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.
AWARDS
| 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 |