2017-18 Levinson Scholars

Mackenzie is currently a senior at the University of Washington studying bioengineering and neurobiology. She is in the Interdisciplinary Honors program as well as pursing Departmental Honors in neurobiology. She comes from a family background that has strongly motivated her research in the field of neuropharmacology to study the disease of addiction. In her current research, Mackenzie is designing a device to optically stimulate multiple brain regions while simultaneously recording the electrophysiological activity of those brain regions in an awake and behaving animal. She will also be writing the software to process and analyze the recordings in the hopes of correlatively determining whether the regions of interest are communicating to drive specific behaviors. Mackenzie will be expanding her project into the 5th year Master’s degree offered by the UW fprogram. After graduation, she is planning to go into industry to pursue a device design career. She would like to thank her mentor, Dr. Antony Abraham, for his invaluable guidance as well as her PI, Dr. Charles Chavkin for his consistent support of her project. Last but not least, she would like to express her gratitude to Dr. and Mrs. Levinson for their generous contribution to her current and future research.

Mentor: Charles Chavkin, Pharmacology; Antony Abraham, Pharmacology

Project Title: Basis for Dual-Site in vivo Recording of Neuronal Activity

Abstract: Drug addiction is a highly prevalent disease with common potentiating risk factors including stress-exposure, anxiety, and depression. A number of brain regions have been linked to behaviors that drive drug seeking and abuse, however little is known about how these regions communicate to regulate those behaviors. Currently, instruments can be used to record neuronal activity in vivo, however, these devices are typically only able to record from one brain region at a time and don’t allow for specificity of neuronal stimulation. In order to improve the understanding of how brain regions communicate to drive behavior, there is a need to develop a multiple-site in vivo recording device that can record broad excitation signals while allowing optical stimulation of specific subtypes of neurons. In order to fill this need, I intend to design a dual-site optic delivering electrode or ‘optrode.’ This device would be small enough to mount on a mouse’s skull to promote naturalistic behavior with the ability to record non-specific electrical signals from the brain regions of interest, as well as optically stimulate specific subtypes of neurons. I will also be designing a program to process and analyze the data recorded by the device. If this device is successful, it will improve our understanding of how brain regions communicate to drive addiction-associated behaviors which could lead to therapeutic solutions for the treatment of addiction.

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. Camille’s current research focuses on vagus nerve stimulation (VNS) for augmentation of targeted neuroplasticity and enhancement of cognitive performance in non-human primates. In the past, she has investigated the potential efficacy of the prefrontal cortex as a site for brain-computer interface control and used the Neurochip-3 to study 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. Levinson for their remarkable support of undergraduate research.

Mentor: Eberhard Fetz, Physiology & Biophysics

Project Title: Noninvasive Vagus Nerve Stimulation to Augment Targeted Cortical Plasticity

Abstract: The primary aim of this project is to establish a protocol for noninvasive vagus nerve stimulation that will augment targeted neuroplasticity and enhance cognitive performance in normal nonhuman primates. Specifically, we will use left auricular branch VNS to promote targeted synaptic plasticity between specific areas of the cerebral cortex and to enhance behavioral performance in a cognitive task that involves these areas. This nonhuman primate study will be directly applicable to the development of noninvasive vagus nerve stimulation technology that can be used to enhance neuroplasticity and cognitive performance in healthy adults.

Kyle is a senior at the University of Washington, majoring in chemistry and biochemistry with minors in mathematics and physics. He joined Dr. David Mack’s lab at the UW Institute of Stem Cell and Regenerative Medicine in June of 2016. His current project focuses on generating a model enteric nervous system from patient derived stem cells to be able to test different drug treatment methods for the gut motility issues that plague many children with Autism Spectrum Disorder. After graduation, Kyle intends to pursue medical school and hopes to continue conducting research in the medical field as a physician. He would like to thank Dr. David Mack for his mentorship and support, as well as Dr. and Mrs. Levinson for their generosity in promoting undergraduate research.

Mentor: David Mack, Rehabilitation Medicine

Project Title: Generating a Model Enteric Nervous System to Treat SHANK3 Deficiency Associated with Phelan-McDermid Syndrome

Abstract: Many children with Autism Spectrum Disorder (ASD) suffer from gut motility issues that manifest as debilitating chronic constipation, which in turn leads to an unhealthy aversion to food. We hypothesized that the same neurological defects that cause the hallmark cognitive impairments in ASD also negatively impact the enteric nervous system controlling gut peristalsis. Within the autism spectrum, we chose to study one specific condition called Phelan-McDermid Syndrome (PMDS) because every patient with the diagnostic chromosome 22 micro-deletion has a dramatic decrease in gut motility. We believe the gene of interest in the deleted region is SHANK3 because mice with haploinsufficiency of SHANK3 show decreased postsynaptic density of neurotransmitter receptors. The goal of this project is to develop novel drug treatments for patients with PMDS and ASD. Finding a new compound that can increase or bypass postsynaptic receptor density could remedy these patients’ gut motility problems. However, other enteric nervous system models involve either invasive biopsy procedures to remove enteric tissue from patients or the use of animal models that fail to replicate the pathology observed in humans. Therefore, our goal is to create a disease-in-a-dish model of enteric nervous system dysfunction by generating stem cells from PMDS patients and differentiating them into enteric neurons. We predict that molecular characterization of SHANK3-deleted enteric neurons will illuminate abnormal signaling pathways suitable for therapeutic intervention. Preliminary experiments from our laboratory have demonstrated the feasibility of differentiating patient-derived induced pluripotent stem cells into neural crest cells, which are necessary precursors to making enteric neurons. Therefore, the proposed project will seek to develop and optimize a smooth muscle co-culture procedure to further differentiate wild-type and SHANK3-deficient neural crest cells into enteric neurons and characterize the resulting enteric neurons to discover phenotypic defects consistent with a SHANK3 mutation.

Jasmine is a senior at the University of Washington studying bioengineering. After becoming interested in diagnostic devices, she joined the Human Photonics Lab to work on an optical pH project. Jasmine is developing a non-invasive pH measurement of the oral bacteria that cause caries, commonly known as dental cavities. Bacterial acid degrades tooth minerals resulting in cavities, so early caries can be identified by low pH. Jasmine is currently investigating fluorescence dyes that shift spectrally with oral bacteria pH, with the intent of testing this pH measurement in clinical trials. After graduating, she plans to focus on diagnostic devices in a bioengineering PhD program, and then work in the biotech industry to translate medical devices to clinical use. Jasmine thanks her mentors, Dr. Eric Seibel and Dr. Leonard Nelson, as well as Dr. and Mrs. Levinson for their generous support.

Mentor: Eric Seibel, Mechanical Engineering

Project Title: Optical Measurement of Acidification of Human Dental Plaque

Abstract: Dental caries, also known as cavities or tooth decay, affects billions of people worldwide. Caries is caused by the consumption of high sugar foods that are converted into acids from the metabolism of oral bacteria. These low pH acids dissolve the mineral structure in tooth enamel and dentin. When untreated, caries causes inflammatory pain and infections that decrease quality of life and increase societal and economic burdens. There is no clinical method of imaging that provides accurate feedback on caries prevention methods and assesses caries risk before mineral damage accumulates. Therefore, there is a need for an accurate, high sensitivity system using a novel fluorescence marker for the rapid assessment of dental caries. A high specificity spectral analysis system will quantitatively measure caries bacteria activity, solving problems with existing measurement methods by offering a non-contact, lower cost method of monitoring oral pH. The correlation between the fluorescence spectral shifts of optical agents and pH changes measured after a sugar rinse will yield an optical measurement that can be used to predict caries activity. With a quantitative imaging device for clinical and personal use, early signs of caries can be identified by users, and dentists, patients, and patients’ families will be better informed about the effectiveness of caries preventive measures.

Arielle Howell is a junior undergraduate in the Department of Bioengineering. She joined the Yager lab her freshman year and began research of porous membrane systems for diagnostic devices. This beginning sparked a passion for developing diagnostic devices aimed at low resource environments. This focus bridges her interests of expanding access to healthcare and developing new technologies. Her project will be focused on integrating nucleic acid capture and amplification using a porous membrane system. She also plans to incorporate a hydrogen fuel cell to provide power for device automation. In her free time, Arielle enjoys playing water polo on the University of Washington’s women’s club team, volunteering at Swedish Medical Center – First Hill Campus, and contributing to the University of Washington Rotaract’s various philanthropic projects. She would like to thank her mentors, Dr. Paul Yager and Dr. Joshua Buser for their continued support and advice in her research career. Arielle is also grateful for the support Dr. and Mrs. Levinson have provided for her research.

Mentor: Paul Yager, Bioengineering

Project Title: A Self-powered Diagnostic Device for Pathogens in Urine: Joining Nucleic Acid Capture and Amplification with Fuel Cells

Abstract: Future medical practice will rely on affordable, disposable diagnostic devices, expanding high quality diagnostic testing into low-resource settings. Currently, well-equipped labs and expensive machinery are often required to analyze clinical samples. There is not currently a device that includes nucleic acid capture, amplification, and detection without the use of an outside power source. I am proposing that in a porous membrane based system these three could be incorporated to create a fully integrated device that is also portable and disposable. This project hinges on technologies previously developed in the Yager lab, capturing nucleic acids using a charged carbohydrate and controlled pH in various buffers. I will focus on capturing DNA to be amplified using an isothermal method. To run the amplification our lab has developed a chemical heater that undergoes an exothermic reaction that emits hydrogen gas. While collaborators in the lab focus on the fluorescence quantification of the DNA present in the sample using photodiodes and LEDS, I will work on an on-board hydrogen fuel cell to power this system. The excess hydrogen from the heater will be used to power the cell. The power can also be used to further automate the device with timers to simplify the device for the user. Such a device would increase diagnostic availability through a simple-to-use platform that would incorporate the entire diagnostic process.

Linxing is a senior in the Paul G. Allen School of Computer Science & Engineering. His work focuses on the development of Brain Computer Interfaces and using machine learning to decode EEG signals, as well as analyzing how external stimulation like TMS could affect human perception. In his current project, he is working on the first three-person brain-to- brain communication model for completing a game of Tetris. Linxing plans to finish his Master’s degree with the 5th year Master program in CSE and pursue a Ph.D. in computer science afterwards with focus on Brain Computer Interface and computational neuroscience.

Mentor: Andrea Stocco, Psychology
Mentor: Rajesh Rao, Computer Science and Engineering

Project Title: BrainNet: First Three-Person Brain-To-Brain Communication Interface

Abstract: BrainNet is designed to be the first three-person direct brain-to-brain interface in human brains. This interface combines electroencephalography (EEG) as input to record brain signals with transcranial magnetic stimulation (TMS) as output to deliver information to the brain. Through this interface, three subjects complete a Tetris-like filling-line block game using direct brain-to-brain communication. Two of the three subjects are “senders” whose brain signals will be decoded by EEG analysis. The decoded information contains their decisions about if a block needs turning 180 degrees before being dropped to fill the line. Then, this information is sent via TCP network and directly delivered to the brain of the “receiver” who cannot see the game screen. The receiver makes the decision based on the information he or she acquired from the senders and conveys this decision through EEG analysis to the computer, which finishes the action of turning the block or staying still. The performance of the interface is evaluated in terms of the accuracies attained in (1) decoding decisions through EEG analysis, (2) encoding information through TMS, and (3) the completeness of the block game.

Hyeon-Jin Kim is a senior majoring in Applied Computational Mathematical Science – Biological and Life Sciences, biochemistry, and chemistry. In the spring quarter of his freshman year, he joined the Vaughan Group from Department of Chemistry to help enhance super resolution techniques for bioimaging. His previous work involved developing methods that enable Expansion Microscopy with conventional antibodies and fluorescent proteins and extending this method to model organism Drosophila melanogaster to study dendrite-epidermis interactions. Now, Hyeon-Jin is working on a new collaboration between the Vaughan Group and the Kueh Group in the Department of Bioengineering. In this collaboration work, he hopes to develop a higher resolution epigenetic profiling method and use this method to study cell fate decisions in hematopoiesis. His current research focuses on setting up a pipeline for analyzing published chromatin immunoprecipitation followed by sequencing (ChIP-seq) data to identify potential genes that are differentially regulated by histone markers at different T-cell development stages. After he finishes his studies at UW, he plans to attend graduate school to pursue a doctorate in quantitative biology or related discipline. Hyeon-Jin would like to thank everyone in the Vaughan Group, Kueh Group, and his collaborators for help and support. He is honored to be a Levinson Emerging Scholar and appreciates the generosity and support from Art and Rita and the URP.

Mentor: Hao Yuan Kueh, Bioengineering

Project Title: Development of High Resolution Epigenetic Profiling For the Study of Hematopoiesis

Abstract: Epigenetic modifications regulate chromatin structure and function, playing important roles in altering DNA transcription levels and subsequently cell fate decisions. Various next-generation sequencing (NGS) methods have been developed to detect these epigenetic changes in the genome, such as chromatin immunoprecipitation followed by sequencing (ChIP-seq). Even though ChIP-seq is extensively used to analyze DNA and histone modification levels, this method is limited to one histone marker at a time and requires significant amount of input cells, which masks the profiles of cell-to-cell variation and the complex interaction between the epigenome and gene expression. To overcome these limitations in current next-generation sequencing methods, I propose to develop a multiplexed assay that could detect multiple epigenetic modifications in single cells. In this proposed research, I will (1) develop a NGS data analysis pipeline to identify potential gene candidates that are highly differentially modified by histone markers, (2) use these gene candidates as templates to design DNA-fluorescent in situ hybridization (DNA-FISH) probes, and (3) perform Expansion Microscopy and DNA-FISH with these probes to link histone modifications to specific gene loci at high resolution. After the assay is fully developed and validated, I plan to utilize the assay to take the epigenetic profiles of hematopoietic stem cells and study cell fate decisions in hematopoiesis.

Amanda is currently a senior in chemical engineering at UW. Since her freshman year, she has been working in the Posner Research Group, under mechanical and chemical engineering Professor Dr. Jonathan Posner, where she has been focused on developing next generation point-of-care diagnostic devices for infectious diseases. These devices have sensitivity comparable to lab-based tests, yet remain fast and inexpensive, giving them the potential to greatly improve healthcare in developed countries and low-resource settings. Amanda is passionate about this research because it has enabled her to contribute to combatting the world’s need for more accessible and efficient diagnostic tests that can lead to improved patient care and better use of healthcare resources. This work sparked Amanda’s love for research and has inspired her to pursue graduate school to obtain a PhD in chemical engineering, focused on translating engineering solutions to medical settings. Outside of research, Amanda is passionate about supporting young women in STEM and providing them with the resources they need to achieve their educational and professional endeavors. Over the past three years, Amanda has served as a Career Fair Director and Vice President of Professional Development for the UW chapter of Society of Women Engineers (SWE), is currently a Collegiate Communications Editor for a regional chapter of the SWE, and is a founding member and President of the recently founded Women in Chemical Engineering group on campus. Amanda plans to continue incorporating her work with women in engineering groups into her graduate school experience. Amanda is incredibly grateful for the support of her research mentors, Dr. Jonathan Posner, Dr. Charlie Corredor, Dr. Mark Borysiak, and graduate student Andrew Bender. Lastly, Amanda is incredibly thankful to Art and Rita Levinson for their generous support for her educational and professional goals.

Mentor: Jonathan Posner, Mechanical Engineering

Project Title: Sample Preparation of Whole Blood to Detect HIV-1 RNA in Point-of-Care Viral Load Test

Abstract: As of 2016, approximately 36.7 million people worldwide were living with HIV/AIDS, of which almost 15 million receive antiretroviral therapy (ART). These patients require regular HIV-1 viral load (VL) tests to monitor ART effectiveness and compliance. However, the majority of affected people live in low-resource settings, where accurate diagnosis and disease monitoring through lab-based instrumentation systems, such as nucleic acid amplification tests (NAATs), are inaccessible. Thus, there is an increasing need for accurate, affordable HIV-1 VL tests at the point-of-care (POC). Previously, we demonstrated the ability to leverage an electrokinetic separation and preconcentration technique, isotachophoresis (ITP), and an isothermal nucleic acid amplification method, recombinase polymerase amplification (RPA), to develop a proof-of-concept, integrated POC NAAT for extraction, amplification, and detection of synthetic nucleic acids in whole blood. Our future work will be geared toward targeting HIV-1 virions spiked into whole blood samples, leading to a rapid VL test appropriate for clinics in low resource settings. This project focuses on improving the limit of detection (LoD) of our test by enhancing the sample preparation (SP) of whole blood spiked with HIV-1 virions. To accomplish this, we will be decoupling our integrated POC NAAT, using paper-based ITP for SP and subsequently leveraging off-chip RPA for amplification and detection, to semi-quantitatively analyze the effects of various SP parameters on our LoD. Such parameters include sample lysis chemistries, substrate pre-treatment chemistries, and ITP chemistries for increased extraction efficiency. The completion of this work will result in a procedure for effectively purifying and separating HIV-1 RNA from whole blood, ultimately resulting in a reduction of target loss, and a clinically relevant LoD. The SP protocol developed from this work and our POC NAAT can be leveraged for other infectious disease diagnostic tools.

Ben Pedigo is a senior in Bioengineering with a minor in Applied Math. He is working in the lab of Chet Moritz in the Departments of Rehabilitation Medicine and Physiology & Biophysics. Ben’s research investigates how optogenetic stimulation of the spinal cord may be able to improve upper-limb motor function after a spinal cord injury. He is optimizing the lab’s implantable optogenetic stimulation methods for use in long-term studies in rodents. Ben also helped to start a new student organization for neural engineering called Synaptech. He hopes to introduce more students at UW to neural engineering research. After graduating, Ben hopes to enter a Ph.D. program, studying the intersection of neuroscience, engineering, and computation. He wishes to thank Sarah Mondello, Chet Moritz, and the rest of the Moritz lab for their mentorship and support. He would also like to thank Dr. and Mrs. Levinson for their generous gift and their continued support of undergraduate research.

Mentor: Chet Moritz, Rehabilitation Medicine and Physiology & Biophysics

Project Title: Optimization of Optogenetic Spinal Cord Stimulation

Abstract: Spinal cord injury (SCI) is a debilitating disease with few treatment options available for recovering motor function. Based on past studies using electrical stimulation of the spinal cord, we believe that long-term optogenetic spinal stimulation (OSS) may improve motor function after a spinal cord injury. Current methods of delivering light stimulation to the spinal cord in a live animal are not biocompatible, likely due to heat production from the LED light source. Researchers desire a biocompatible light source that can be implanted on the rat spinal cord for at least 8 weeks without causing damage to the surrounding tissue. I will improve upon current LED implants by incorporating a thermistor to track temperature. This device will be used to inform better stimulation parameter choices that will not damage tissue. This system will then be used to study the effects of OSS on improving motor function. An optimized OSS methodology has the potential to dramatically improve the lives of those with an SCI by improving their capability for volitional movement.

Meena Sethuraman is a senior majoring in neurobiology. 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 clone large genomic regions of DNA containing cell-specific enhancers to enhance transgene expression ofAPOAI, 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 a part of the UW Campus Philharmonia Orchestra. Meena would like to thank Dr. and Mrs. 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: Using Large Regulatory Regions of Endothelial Cell-Specific Genes for Enhancing Transgene Expression of APOAI

Abstract: Gene therapy for atherosclerosis requires high-level transgene expression. High-level transgene expression increases the likelihood that gene therapy will be effective. High-level transgene expression also increases safety by allowing use of lower vector doses (minimizing vector-related toxicity). Our goal is to increase expression of an apolipoprotein A-I (apoA-I) transgene, which we showed can prevent or reverse atherosclerosis in rabbits. Previously, we used an in silico bioinformatics approach to identify endothelial cell-specific cis-regulatory modules (CRMs), short enhancer regions of DNA that are expected – when introduced into endothelial cells – to increase transcriptional activity of a nearby gene. The CRMs we identified are located in the CDH5, EFEMP1, THBS1, and VWF genes. We hypothesize that insertion of these CRMs into a helper-dependent adenoviral vector encoding apoA-I will increase apoA-I expression. In addition, we hypothesize that the genomic regions that contain these CRMs contain additional sequences that, in concert with the CRMs, could increase transgene expression above levels obtained with the CRMs alone. Our helper-dependent adenoviral vectors have a larger capacity for the insertion of DNA sequences than the previously used adeno-associated viral (AAV) vectors. Thus, we can compare CRMs linked to heterologous promoters with CRMs in their native genomic context. I will clone large CRM-containing regions for the 4 genes listed above and insert the apoA-I gene into the translational start sites of these genes. We will test the vectors containing individual CRMs and the vectors containing the larger CRM-containing regions in cultured endothelial cells (in vitro) and in rabbit carotid arteries (in vivo) to identify CRM-containing constructs that express the highest levels of apoA-I. My project may provide higher-expressing vectors for use in endothelial cell-mediated gene therapy. My project may also reveal a general approach to vector design that can be applied to gene therapy directed at other cell types.

Margaret is currently a senior at the University of Washington studying general biology and minoring in Jewish studies. She began her research career in the McKnight Pharmacology Lab, where she studied the role of the AKAP7 mouse gene in spatial discrimination. In the summer following her junior year, Margaret participated in the Scan Design Innovations in Pain Research Program under Dr. Tonya Palermo’s mentorship. Through this program she had the opportunity to conduct research that helped characterize and understand the experience of children who are on the waitlist to be seen in pain medicine clinics. As a Levinson Emerging Scholar, Margaret will be continuing her work in Dr. Tonya Palermo’s lab. Her project focuses on designing and piloting an online cognitive-behavioral therapy for use among the chronic pancreatitis population. Following graduation, Margaret plans to pursue a career in medicine. She would like to thank Dr. G. Stanley McKnight and Dr. Tonya Palermo for their continued support and mentorship. She would also like to extend her gratitude to Dr. and Mrs. Levinson for their generous support of undergraduate research.

Mentor: Tonya Palermo, Anesthesiology and Pain Medicine

Project Title: Internet-based Pain Management Program for Persons with Chronic Pancreatitis: Initial Development and Pilot Trial

Abstract: Chronic pancreatitis (CP) can be a very painful condition, and available medical treatments provide limited pain relief. In other painful conditions, self-management pain programs enable patients to improve their understanding and control of pain, allowing them to maintain better physical and psychosocial health. This study aims to 1) adapt a generalized internet-delivered pain management program specifically for use by adults with CP, and 2) conduct a pilot clinical trial in the target population to assess feasibility and acceptability of the program that will then guide a large randomized controlled trial. The Pain Course, an existing online cognitive behavioral therapy (CBT) program will be modified for use in the adult CP population as the Pancreatitis Pain Course. In the first part of the study the modified course will be delivered to 10 CP Patients, who will complete it and provide feedback through qualitative interviews. The feedback will be used to further adapt the course, after which it will be used in the second part of the study to conduct a pilot randomized controlled trial in 30 adult CP patients. The primary purpose of the pilot trial is to assess patient accrual, treatment engagement and adherence, and treatment acceptability. Data regarding treatment outcome measures of pain-related disability, pain symptoms, anxiety, depression, quality of life, and sleep quality will also be analyzed, and data will be collected at baseline, following course completion, and at three months post-intervention. After the pilot trial, additional qualitative interviews will be conducted to further understand patient perspectives regarding the efficacy and relevance of the Pancreatitis Pain Course. The Pancreatitis Pain Course has the potential to change clinical practice, as it is an economical, non-pharmacological treatment that poses low risk and could be widely disseminated.

Amy is a senior in the honors program of Materials Science Engineering at UW. Her research is in the Thomas lab in Bioengineering. Amy is also a NASA Space Grant Scholar and a Mary Gates Research Scholar. She is vice president for Women in Materials Science Engineering, and believes strongly in promoting diversity and inclusiveness. Amy is interested in investigation biological materials on the nanoscale, and to that end she is currently using DNA as a building material. Amy plans to continue researching bio materials as a PhD candidate. Amy would like to thank her mentors Dr. Wendy Thomas and Molly Mollica, and Dr. and Mrs. Levinson for their funding. Research is the greatest asset in school and making research accessible to undergraduates is greatly appreciated.

Mentor: Wendy Thomas, Bioengineering

Project Title: DNA Origami for Single Molecule Force Measurements

Abstract: Characterizing biological functions on a single molecule scale aids prevention, diagnosis, and targeted treatment of disease. Single molecule measurements are a crucial part of characterizing molecular interactions. Although atomic force microscopy (AFM) and magnetic tweezers are able to measure the response of single molecules to mechanical force, it is challenging to ensure single molecules are being measured. In this project, a precise DNA Origami structure will be used to space molecules for single molecule force measurements. Base pair association between DNA nucleotides will allow specific nanostructures to be designed and fabricated. Molecules of interest will self-assemble to specific sites of the structure. AFM will be used for both imaging and obtaining force measurements. This project will be investigating the strength of adhesion for double stranded DNA when subjected to different loading rates as a proof of concept. In the future, this structure will be used to determine force properties of diverse molecular interactions.

Jie is currently a senior at the University of Washington studying Biochemistry and Microbiology with Departmental Honors. She became interested in cancer metabolism after attending a biochemistry seminar at the UW. Her curiosity about cancer biology motivated her to join the Lagunoff lab in her sophomore year. Intrigued by viral oncogenesis, Jie is thrilled to study how Kaposi’s sarcoma-associated herpesvirus (KSHV) alters endothelial cells’ metabolism to maintain viral latency. She specifically focuses on understanding the viral mechanism that induces the Warburg effect, which is a common metabolic alteration in cancer cells, in human endothelial cells. The Warburg effect is shown to be required during the maintenance of KSHV latency. She aims to evaluate the role of hypoxia-induced factors (HIFs) in KSHV induction of the Warburg effect. The goal of her project is to elucidate a HIF-induced mechanism for pro-survival changes to cellular metabolism during KSHV infection. Jie hopes that these results will aid in the future efforts to develop antiviral drugs that inhibit viral latency by targeting metabolism. After graduation, Jie plans to do translational research that focuses on cancer treatments prior to attending medical school. In the future, she intends to pursue a career in medicine and clinical research. Jie is incredibly grateful for the remarkable mentorship of Dr. Michael Lagunoff and Ph.D. candidate Daniel Holmes and for the generous support of Dr. and Mrs. Levinson that drives her forward in her research and future endeavors.

Mentor: Michael Lagunoff, Microbiology

Project Title: Hypoxia Induced Factors in Latent Kaposi’s Sarcoma Herpesvirus Infected Endothelial Cells

Abstract: Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi’s Sarcoma (KS), a highly vascularized tumor made up of cells of endothelial origin. KSHV establishes a predominantly latent infection in endothelial cells in culture and in the KS tumor. A previous study has shown that KSHV induction of the Warburg effect is required for the maintenance of latently infected endothelial cells. The Warburg effect, a common metabolic alteration in cancer cells, refers to an increase in glycolysis and a decrease in oxidative phosphorylation. The mechanism of Warburg induction by KSHV is currently unknown. I propose to evaluate the role of hypoxia-induced factors (HIFs) on KSHV Warburg induction since HIFs have been implicated in Warburg induction in other types of cancer. I hypothesize that either HIF1α or HIF2α is responsible for KSHV Warburg induction. I constructed HIF2α knock-out cells using the CRISPR/Cas9 gene editing technique in a lentivirus vector. I expressed the endonuclease Cas9 and guide RNAs that lead Cas9 to cleave at the HIF2α coding sequences leading to genomic mutations in HIF2α. To determine if HIF1α or 2α is required for the survival of latently infected endothelial cells, I will infect HIF1α or 2α knockout with KSHV and measure cell death at 48 hours post infection (HPI). I expect HIF knockouts will lead to increased cell death of the infected cells but not the uninfected cells, indicating HIFs are required for the survival of infected cells. To evaluate if HIFs are required for KSHV Warburg induction, I will determine if HIF knockouts produce less lactic acid and increase oxygen consumption at 48 HPI as compared to infection of wild type cells indicating the Warburg effect is not being induced by KSHV in HIF knockouts. These results will aid in the future efforts to develop antiviral drugs by inhibiting viral latency.