What we do
Why do patients with cancer (irrespective of cancer type) frequently experience systemic symptoms like pain, cognitive impairment, deficits in appetite, and disrupted sleep/wake cycles? What is the underlying biology governing these phenomena, and how can this biology be leveraged to improve peoples’ lives? To answer questions such as these, the Borniger lab investigates bi-directional communication between the brain and periphery in the context of cancer. The lab aims to determine how tumors disrupt neural circuit function, how aberrant cellular activity promotes cancer-associated systemic dysfunction, and how reciprocal outputs from the brain regulate cancer growth and metastasis. Specifically, the Borniger lab use techniques from systems neuroscience (e.g., optogenetics, calcium imaging, circuit mapping, electrophysiology, and behavioral assays) to dissect how factors in the tumor microenvironment alter host physiology and behavior. Recent work has focused on how central neuromodulator populations participate in cancer-associated sleep and metabolic disruption. The lab discovered that non-metastatic mammary tumors distally alter immune and endocrine signaling to aberrantly activate lateral hypothalamic hypocretin/orexin (HO) neurons. This resulted in disrupted sleep and hepatic glucose metabolism, the latter being driven by the sympathetic nervous system (Borniger et al., 2018 Cell Metabolism). This research, in combination with clinical work, will facilitate the development of novel treatments to improve outcomes for patients with cancer.
Questions that we are actively pursuing include:
– How does breast cancer influence subcortical neuronal activity to disrupt sleep?
– What is the link between sleep disruption and breast cancer initiation, progression, and metastasis?
– How do neuronal circuits in the hypothalamus regulate systemic immunity?
High Throughput EEG/EMG
The electroencephalogram and electromyogram (EEG/EMG) biopotentials can be used to objectively determine arousal states in both humans and other non-human mammals. In our lab, we use a wireless, high-throughput system to monitor EEG/EMG signals in 16 mice simultaneously in tandem with calcium imaging and optogenetics.
Monitoring Neuronal Activity in Real Time
We use genetically encoded calcium indicators (GECIs) and other fluorescent activity indicators to understand how ensembles of genetically-defined neurons fire during different arousal states and in response to changes in the body.
Millisecond Timescale Control of Neuronal Activity
To test the role identified neuronal populations play in our models, we use adeno-associated viruses (AAVs) carrying transgenes encoding optogenetic actuators (e.g., ChR2, gtACR2.0…). As these can be engineered to require Cre- or Flp mediated recombination, we can target them to specific genetically defined neuronal subtypes.
Neuronal Tract Tracing
Use of AAVs, modified rabies virus, and retrobeads to delineate the input-output relationships
Connecting cancer to the brain
A key gap in our knowledge revolves around how tumors growing in the body hijack host physiology to facilitate their own growth. This results in a slew of symptoms that negatively influence one’s life, like chronic fatigue, sleep disruption, low grade inflammation, and pain, among others. The brain constantly senses and responds to changes in the body to ensure that systemic homeostasis is maintained. However, we hardly know anything about how this homeostatic ‘push and pull’ becomes disrupted in cancer. To investigate this, we use genetically-encoded calcium indicators (GECIs), such as GCaMP6f, to visualize neuronal activity in real-time.