Staff profile for A/Prof Janet Keast

Position

Director of Basic Research, Pain Management, NHMRC Senior Research Fellow, Group Leader

Job description

Research Scientist

Organisation

Research Scientist, University of Sydney

Qualifications

BSc (Hons), PhD

Education

BSc (Hons1), University of Adelaide (1981) PhD, Flinders University (1986)

Research interests

We are interested in the peripheral nervous system and spinal cord, especially the neurons involved in urogenital reflexes and in signaling visceral pain. Our studies are focused on the development of these pathways (e.g. what causes male-female differences in these neurons) and also what factors can change the behavior of these neurons in adults (e.g. injury, inflammation, hormone exposure). Many of our studies focus on gonadal steroids, neurotrophic factors (especially the GDNF family) and, more recently, guidance factors. Our current work on adult neurons has particular relevance to spinal cord injury, surgically-induced injury (e.g. peripheral nerve injury occurring during prostatectomy and leading to erectile dysfunction) and pelvic inflammatory pain states such as interstitial cystitis.

Project

Mechanisms of androgen action in the development and maintenance of the male pelvic autonomic nervous system Effects of estrogens on bladder pain (especially inflammatory pain, such as in interstitial cystitis) The role of neurturin and GDNF in the development of pelvic autonomic nerve circuits, and regeneration of urogenital autonomic nerves after injury Changes in structure and activity of spinal nociceptive pathways after spinal cord injury Plasticity of autonomic and sensory pathways innervating urogenital organs after spinal cord injury, especially the role of guidance factors and neurotrophic factors

Grants/Awards

NHMRC Senior Research Fellowship (Keast) 2005-2009;  NHMRC Project Grants (Keast) 2008-2010, (Keast and Nangle (2009-2011);   NSW Ministry for Science and Medical Research, “Spinal Cord Injury and Other Neurological Conditions” Grant Program (Keast, Christie, Cousins, Osborne, Siddall) 5/2005-4/2009; National Institutes of Health USA / NIDDK RO1 grant (PI: Keast) 2005-2010; ANZCA Project Grant 2009 (Cousins, Keast).

Publications

Kalous A, Osborne PB, Keast JR (2009) Spinal cord compression injury in adult rats initiates changes in dorsal horn remodelling that may correlate with development of neuropathic pain. J Comp Neurol 513: 668-684.

Nangle MR, Keast JR (2009) Deafferentation and axotomy each cause neurturin-independent upregulation of c-jun in rodent pelvc ganglia. Exp Neurol 215: 271-280. 

Xu S, Cheng Y, Keast JR, Osborne PB (2008) 17beta-estradiol activates ERbeta signalling and inhibits TRPV1 activation by capsaicin in adult rat nociceptor neurons. Endocrinology 149: 5540-5548.

Yan H, Keast JR (2008) Neurturin regulates postnatal differentiation of parasympathetic pelvic ganglion neurons, initial axonal projections and maintenance of terminal fields in male urogenital organs. J Comp Neurol 507: 1169-1183.

Forrest SL, Keast JR (2008) Expression of receptors for glial cell line-derived neurotrophic factor family ligands in sacral spinal cord reveals separate targets of pelvic afferent fibers. J Comp Neurol 506: 989-1002.

Nangle MR, Keast JR (2007) Reduced efficacy of nitrergic neurotransmission exacerbates erectile dysfunction after penile nerve injury despite axonal regeneration. Exp Neurol 207: 30-41.

Purves-Tyson TD, Arshi MS, Cheng Y Handelsman DJ, Keast JR (2007) Androgen and estrogen receptor mediated mechanisms of testosterone action in male rat pelvic autonomic ganglia. Neuroscience 148: 92-104.

Kalous A, Osborne PB, Keast JR (2007) Acute and chronic changes in dorsal horn innervation by primary afferents and descending supraspinal pathways after spinal cord injury. J Comp Neurol 504: 238-253.

Brock JA, Handelsman DJ, Keast JR (2007) Postnatal androgen deprivation dissociates the development of smooth muscle innervation from functional neurotransmission in mouse vas deferens. J Physiol 581: 665-678.

Wanigasekara Y, Keast JR (2006) Nerve growth factor, glial cell line-derived neurotrophic factor and neurturin prevent semaphorin 3A-mediated growth cone collapse in adult sensory neurons. Neuroscience 142: 369-379

Palma CA, Keast JR (2006) Structural effects and potential changes in growth factor signalling in penis-projecting autonomic neurons after axotomy. BMC Neuroscience 7: 41-53

Nangle MR, Keast JR (2006) Loss of nitrergic transmission to mouse cavernosum in the absence of neurturin is accompanied by increased response to acetylcholine. Br J Pharmacol 148: 423-433.

Keast JR (2006) Structure and chemistry of pelvic autonomic ganglia. Int Rev Cytol 248, 141-208.

Llewellyn-Smith IJ, Weaver LC, Keast JR (2006) Effects of spinal cord injury on synaptic inputs to sympathetic preganglionic neurons. Prog Brain Res 152, 11-26.

Wanigasekara Y, Keast JR (2005) Neurturin has multiple neurotrophic effects on adult sacral parasympathetic ganglion neurons. Eur J Neurosci 22, 595-604

Llewellyn-Smith IJ, DiCarlo SE, Collins HL, Keast JR (2005) Enkephalin-immunoreactive interneurons extensively innervate sympathetic preganglionic neurons regulating urogenital function. J Comp Neurol 488, 278-289.

Osborne PB, Halliday GM, Cooper HM, Keast JR (2005) Localization of DCC, the receptor for the guidance factor netrin-1, in ventral tier dopamine projection pathways in adult rodents. Neuroscience 131, 671-681.

Purves-Tyson TD, Keast JR (2004) Rapid actions of estradiol on CREB phosphorylation in dorsal root ganglion neurons. Neuroscience 129, 629-637 Keast JR (2004). Remodelling of connections in pelvic ganglia after hypogastric nerve crush. Neuroscience 126, 405-414.

Wanigasekara Y, Airaksinen MS, Heuckeroth RO, Milbrandt J, Keast JR (2004) Neurturin signaling via GFRalpha2 is essential for innervation of glandular but not muscle targets of sacral parasympathetic ganglion neurons. Mol Cell Neurosci 25, 288-300

Middleton JW, Keast JR (2004) Artificial autonomic reflexes: using functional electrical stimulation to mimic bladder reflexes after injury or disease. Auton Neurosci: Basic and Clinical 113, 3-15.

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