Dr. Berkley Gryder is a chemist who retrained as a molecular biologist and computer scientist. He is passionate about understanding how cancer cells control their genes, and developing new chemical strategies to stop cancer cell’s addiction to gene transcription. Along the way, he has proposed paradigm shifts and surprises that are explaining old conundrums. Recognizing that the “right” answer to a tough question is often out of reach with current tools, Dr. Gryder is always innovating techniques with an ultra-high level of spatial and temporal precision to study gene control/epigenetics.
The Gryder lab studies how transcription is controlled by the 3D folding of the epigenome, through the lens of 3D chromatin sequencing techniques and biomolecular condensates. We are especially interested in using these approaches to understand the mechanism of action for new anti-cancer therapies that target proteins involved in regulating chromatin (transcription factors, epigenetic machinery). The diseases we work on most include childhood sarcomas and advanced forms of prostate cancer.
Nuclear organization and gene regulation in 3D
The massively complex human genome is a super-computer that carefully controls its information. It uses chemical-genetic circuits, 3D folding, and signal integration to maintain cell identity and all biological functions. Our lab is excited to unravel the principles of the super-computer we call the epigenome.
(read more: Gryder et al, Nature Genetics 2019, Gryder et al, Nature Protocols, 2020, Gryder et al, iScience 2020)
Areas of innovation: Systems biology, bioinformatics, computational biology, machine learning, novel wet-lab technology.
Chemistry targeting transcription in cancer
Cancer can’t live without transcribing its favorite oncogenes, especially those at the highest expression levels that are also cancer-type-specific. Genetic CRISPR screening has highlighted that many excellent targets for killing cancer cells are the proteins needed for high-level transcription (ie, BRD4, CBP/p300, MYC). We are designing new chemical approaches to drugging transcription selectively and giving mechanistic credentials to new ways of hitting cancer where it hurts.
(read more: Gryder, Wu, et al, Nature Communications 2019)
Areas of innovation: Chemical biology, medicinal chemistry.
Phase separation and nuclear condensate formation
The idea that proteins congregate into “droplets”, like oil in water, to concentrate their collective activity at a specific location in the epigenome, is quite fascinating. Since so much of the epigenome machinery is devoted to molecular recognition of either DNA sequence (transcription factors) or to recognition of post-translational modifications (“epi-marks” like H3K27ac), our lab is intrigued to investigate how these “friend-finder” capacities lead to the formation and function of nuclear condensates at active genes.
(read more: Gryder et al, Nature Genetics 2019)
Areas of innovation: nuclear condensate biology, transcriptional control, post-translational modification of transcription factors and transcriptional co-activators.
Cancers we aim to cure
In addition to being motivated by the sheer beauty of biology (yes, even when studied in something as ugly as cancer), we’re also inspired by the tireless efforts of the patients, doctors, family members, and friends that battle cancer. We believe that the deeper we understand epigenetics and gene control, the better we will be at developing new ammo in the war against cancer. Our lab is currently testing new epigenetic therapies for childhood cancers, especially Rhabdomyosarcoma and lethal forms of Prostate Cancer.
We patent new molecular strategies to cure these cancers and test them in the most disease-relevant models. We also work with teams of medical doctors and chemists across multiple institutions and aim to take our most exciting molecules into the clinic.