Dr. Jason Cai from the Yale PET Center is the 2018 Archer Award recipient. His research project is Novel PET Tracers to Quantify Synaptic Loss. PET imaging of β-amyloid (Aβ) plaques and neurofibrillary tau tangles has expanded our understanding of the pathophysiology of Alzheimer’s disease (AD) in recent years, by allowing us to identify pathological biomarkers of AD in living subjects. Because early identification of AD may lead to more effective interventions, and regional synaptic loss in the hippocampus and prefrontal cortex is directly related to cognitive dysfunction and memory loss and is one of the earliest biomarkers of AD, Dr. Cai and his colleagues are developing PET tracers that measure a component of the neurodegeneration itself to provide a noninvasive, reliable, and sensitive method for quantifying synaptic loss, hopefully allowing for the detection of AD at its early stage and for monitoring the efficacy of disease-modifying interventions.
Their imaging target is a protein called synaptic vesicle glycoprotein 2A (SV2A), which is ubiquitously expressed in all synapses and plays important roles in synaptic vesicle trafficking and neurotransmission. The lead imaging probe, 11 C-UCB-J, a derivative of the SV2A targeted antiepileptic drug levetiracetam (Keppra ® ), has demonstrated its validity as a biomarker for quantifying synaptic loss in MCI/AD. This project is to translate an 18 F-labeled SV2A PET imaging probe to its first-in-human studies. The 18 F-labeled PET imaging probe will allow for multicenter clinical trials to test their hypothesis. Such an agent also holds the potential to be commercialized and widely used as a clinical biomarker for neurodegeneration.
Jason Cai obtained his B.S. degree at Tianjin University in 2005, and his Ph.D. degree at the University of Missouri-Columbia in 2011. Then, he did his postdoc training in Carolyn Anderson’s lab at the University of Pittsburgh. In 2015, he moved to Yale University as an Associate Research Scientist and became an Assistant Professor in 2018. His research group is currently focusing on the development and translation of novel PET imaging probes for the investigation of neurodegenerative disorders.
Dr. Katrin Andreasson at Stanford University's Neuroscience Institute is the 2017 recipient of the three-year Archer Award. Her research project is Novel Immune PET Radioligands in Alzheimer’s Disease. A significant impediment in Alzheimer's Disease therapeutic development has been the absence of a sensitive biomarker that detects early changes in preclinical progression to Alzheimer's Disease. Data recently acquired by the Andreasson lab indicates that increased microglial TSPO expression occurs even in the setting of a beneficial microglial immune response, suggesting that TSPO PET ligands cannot distinguish between toxic and beneficial inflammatory responses.
Thus, consensus in the field has argued for the need of a more specific marker of maladaptive inflammation,
not only for Alzheimer's Disease, but for other neurodegenerative diseases such as Parkinson’s disease, that are similarly characterized by a dysfunctional immune response.
Dr. Andreasson's research aims to synthesize a new class of PET tracers that target a novel biomarker of myeloid-cell-driven immune responses, i.e., triggering receptor expressed on myeloid cells 1 (TREM1). She is developing a translatable, non-invasive imaging technique for detecting and tracking neuroinflammation at different stages of Alzheimer’s disease.
A professor in the Department of Neurology and Neurological Sciences, Dr. Andreasson is a neurologist who treats patients with dementia and also is engaged in basic research in neurodegenerative disorders. Dr. Andreasson received her M.D. degree at Columbia University College of Physicians & Surgeons and completed her residency in Neurology at Johns Hopkins School of Medicine.
The 2016 recipient of the $300,000 three-year Archer Award is Dr. Daniela Kaufer at UC Berkeley's Integrative Biology and Helen Wills Neuroscience Institute. Her research project is Vascular Damage-Induced Astrocytic Signaling in Neurodegenerative Disease. Dr. Kaufer's research aims to characterize the earliest stages of progressive neurological diseases and, using an identified novel target that can be readily detected via companion MRI diagnostics, provide treatment to reduce symptoms and slow disease progression.
By uncovering a previously unknown role for glial signaling induced by vascular damage as a key cause of neural pathology and cognitive decline, Dr. Kaufer identified a target - a single biological mechanism that presents a druggable target and biomarker that is itself a causal mechanism. This presents a personalized, biologically-driven approach to solving neurodegenerative disorders. For those identified at risk, guided treatment can be provided along with targeting, by small molecule drugs, to prevent ongoing decline.
Daniela was born and raised in Israel, and did her B.Sc and Ph.D. in the Technion and the Hebrew University. She moved to the United States for a post-doc at Stanford and in 2005 took a faculty position at U.C. Berkeley.
The 2015 recipient of the $300,000 three-year Archer Award is Dr. Xinnan Wang for her research project, Miro, an Early Molecular Measurement for Parkinson's Disease. Dr. Wang’s research aims to understand the regulatory mechanisms controlling mitochondrial transport and function and the mechanisms by which misregulation of these processes may contribute to neurological disorders such as Parkinson’s Disease (PD).
In a Parkinson's affected nerve cell, the mitochondria, or power sources, are damaged. In healthy individuals, the damaged mitochondria are removed (mitophagy) to maintain a healthy pool of mitochondria. Miro is an outer mitochondrial membrane protein anchoring the microtubule motors to mitochondria and controls mitochondrial motility. Dr. Wang's research revealed a common impairment in degrading Miro and initiating mitophagy in skin fibroblasts of PD patients. Dr. Wang plans to obtain a larger number of fibroblast lines and detect Miro protein turnover in order to quantitatively conclude the association of Miro with PD. This award aims to further advance her research to validate how Miro protein turnover can serve as a diagnostic measurement for Parkinson's patients with a wider range of genetic backgrounds. This approach holds promise to transform the field of PD clinical care, providing a painless way to distinguish people at risk.
Xinnan Wang, MD, PhD, earned a MD/MSc from the China Medical University in 2003; earned a PhD in genetics from the University of Cambridge, United Kingdom in 2007; and completed post-doctoral work in neurobiology at Harvard Medical School in 2011. Dr. Wang has been assistant professor at the Stanford University School of Medicine since 2012.
Wang X, Winter D, Ashrafi G, Schlehe J, Wong YL, Selkoe D, Rice S, Steen J, LaVoie MJ, Schwarz TL: PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility. Cell 2011, 147:893-906.