Anthony Umpierre , Ph.D.

E-MAIL: [email protected]

Research Interests:

A variety of injuries can transform the brain from a healthy state into a state capable of producing spontaneous, recurrent seizures. Clinically, this state is known as epilepsy. We are interested in understanding the underlying biological processes which transition the brain into a seizure-prone state, focusing on the role of microglia and neuroinflammation in this process.  Microglia, as brain immune cells, play a major role in sensing the molecular patterns of brain damage and responding to those signals with a variety of potential effector functions, including pro-inflammatory cytokine production, recruitment of outside immune cell populations into the brain, and phagocytosis (or 'eating') of nearby cells or cellular compartments. We hypothesize that the post-damage response of microglia may inadvertently exacerbate cell damage and cell loss within the brain, potentially impacting network stability, cognition, and the risk for later epilepsy development.

Our lab uses a variety of techniques to study microglia, inflammation, and the epilepsy development process. To investigate microglia and other cellular interactions in real-time, we employ two-photon imaging in the awake mouse to study damage signal release (using biosensors), microglial calcium activity, and neuronal function. Microglia exhibit a unique pattern of calcium activity in the brain, often displaying low-to-absent calcium signaling in a basal (healthy) state, with highly elevated calcium activity post-injury. This has led us to hypothesize that calcium may be a critical secondary messenger system for microglia to transition from a 'resting' to a more 'reactive' state following injury or shifts in brain homeostasis. Our previous work suggests that calcium signaling can be critical for microglia to enhance their production of certain pro-inflammatory cytokines (under the NF-kB pathway) and perform phagocytosis. To further evaluate immune effector functions, we utilize flow cytometry, transcriptomic, and immunofluorescence techniques. Finally, to evaluate the risk of epilepsy development, we employ 24/7 EEG analysis to detect seizures and aberrant forms of neuronal activity.

Our ultimate goal is to identify early response pathways promoting inflammation and exacerbating brain damage. By arresting these processes within a critical window following injury, we may be able to alleviate post-injury morbidity (cell loss, cognitive decline) and even reduce the risk for future epilepsy development. 

Publications

• Umpierre AD, Li B, Ayasoufi K, Simon WL, Zhao S, Xie M, Thyen G, Hur B, Zheng J, Liang Y, Bosco DB, Maynes MA, Wu Z, Yu X, Sung J, Johnson AJ, Li Y, Wu LJ. Microglial P2Y6 calcium signaling promotes phagocytosis and shapes neuroimmune responses in epileptogenesis. Neuron. 2024 Apr 10:S0896-6273(24)00195-8.
  
• Zhao S, Umpierre AD, Wu LJ. Tuning neural circuits and behaviors by microglia in the adult brain. Trends Neurosci. 2024 Mar;47(3):181-194. 
  
• Haruwaka K, Ying Y, Liang Y, Umpierre AD, Yi MH, Kremen V, Chen T, Xie T, Qi F, Zhao S, Zheng J, Liu YU, Dong H, Worrell GA, Wu LJ. Microglia enhance post-anesthesia neuronal activity by shielding inhibitory synapses. Nat Neurosci. 2024 Mar;27(3):449-461. 
  
• Umpierre AD, Wu LJ. How microglia sense and regulate neuronal activity. Glia. 2021 Jul;69(7):1637-1653.
  
• Umpierre AD, Bystrom LL, Ying Y, Liu YU, Worrell G, Wu LJ. Microglial calcium signaling is attuned to neuronal activity in awake mice. Elife. 2020 Jul 27;9:e56502.
  
• Liu YU, Ying Y, Li Y, Eyo UB, Chen T, Zheng J, Umpierre AD, Zhu J, Bosco DB, Dong H, Wu LJ. Neuronal network activity controls microglial process surveillance in awake mice via norepinephrine signaling. Nat Neurosci. 2019 Nov;22(11):1771-1781.
  
• Umpierre AD, West PJ, White JA, Wilcox KS. Conditional Knock-out of mGluR5 from Astrocytes during Epilepsy Development Impairs High-Frequency Glutamate Uptake. J Neurosci. 2019 Jan 23;39(4):727-742.
  
• Umpierre AD, Bennett IV, Nebeker LD, Newell TG, Tian BB, Thomson KE, White HS, White JA, Wilcox KS. Repeated low-dose kainate administration in C57BL/6J mice produces temporal lobe epilepsy pathology but infrequent spontaneous seizures. Exp Neurol. 2016 May;279:116-126.
  
• Umpierre AD, Remigio GJ, Dahle EJ, Bradford K, Alex AB, Smith MD, West PJ, White HS, Wilcox KS. Impaired cognitive ability and anxiety-like behavior following acute seizures in the Theiler's virus model of temporal lobe epilepsy. Neurobiol Dis. 2014 Apr;64:98-106.