Welcome to the Shamloo Lab

My laboratory aims to better understand normal and pathological brain function so that we can contribute to the discovery of novel therapeutic approaches for neurologic disorders such as stroke, Alzheimer’s disease (AD), and autism. We have focused our efforts on a subset of genes/proteins involved in neuroprotective or neurodegenerative pathways, which we have shown to be regulated in the diseased brain.

In our Npas4 research program, we characterized Npas4 (neuronal Per–Arnt–Sim (PAS) domain protein) in the rat brain following ischemic injury and demonstrated its importance as a key molecule in memory formation and social behavior. Npas4 is activated by excitatory synaptic activity, regulating the formation and maintenance of inhibitory synapses on excitatory neurons. Our research demonstrated that this transcription factor is specifically upregulated in ischemic tissue following brain injury, with particularly strong expression in the limbic system, thalamus, and cortex. Using animal modeling, we have shown Npas4 null mice display substantial learning, memory, and social function deficits. This mouse also displays larger brain infarctions when compared to control mice, thereby indicating a neuroprotective function for this protein. We are continuing to study the role of Npas4 and its regulatory function as a key player following injury, stress, and autism as well as neurodegenerative disorders.

Another of our translational research projects is focused on Beta 1- adrenergic (β1-ADR) ligands as memory enhancers for cognitive disorders, and exploring the use of β1-ADR as a significant therapeutic target for AD. Our research demonstrates significant cognitive defects in β1-ADR knockout mice, and also that chronic or acute dosing with a selective partial agonist of β1-ADR leads to improved cognitive functions in three distinct animal models; two independent models of AD and a Ts65Dn mouse model of Down syndrome. This class of compounds can cross the blood-brain barrier in rodents and induces an activation of microglia and increased clearance of amyloid-beta aggregates following low dose chronic treatments. In addition to our proof of concept studies showing the cognitive deficits of β1-ADR knockout mice, we have also shown that memory deficits induced by pharmacological inhibition of β1-ADR can be reversed in a dose-dependent manner with Xamoterol. We are currently investigating whether restoring the noradrenergic neurotransmission mediated by β1-ADR will rescue the cognitive deficits and therefore reduce some of the neuropathology associated with AD.