Jared Barrott, Ph.D.

Summary: My diverse training in multiple research disciplines (i.e. developmental genetics and cancer pharmacology) and top-quality pedagogical training will not only help me to accomplish my scientific aspirations but will help me to teach students and trainees so they can achieve theirs. I have a particular interest in the personalized approaches of treating cancer because it interweaves two disciplines that I am very passionate about: pharmacology and genetics. Many clinical efforts are already being made to analyze genetic profiles for individual patients that expose the driving mutations of the cancer. However, the complexity of cancer in its heterogeneity and temporal regulation make it difficult to assign effective treatments to a single snapshot obtained by the current diagnostic techniques. Future efforts should focus on the technology that will facilitate multiple assessments throughout the course of a treatment therapy. My lab focuses on one of the more genetically complex pediatric tumors: osteosarcoma. Within osteosarcoma there is a potential to shift the paradigm on how we view genetically complex tumors and the interaction with epigenetic regulation, as we have recently discovered through a forward genetic screen that chromatin remodeling genes associated with faster tumorigenesis. We have disease models that will allow us to evaluate the epigenetic regulations in several sarcomas, and especially in osteosarcoma. Dynamic changes in genetics and epigenetics, assessed by multiple sequence testing will help establish protocols for treating and monitoring outcomes in a near real-time fashion. In studying the epigenetic regulations in these genetically complex pediatric tumors, we will delineate druggable enzymes that should advance treatment or prevent resistance for pediatric sarcomas that are currently static in developing effective treatments.

Minimum classes: No prerequisites are required

Projects:

Project I – Inhibiting the Renin-Angiotensin System in advanced osteosarcoma

This project will implement gene editing technology CRISPR-CAS9 to introduce a deletion of the ARID1A gene in osteosarcoma cells. Then using novel inhibitors of the Renin-Angiotensin System, we will determine if the therapy works better in osteosarcoma cells with or without ARID1A.

Project II – Inhibiting HSP90 in metastatic synovial sarcoma

This project will implement microscopic detection of extracellular HSP90 in metastatic synovial sarcoma cells versus non-metastatic synovial sarcoma cells. Using HSP90 small molecule inhibitors, we will treat both cells grown in a dish and genetically engineered mice with synovial sarcomas to see how effective the treatment is against the metastatic disease.

Project III – Dissecting the interactions between epigenetic mechanisms and chromothripsis in osteosarcoma

This project will genetically dissect the interactions between the SWI/SNF chromatin remodeling complex and a genetic phenomenon called chromothripsis where the chromosomes shatter in multiple fragments and are reassembled haphazardly. To do this, we will cross genetic strains of mice and perform plasma DNA sequencing to look for these chromosomal rearrangements.