Abstract - Marcelo Wood

Our understanding of the role of epigenetics in neuronal plasticity, memory, and aging is accelerating rapidly as new tools become available. However, the ability to translate these basic findings into human research, and more importantly therapeutic approaches, remains significantly limited. In this proposal, we will examine the ability of a novel positron emission tomography (PET) imaging probe, called [11C]Martinostat, to determine the activity of a specific epigenetic mechanism required for memory formation in rodents and humans. This mechanism involves histone deacetylases (HDACs), which are powerful negative regulators of memory formation. [11C]Martinostat selectively binds key HDACs with subnanomolar potency and fast binding kinetics. We will use [11C]Martinostat to determine HDAC enzyme density in young and old rodents, as well as young and old humans, and its relationship to object location memory (OLM) formation. OLM is hippocampus-­‐dependent and a form of memory that is significantly impaired in aged rodents, nonhuman primates, and humans. We have assembled a unique multidisciplinary team of investigators for this project—a project that promises to develop a novel imaging probe that harnesses the power of epigenetics and will lead to significant new inroads into the understanding, diagnosis, and potential treatment of disorders associated with memory dysfunction.

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Principal Investigator Institution Title Abstract
Andersen, Richard California Institute of Technology Engineering Artificial Sensation View
Andrews, Anne University of California, Los Angeles Nanoscale Neurotransmitter Sensors View
Bloodgood, Brenda University of California San Diego A novel toolkit for visualizing and manipulating activity-induced transcription in living brain. View
Chaumeil, Myriam University of California, San Francisco In vivo metabolic imaging of neuroinflammation using hyperpolarized 13C View
Cleary, Michael University of California, Merced Capturing physiological maps of neural gene expression View
Cohen, Bruce University of California, Lawrence Berkeley National Laboratory Nano-optogenetic control of neuronal firing with targeted nanocrystals View
Dai, Hongjie Stanford University  Deep brain imaging of single neurons in the second near-infrared optical window View
Hall, Drew University of California, San Diego Magnetic Monitoring of Neural Activity using Magnetoresistive Nanosensors View
Krubitzer, Leah University of California, Davis An integrated system to monitor, image, and regulate neural activity View
Kubby, Joel University of California, Santa Cruz Three-Photon Microscopy with Adaptive Optics for Deep Tissue Brain Activity Imaging View
Melosh, Nicholas Stanford University Parallel Solid State Intracellular Patch-Clamping with Biomimetic Probes View
Park, B. Hyle University of California, Riverside  Label-free 4D optical detection of neural activity View
Portera-Cailliau, Carlos University of California, Los Angeles High-speed interrogation of network activity with frequency domain multiplexing View
Shanechi, Maryam University of Southern California Control-Theoretic Neuroprosthetic Design Using Electrocorticography Signals View
Smith, Will University of California, Santa Barbara Whole brain imaging in a primative chordate View
Wood, Marcelo University of California, Irvine Epigenetic PET tracer for cross-species investigation of age-related memory dysfunction View