Co-Mentors: Rajeev Sivasankaran, PhD and Ricardo Dolmetsch, PhD
Cambridge, Massachusetts, United States
In chronic neurodegenerative disorders, there are common pathological features underlying progressive neuronal degeneration. These include accumulation of abnormal protein aggregates, glial activation, and pro-inflammatory cytokine release, which amplify neurotoxic effects in affected brains. Our current research focuses on understanding cellular and molecular mechanisms that drive these processes. We are particularly interested in identifying core mechanisms that drive pathogenesis of frontotemporal dementia (FTD), the second most common form of pre-senile dementia which primarily affects the frontal and temporal lobes of the brain – the areas generally associated with personality, behavior, language and motor functions. We have established robust cellular assays to monitor neuronal and microglial dysfunction in FTD. Furthermore, using innovative proteomic technology, we have identified unique approaches to interrogate signaling pathways implicated in neuronal survival and neuroinflammatory processes. Our current aim is to validate and investigate pathways that go awry in pathological conditions, with the ultimate goal of developing disease modifying therapies for FTD and related neurodegenerative disorders.
Human LilrB2 is a β-amyloid receptor and its murine homolog PirB regulates synaptic plasticity in an Alzheimer's model.
*Kim T, Vidal GS, Djurisic M, William CM, Birnbaum ME, Garcia KC, Hyman BT, *Shatz CJ.
Science. 2013 Sep 20;341(6152):1399-404.
Neuroprotection from stroke in the absence of MHCI or PirB.
Adelson JD, Barreto GE, Xu L, Kim T, Brott BK, Ouyang YB, Naserke T, Djurisic M, Xiong X, Shatz CJ, Giffard RG.
Neuron. 2012 Mar 22;73(6):1100-7.
NRH2 is a trafficking switch to regulate sortilin localization and permit proneurotrophin-induced cell death.
Kim T, Hempstead BL.
EMBO J. 2009 Jun 3;28(11):1612-23.
Click here for additional publications.