Multitudinous aspects of human health and disease are influenced by cell death. On one hand, too little cell death can lead to tumor formation, or can block cancer therapeutics from working properly. We would like to understand these resistance mechanisms so that we can overcome them for the better prevention and treatment of cancer. On the other hand, too much cell death is responsible for degenerative diseases, such as Alzheimer’s disease (AD), diabetes, or in course of infections and aging. Similarly here, we endeavor to learn the mechanism of why cells die due to these diseases and how to prevent it.
We apply the technologies described below for targeting novel pathways with engineered therapeutics.
We use forward genetics to identify novel cell death pathways in somatic cells. The CRISPR toolbox has powerful new toys which we employ to investigate new players in apoptotic and programmed non-apoptotic cell death pathways. To support these efforts we have developed in-house software to rapidly identify significant new proteins that accelerate the usage of CRISPR-based screening in novel applications. Newly discovered members serve as a basis for pharmacological intervention as well as to elucidate control mechanisms in cell physiology.
We have developed a wholistic genetics platform for discovery of novel cell death networks and pharmacologicals using CRISPR knockouts, knockdown (CRISPRi), and overexpression (CRISPRa). Paired with modern -omics techniques, we not only identify linear cell death pathways, but also interrogate larger cell death networks. Together with pharmacological tools, these methods have the potential to reveal combinational therapies for cancer and degenerative diseases.