Molecular Screening Shared Resource (MSSR)

University Of California Los Angeles, Los Angeles CA

Investigators

Linked publications & trials

Abstract

MOLECULAR SCREENING SHARED RESOURCE (MSSR) ABSTRACT The UCLA Jonsson Comprehensive Cancer Center (JCCC) Molecular Screening Shared Resource (MSSR) objective is to provide transformative high throughput screening (HTS) for small and large molecules to the JCCC research community. This objective is achieved through three Specific Aims: (1) To expand screening capabilities with state-of-the-art approaches; (2) To expand functional genomics screening capabilities; and (3) To enhance drug development capabilities. MSSR offers a comprehensive array of HTS services enabling JCCC investigators to discover new molecular targets, identify agents for these targets, and characterize and optimize agents for translation. Established in 2003, MSSR and has grown from 950 to 3,600 sq. ft. of BSL2+ space. From 2019 – 2023, 43 JCCC investigators used MSSR accounting for 41% of total usage. Of JCCC member usage, 66% was by peer-review funded investigators. MSSR services, including assay development, HTS, data analyses, and follow-up, such as potency, toxicity, and selective testing, for both small and large molecular drugs, contributed to 50 cancer-relevant publications with 42% in high impact (IF ≥10) journals. MSSR offers access to >300K compounds in multiple libraries for chemical genomics, repurposing, and drug discovery. MSSR also offers a wide array of functional genomics libraries, such as >60K human lentiviral CRISPR gRNAs, shRNA lentiviral constructs, siRNAs covering druggable mouse and human genomes, and a genome wide lentiviral and transfection ready cDNA library. Projects are supported by three expert MSSR scientists on six fully automated, robotic screening systems, one new since 2019, with a daily capacity >100K samples. All plate reader assays and plate formats are addressable with ≥1,536-well plates, as are advanced assay readouts including confocal spinning disk microscopy. MSSR uses a collaborative model integrating users into a project team consisting of the JCCC investigator, MSSR leadership, and MSSR scientists. This approach brings in expert and often nuanced knowledge while keeping MSSR headcount and associated costs low but scalable with demand. Moreover, this provides an excellent educational opportunity, with 204 students learning in one-on-one training from MSSR experts since 2019. MSSR provides workshops on assay development, AI based image analysis, and data mining. All projects advance using industry best practices including generation of standard operating procedures (SOPs) and milestone driven project management. MSSR Director Robert Damoiseaux, PhD (CSCB) is an international expert in HTS with industry background. Damoiseaux guides each project, ensuring research excellence. MSSR management is overseen by JCCC Associate Director for Shared Resources, Zoran Galic, PhD (TII), with additional support and guidance from a five member MSSR Faculty Advisory Committee (FAC), comprised entirely of JCCC members. Examples of MSSR impact include the first MSSR small molecule agent, TRE-515, passing a Phase I dosing trial in 2023, and the first large molecule MSSR drug, DUNP19, entering cGMP production to prepare for clinical trials after receiving FDA orphan drug designation in 2022.