C.  Research Support

ONGOING
R01 NS41783  Shen (PI)           05/15/2001-01/31/2011  
NIH/NINDS              
Presenilins in Synaptic Plasticity and Neurodegeneration
The goal of the project is to determine the role of presenilins in pre- and post- synaptic plasticity using forebrain-, hippocampal CA1- and CA3- restricted presenilin double conditional knockout mice.  Role: PI

R01 NS41779  Shen (PI)           05/15/2001-05/31/2010  
NIH/NINDS
PINK1 and Recessive Parkinsonism
The goal of this project is to determine whether lack of PINK1 causes dopaminergic defects and mitochondrial dysfunction, and to determine whether mice lacking PINK1, parkin and DJ-1 have accelerated dysfunction and degeneration of DA neurons.  Role: PI

R01 NS052745 Shen  (PI)           09/01/2005-06/30/2010 
NIH/NINDS     
DJ-1 in Dopaminergic Neuronal Function and Survival  
 The goal of this project is to determine whether loss-of-function mutations in the DJ-1 gene alter the normal physiology of dopaminergic neurons in the substantia nigra, ultimately leading to their degeneration and production of parkinsonian phenotypes.  Role: PI

R01 NS-42818 Shen (PI)           12/15/01-1/30/08 (no cost extension)
NIH/NINDS 
PS1 and PS2 in Cortical Development and Notch Signaling 
The goal of the project is to determine the role of PS1 and PS2 in neurogenesis, gliogenesis, neuronal differentiation and migration as well as the regulation of the Notch signaling pathway during neural development.  Role: PI

P50 NS38375  Lansbury (Program Director)        08/01/2000-08/31/2010
NIH/NINDS    
Morris K. Udall Parkinson’s Disease Research Center of Excellence
Project 3:  Development of Mouse Models of Parkinson’s Disease   Shen (PI)    
The goal of this project is to study the molecular pathogenesis of Parkinson’s disease through the generation and analysis of LRRK2 knockout and conditional knockout mice.  Role: PI

Investigator Initiated Research Grant  Shen (PI)       12/01/07-11/30/10
Alzheimer's Association 
Mechanisms of Neurodegeneration Caused by Loss of Presenilin Function
The goal of this project is to investigate the cellular and molecular mechanisms by which loss of PS function causes age-dependent neurodegeneration in the adult mouse cerebral cortex. Role: PI

Development of Progressive Mammalian Models of PD  Shen (PI)  06/15/2006-06/14/2008
Michael J. Fox Foundation       
LRRK2 and PD Genetic Mouse Models      
The goal of this project is to generate and characterize LRRK2 transgenic and knockin mice for PD-like phenotypes.

Fidelity Foundation Shen (PI)            11/1/06-04/30/08
Generation of Presenilin-1 Knockin Mice for Frontotemporal Dementia
The goal of this project is to introduce the G183V mutation into the presenilin-1 locus and to analyze the knockin mouse for deficits in memory and synaptic plasticity and for neurodegeneration.

Fidelity Foundation Shen (PI)            12/1/07-07/31/08
Presenilins, Gamma-Secretase and Notch in Neuronal Death  
The goal of the project is to determine the role of Notch receptors in memory, synaptic plasticity and neuronal survival in the adult cerebral cortex, and to investigate whether the essential roles of PS are mediated in a gamma-secretase-dependent or independent manner through comparative analysis of nicastrin cKO and PS cDKO mice.
PENDING
R01 NS42818  Shen (PI)   competing continuation    08/01/2008 – 07/31/2013
NIH          
Presenilins, Gamma-Secretase and Notch in Neuronal Death  
The goal of the project is to determine the role of Notch receptors in memory, synaptic plasticity and neuronal survival in the adult cerebral cortex, and to investigate whether the essential roles of PS are mediated in a gamma-secretase-dependent or independent manner through comparative analysis of nicastrin cKO and PS cDKO mice. (The application was scored at 0.3th percentile)