Current projects in the lab include:

• Mechanisms of neuroprotection across the lifespan. One of the main areas we are currently working on is to dissect how exercise-related pathways can boost neuroprotection. We are focused specifically on myokines, which are biological compounds that are released into circulation from skeletal muscles upon exercise. We have shown that injecting a specific myokine called Irisin directly into the hippocampus of male mice prevents the deleterious effects of acute stress on memory function and avoidance behaviors. Strikingly, these effects are not observed in females. We have expanded these results to include different exercise paradigms that can physiologically boost the release of myokines and thus could improve cognitive outcomes. Furthermore, our results have indicated that circadian rhythms might have a significant impact on how beneficial exercise can be. We have several ongoing projects exploring the neural mechanisms underlying such differences in exercise derived neuroprotection, including dissecting specific sex-dependent pathways and circadian modulation. Our goal is to deepen our understanding of how exercise can confer resilience to a variety of noxious stimuli that can negatively impact brain function, including neurodegenerative disorders (such as Alzheimer’s disease).
• Neuromodulatory pathways. In addition to myokines, we are exploring other mechanisms of neuromodulation that can be used to boost endogenous resilience and can be potentially druggable targets. We are focusing on specific hypothalamic neuropeptides such as melanin concentrating hormone (MCH) and neuropeptide Y (NPY), that have been shown to confer neuroprotection in different models of neuropathology. For these studies we are leveraging mouse models and specific viral tools to manipulate such signaling pathways in specific cells and sensory systems in the brain. We are also testing the contributions of such neuropeptides to cognitive processes involved in learning and memory.
• Neural mechanisms underlying fungal brain infection. Fungal meningitis is often caused by infection by Cryptococcus neoformans, an encapsulated fungus that is found in the environment (usually in pigeon excrement). We are part of a multi-disciplinary team dissecting specific pathways that lead to brain infection in immuno-compromised individuals (such as AIDS patients). Our collaborative project is an in-depth multi-approach examination of mechanisms underlying direct effects of this fungal pathogen on neurons and glial cells in different brain regions. Importantly, because this fungus produces a surrounding capsule that has been shown to not induce inflammation when invading the brain, we are especially interested in testing the hypothesis that the isolated capsule material can be a druggable target that can be used to reduce inflammation in other pathological conditions such as neurodegenerative disorders or during typical aging.