Research Focus

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 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. Specifically, 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. 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?

Tumors alter leptin/ghrelin signaling, which results in aberrant activation of hypothalamic hypocretin/orexin neurons. This promotes poor sleep, and changes in glucose metabolism via the sympathetic nervous system. (from: Borniger et al., 2018)

Tumors alter leptin/ghrelin signaling, which results in aberrant activation of hypothalamic hypocretin/orexin neurons. This promotes poor sleep, and changes in glucose metabolism via the sympathetic nervous system. (from: Borniger et al., 2018)

Common Techniques

We are equipped to do experiments spanning both the basic biology of cancer and systems neuroscience.

  • Viral vectors for transgene delivery into the brain and tract tracing (AAVs/lenti/rabies)

  • Optogenetics

  • Chemogenetics

  • Calcium imaging/fiber photometry

  • rt-qPCR

  • Flow cytometry/Mass cytometry

  • Wireless EEG/EMG telemetry

  • Proteomics/ELISAs

  • Behavioral assays

  • Cell culture (BSL-2 & BSL-2+) + Live cell imaging (Keyence)

  • High-density multielectrode arrays (4096 recording/stimulating electrodes per chip)

Banner image: REM sleep wavelet during optogenetic stimulation of lateral hypothalamic GABA neurons (JCB).