Project Summary: The Vanderbilt-Ingram Cancer Center (VICC) is an NCI-designated Comprehensive Cancer Center with over 270 members focused on cancer-related research. The Vanderbilt Institute of Chemical Biology (VICB) High- Throughput Screening (HTS) core facility was established to provide screening-based services for investigators for molecular probe and pharmacological discovery. Dr. Joshua Bauer plays an integral role in the interface between the cancer research and chemical biology programs at Vanderbilt. He has a strong background in cancer biology, pharmacology, and biochemistry. His main goal is to use chemical genomic approaches, including functional genomics screening and high-content imaging, to identify novel drug targets and to better understand the molecular and genetic mechanisms that underlie how cancer cells respond to therapeutics. To achieve this goal his cancer-related projects within the HTS facility are focused on three areas: 1) compound/drug library screening (i.e., HTS), 2) functional genomics (siRNA/CRISPR) library screening, and 3) high-content screening (HCS) and analysis. To date, Dr. Bauer has provided support and intellectual contributions to over 80 HTS projects, including collaborations with at least 41 Cancer Center members, including 31 that are NCI funded. These continued collaborations have allowed him to develop innovative assays and novel screening projects that contribute to the success of the Vanderbilt HTS core and cancer research program. His vital role and success stems from his ability to conceive, collaborate, design and perform screens, and intellectually contribute to projects, grant proposals, and manuscripts. In addition, through participation in conferences, meetings and workshops Dr. Bauer strives to bring state-of-the-art technologies and ideas to the Vanderbilt HTS facility. The blend of his skills, expertise, and knowledge provide a unique role within Vanderbilt to mend cancer research, chemical biology, genomics, drug discovery, and translational drug investigation. Through his previously funded R50 award, Dr. Bauer has already further advanced his areas of focus in HTS and his career development. So far on the award (2016-20), he has been co-authored on 11 papers, has supported 38 cancer-related grant proposals, supported and trained over 50 graduate students and postdocs on HTS instrumentation or software, has developed several novel functional genomics screens (CRISPR and ORFeome), and has pioneered several high-throughput 3D organoid models for high-content drug screening. Dr. Bauer has become a member of the NCI- Chemical Biology Consortium where he has been exposed to world-class drug discovery experts. Finally, the results of Dr. Bauer's work and collaborations have influenced the design of clinical trials, initiated sponsored research, and has led to lead molecules for further development. Therefore, Dr. Bauer's continued role as a Cancer Pharmacologist & HTS Scientist is completely...