Catalyzing cancer research through the use of advanced functional genomics and cell engineering technologies

About This Grant

Project Summary Technological advances like genome sequencing, RNA interference (RNAi), and CRISPR have transformed functional genomics by speeding up genetic discoveries and enhancing our understanding of diseases and personalized medicine. Dr. Molishree Joshi, the PI of the proposal and the Associate Director of the Functional Genomics Shared Resource (FGSR) at the University of Colorado Cancer Center (UCCC), has significantly contributed to this field by providing essential resources to academic labs in Colorado. UCCC, one of 71 NCI- Designated Comprehensive Cancer Centers, is funded by the NCI-P30 under Dr. Richard Schulick and supports four interdisciplinary research programs and twelve shared resources, including FGSR. Initially, FGSR functioned as a repository for small hairpin RNA (shRNA) from The RNA Consortium (TRC) library. Significant advancements began when Dr. Molishree Joshi became Manager and Scientific Consultant in 2013. As the sole full-time employee, she expanded FGSR's capabilities by strategically securing local funding and proactively integrating complementary technologies and instrumentation for automation. Today, FGSR supports three major platforms: shRNA, Open Reading Frame (ORF), and CRISPR, providing pre-made reagents and customized solutions. The addition of services to create custom CRISPR libraries, assistance with CRISPR screens, and gene editing in complex cancer cell lines has led to groundbreaking discoveries. Owing to Dr. Joshi’s relentless efforts, FGSR is one of the most utilized core facilities in Colorado; it has provided services to >360 academic labs across four campuses, contributed to >250 peer-reviewed publications, facilitated over 85 NCI-funded grants, and helped initiate several clinical trials. Dr. Joshi goes above and beyond, and she continues to innovate. The ongoing noteworthy developments include 1) Copy-number analysis and mutation detection in cancer cells and measurement of CAR-T cell dynamics in immunotherapy patients using digital PCR, 2) Robust protocol development for heterozygous gene editing in cancer cells and iPSCs, 3) Protocol optimization for single-cell and spatial CRISPR screens, 4) CRISPR editing in 3D cell cultures, 5) Repurposing of CRISPR-Cas9 technology to target tumors with genomic amplification and 6) Applying for the NIH S10 Shared Instrumentation Grant to procure CellCelector Flex for precise cell isolation. Dr. Joshi also contributes to education by giving seminars and teaching multiple graduate-level courses focused on genome editing and precision medicine on the Anschutz campus. Thus, Dr. Joshi’s scientific and administrative acumen have been the key to the evolution and success of FGSR. Dr. Joshi's outstanding contributions have garnered her the prestigious Outstanding Scientist Award from ABRF and a promotion to Associate Director of FGSR in 2023. UCCC is committed to championing both FGSR and Dr. Joshi’s career. The R50 award will be a game-changer, empowering Dr. Joshi to drive groundbreaking cancer research and ensuring a stable and impactful future for her work.