The Fonken lab investigates neuroimmune interactions during brain development and aging, with a focus on behavioral outcomes. I am particularly interested in how environmental perturbations alter the function of microglia, key innate immune cells of the central nervous system. I have two main research directions.
First, I am exploring how to promote effective microglial responses in the aged brain. Over the course of an animal’s lifespan, microglia tend to become more reactive or ‘primed’. This can worsen pathological outcomes when aged animals encounter immune challenges (e.g. infection or injury). I am investigating mechanisms that underlie microglia priming with age, and am exploring strategies to dampen priming of aged microglia. In particular, I am studying the mechanisms by which a novel mycobacterium, M. vaccae, upregulates anti-inflammatory signaling pathways in the aged brain and buffers against immune challenges.
Second, I aim to understand how the circadian system regulates neuroinflammatory function. In my postdoctoral research, I established that microglia express circadian timekeeping mechanisms which can gate the inflammatory response. Current projects will reveal the timing of circadian development in microglia and how developmental disruptions of the circadian system affect neuroimmune function.
Selected publications (Full list)
Fonken, L.K., Workman, J.L., Walton, J.C., Weil, Z.M., Morris, J.S., Haim, A., & Nelson, R.J. (2010). Light at night increases body mass by shifting the time of food intake. Proceedings of the National Academy of Sciences, 107 (43): 18664-18669. * featured in F1000 and popular press
Fonken, L.K., Xu, X., Weil, Z.M., Chen, G., Sun, Q., Rajagopalan, S., & Nelson, R.J. (2011). Air pollution impairs cognition, provokes depressive-like behaviors, and alters hippocampal cytokine expression and morphology. Molecular Psychiatry. 16 (10): 987-995.
Fonken, L.K. & Nelson, R.J. (2014). The effects of light at night on circadian clocks and metabolism. Endocrine Reviews 35 (4): 648-670.
Fonken, L.K., Frank, M.G., Kitt, M.M., Barrientos, R.M., Watkins, L.R., & Maier, S.F. (2015). Microglia inflammatory responses are controlled by an intrinsic circadian clock. Brain, Behavior, and Immunity 45: 171-179.
Fonken, L.K., Frank, M.G., Kitt, M.M., D’Angelo, H.M., Norden, D.M., Weber, M.D., Barrientos, R.M., Godbout, J.P., Watkins, L.R., & Maier, S.M. (2016). The alarmin HMGB1 mediates age-induced neuroinflammatory priming. The Journal of Neuroscience 36 (30): 7946-7956.