Basic Research

Heinricher laboratory

Dr. Heinricher's laboratory investigates brainstem mechanisms involved in pain modulation. Their focus is on opioid-sensitive circuits within the rostral ventral medulla (RVM), which is a crucial element in a pain-modulating network with links in the midbrain, medulla and spinal cord. This network contributes to the variability in pain sensitivity seen in different situations (for example under conditions of fear or extreme stress), and it is an important substrate for opioids and other analgesic drugs such as cannabinoids. The laboratory uses single cell recording in combination with pharmacological tools to analyze how this system is activated, and they have identified two distinct classes of pain modulating neurons.

• ON cells are directly sensitive to opioids, and they recently showed that these neurons facilitate nociceptive transmission.
• OFF-cells exert a net inhibitory effect on nociception, and they were able to demonstrate that disinhibition of these neurons is central to the antinociceptive actions of opioids within the medulla.

Currently, they are interested in identifying neurotransmitters that activate these two cell classes differentially to promote or suppress pain. They are also interested in how this modulatory system is activated under physiological conditions, and are looking at the inputs from limbic forebrain structures such as the hypothalamus to the rostral ventral medulla in an attempt to investigate this issue.

Baumann laboratory

Dr. Baumann's laboratory investigates transduction and signaling by somatosensory primary afferent neurons. They use patch clamp recording, immunofluorescence, molecular biology and functional imaging techniques to study ion channels which are responsible for the transduction of chemical, mechanical and thermal stimuli. They also investigate how ion channels are modulated by inflammatory mediators. These studies are important for a better understanding of the cellular mechanisms that are involved in sensory transduction and primary hyperalgesia. In addition, they utilize two approaches for studying peripheral neural mechanisms of chronic pain. One approach focuses upon the biophysical, pharmacological and immunohistochemical characteristics of neurons obtained from diabetic animals and patients treated by ganglionectomy for intractable pain due to nerve injury. A second approach utilizes microneurographic recordings in patients with trigeminal neuralgia or complex regional pain syndrome. These more clinically oriented studies seek to elucidate the cause of abnormal action potential discharge in injured neurons.

Anderson laboratory

Abnormal movement of water into and out of the brain plays a key role in many neurodegenerative disorders. Dr. Anderson's laboratory is focused on the application of high-field magnetic resonance techniques to the study of water permeability and the vascular microenvironment of Alzheimer's disease.

Selden laboratory

Dr. Selden's laboratory investigates the mechanisms involved in control of chronic pain. Chronic pain is a ubiquitous, debilitating and costly affliction of both children and adults.  Important aspects of pain-related behavior are mediated by supraspinal mechanisms.  The rostral ventromedial medulla (RVM) has both anti- and pro-nociceptive modulatory capabilities, each referable to a distinct, physiologically identified cell class.  OFF-cells are proposed to inhibit, and ON-cells to facilitate, nociceptive processing.  The remaining RVM neurons, NEUTRAL-cells, do not alter their activity in relationship to nocifensive behavior, and their role in pain modulation is currently unclear.  His research employs complementary electrophysiological and anatomical approaches (single cell recording and iontophoresis, juxtacellular labeling, and immunohistochemistry) to characterize the distribution of purinergic receptors on the three cell classes. 

Guillaume laboratory

Dr. Guillaume's laboratory is aimed to improve treatment of pediatric brain tumors, particularly medulloblastoma, and associated hydrocephalus that occurs due to leptomeningeal spread of tumor cells. Chemotherapy has been relatively ineffective for treatment of brain tumors because the blood-brain barrier and blood-tumor barrier limit agent delivery and dose intensity at the tumor, and systemic toxicities limit dose escalations. Working with Dr. Ed Neuwelt’s laboratory, we are investigating methods to increase dose intensity and decrease non-specific drug cytotoxicity by using chemo-enhancers and chemo-protectors, respectively. Tumors such as medulloblastoma have a high tendency for cerebrospinal fluid spread, causing hydrocephalus in many cases. We are investigating the effect of chemo-enhancers and chemo-protectors on leptomeningeal tumor spread and cerebrospinal fluid circulation.