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The Gill Center for Biomolecular Science

Gill Seminars

Previous Speakers

Upcoming Speakers

September 27, 2017
Clifford J. Woolf, M.B., B.Ch., Ph.D.

FM Kirby Neurobiology Center and Program in Neurobiology
Boston Children's Hospital
Harvard Medical School

Seminar will take place in the Indiana Memorial Union, Whittenberger Auditorium
during the 2017 Gill Symposium

Title: Unravelling pain one millisecond at a time

Abstract: Pain is initiated by the activation of high threshold sensory neurons; the nociceptors – which serve to detect danger. We are using stem cell technology, live nociceptor imaging in the whole animal, optogenetics and automated behavior analysis to tease out what behaviors are elicited by these danger detectors. This turns out to be a repertoire of complex, widespread, context-dependent subsecond behaviors which reveal new insight into how the nervous system operates at the cell, circuit and system level.

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September 27, 2017
Diana Bautista, Ph.D.

University of California, Berkeley

Seminar will take place in the Indiana Memorial Union, Whittenberger Auditorium
during the 2017 Gill Symposium

Title: Neural control of chronic itch and inflammation in atopic disease

Abstract: Chronic itch is a highly prevalent and debilitating disorder with few effective treatments. The most common chronic itch disorder is atopic dermatitis (eczema), an inflammatory skin condition affecting 10-20% of people worldwide. In a process termed the atopic march, atopic dermatitis is often followed by the onset of additional atopic diseases, including allergic rhinitis, asthma and allergy. Atopic disease is thought to arise from loss of skin barrier integrity and dysregulated immune cell activity. Our recent studies show that the peripheral nervous system also plays a key role in atopic disease pathogenesis. I will discuss our recent studies highlighting the molecular crosstalk between epithelial cells, immune cells and peripheral somatosensory neurons that promote chronic itch and inflammation.

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September 27, 2017
Xinzhong Dong, Ph.D.

Johns Hopkins University School of Medicine

Seminar will take place in the Indiana Memorial Union, Whittenberger Auditorium
during the 2017 Gill Symposium

Title: The mechanisms of itch and inflammation

Abstract: Despite of the clinical importance, cell surface receptors mediating non-histaminergic itch are largely unknown. We identified a large family of G protein-coupled receptors in mice called Mrgprs. Many of these receptors are exclusively expressed in distinct subsets of small-diameter dorsal root ganglion (DRG) neurons. We found that MrgprA3 functions as a receptor for chloroquine (an anti-malaria drug) and is required for chloroquine-induced itch. Besides chloroquine, Mrgprs also respond to several itch-inducing compounds such as BAM8-22, SLIGRL, and beta-alanine suggesting that Mrgprs are novel itch receptors by directly sensing these compounds. Our data have shown the involvement of Mrgprs in mouse chronic itch models such as dry skin, contact dermatitis, and allergic itch. Importantly, some of the results have been confirmed in human psychophysical studies. In addition, we demonstrated for the first time that itch-specific sensory neurons do exist and are distinct from pain-sensing neurons. Besides the sensory neuron specific Mrgprs, we discovered another member of the gene family, MrgprB2, is exclusively expressed in mast cells, a type of innate immune cells, which secret many pro-inflammatory mediators like histamine upon activation. We found that human MrgprX2 and mouse MrgprB2 are the sole receptor of many basic secretagogues mediating IgE-independent mast cell activation and responsible for many drug-induced pseudo-allergic side effects. Therefore, we believe that targeting human Mrgprs may lead to novel treatment of various diseases in the future. ​

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September 27, 2017
Michael W. Salter, M.D., Ph.D., FRSCC
Hospital for Sick Children (Sick Kids) and University of Toronto

Seminar will take place in the Indiana Memorial Union, Whittenberger Auditorium
during the 2017 Gill Symposium

Title: Sex, pain and microglia

Abstract: Neuron-microglial interactions are increasingly recognized as being key for physiological and pathological processes in the central nervous system.  Microglia have been found to play a causal role in neuropathic pain behaviours resulting from peripheral nerve injury, and a core neuron-microglia-neuron signaling pathway has been elucidated. Within the dorsal horn, microglia suppress neuronal inhibition by a cascade involving activation of microglial P2X4 receptors causing the release of brain derived neurotrophic factor (BDNF).  BDNF acts on trkB receptors which leads to a rise in intracellular Cl- concentration in dorsal horn nociceptive output neurons, transforming the response properties of these neurons.   In addition to suppressing inhibition, peripheral nerve injury causes activity-dependent potentiation at dorsal horn glutamatergic synapses which enhances nociceptive transmission. BDNF mediates the enhancement of synaptic NMDAR responses through activation of TrkB and the Src-family kinase, Fyn. We have discovered that microglia-to-neuron signaling is not only critical for pain hypersensitivity after nerve injury but also for the paradoxical hyperalgesic effect of morphine and other opioids.  This core signaling pathway has been extensively characterized, in studies using male mice.  We have recently discovered that microglia-neuron signaling is dispensable in female mice.  Rather, pain hypersensitivity in female mice depends upon the adaptive immune system, likely upon T cells.  Despite this profound difference in cellular mechanisms, pain hypersensitivity in female mice is as robust as that in male mice.  Taking into consideration sex differences in the spinal immune-neuronal signaling has important implications ranging from diagnostics, to therapeutics, to prevention of chronic pain.
 
Funding: Supported by CIHR, Krembil Fdn, CRC, Anne and Max Tanenbaum Chairs, and Northbridge Chair.