About the Jones Lab
We are a husband and wife co-PI team. We effectively combine Dr. T. Jones’ expertise in molecular biology, developmental biology and cell biology with Dr. P. Jones’ expertise in epigenetics, gene regulation and biochemistry to address questions from multiple angles. We were founded in 2001 as an epigenetics lab interested in gene regulation and epigenetic processes that occur during development and disease. However, in 2003, an FSHD patient (and graduate student) introduced us to FSHD as an emerging epigenetic disease and we gradually shifted our lab's focus to FSHD. Today we still investigate the fundamental epigenetic dysregulation of the chromosome 4q35 D4Z4 locus that leads to the pathogenic gene expression causing FSHD. We are using what we learn about fundamental FSHD pathogenic mechanisms to identify new drug targets for therapy, design therapeutic CRISPR-based strategies, develop novel FSHD-like animal models, identify FSHD disease biomarkers, and improve FSHD diagnostics.
Our most advanced therapeutic program is a gene therapy utilizing CRISPR-inhibition (CRISPRi) to silence pathogenic DUX4 gene expression in FSHD1 and FSHD2.
In addition, we are using AI to develop novel small molecules to specifically block DUX4 expression in human FSHD cells.
We are continuing to develop and characterize several novel FSHD-like mouse models for developmental studies and to serve as tools for preclinical testing of potential FSHD therapeutics. Importantly, these have been useful as discovery tools for FSHD biomarkers.
An exciting new project is our development of FSHD-like mini-pig models. We recognized that the lack of any large animal model of FSHD is a huge gap in the therapeutic pipeline and decided to directly address this need. These DUX4-expressing FSHD-like mini-pigs (~30kg) will allow us to test therapeutic safety and efficacy in an FSHD-like animal model much more closely resembling human size and musculature than the current mouse (25g) models. This will take a lot of the guesswork out of scaling up from mice or human cell culture to people and should increase the likelihood of success for clinical trials.
Many FSHD patients and families know us best for our FSHD research-grade diagnostic testing project. This new diagnostic is based on the distinctly different epigenetic (DNA methylation) signatures between those with FSHD1, FSHD2, and without FSHD. A key advance is the ability to identify these diagnostic signatures using DNA isolated from saliva, which means samples can be collected through the mail from anywhere in the world. Equally important, this greatly decreases the cost of performing the testing. Currently this is offered as a research test as part of a research project and the results are not for clinical use, however, they are highly accurate. Individuals of any age an in any country can participate. We are in the process of making this into a CLIA-grade test for clinical use.
We are part of the worldwide FSHD community, not only as researchers, but also as educators and advocates. We have always been happy to attend fundraisers and community events or participate in public service announcements to raise awareness for FSHD. Below are some examples of our community involvement. Together we are going to beat this disease!