Center for Advanced Preclinical Research: Preclinical Technology & Optimization Team

The Preclinical Technology and Optimization (PTO) team performs a broad spectrum of tasks aimed at identifying any unmet needs in CAPR's portfolio, which includes both genetically engineered mouse (GEM) and biologically engineered murine preclinical models. The PTO team then designs and develops best-in-class resources for preclinical assessment of these models. Our expertise includes optimizing new molecular tools for targeted modification of mammalian genomes, rapid engineering of novel modified alleles for next generation preclinical models, and developing strategies to enhance molecular imaging of both early stage and metastatic disease.

Team Leader

Serguei Kozlov, PhD, MBA, PMP, Principal Scientist

Expertise

• Optimizing and applying a comprehensive set of  molecular tools for targeted gene modification and genome editing to improve murine cancer models, both for discovery and preclinical drug development.
• Applying re-tooled models for clinically challenging cancers (e.g., pancreatic, lung, prostate) to mechanistically evaluate the disease process and assess potential therapeutic strategies.
• Enhancing pluripotent stem cell technologies (e.g., embryonic, induced) to streamline and accelerate preclinical assessment in non-germline genetically engineered models.
• Developing and validating novel engineered alleles that enable more accurate monitoring of disease via in vivo imaging techniques (e.g., bioluminescence, PET/SPECT).
• Designing the next generation of “tool” mouse lines to produce more practical, affordable, and tractable GEM models to improve the preclinical workflow.
• Adopting new methods for deriving and maintaining in vitro cell culture models (e.g., 3D, tumorgrafts, microtumor) to establish a scalable platform for screening compound libraries and assessing early-stage drug efficacy.
• Implementing multiple partnership mechanisms designed to optimize the public-private partnership concept, with the goal of improving the quality of cancer therapeutics available to patients while shortening the drug development process.

Initiatives

Our collaborators and partners include NCI intramural investigators, academic institutions, non-profit organizations, and private industry. Current projects include evaluation of targeted therapeutics and biomarkers in mouse models for:

• pancreatic ductal adenocarcinoma (PDAC)
• Alk-fusion-driven non-small cell lung cancer (NSCLC)

Team Members