Ian Miller presents work at Fred Hutchinson Cancer Research Center

Grad student Ian Miller presented his work on thermal control of CAR T cells at the Fred Hutch Immuno-Oncology Graduate Student Symposium hosted by Fred Hutch’s Immunotherapy Integrated Research Center (IIRC). Here participants met faculty, learned about the breadth of research done in immuno-oncology, visited research laboratories and shared resource facilities, and toured Fred Hutch’s Bezos Family Immunotherapy Clinic at the Seattle Cancer Care Alliance, our clinical partner.

Noina Phuengkham joins LSI as a post-doctoral fellow

Hathaichanok “Noina” Phuengkham joins LSI as a new post-doc. Noina originally hails from Thailand and completed her Ph.D. studies at Sungkyunkwan University in South Korea where she developed biomaterials to alter immunosuppressive tumor microenvironments with Dr. Yong Taik Lim. Read more about Noina here.

Dr. Kwong presents at Transplant Immunosuppression 2019

Dr. Kwong was invited to speak at the Transplant Immunosuppression 2019 Conference in Minneapolis, MN. The course focused on current options for immunosuppression (and what’s in the pipeline), with particular attention to individualization of immunosuppression based on clinical and/or laboratory parameters; prevention, diagnosis and treatment of antibody-mediated rejection; improving long-term transplant outcomes; and major issues in transplant-related infectious disease, living donation, and patient-centered care.

Computational methods for deconvolving protease signatures

Our work on developing computational methods for estimating protease activities was published in PLoS Computational Biology!

“The activity of enzymatic proteins, which are called proteases, drives numerous important processes in health and disease: including cancer, immunity, and infectious disease. Many labs have developed useful diagnostics by designing sensors that measure the activity of these proteases. However, if we want to detect multiple proteases at the same time, it becomes impractical to design sensors that only detect one protease. This is due to a phenomenon called protease promiscuity, which means that proteases will activate multiple different sensors. Computational methods have been created to solve this problem, but the challenge is that these often require large amounts of training data. Further, completely different proteases may be detected by the same subset of sensors. In this work, we design a computational method to overcome this problem by clustering similar proteases into “subfamilies”, which increases estimation accuracy. Further, our method tests multiple combinations of sensors to maintain accuracy while minimizing the number of sensors used. Together, we envision that this work will increase the amount of useful information we can extract from biological samples, which may lead to better clinical diagnostics.”

LSI awarded talks at BMES 2019

Multiple students were awarded podium talks at the 2019 BMES Annual Meeting in Philadelphia, PA. They are:

Brandon Holt – “Synthetic biological circuits for treating prodrug-resistant bacteria”

Brandon Holt – “Proteases as biological bits for programmable medicine”

Ian Miller – “Remote Control of CAR T Cells Using Thermal Cues”

Shreyas Dahotre – “Ultrasensitive Detection of Protein and Cellular Biomarkers by CRISPR-Cas12a”

Lena Gamboa – “Heat-triggered CRISPR-dCas9 for the remote control of therapeutic T cells”

Quoc Mac – “Activity Therasensors for Predictive Monitoring of Response to Checkpoint Blockade Immunotherapy”

Lee-Kai Sun – “Designing Synthetic Gene Switches for Single-cue Thermal Control of Engineered T Cells”

Anna Romanov – “Precise T Cell Drug Delivery Using pMHC Liposomes”

Look forward to seeing you in Philly!

LSI awarded NSF grant to develop cell sorting technologies

LSI awarded $500,000 from the NSF Division of Chemical, Bioengineering, Environmental, and Transport Systems (CBET) for “Ultra-fast transient cell adhesion and its application for high-throughput microfluidic cell sorting”. Our co-PI’s are Dr. Alexander Alexeev (associate professor, The George W. Woodruff School of Mechanical Engineering) and Todd Sulchek (professor, The George W. Woodruff School of Mechanical Engineering).

“Biological cells use various adhesion molecules on their surfaces to interact with each other and their environment. The type, amount, and combination of these adhesion molecules, which carry important information about specific cell conditions, can be used to characterize cells and diagnose disease. Sorting and separating cells based on their expressions of adhesion molecules are critical steps in many biomedical assays. Current cell sorting approaches use tags that bind to cells expressing specific adhesion molecules. These attached tags enable high purity sorting, but the tags can alter cell state and can lead to unwanted cell activation preventing further use of the labeled cells. This project will develop a microfluidic technology that enables rapid and efficient sorting of biological cells based on the expression of adhesion molecules without the use of any tags or labels. The technology utilizes a microfluidic channel with periodic constrictions coated with molecules that briefly interact adhesion molecules on the cells’ surfaces. The interaction causes a change in the trajectories of the cells of interest without inducing unwanted activation. The project will investigate the mechanics of cell interactions within the microchannel and will probe the use of this microfluidic separation technique to isolate lymphocytes with highly specific adhesion molecules that can be used in cancer therapies. The research will involve undergraduate and graduate students, and the team will conduct several outreach activities to students at all levels, including developing projects for science and engineering competitions.

This project will develop a microfluidic approach for high-throughput, label-free cell sorting and separation based on the affinity of molecular surface markers for target ligands. Identifying and isolating cells that express desired molecular surface markers are required in a variety of applications in the biological sciences, cell therapy, and medical diagnostics. The project will integrate microfluidic experiments and computer simulations to examine transient adhesion of biological cells at ultrafast time scales that have not yet been explored. Cells will be propelled through a microfluidic channel decorated with diagonal ridges that slightly compress the cells to promote binding between adhesion molecules and ligands covering the microchannel surfaces. The binding events alter cell trajectories in the microchannel characterizing cell adhesion. The short contact time between cells and microchannel surfaces will prevent unwanted cell activation. The project will systematically probe effects of confinement on transient cell adhesion for a wide range of time scales. Furthermore, the project will employ the microfluidic cell sorting technique to examine T cell selectivity to target antigens, which is important in clinical applications, without activating the cells. Positive and negative selection to T cell neoantigens will be investigated to identify disease-selective T cells. The results of this research project, a new microfluidic method for high-throughput label-free cell separation, will have broad implications in medical diagnostics, therapeutics, cell engineering, and cell manufacturing. Furthermore, the microfluidic method can enable direct measurements of transient interactions between important physiological ligands and adhesive cell molecules that will benefit the development of novel diagnostic methods.”

LSI wins seed grant from the Petit Institute

The labs of Gabe Kwong (assistant professor, Coulter Department of Biomedical Engineering) and M.G. Finn (professor, School of Chemistry and Biochemistry) were awarded a grant for “Activity biosensors that implement Boolean logic as precision diagnostics for immunotherapy.” The researchers reason that disease detection and evaluation of treatment responses in vivo depend on the ability to extract clinically useful information from complex biological systems. Noting that previous work in biological computing led to the use of genetic and cell-based tools, they propose that developing programmable biomaterials to perform basic computations, such as Boolean logic, may provide a new framework to increase detection precision and resistance to biological noise.

The Petit Institute Seed Grants provide year-one funding of $50,000 with equivalent year-two funding contingent on submission of an NIH R21/R01 or similar collaborative grant proposal within 12 to 24 months of the year-one start date (July 1, 2019).

LSI part of multi-institute effort to develop new treatments for influenza infection

The Laboratory for Synthetic Immunity is part of a $21.9 million award from DARPA to develop gene therapies to enable protection against a wide range of influenza strains and improve immune responses and efficacy of current influenza vaccines. The work, led by Phil Santangelo at Georgia Tech, is being performed by researchers at GT, Duke, Emory, UGA, ULL, Rockefeller, Acorda Therapeutics, and the CDC.

Learn more about the project here and here.