Welcome to the Lee Lab!
Our lab is a neurotoxicology and neuropharmacology laboratory in the Florida A & M University College of Pharmacy and Pharmaceutical Sciences. Our research focuses on investigating molecular mechanisms of neurotoxicity caused by environmental toxicants such as manganese (Mn), as well as the neuroprotective effects of estrogenic compounds at the transcriptional level. We have discovered several genes that are associated with these neurotoxicity and neuroprotection mechanisms. Our goal is to identify the potential molecular targets to treat Mn toxicity as well as other neurodegenerative diseases at genetic and epigenetic levels in pursuit of novel neuropharmacotherapies
Overview of Neurodegenerative Diseases
Neurodegenerative diseases such as Parkinson’s disease (PD) and Alzheimer’s disease (AD) result from the gradual and progressive loss of brain cells, leading to nervous system dysfunction. Mn neurotoxicity, referred to as manganism, shares many pathological features of PD. Here in the Lee lab, we study the molecular mechanisms associated with those neurodegenerative diseases in different neural cell types such as astrocytes, neurons and microglia.
Symptoms of manganism are very similar to those of Parkinson’s–shaking of the hands, arms and other appendages, loss of motor control, fixed facial expressions or facial muscle spasms, difficulty swallowing, etc.
Tripartite Neural system
The human brain contains not only neurons, but also glial cells such as astrocytes and microglia. Neurons are main cell types to generate signals in the brain, but glial cells must coordinate with neurons for the proper neuronal signals and functions, known as tripartite synapses. One of the major focuses of our lab is to use in vitro cell cultures and in vivo animal models of Mn-induced neurotoxicity, focusing on dopaminergic neurons, astrocytes and microglia. Since Mn induces similar toxicities to those of PD, our studies also help us to understand PD pathogenesis.
One of the major pathological signs of manganism and PD is progressive dopaminergic neuronal loss and neuronal dysfunction. We are particularly interested in understanding how Mn-induced dysregulation of astrocytic glutamate transporters affects dopaminergic neurodegeneration, as these transporters directly regulate excitotoxicity of dopaminergic neurons at the tripartite synapse. The goal of our work is to better understand the underlying mechanisms of Mn-induced neurotoxicity, leading to identification of molecular targets to develop therapies for neurodegenerative diseases.