Taher Darreh Shori

Our research focuses on cholinergic pathology in a broad spectrum of neurodegenerative diseases, including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and atypical parkinsonian disorders such as Progressive Supranuclear Palsy (PSP) and Corticobasal Degeneration (CBD). We investigate intracellular cholinergic signaling and how mitochondrial dysfunction contributes to neuronal vulnerability, including the role of the mitochondrial serine protease OMI/HtrA2 within the apoptosis axis.

A major part of our work explores how amyloid‑beta (Aβ) peptides interact with cholinergic systems to drive pathological cascades involving synaptic disturbances, mitochondrial stress, and activation of pro‑apoptotic pathways. Increasing evidence highlights neuroinflammation and synaptic dysfunction as central contributors to early neurodegenerative processes.

In parallel, we advance cholinergic‑targeted therapeutic strategies, including the development of choline acetyltransferase–positron emission tomography (ChAT‑PET) tracers for in vivo mapping of cholinergic networks, innovative ChAT‑potentiating ligands (CPLs) to enhance endogenous acetylcholine synthesis, and our newly engineered ultra‑active ChAT nanoparticles that act as biocatalytic platforms to restore cholinergic function.

Our group also develops and applies advanced molecular imaging tools, including the synaptic PET tracer UCB‑J and the astrocytic PET tracer BU99008, to map synaptic density and astroglial activation in vivo. These imaging‑oriented subprojects are spearheaded by Dr. Amit Kumar in our laboratory.

Together, these integrated approaches aim to improve early diagnostics and enable disease‑modifying therapies across AD, ALS, PD, PSP, CBD, and other neurodegenerative disorders.