POSTERS
Posters are presented in the Foege North Lobby at 10:45AM - 11:30AM, and 2:15PM - 3:00PM.
Presenters
Becky Zaunbrecher, UW Regnier Lab
Bryan Howie, Adaptive Biotechnologies
Jasmin Chen, UW Dan Ratner Lab
Jason Murray, UW Regnier Lab
Jiayi Dou, UW Baker Lab
Keenan Bashour, Juno Therapeutics
Nirveek Bhattacharjee, UW Folch Lab
Scott Braswell & Ellen Lavoie, UW Molecular Analysis Facilty
Becky Zaunbrecher, UW Regnier Lab
Title: Heart and Muscle Mechanics Lab
Abstract: The goal of the Regnier lab's research is to understand the molecular and cellular mechanisms that regulate muscle contraction, using a variety of molecular biology, genetic and biomechanical approaches. This information is used to develop complex computational models of contraction at the protein and sarcomere level. Models contain spatial (geometry) and kinetic information, and provide clues to the mechanistic processes that are difficult to obtain from experimental measurements. A more recent interest in our group is to apply knowledge gained from these experiments to design therapies to improve the performance of diseased cardiac and skeletal muscle.
Bio: Becky is a third year graduate student in the Bioengineering PhD program. She is co-advised by Drs. Chuck Murry and Mike Regnier.
Bryan Howie, Adaptive Biotechnologies
Title: High-throughput pairing of T cell receptor alpha and beta sequences
Abstract: The adaptive immune system protects our bodies from a wide variety of pathogens, and one of its key actors is the T cell. An immune response is initiated when a T cell binds a non-self antigen. Collectively, T cells can bind almost any antigen, and each T cell binds specific antigens via a surface protein called the "T cell receptor" (TCR). The TCR protein is a heterodimer coded by two gene segments (TCR-alpha and TCR-beta, or TCRA and TCRB) on different chromosomes. In developing T cells, these genes undergo somatic modifications that create different binding specificities and ensure that each T cell carries a nearly unique pair of TCRA/B sequences. To perform functional studies of T cell binding and to develop TCR-based therapeutics, it is essential to recover paired TCRA/B sequences from complex mixtures of cells. I will present a novel technology, called "pairSEQ," for pairing TCR sequences at high throughput.
Bio: As an undergraduate at the University of Washington, I was a member of the first class to be granted BS degrees in Bioengineering. I subsequently went on to study statistical genetics at the University of Oxford and the University of Chicago. I am currently a Senior Computational Biologist at Adaptive Biotechnologies, a Seattle company that studies the immune system and its role in a variety of diseases.
Jasmin Chen, UW Dan Ratner Lab
Title: Nanostructured glycopolymer functional liposomes to elucidate carbohydrate receptor mediated targeting
Abstract: Carbohydrates play an essential role in a myriad of biological processes, including carbohydrate-protein interactions for the targeting of glycans to receptors on cells and tissues. Alveolar macrophage express carbohydrate receptors that enable them to recognize microbial-associated markers, localize and isolate infectious events, and trigger adaptive immunity. Understanding the nuances of receptor-mediated uptake pathways is critical to improve delivery and therapeutic applications involving host effector cells, such as the macrophage.
In this study, we synthesized and formulated RAFT-based mannose and galactose glycopolymers copolymerized with a cholesterol methacrylate, enabling the polymers to be incorporated into liposomes to elucidate receptor-mediated uptake in various macrophage cell lines. The significance of this study is to elaborate the contribution of carbohydrate receptors in cell targeting and leverage this knowledge to enhance drug delivery applications in receptor- targeted drug delivery strategies.
Bio: Jasmin is a current graduate student in bioengineering advised under Daniel Ratner, working on carbohydrate facilitated polymeric prodrugs to target host cells via carbohydrate receptors to combat intracellular infections.
Jason Murray, UW Regnier Lab
Title: Ribonucleotide reductase overexpression does not alter cardiomyocyte mitochondrial respiration
Abstract: Heart disease is already the leading cause of death in the United States. People over 65 years of age are the fastest growing age group, and the incidence of heart failure is expected to increase further in the coming decades. We have previously demonstrated that upregulation of ribonucleotide reductase (RNR) in cardiomyocytes results in an elevation in the cytosolic concentration of 2-deoxy-ATP (dATP) and subsequent increase in contractility. For this approach to be an effective therapeutic option for treatment of heart failure we need to determine whether elevated cardiac dATP can be maintained long term and that it does not compromise cardiomyoctye metabolism. My data suggest that cardiomyocytes can generate dATP from dADP through the same metabolic pathways as ATP, levels of dADP associated with upregulation of RNR do not alter the cell’s ability to synthesize ATP, and that elevated RNR does not alter the cell’s metabolism.
Bio: Jason Murray is a PhD student in the Department of Physiology and Biophysics, focusing on cardiac metabolism and mechanics. He likes bicycles. Were he a Jedi, his lightsaber would be green.
Jiayi Dou, UW Baker Lab
Title: Computational design of ligand-binding proteins
Abstract: Specific interactions between proteins and small-molecule ligands are essential for many biological functions. The ability to engineer this fundamental molecular recognition process would enable development of many novel biotechniques. We develop and use the computational biomolecular modeling software, Rosetta, to design novel binding sites for various small molecules. Our targets cover a diverse range of molecular hydrophobicity and conformational flexibility. Designed proteins undergo biophysical and structural studies to gain feedback for further improving our ability to model and design future interactions.
Bio: Jiayi Dou is a Ph.D. candidate in Professor David Baker's research group at the University of Washington. She has been focused on designing and characterizing de novo ligand-binding proteins since she joined the lab in 2012. Jiayi came to the United States after finishing her college at the University of Science and Technology of China.
Keenan Bashour, Juno Therapeutics
Title: Functional characterization of a T cell stimulation reagent for the production of therapeutic chimeric antigen receptor T cells
Abstract: Adoptive cell therapy using gene-modified T cells has demonstrated promising clinical outcomes in hematologic malignancies. Production of gene-modified T cells involves the selection of patient T cells, activation via stimulation through the endogenous T cell receptor (TCR) complex and a costimulatory domain, followed by introduction of a tumor antigen-specific TCR or chimeric antigen receptor (CAR) through gene modification. Here we characterize a soluble T cell stimulation reagent, known as an ExpamerTM reagent, in the production of therapeutic CAR T cells. The Expamer reagent is designed to be a late-stage clinical and commercial manufacturing ancillary material with two attributes that make it highly attractive from a manufacturing and regulatory standpoint; it is a soluble and dissociable reagent. These attributes provide products manufactured with this reagent consistent product quality and purity.
Bio: Keenan has been a Scientist in the Process Development group at Juno Therapeutics for the past two years, where he works on methods to improve cellular activation and response. Prior to Juno, Keenan received his Ph.D. in Biomedical Engineering at the Microscale Biocomplexity Lab at Columbia University, where he developed micro and nanoscale methods to dissect T cell biology. He currently spends his free time playing the cello, cooking and eating amazing food, occasionally sailing and kicking soccer balls really really hard.
Lael Wentland, UW Thomas Lab
Title: Creation of a Switchable Binding Protein Through FimH Allosteric Regulation
Abstract: This project proposes the design of a switchable binding protein, a protein whose affinity for its binding target can be modulated by environmental change. We hypothesize that this switchable binding can be triggered by light if a photoswitchable linker is attached to the binding protein's key residues. The protein scaffold chosen is FimH, a protein commonly found on the end of bacteria pili and its binding is naturally allosterically regulated by force. The physical switch of the linker will act in place of the force, allowing for specific control of binding. In the future, this could be beneficial because the protein could increase specificity of a diagnostic by being able to pre-concentrate the sample without contamination.
Bio: Lael Wentland is a senior undergraduate in bioengineering at University of Washington.
Nirveek Bhattacharjee, UW Folch Lab
Title: Immunotherapy-in-a-Chip
Abstract: Adoptive T-cell therapy involves engineering a patient’s own immune cells to recognize and attack their tumors. However, making the therapeutic cell-product requires expensive, multi-step processes in GMP facilities. We are developing a microfluidic device that would go from blood-bag to T-cells, genetically transformed with chimeric antigen receptors (CAR), under sterile conditions and without the need for specialized facilities. The “Immunotherapy-in-a-Chip” device consists of three modules that will be integrated together and operated under continuous flow – (1) size-based separation of lymphocytes from blood, using deterministic lateral displacement (DLD), (2) magnetophoretic isolation of T-cells with specific markers, and (3) electroporation of cells with plasmids. In preliminary experiments we have separated over 80% of lymphocytes from blood, magnetophoretically purified CD3 labeled lymphocytes from PBMC, and microfluidically electroporated mammalian cell lines. We envision that such an inexpensive, automated GMP-compatible microfluidic platform can make cell-based cancer immunotherapy more accessible and affordable.
Bio: Nirveek Bhattacharjee is a senior research fellow in the Department of Bioengineering at the University of Washington, working on microfluidic systems for cellular assays, in the Albert Folch group. He completed his Ph.D. in Biomedical Engineering from the Johns Hopkins University under the supervision of Nitish Thakor, working on live-cell microarrays. He has a Bachelors (Honors) in Electrical Engineering from the Indian Institute of Technology, Kharagpur, India.
Scott Braswell, UW Molecular Analysis Facility
Title: Instrumentation Capabilities of the UW Molecular Analysis Facility
Yuanhua Cheng, UW Regnier Lab
Title: HCM associated Cardiac Troponin I Mutations Alter Cardiac Troponin Function,Contractile Properties and Modulation by PKA mediated Phosphorylation
Abstract: Two HCM-associated mutations, R146G and R21C, are located in the inhibitory-peptide and the cardiac-specific N-terminus of cTnI, respectively. We previously reported these regions may interact when Ser23/Ser24 are phosphorylated, weakening cTnI interaction with cTnC. Our measurements demonstrated that both mutants blunted the ability of PKA phosphorylation to decrease pCa50 and accelerate the early, slow-phase relaxation. By using computational modeling studies, we found that introduction of either HCM mutation blunted the ability of cTnI phosphorylation to reposition the N-terminus extension to interact the inhibitory-peptide region. This suggests a structural mechanism that can explain the loss of PKA-mediated modulation of thin filament activation and relaxation of myofibrils that need to occur with increasing heart rate during β-adrenergic stimulation and increased physical activity. In ongoing studies, we are examining two additional HCM-associated cTnI mutations, P83S or A158V, located in the I-T arm and switch-peptide of cTnI, respectively.
Bio: Dr. Yuanhua Cheng received her doctor degree from the Department of Chemistry, Tsinghua University (Beijing, China) in 2011. After graduation (in 2012), she joined Dr. Regnier’s lab (the Heart and Muscle Mechanism, HAMM) at the University of Washington and Dr. McCammon’s lab (joint supervisor, located at University of California, San Diego) as a senior fellow to study the disease-related mutations in contractile proteins using both experimental and computational approaches. Her current research is focused on understanding how HCM-associated mutations in key contractile proteins (e.g, cardiac troponin I) and PKA-mediated phosphorylation during β–adrenergic stimulation affect cardiac muscle contraction and relaxation, and how these properties affect in the progression of heart failure. She was awarded a postdoc fellowship from American Heart Association (AHA) in 2015.