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2019 Postdocs at the Interface

Stanford ChEM-H solicited seed grant proposals from the Stanford community of postdoctoral fellows for exploratory projects that align with the Institute’s mission. Successful proposals combined the complementary expertise of two or more postdoctoral researchers (including Ph.D. holders, M.D. residents and M.D. clinical fellows) seeking to collaboratively explore a potentially transformative new idea with the support of their mentors. The two proposals selected were each funded with $50,000 for one year.

"Charge Altering Releasable Transporters (CARTs) as a tunable platform for delivery of nucleic acids to the lung: new formulation for a novel universal therapeutic for influenza A virus (IAV)"

Postdoctoral Scholars:

Timothy Blake, Waymouth Lab
David Paul Walton, Wender Lab
Rachel Hagey Saluti, Glenn Lab

Mentors:

Jeffrey Glenn, Medicine - Gastroenterology and Hepatology, Microbiology & Immunology
Robert Waymouth, Chemistry
Paul Wender, Chemistry, Chemical and Systems Biology

Project Summary:

Emerging DNA and RNA technologies have the potential to revolutionize medicine and life science research. Clinical progress of such therapeutics, however, is currently stifled by a lack of safe and effective delivery. Pulmonary drug delivery, in particular, is an area of clinical importance that suffers from these difficulties and is further confounded by the complexity of the respiratory tract, which has evolved to keep inhaled particles out and limit cellular uptake. Charge Altering Releasable Transporters (CARTs) developed by the Wender-Waymouth laboratories encompass a platform technology that promises safe and effective delivery of nucleic acids, with the potential to propel DNA and RNA therapeutics through the clinic. CARTs already outperform commercial reagents and allow the targeting of more challenging organs and tissues. With this ChEM-H seed grant initiative, we seek to apply the CART platform technology to develop a first-of-its-kind formulation for delivery of a novel nucleic acid inhibitor with broad-spectrum activity against influenza A virus developed by the Glenn laboratory, specially optimized for the lung. This proof-of-principle work has a path to the clinic as a nebulized universal flu therapeutic possessing a high barrier to antiviral resistance, and serves to pave the way for similar nucleic acid delivery strategies in other disease models of clinical interest.


"Development of Novel Molecular Imaging Agents for Visualization of Cytotoxic T-cells and evaluation of CAR-T cell therapy in preclinical models of glioblastoma"

Postdoctoral Scholars:

Corinne Beinat, Gambhir Lab
Chirag Patel, Recht Lab

Mentors:

Sanjiv Sam Gambhir, Radiology
Lawrence Recht, Neurology and Neurological Sciences 

Project Summary:

Glioblastoma is the most common and lethal type of primary brain cancer, with half of patients dying within 14-18 months of their diagnosis, and 5.6% of patients alive five years after their diagnosis. One promising approach for the treatment of glioblastoma is immunotherapy. Immunotherapy is a type of cancer treatment that boosts the body’s natural immune system to fight cancer. Immunotherapy involves natural or laboratory-manufactured agents to amplify or restore immune system function, which in turn helps our body’s immune system to recognize and destroy cancer cells. One of the key challenges in the successful treatment of glioblastoma with immunotherapy is the lack of appropriate methods to visualize and monitor the killing of cancer cells by the immune system. This proposal aims to overcome this challenge by developing a novel imaging agent to visualize and quantify perforin, a specific protein that immune cells use to kill cancer cells. This would allow clinicians and researchers to visualize and have real-time information of the killing of cancer cells by the immune system and make informed decisions about the effectiveness of immunotherapy for individual patients with glioblastoma.