SPEAKERS
Presenters
James Carothers, UW Carothers Lab
Bryan Howie, Adaptive Biotechnologies
Alicia Moreno-Gonzalez, Presage Biosciences
Chris Neumann, Seattle Genetics
Dean Pettit, Just Biotherapeutics
Daniel Ratner, UW Dan Ratner Lab
Alissa Bleem, UW Dagget Lab
Title: Designed peptides for inhibition of amyloid fibrilogenesis in medical biofilms
Abstract: Nosocomial infections affect millions of patients worldwide each year, and approximately 60% of these infections are associated with biofilm formation on an implanted medical device. Biofilms are dense communities of microorganisms in which cells associate with surfaces and each other using a self-produced extracellular matrix (EM). Proteins in the EM take on a variety of forms, but the most common structure is the amyloid fold. Amyloids have long been associated with neurodegenerative diseases, but recent research has demonstrated that several bacteria utilize the amyloid fold to fortify the biofilm matrix and thereby resist antibiotic treatments. We hypothesize that the intermediate stage of fibril production in the EM is characterized by the creation of specific oligomeric structures; therefore, molecules designed to bind these oligomeric intermediates may be capable of disrupting biofilm formation, leading to new biofilm prevention strategies for improved patient outcomes.
Bio: Alissa received her B.S. in Chemical Engineering at Montana State University, and she is now a second year graduate student working with Dr. Valerie Daggett and Dr. James Bryers. Her research utilizes computational protein design and molecular dynamics to develop novel anti-microbial agents and prevent biofilm-associated infections.
Cassie Bryan, UW Baker Lab
Title: The Computational Design of Protein Binders Targeting PD-1 for Cell-Based Immunotherapies
Abstract: Programmed Cell Death Protein 1 (PD-1) inhibits activated T cells to prevent an excessive immune response. This pathway is taken advantage of by tumor cells that over-express the ligands of PD-1, PD-L1 and PD-L2, to evade the immune system. Two antibodies targeting PD-1 (nivolumab, pembrolizumab) received FDA approval in 2014 and have since transformed the way cancer is treated. While these confirm PD-1 as an important protein to target for cancer, they do not translate to cell-based technologies that show promise as the next generation of immunotherapies. Using a combination of computational design and experimental approaches, I have developed several small de novo proteins that specifically bind PD-1 with high affinity. In collaboration with Stan Riddell (Fred Hutchinson Cancer Research) and Courtney Crane (Seattle Children’s), we are applying these PD-1 inhibitors to cell-based immunotherapy platforms, including CAR-T cells and engineered macrophages, to reactivate the immune system in the tumor microenvironment.
Bio: I received my B.S. in Biochemistry/Cell Biology from the University of California, San Diego. After undergrad, I spent one year in biotech at Beckman Coulter building custom MHC tetramers and two years in Wesley Van Voorhis' lab at UW doing structural genomics before deciding to go back to school. I am now in my fifth year of graduate school in David Baker's lab doing computational design of protein-protein interfaces.
James Carothers, UW Carothers Lab
Title: RNA aptamer nanosensors for profiling metabolic output on a massive scale
Abstract: Microbes produce and secrete molecules for communication and survival in changing environments. Understanding how variations in metabolic output impact antibiosis, sporulation and biofilm formation could have broad implications for health and medicine and for applications in metabolic engineering. We are developing RNA-aptamer based nanosensor platforms as technologies for multiplexed detection of cellular metabolites produced by commensal and engineered bacteria. Our goals are to dramatically reduce the time needed to create systems for ultra-selective label-free molecular detection, and to demonstrate the immediate utility of these technologies for investigating and engineering metabolic output. In this presentation, I will briefly describe a new approach for engineering RNA aptamer nanosensors using 'time-resolved' computational design and highlight our proof-of-concept work to create physical architectures for profiling metabolic output on a massive scale.
Bio: Dr. James Carothers is an assistant professor of chemical engineering, adjunct assistant professor of bioengineering, and an affiliated investigator of the NSF Synthetic Biology Engineering Research Center.
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.
Brynn Livesay, UW Pun Lab
Title: Identifying Synthetic Targeting Ligands for Cancer Immunotherapy Applications
Abstract: Library screening techniques like peptide phage display, yeast display, and aptamer SELEX have been used for many years in industry and academia to identify new targeting ligands. In the past few years, the Pub Laboratory at the University of Washington has developed methods to combine high throughput screening, sequencing, analysis, and validation for efficient ligand identification. With these methods, our lab has begun to identify chemically synthesizable targeting ligands against immune system cells and targets.
Bio: Brynn Livesay is a 3rd year NSF graduate research fellow working under the direction of Dr. Suzie Pun in the Department of Bioengineering at UW. Her research focuses on developing novel biomaterials for the emerging field of cell-based cancer immunotherapies, where a patient’s own immune system is trained to recognize and eliminate cancer cells. She aims to develop synthetic targeting ligands through peptide and aptamer library screening methods, that can be used in cell sorting and targeted delivery applications.
Alicia Moreno-Gonzalez, Presage Biosciences
Title: A Precision Oncology Diagnostic with Cancer Drug Development Applications
Abstract: Presage Biosciences is a biotechnology company focused on improving the cancer drug development process so that patients can receive the most effective treatment possible. The company’s proprietary CIVO assay system is intended to help inform clinical drug development decisions. CIVO enables side-by-side comparison of a patient’s tumor response or non-response to multiple drugs or drug combinations. With its patented CIVO intratumoral drug microinjection device and ex-vivo analytical tools, Presage is pioneering the incorporation of human efficacy data much earlier in the drug development and clinical trial processes. Presage was founded in 2008 based on technology invented at the Fred Hutchinson Cancer Research Center. This technology is being used to advance a portfolio of drug candidates for treating patients with solid tumors. Presage is a privately held company headquartered in Seattle, WA.
Bio: Dr. Alicia Moreno Gonzalez is the Associate Director of Clinical Development at Presage Biosciences. She leads the engineering, clinical and regulatory efforts aimed at advancing the CIVO Precision Oncology program. The company’s proprietary CIVO assay is intended to improve the cancer drug development process so patients can receive the most effective treatment possible. CIVO enables side-by-side comparison of a patient’s tumor response or non-response to multiple drugs or drug combinations. Originally from Mexico; Alicia received her Bachelor’s degree in Engineering Physics from the ‘Tec de Monterrey’. She then moved to Seattle in 2000 to pursue her graduate education at the University of Washington and received her Ph.D. in Bioengineering. Throughout her career, she has gained extensive experience with both cell-based and animal models of disease, ranging from cardiovascular disease to cancer.
Chris Neumann, Seattle Genetics
Title: Antibody-drug conjugates: Empowered Antibodies for Cancer Therapy
Abstract: Antibody-drug conjugates combine the targeting ability of unmodified antibodies with the cytotoxic activity of chemotherapeutic agents. The Seattle Genetics technology platform provides cancer-targeted ADCs with proven clinical benefit. Continued pre-clinical development of our technology is providing ADCs with enhanced activity in model systems, and sets the stage for a next generation of clinical candidates in diverse cancer indications.
Bio: Chris Neumann is a Senior Scientist in the research chemistry group at Seattle Genetics. Prior to joining the company in 2012, he did his scientific training in the areas of synthetic organic chemistry, natural products biosynthesis, and enzymology. His work currently focuses on designing new linker-payload systems that can enable antibody-drug conjugates for diverse therapeutic areas.
Dean Pettit, Just Biotherapeutics
Title: Transforming Biologics Manufacturing for Low Cost:Integrated Design from Molecule to Plant
Abstract: Over the past 3 decades the biotechnology industry has been "writing the book" on the production of biotherapeutics. Tremendous progress has been made as exemplified by meeting the large and growing demand for numerous high dose biotherapeutics. I will give a perspective on state-of the-art approaches to protein design for manufacturability and delivery, process operations designed for low cost and high quality products, and manufacturing facilities designed for flexibility and rapid, low cost deployment. I will also consider the innovation required to "write the next chapter of the book" in order to further drive down costs and improve global access to these important medicines.
Bio: Dean began his career working with medical devices at Allergan and then earned his Ph.D. and completed a postdoctoral fellowship in Protein Engineering at the University of Washington Department of Bioengineering. Over his career, Dean has held numerous leadership roles in process development functions at Immunex and Amgen, including Drug Delivery, Formulation, Analytical and Formulation Sciences. Most recently, Dean served as Executive Director of Drug Substance Development at Amgen, responsible for Cell Culture and Cell Line Development, Purification, Analytical, and Bio-characterization functions. Dean is now a founding partner and CSO of Just Biotherapeutics.
Daniel Ratner, UW Dan Ratner Lab
Title: Engineering Tools for Glycomics: Carbohydrates Interactions in Drug Development
Abstract: The burgeoning field of glycomics has been stymied by a scarcity of biophysical and molecular tools. Detecting glycan interactions is cumbersome and carbohydrates have no biological amplification counterpart to the polymerase chain reaction (PCR) or recombinant protein expression. This talk will give a brief overview of the tools being employed to explore the role of carbohydrate-mediated molecular recognition and their use in developing drug delivery platforms and anti-infective agents.
Bio: Daniel M. Ratner trained in carbohydrate chemistry and microarray fabrication at the Massachusetts Institute of Technology with Professor Peter Seeberger, where he received his PhD in Synthetic Organic Chemistry. He subsequently joined the Section of Infectious Diseases at Boston Medical Center / Boston University as an NRSA Postdoctoral Fellow with the Training Program in Host-Pathogen Interactions. In September 2007 he became a member of the faculty of the University of Washington in the Department of Bioengineering. The Ratner laboratory is developing new chemical and biophysical tools to probe carbohydrate-mediated interaction using SPR and silicon photonic biosensors and develop smart neoglycopolymer systems for drug delivery.
Wendy Thomas, UW Thomas Lab
Title: Engineering Adhesive Proteins in E. coli Towards Improved Vaccine Design
Abstract: Adhesive proteins on the surface of eukaryotic cells, bacteria and viruses are critical receptors in cell adhesion or signaling and are primary targets for the development of vaccine and therapeutic antibodies. However, the ligand-binding pocket of many adhesive proteins can shift between an active and an inactive conformation. We engineered one of the vaccine target proteins, Escherichia coli fimbrial adhesin FimH, in order to raise monoclonal antibodies that stabilize the inactive form. We show that these are more effective in inhibiting bacterial adhesion and infection relative to other types of monoclonal antibodies against FimH, some of which actually active adhesion. This work provides new insights into vaccine design.
Bio: Wendy Thomas earned a BA degree in Molecular Biology at Princeton University in 1987, and then worked as a research technician for 10 years at Howard Hughes Medical Institute studying lipid biochemistry. She then earned a master’s degree in Applied Math and a Ph. D. in Bioengineering at the University of Washington in 2003. In 2004, she accepted a tenure track faculty position in Bioengineering at the University of Washington, where she is now an Associate Professor. Wendy has applied her interests in molecular biology, math, and bioengineering to combine experimental and computational approaches to study biological adhesion and to design new biotechnologies based on her discoveries.
Alex Zanghellini, Arzeda
Title:
Abstract:
Bio: Alexandre Zanghellini co-founded Arzeda and currently serves as its Chief Executive Officer. He leads Arzeda’s product and technology development and corporate strategy. Alex is one of the key inventors of Arzeda’s synthetic biology platform for novel enzyme and metabolic pathway design and is a keen believer in the power of biotechnology to solve some of our biggest societal challenges. Before founding Arzeda, Alex held positions in research and development both in academia and industry. He holds a Ph.D. in biochemistry from the University of Washington in Seattle, a M.Sc. Eng. in Computer Engineering from ENSTA/ParisTech and a MS in Computer Science from the University of Paris Pierre et Marie Curie/Paris VI.