Orthoflavivirus infection of the central nervous system
Our lab uses orthoflavivirus infection as a powerful experimental framework to understand how immune signaling reshapes the nervous system across multiple biological scales. Orthoflaviviruses include several major human pathogens, including West Nile virus and Zika virus, which are known to invade the CNS and cause a variety of neurologic syndromes. We study how CNS viral infection alters neuroimmune signaling, neurotransmission, behavior, and neurodevelopment, with a particular focus on how innate immune pathways in neural-lineage cells influence brain function and disease outcomes. To address these questions, we use a combination of cutting-edge approaches, including intersectional mouse genetics, virology, transcriptomic profiling, immunophenotyping, imaging, behavioral analysis, and in vivo neurophysiology. This integrated approach allows us to interrogate important questions spanning from cellular and molecular biology, to organ system function, to organismal outcomes in rodent disease models. We ultimately aim to define new mechanisms by which neuroimmune interactions underlie pathogenesis and host protection, with the goal of identifying new targets and strategies for the treatment of neuroinflammatory and neuroinfectious diseases.
We study how resident cells of the central nervous system coordinate specialized immune responses to infection and injury.
The Daniels lab is pursuing diverse projects in the area of neuro-immune cross talk. We are particularly focused on understanding the intrinsic immune activities of neural cells, including neurons and astrocytes, with the goal of defining their contributions to immune homeostasis, pathogen clearance, and immunopathology during CNS disease states.
Co-regulation between neurotransmission and neuroinflammation
The nervous and immune systems have historically been studied as distinct biological networks, but it is increasingly clear that they are deeply intertwined. Neurons are immunologically active cells that sense and respond to inflammatory cues, while immune cells can produce and respond to neurotransmitters.
Our lab investigates how this bidirectional crosstalk shapes brain function, neuroinflammation, and disease pathogenesis. Current projects examine how innate immune signaling pathways intersect with neurotransmitter receptor function in the CNS. One major focus is understanding how immune-associated kinases and phosphatases regulate glutamatergic synaptic signaling and influence susceptibility to excitotoxic injury during viral encephalitis. We are also defining endogenous immunoregulatory roles for dopamine beyond its traditional functions in neurotransmission, including how dopamine-dependent CaMKII/CREB signaling interacts with NF-κB-dependent inflammatory programs during CNS viral infection. Together, these studies seek to illuminate how evolution has shaped interactions between the nervous and immune systems.
Recent work in our lab defined an unexpected, pro-survival function of the canonical death-inducing kinase RIPK3 in neurons. RIPK3 promotes neuronal survival during CNS viral infection via suppression of excitotoxic glutamatergic neurotransmission.