After receiving her undergraduate degrees in chemistry and economics from Caltech, Dr. Jenny Treweek went on to pursue her chemistry PhD in the laboratory of Dr. Kim Janda. Her PhD consisted of the design and in vivo testing of active and passive vaccination strategies, which entailed: (1) using organic synthesis and conjugation chemistry to create small-molecule-based haptens for attachment to carrier proteins via an optimized linker moiety; (2) designing and producing antibody-based scaffolds using cloning and protein-engineering; and 3) assaying the PK-PD properties and preclinical utility of candidate vaccines in rodent models.Dr. Treweek went on to complete her postdoctoral training with Dr. Viviana Gradinaru at Caltech, where she leveraged her chemistry background to develop tools for systems neuroscience research. Under Dr. Gradinaru’s expert guidance, Dr. Treweek pioneered various tissue-hydrogel embedding, tissue-clearing and biomolecular labeling methodologies, which were productively applied to a variety of biological applications: from high-resolution, 3-D mapping of complex cellular niche and neural pathways within the rodent body, to high-throughput screening of adeno-associated viral (AAV) vector libraries for use in gene therapy.
In 2019, Dr. Treweek founded her BME lab at USC on the principle of engineering novel intersectional-genetic tools and miniaturized ultrasound devices for probing neural circuits of the CNS and PNS. Herein, her lab hopes to apply these noninvasive gene delivery and neuromodulation strategies to treating the most pressing issues in neurological disease.
3D Analysis of Retinal Degeneration through Tissue-Clearing and Advanced Microscopy
The Royal College of Surgeons (RCS) rat serves as a powerful tool for modeling the pathogenesis of inherited degenerative diseases of the retina. To forward the characterization of retinal disease progression and to evaluate the therapeutic potential of novel treatment modalities in this rodent model, we developed a tissue-clearing, labeling, and 3D imaging pipeline that grants high-resolution visualization of the intact laminar architecture and cellular content of the retina via light-sheet microscopy (LSM). In addition, a semi-automated computational workflow was created for quantifying the major pathological signs of degeneration, including retinal cell loss, deterioration of the laminar structure, vascularization, and gliosis, across all retinal layers and at multiple regions-of-interest (ROI, e.g., temporal, nasal, inferior, and superior locations) within terabyte-sized datasets. Taken together, this pipeline provides a more accurate and more sensitive approach to studying the intact retina, as it avoids the tissue damage and loss-of-information inherent to thin-sectioning, flat-mounting, and serial sampling techniques of traditional histology. Current research focuses on extending this pipeline to the spatial characterization of RNA transcripts in order to refine the phenotyping of retinal cell subtype and cell health during disease progression.