On Demand Webinar: Exploiting the Mitochondrial Pathway of Apoptosis for Precision Medicine
Overview
Evasion of cell death is a hallmark of cancer, and understanding the intrinsic, or mitochondrial, pathway of apoptosis has produced potent targeted therapies such as venetoclax.
The BCL2 family, which regulates apoptosis and includes the target of venetoclax, is large with a complex web of interactions that makes predictions of its behavior challenging. iBH3 is a functional assay optimized for flow cytometry that interrogates the mitochondria directly using a combination of peptides and compounds that specifically target different proteins in the BCL2 family, and detect the commitment to mitochondrial outer membrane permeabilization (MOMP), based on cytochrome c retention.
Apoptotic priming, or how readily mitochondria will undergo MOMP, correlates with chemosensitivity and can reveal what anti-apoptotic BCL-2 family proteins cells are using for their survival.
We illustrate how iBH3 can validate the on-target behavior of new BH3 mimetic drugs. We demonstrate how the maturation state of ALL can influence choice of BH3 mimetic treatment. Finally, we show how BH3 profiling can explain resistance to BH3 mimetics and how to determine therapies in the relapse or refractory setting using dynamic BH3 profiling.
Key Takeaways
The webinar includes discussion on how:
- BH3 profiling can rapidly determine how readily cells will undergo apoptosis.
- BH3 profiling can validate the direct mitochondrial activity of new BH3 mimetic drugs.
- Apoptotic priming correlates with the maturation state of cells in T-ALL and which BH3 mimetic can clear them.
- BH3 profiling reveals the mechanism behind and how to choose next line therapy in venetoclax resistant AML.
Webinar Speaker
Jeremy Ryan
Staff Scientist,
Dana-Farber Cancer Institute, Boston, MA, USA
Jeremy Ryan moved from Minnesota to Maryland for undergrad and then to Massachusetts for graduate school.
He started in Dr. Letai’s laboratory as a technician in 2006 with notable contributions including the evolution of BH3 profiling from a demanding ELISA to the modern flow and microscopy platforms. He engaged in many collaborations, where he adapted BH3 profiling to answer questions of apoptotic control in cancer and senescence.
As a staff scientist, he currently leads the BH3 Profiling Flow Core at Dana-Farber where, among other projects, profiling is being adapted to clinical trials as a biomarker in diseases such as CLL, ALL, and AML. He has also modified profiling to be smaller and closer to an off-the-shelf kit.
Jeremy often serves as an instructor for new profilers at Dana Farber and around the world.
Outside of the lab, he enjoys animated films, photography, astronomy, drawing, and story writing.
