http://www.graemedavislab.com/about daily 0.75 2017-05-23 https://images.squarespace-cdn.com/content/v1/558a32c4e4b0ed326096c87c/1493093046851-2QJT1CTIHBRG8WHB5X9S/image-asset.jpeg People https://images.squarespace-cdn.com/content/v1/558a32c4e4b0ed326096c87c/1493095188667-0RHBFARMHFL52PDCUCMG/anna-headshot People Anna Hauswirth: MSTP Student https://images.squarespace-cdn.com/content/v1/558a32c4e4b0ed326096c87c/1493612245184-YQ9WI7RUFJ1V7WSKJ1P8/image-asset.jpeg People Kenton Hokansen: Grad Student https://images.squarespace-cdn.com/content/v1/558a32c4e4b0ed326096c87c/1493611075239-K40GCMYIGZRBLPZG0SLR/image-asset.jpeg People Nathan Harris: Grad Student https://images.squarespace-cdn.com/content/v1/558a32c4e4b0ed326096c87c/1493609700759-UKCJUH984HIVVQB1NDCQ/image-asset.jpeg People Richard Fetter: Specialist - Electron Microscopy. https://images.squarespace-cdn.com/content/v1/558a32c4e4b0ed326096c87c/1493094200671-7UUAQP1SDHAX7OVWQYPO/image-asset.jpeg People Tingting Wang: Postdoc https://images.squarespace-cdn.com/content/v1/558a32c4e4b0ed326096c87c/1493409837068-NFAP1W5V8V6A0L4OSZ3I/image-asset.jpeg People Alyssa Johnson: Postdoc https://images.squarespace-cdn.com/content/v1/558a32c4e4b0ed326096c87c/1493610331868-8L7X0GZN0D2IJWD137I6/image-asset.jpeg People Ashley Smart: Grad Student https://images.squarespace-cdn.com/content/v1/558a32c4e4b0ed326096c87c/1493094924521-9P8DK1V5BK3H013HFBY2/ozgur-headshot.jpg People Ozgur Genc: Postoc https://images.squarespace-cdn.com/content/v1/558a32c4e4b0ed326096c87c/1493610884235-GZ3PXQNOIYQBYZV6Q58R/image-asset.jpeg People Yelena Kulik: Grad Student https://images.squarespace-cdn.com/content/v1/558a32c4e4b0ed326096c87c/1493610275585-NBBSV0D2HW754LUEFWA7/image-asset.jpeg People Jennifer Ortega: Grad Student https://images.squarespace-cdn.com/content/v1/558a32c4e4b0ed326096c87c/1493612668991-HHP6KOR0ZZQW53SZ4VXL/image-asset.jpeg People Brian Orr: Postdoc https://images.squarespace-cdn.com/content/v1/558a32c4e4b0ed326096c87c/1493609727528-2KN6JWMODB5SD0RX6NVB/amy-tong-headshot.jpg People Amy Tong: Specialist - Molecular Biology http://www.graemedavislab.com/work daily 0.75 2017-07-16 https://images.squarespace-cdn.com/content/v1/558a32c4e4b0ed326096c87c/1483072708263-P4M3DOSUP58H2EELSWO4/image-asset.jpeg The Science https://images.squarespace-cdn.com/content/v1/558a32c4e4b0ed326096c87c/1483071103053-78O711Q1Q8LEUDPB84WZ/image-asset.jpeg The Science https://images.squarespace-cdn.com/content/v1/558a32c4e4b0ed326096c87c/1483077928479-Z3230ZAX0GINWZFTF3XI/image-asset.jpeg The Science Homeostatic signaling systems are built upon feedback control. A simplistic signaling system is diagrammed to illustrate how much remains to be learned. Baseline neural function is detected by a sensor. The information from the sensor is compared to the cell set point, which is genomically defined. If the sensor and set point differ, an error signal is produced, integrated over time and fed back into the system as negative feedback. If the error is offset to zero, perfect homeostasis is achieved. We do not know the nature of a true sensor for neural activity, nor do we know how this information is communicated to a genomically defined set point. Therefore, the chemical identity of the error signal and the nature of signal integration remain unknown. Ultimately, cellular and molecular mechanisms must be able to explain the concepts defined in red. Recent work has highlighted the first mechanisms responsible for the bi-directional control of neurotransmission (Gavino et al., 2015). Additional work has defined mechanisms for the analogue control of presynaptic release (Younger et al., 2013). We have begun to define the intercellular signaling systems that achieve homeostatic communication between cells in the nervous system (Wang et al., 2014; Harris et al., 2015). https://images.squarespace-cdn.com/content/v1/558a32c4e4b0ed326096c87c/1497900992831-KH5LE0KTD76OCBNENDHZ/image-asset.jpeg The Science - If homeostatic signaling is impaired, the nervous system will be less robust to perturbations including genetic, immunological or environmental stress. We are actively exploring the intersection of homeostatic signaling with the genetics of both autism and neurodegenerative disease. We are translating our mechanistic advances to search for novel, disease modifying strategies using mice and other models of disease. The broad clinical expertise at UCSF provides an ideal environment for collaboration. https://images.squarespace-cdn.com/content/v1/558a32c4e4b0ed326096c87c/1483069332906-6T5P0EB500YNZ42LSSPG/St+Jerome.jpg The Science http://www.graemedavislab.com/contact-us daily 0.75 2017-06-19 https://images.squarespace-cdn.com/content/v1/558a32c4e4b0ed326096c87c/1483068869561-RPOZFZR87BRX83F6D815/Mission+Bay+Picture.jpg Contact Info http://www.graemedavislab.com/the-science daily 0.75 2015-06-24 http://www.graemedavislab.com/publications daily 0.75 2017-06-19 https://images.squarespace-cdn.com/content/v1/558a32c4e4b0ed326096c87c/1495512165275-RBJQRDSG78F9PGCZ0AR8/image-asset.jpeg Publications - Genç Ö, Dickman DK, Ma W, Tong A, Fetter RD, Davis GW. (2017) MCTP is an ER-resident calcium sensor that stabilizes synaptic transmission and homeostatic plasticity. Elife. May 9: e22904. In a forward genetic screen for mutations that block presynaptic homeostatic plasticity, we identified mctp (Multiple C2 Domain Protein with Two Transmembrane Regions). MCTP localizes to the membranes of the endoplasmic reticulum (ER) that elaborate throughout the soma, dendrites, axon and presynaptic terminal. MCTP is a novel, ER-localized calcium sensor that stabilizes baseline transmission, short-term neurotransmitter release dynamics and homeostatic plasticity. https://images.squarespace-cdn.com/content/v1/558a32c4e4b0ed326096c87c/1495516071655-PYTLBN6FCY60G6B3GWDW/image-asset.jpeg Publications - Wang T, Hauswirth AG, Tong A, Dickman DK, Davis GW. (2014) Endostatin is a trans-synaptic signal for homeostatic synaptic plasticity. Neuron 83, 616-29. Multiplexin is the Drosophila homolog of Collagen XV/XVIII, a matrix protein that can be proteolytically cleaved to release Endostatin, an antiangiogenesis signaling factor, never previously been studied in the nervous system of any organism. We demonstrate that Multiplexin controls calcium channel abundance, presynaptic calcium influx, and neurotransmitter release. Remarkably, release of Endostatin is essential the homeostatic modulation of presynaptic calcium influx and neurotransmitter release. This work identifies a novel form of trans-synaptic signaling during homeostatic plasticity. https://images.squarespace-cdn.com/content/v1/558a32c4e4b0ed326096c87c/1495513207750-1G6W7BZ54KY7HZQYA9Q7/image-asset.jpeg Publications - Harris N, Braiser DJ, Dickman DK, Fetter RD, Tong A, Davis GW. (2015) The Innate Immune Receptor PGRP-LC Controls Presynaptic Homeostatic Plasticity. Neuron. 88, 1157-64. The brain is immunologically active. However, it remains generally unknown whether innate immune signaling has a function during the day-to-day regulation of neural function in the absence of pathogens or damage. We identify a novel, neuronal function for an innate immune receptor (PGRP-LC), demonstrating a required during homeostatic synaptic plasticity. PGRP-LC is a candidate receptor for retrograde, trans-synaptic signaling, a novel activity for innate immune signaling in any organism. https://images.squarespace-cdn.com/content/v1/558a32c4e4b0ed326096c87c/1495515034019-9LB8QENXTE38A7J93OFD/image-asset.jpeg Publications - Johnson AE, Shu H, Hauswirth AG, Tong A, Davis GW. (2015) VCP-dependent muscle degeneration is linked to defects in a dynamic tubular lysosomal network in vivo. Elife. Jul 13;4. Lysosomes are classically viewed as vesicular structures to which cargos are delivered for degradation. Here, we identify a network of dynamic, tubular lysosomes that extends throughout Drosophila muscle, in vivo. The dynamics and integrity of this tubular lysosomal network requires VCP, an AAA-ATPase that, when mutated, causes degenerative diseases of muscle, bone and neurons. We propose that VCP sustains sarcoplasmic proteostasis by controlling the integrity of a dynamic tubular lysosomal network. https://images.squarespace-cdn.com/content/v1/558a32c4e4b0ed326096c87c/1495514103997-AVACQ9J91Y6271TXCOYF/a2d3_slide4.jpg Publications - Wang T, Jones RT, Whippen JM, Davis GW. (2016) α2δ-3 Is Required for Rapid Transsynaptic Homeostatic Signaling. Cell Reports 16, 2875-88. The α2δ gene family has been linked to chronic pain, epilepsy, autism, and the action of two psychiatric drugs: gabapentin and pregabalin. Here, we demonstrate that loss of α2δ-3 blocks both the rapid induction and sustained expression of homeostatic plasticity due to a failure to potentiate presynaptic calcium influx and the readily releasable vesicle pool. α2δ proteins reside at the extracellular face of presynaptic release sites throughout the brain, a site ideal for mediating rapid, trans-synaptic homeostatic signaling. http://www.graemedavislab.com/read-me daily 0.75 2025-05-12 https://images.squarespace-cdn.com/content/v1/5310cef7e4b08602cbfa36bf/1412689652885-P9TPK298WCTZU748L0SG/Lifestyle03.jpg Read Me