seibel, Mechanical Engineering

Project Title: Surface Imaging System for Needle Biopsy to Detect its Adequacy and Rapid Cancer Lesion through Milli-Fluidic Device

Abstract: Core needle biopsy (CNB) is used as a minimally invasive method to diagnosis breast and other cancers. However, this method still has limitations of getting non-diagnostic and inadequate CNBs due to sampling error. Thus extra CNBs are often taken and other time-consuming tests that look at surface cellularity such as histological evaluation on tissue smears are done to reduce probability of this error, which leads to needless pain and cost. Therefore, we propose to design a rapid-on-site evaluation system by imaging the outer surface of needle biopsy samples. This system generates a whole surface image of CNBs that contain cellularity information as a quicker and more informative adequacy testing of CNBs. This proposed project aims to develop cost-efficient imaging for obtaining sub-cellular and structural information from CNBs at the point-of-care. There are three phases: Design of System, Development Image Stitching Algorithm, and Integration, testing, and generating surface image. Phase I aims to determine the optimal optical imaging system and developing a staining protocol for CNBs. Phase II is developing an image stitching algorithm that takes in images from Phase I. Phase III will integrate I and II and generate a whole surface image of CNBs to provide morphological features for clinicians so that they can determine the adequacy of biopsy and needs for additional biopsies. The main criterion of this design is to perform evaluation within 20 minutes while still maintaining intactness of specimen. If the design becomes successful a commercial device will speed the process by 10x (<2 minutes), while maximizing use of CNBs and reduce the number of biopsy taken to minimize suffering of patients. It may also accelerate diagnosis speed for breast cancer. Importantly, this design can be applied to other types of cancer diagnosis, such as remote radiology clinics where a pathologist is typically not available.