PhD VP, Translational Biology - Preclinical & translational lead
Tiaki Translational Models
- Target validation using adult mouse ex vivo and in vivo models leveraging functionally conserved pathways
- Models human neuroinflammation, complex cellular communication and brain microenvironment
- Transcriptome, proteome, secreted biomarkers, functional endpoints
Principal Scientist Neuroscience –Neuroimmunology
Merck & Co.
In order to successful leverage a peripheral biomarker in the clinic we need to answer some key questions:
- Can we develop robust, highly sensitive and high throughput assays for the detection of pSer935
- Are there species and/or genotype (WT vs G2019S) differences in PBMC pSer935 response?
- Is the PBMC pSer935 response reflective of brain pSer935?
- Are there differences in peripheral and central exposure in preclinical species? Humans?
MS & Neurorepair Research Unit
The few functionally defined microglial subtypes are only existing in perturbation settings and translation to human remains unknown.
- TREM2-dependent DAM subsets, identifiable by CD11c, develop during neuroinflammation/neurodegeneration
- MGnD subset, identifiable by CLEC7A+ and the downregulation of homeostatic markers such as P2RY12
- TREM2-independent PAM subset, associated with the clearance of newly formed and dying oligodendrocytes during post-natal development (up to P7)
Exclusive Speaker Interview:
Third Rock Ventures
Where do you think the field needs to focus for success?
You have to define success first and the success that matters to me is making a difference for patients. So, where I think the field needs to focus is derived from the three main challenges. So, one is to develop a set of models that gives you some confidence going into the clinic. And here we will need an integrated combination of in vitro and in vivo models. So, that’s one area of focus. The other is to replicate in astrocytes and OPCs, the blood brain barrier cells and pericytes as well. We need to develop an understanding of the circumstances in which these cells play a role in neurodegenerative diseases. That understanding must start with germline disease genetics...