Jonathan Yen Lab

The Yen lab focuses on both translational and exploratory research projects feeding the genome editing–clinical pipeline. Working with other St. Jude faculty and industry collaborators, we develop and apply new genome editing tools to model and treat nonmalignant hematological diseases, such as sickle cell disease, while optimizing existing approaches to minimize deleterious consequences.

We are particularly interested in how genome editing tools beyond Cas9, such as base editors and prime editors, can be used to treat blood disorders. Base editors are capable of installing more precise nucleotide changes through methods that don’t require the formation of double-strand DNA breaks, which can potentially lead to harmful chromosomal rearrangements and large deletions. Our collaborations have led to meaningful progress in the field, including developing a new strategy to potently induce fetal hemoglobin (HbF) by using the adenine base editor to create a de novo TAL1 transcription binding site at position -175 of the g-globin promoter; this approach outperformed Cas9 nuclease strategies 2-3–fold. 

Developing and adapting novel genome editing technologies for modeling and treating hematological diseases is only the first step in our work. Another important aspect of our research is to make autologous therapies available to affected individuals within the United States and the developing countries where hemoglobinopathies are most prevalent. This requires creating novel manufacturing and delivery strategies to get genome editing tools to the patients who need them. This research aims to simplify manufacturing processes and scale up treatment production to increase accessibility. To achieve these goals, our lab works with the St. Jude Good Manufacturing Practice (GMP) and the Experimental Therapeutics Laboratory (ECTL) to develop optimized clinical-scale genome editing tools. 

Finally, the Yen Lab leads and conducts investigational new drug (IND)–enabling studies in collaboration with the St. Jude GMP and within the Department of Hematology. Our work has proven promising, enabling us to pursue clinical trials for treating sickle cell disease using genome-editing technology through the SAGES program.

Bright Arthur
Lead Researcher

Adithi Danda, PhD
Associate Scientist

Erin DeWitt
Researcher

Yoonjeong Jan, DVM, PhD
Lead Researcher

Rachel Levine, PhD
Lead Researcher

Muralidhar Reddivari, PhD
Senior Scientist

Randi Rooney
Senior Veterinary Technologist

Kalin Mayberry
Senior Researcher

Nikithha Nimmagadda
Senior Researcher

Zetian Zhang
Researcher

Dr. Jonathan Yen brings more than a decade of expertise in stem cell biology and gene therapy to the research and treatment of pediatric blood disorders. He received his PhD in Bioengineering from the University of Illinois at Urbana-Champaign and completed his postdoctoral fellowship in Chemical Biology and Therapeutics at Novartis Institutes for Biomedical Research. As a faculty member and director of the Therapeutic Genome Engineering lab at St. Jude, Dr. Yen leads research efforts to advance genome engineering and its applications for treating blood disorders. His efforts advance the use of genome engineering for upcoming clinical trials and clinical protocols.