Our work deals with identifying the molecular mechanisms involved in the manifestation of synaptic plasticity and memory. We have focused on identifying how molecular lesions in protein synthesis initiation signaling pathways and the regulation of the phosphatase, calcineurin, play a role in the manifestation of cellular and behavioral deficits in neurological disorders and disease. Using mouse models of human disease, we study cognitive disorders like Down syndrome (DS), autism spectrum disorders (ASD)s, and schizophrenia. We are also interested in how translation control and calcineurin pathways impact the manifestation of neurodegenerative diseases like Alzheimer's disease (AD).
For our research, we have focused on using genetic mouse disease and mutant models in combination with behavioral, molecular, and pharmacological approaches to address modeled human behavioral and neuronal deficits. Using these models, it is out long-term goal to translate our basic research findings to therapies aimed at alleviating current research are to (1) examine the role of Akt-mTOR signaling in the expression synaptic and behavioral phenotypes associated cognitive and age-dependent memory deficits related to DS and AD (3) study the role of pathological tau expression in the hippocampal GABAergic dysfunction.
Hoeffer CA, Wong H, Cain P, Levenga J, Cowansage K, Davy C, Majmunder N, Choi Y, McMillan DR, Rothermel B, and Klann E. Regulator of calcineurin 1 (RCAN1) modulates expression of innate anxiety and anxiogenic responses to selective serotonin reuptake inhibitor (SSRI) treatment (2013) J Neurosci. 2013 Oct 23; 33(43):16930-44. doi: 10.1523/JNEUROSCI.3513-12.2013.
Levenga J, Krishnamurthy P, Rajamohamedsait H, Wong H, Franke T, Cain P, Sigurdsson E and Hoeffer C, Tau pathology induces loss of GABAergic interneurons leading to altered synaptic plasticity and behavioral impairments. (2013) Acta Neuropathologica Communications, 1:34 dor:10.1186/2051-5960-1-34.
Hoeffer CA, Santini E, Ma T, Arnold EC, Whelan AM, Wong H, Pierre P, Pelletier J, and Klann E. Multiple components of eIF4F are required for protein synthesis-dependent hippocampal long-term potentiation. (2012) J. Neurophysiology;109(1):68-76, PMID: 23054596.
Hoeffer CA, Tang W, Santillan A, Wong H, Patterson RJ, Martinez LA, Tejada-Simon MV, Hamilton SL and Klann E, Removal of FKBP12 Enhances mTOR-Raptor Interactions, LTP, and Perseverative/Repetitive Behavior. (2008) Neuron 60:832-845, PMID: 19081378/