The Franklin lab investigates the roles of 
massive repetitive DNA elements (a.k.a. satellite repeats) in the contexts of developmental signaling and disease states.
Tandemly repeated DNA sequences make up the largest elements of eukaryotic genomes and can span tens of megabases. These so-called “satellite” repeats were identified in the 1960s, yet we have not fully explored their roles in regulating the genome. At NIMSB, the Franklin Lab will conduct multi-omics profiling of these mysterious repeats to understand how they influence core cell processes in early development signaling and human disease states. The lab will also utilize the unique properties of satellite repeats for biotechnology applications, such as drug screening.
To serve the greater chromatin community, our lab developed a database to centralize functional research on repetitive DNA, called the “repeatome”. We hope to publicly release this resource soon – please reach out if you would like to contribute!
PROJECTS
Project description
High-throughput biochemical assays are typically limited to in vitro systems or indirect measurements of molecular targets. Leveraging our lab’s catalog of repeat-binding factors, we developed a high-throughput screening platform to identify chemical modulators of dozens of transcription factors, many of which are established drivers of human cancers. Importantly, this technology enables a direct, live-cell readout of protein–DNA interactions. By preserving the chromatin architecture and post-translational regulatory states within the cellular milieu, this method recapitulates the complete biological context of transcription factor binding which is absent from traditional biochemical approaches. A patent is pending for this methodology.
PI: Matt Franklin
Start date: February 2025
End date: March 2027
Funded under: Sarafan ChEM-H Nucleus Seed Grant
Project description
Satellite repeats remain one of the final frontiers in understanding the genome. We employed computational and experimental methods to perform the first multi-omic profiling of all human satellite repeats, with an emphasis on repeat-binding transcription factors. The “repeatome” acts as a centralized database to catalog and visualize the multi-omic profiles of satellite repeats across species. Currently, we are focused on satellite repeats, but we hope to expand this resource to interspersed repeat elements. While www.repeatome.org is currently private, we hope to publicly release it soon with a forthcoming publication. Please reach out if you are interested in contributing!
PI: Matt Franklin
Start date: June 2025
Funded under: Stanford GRIPS, NIMSB
TEAM
Group Leader
Dr. Matt Franklin started his scientific career in biochemical engineering (Michigan State University, University of Washington) and structural biology (EMBL-Hamburg). He earned his PhD in Chemical Engineering at Stanford University under the mentorship of Jan Liphardt, with support from the National Science Foundation Graduate Research Fellowship. During his graduate work, Matt investigated multiple biological questions from a physical perspective. While studying the dynamics of Hippo pathway signaling, Matt unexpectedly discovered that the Hippo pathway transcription factor family TEAD directly binds one of the major satellite repeats, Human Satellite 3 (HSat3). Intrigued by this observation, Matt went all-in to understand why such a highly conserved transcription factor targets the largest elements in the genome.
During his multi-lab postdoctoral journey at University of California San Diego, Stowers Institute for Medical Research, and Stanford University, Matt unveiled two core discoveries: [1] the Hippo transcription effectors YAP/TEAD accumulate on satellites inside the nucleolus, allowing YAP to directly activate RNA Polymerase-I, and [2] human satellite repeats encode binding platforms for dozens of transcription factors, including those of highly-conserved signaling pathways. Using experimental and computational approaches, the Franklin Lab aims to uncover how satellite repeats shape genome regulation in health and disease.
Volunteer contributor for repeatome
Carissa Penn is currently co-leading the development of the lab’s repeatome database under mentorship by Dr. Franklin.
Volunteer contributor for repeatome
Isabel Moorhead is currently co-leading the development of the lab’s repeatome database under mentorship by Dr. Franklin.
SELECTED PUBLICATIONS
Franklin, J.M., Dubocanin, D., Chittenden, C., Barillas, A., Jooyoung Lee, R., Ghosh, R.P., Gerton, L. J., Guan, K-L.,* Altemose, N*. Human Satellite3 DNA encodes megabase-scale transcription factor binding platforms. BioRxiv (2025) (doi:10.1101/2024.10.22.616524v2)
Franklin, J.M., Wu, Z. & Guan, KL. Insights into recent findings and clinical application of YAP and TAZ in cancer. Nat Rev Cancer 23, 512–525 (2023). https://doi.org/10.1038/s41568-023-00579-1
Franklin, J.M., Ghosh, R.P., Shi, Q. et al. Concerted localization-resets precede YAP-dependent transcription. Nat Commun (2020) (doi:10.1038/s41467-020-18368-x)
Ghosh, R.P., Franklin, J.M., Draper, W.E. et al. A fluorogenic array for temporally unlimited single-molecule tracking. Nat Chem Biol (2019) (doi:10.1038/s41589-019-0241-6)
Ban, E., Franklin, J.M., Nam, S., Smith, R.L., Wang, H., Wells, G.R., Chaudhuri, O., Liphardt, T.J., and Vivek B. Shenoy, B.V. Mechanisms of Plastic Deformation in Collagen Networks Induced by Cellular Forces. Biophysical Journal (2018) (doi:10.1016/j.bpj.2017.11.3739)