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ALK and Midkine as Novel Neuroimmune Regulators of Alcohol Consumption

The Lasek lab participates in the Integrative Neuroscience Initiative on Alcoholism (INIA)-Neuroimmune consortium funded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA). We are examining brain immune signaling mediated by anaplastic lymphoma kinase (ALK) and midkine (MDK) and will determine where in the brain these proteins function to regulate excessive ethanol consumption. ALK inhibitors are approved by the FDA for cancer treatment and could potentially lead to repurposing of these compounds for alcohol use disorder. 

Compulsive Alcohol Drinking and Cortical Extracellular Matrix

Specialized extracellular matrix structures in the brain, known as perineuronal nets, are important for neuronal activity and learning and memory. We found that perineuronal nets are increased in intensity in the insula, a cortical region that regulates compulsive alcohol drinking, after chronic alcohol use. We are determining how specific protein components in perineuronal nets regulate compulsive drinking in mice. These studies will lead to novel insights into the molecular and cellular mechanisms underlying the transition from moderate alcohol drinking to alcohol use disorder.

Epigenetic Mechanisms of Glia and Neuron Interactions in Alcoholism

As part of the NIAAA-funded Center for Alcohol Research in Epigenetics, this research component will evaluate epigenetic modifications, such as histone acetylation, methylation, and DNA methylation, due to ethanol exposure in astrocytes that may be involved in ethanol-induced hippocampal neural plasticity and depression-like symptoms during withdrawal after chronic ethanol exposure.

Molecular Mechanisms of Estrogen Action in Promoting Binge Drinking

Binge drinking is a form of alcohol abuse that leads to serious adverse health outcomes for women. The ovarian hormone estrogen promotes binge drinking in females. We are examining the molecular and cellular function of estrogen receptors in the ventral tegmental area, a brain region involved in drug reward, in stimulating binge drinking and alcohol reward in mice. The overall goals of this study are to understand sex differences in alcohol use and to use this knowledge to guide interventions to reduce binge drinking by women.