C14439: Anastasis Biosensor (Split version)

INVENTION NOVELTY
This technology involves a biosensor that is able to label and track cells in vitro and in vivo that have reversed apoptosis (Anastasis, Greek for “rising to life”) after they experienced mitochondrial outer membrane permeabilization (MOMP) and caspase-3 activation, the 2 most recognized hallmarks of apoptosis at execution stage.  This biosensor can be used to identify regulator of anastasis (therapeutic targets), and screening for drugs that can promote or suppress reversal of apoptosis.
 
Value Proposition:
This invention is a biosensor that track anastasis, the phenomenon in which dying human cells can recover from the brink of cell death. Promoting anastasis could in principle preserve injured cells that are difficult to replace, such as cardiomyocytes and neurons. Conversely, arresting anastasis in dying cancer cells after cancer therapies could improve treatment efficacy. To develop new therapies that promote or inhibit anastasis, it is essential to identify the key regulators and mediators of anastasis - the therapeutic targets. The technology enables the development of new therapies to fight intractable apoptosis-related diseases such as heart failure, cancers, and degeneration. The current invention aims to:

• detect the key hallmarks of apoptosis
• provide doctors with mechanism to combat anastasis 
• prevent cells from recovering between chemotherapy and radiotherapy treatments 
• decrease likelihood of cancer relapse 
• stop anastasis before DNA is damaged
• rescue injured cells difficult to be replaced like heart cells and neurons

TECHNICAL DETAILS
The anastasis biosensor (split version) will utilize the Split Gal4 system (MOMP-dependent NGal + caspase-dependent CGal = active Gal4) and mammalian Gal4 reporter to label cells that can reverse apoptosis after MOMP and caspase-3 activation. The earlier version of anastasis biosensor, CaspaseTracker biosensor system, was used to demonstrate the reversal of apoptosis in live animals. CaspaseTracker consists of a caspase-activatable yeast transcription factor Gal4 and the G-TRACE fluorescent protein system, both of which are genetically encoded.
 
Stage of Development:
The research group has identified small molecules that can modulate reversal of apoptosis. An in vivo dual color CapaseTracker biosensor demonstrated apoptosis reversal in Drosophila melanogasters. 
 
Publication(s):

• Tang et al. (2009). Br J Cancer 100(1):118-122.
• Tang et al. (2012). Mol Biol Cell 23(12):2240-52.
• Tang et al . (2015).Sci Rep.5(9015).
• Tang et al . (2015) J Vis Exp (96).
• Tang et al . (2017) F1000Res. 6:43 
• JHU Ref. C11872

Category(s):