Brain-Body Research
Welcome to Rolls Lab, a neuroimmunology research lab studying how the nervous system regulates immunity. Click here to explore our recent research and learn more about our ongoing projects.
Brain-Body Connection
The connection between mental state and our ability to cope with disease is evident in epidemiology and our daily experiences. Nevertheless, the mechanism underlying this connection is poorly understood. Hence, in the clinic, we often dismiss some conditions as psychosomatic (“it is in your head”) or ignore the emotional trigger of an autoimmune relapse. We aim to understand these connections from a mechanistic perspective. To uncover the causal relationship between brain activity and changes in physiology and to apply this knowledge to developing new technologies to harness the organism’s therapeutic potential. We use state-of-the-art neuroscience, immunology, genomics, and proteomics tools to dissect the intricate connections between the brain and the immune system.
Join us on our journey.
Feel free to contact us if you would like to engage with our team or explore collaboration opportunities. Our latest publications offer a glimpse into our ongoing research.
Neuronal Mechanisms of Placebo
Hope and motivation are key features of the placebo response. We show that the activity of the dopaminergic neurons in the reward system, which mediates positive expectation and motivation, affects the immune response and disease outcome. We dissect these connections using transgenic mouse models, chemogenetics, optogenetics, and omics.
Immunoception
The brain monitors the state of the body and can retain representations of past experiences. We show that the brain's insular cortex stores representations of past immune experiences. Reactivating these representations (immune engrams) can replay the original inflammatory state, introducing new perspectives to the concept of immune memory. We define these complex interactions between the brain and the immune system as “immunoception”.
Immune Cells in the Brain
Immune cells in the brain play essential roles in maintaining neural health and responding to disease. They can also infiltrate the brain from the periphery. Their activity can influence overall brain function and interact with systemic immune responses. Therefore, it is unlikely that the brain does not have at least some say over its own immune environment. Our work is focused on understanding the mechanisms that enable the brain to regulate the influx of peripheral immune cells to the CNS.
Peripheral mechanisms of neuronal immune regulation
Our lab investigates how stress and the sympathetic nervous system influence immune activity in peripheral organs. We showed, for example, using optogenetics, that the sympathetic nervous system can regulate the ability of immune cells to extravasate from the blood vessel to an inflammatory site. Other studies explore the sympathetic effects on liver acute phase protein production and oral tolerance formation.
Systemic brain-immune Interactions in Cancer
Emerging evidence highlights a strong connection between mental states and cancer prognosis. Recent studies have shown that neurons actively innervate solid tumors, with the extent of tumor innervation correlating to survival outcomes in various cancers. Neuronal activity is also critical in regulating immunity, particularly the anti-tumor immune response. Since neurons innervate immune-related organs, changes in this innervation can impact the development of anti-tumor immunity. Our lab has shown that modulating brain activity can affect cancer progression, and more recent work is focused on how tumors induce alterations in the innervation of immune organs and affect the body’s anti-tumor immune response. Understanding these neuronal-immune interactions not only provides insights into how mental states influence immune function but also opens new therapeutic avenues for cancer treatment, potentially repurposing drugs that target the nervous system.
ERC Funded Projects
ERC consolidator-
NeuroFascia
The fascia is the largest tissue in the body, yet most of us have never heard of it. This connective tissue delineates the skin, surrounds muscles, and closely envelops all organs. Clinically, it is mainly considered a mechanical barrier separating organs and muscles. But why should a simple barrier be populated with immune cells and receive extensive innervation by sensory and sympathetic neurons? Our ERC project, NEUROFASCIA, examines the hypothesis that the fascia generates a sensory platform that detects damage to the tissues it envelops and communicates this information to the brain, which, in turn, initiates corrective programs and modulates immune activity.
ERC PoC-
NEUROGUT
Translation to humans of our preclinical findings highlights the insular cortex as a key brain area in IBD. By targeting and modulating this neural activity, our project aims to reduce chronic inflammation, offering a novel treatment approach that could extend to other autoimmune diseases in collaboration with Dr. Talma Hendler and Dr. Ben Shofti.
ERC starter-
NEIMO
This completed project has resulted in two key publications:
​
Insular cortex neurons encode and retrieve specific immune responses.
Koren T. et.al. Cell (2021).
​
Optogenetic activation of local colonic sympathetic innervations attenuates colitis by limiting immune cell extravasation.
Schiller M., et.al. Immunity (2021).