Our brain is an intricate network of neurochemicals, some of which communicate directly with each other while some others spectate until prompted to carry out a function. Imbalance in or dysfunction of these chemicals often triggers onset of mental illness, and therapeutics are designed to manipulate this brain—or neurochemical—activity. It is thus striking that we still have an incredibly limited understanding of how chemistry appears within the brain; we are developing drugs for something we know so little about! Dr. Jacob Hooker, Associate Professor of Radiology at Harvard Medical School, Associate Neuroscientist at Massachusetts General Hospital, and Director of Radiochemistry at the Martinos Center for Biomedical Imaging, develops imaging tools to non-invasively probe the living human brain at the molecular level during stimulation, at rest, and through drug manipulation. By creating novel techniques to enable data-rich, accessible imaging studies using positron emission tomography (PET) and magnetic resonance (MR), Dr. Hooker hopes to elucidate the molecules involved in healthy and diseased states of the brain and tissue.

Pioneers in visualizing neurochemistry, Dr. Jacob Hooker’s inherently translational and interdisciplinary team involves a diverse group of biologists, chemists, and imaging scientists as well as collaborators in the Martinos Center for Biomedical Imaging and other academic specialists around the world. In order to understand the pathways involved in the onset and progression of disease, it is crucial to be able to see inside the living human brain to study its earlier time points and monitor development of the disease as it relates to physical symptoms over the course of a lifetime. Tool developers partnering with clinical perspectives in neurology, psychiatry for both adults and children, oncology, neurodevelopment, and radiology therefore help observe how the brains in autism, neurodegenerative disease, mental illness, and chronic pain differ from the normal healthy state. The knowledge acquired from these novel imaging tools will ultimately offer invaluable insight into improving diagnostics and identifying better therapeutic targets. 

Current research includes:

• Neuro-epigenetic Imaging: Environmental factors sometimes affect how a brain develops and functions, and based on this knowledge, Dr. Hooker and his team are developing the first tools that will allow them to understand the relationship between environment and genetics. This technology will especially impact studies in Alzheimer's, schizophrenia, Huntington’s disease, and many other brain disease areas as the project continues to grow.
• Platform Project: There are cells in the brain called glia, which are non-neural cells that for a long time were believed to be mere supporters of neurons but are now recognized as playing an important functional role within the brain. The glial cells react to stimuli that can be disease and undergo “reactive processes” to protect neurons, and glial biology that goes awry can unfortunately contribute to being a disease pathway and cause neuroinflammation. Dr. Hooker and his team thus look at glial activation using their imaging tools, studying Lou Gehrig's disease (ALS), Huntington’s disease, autism spectrum disorder, multiple sclerosis, and pain processes like fibromyalgia and chronic back pain as well as migraine.
• Chemical Connectivity: Using advanced imaging tools, Dr. Hooker and his team are trying to map the chemical connectome of the brain and understand how the brain function changes as one part of the neurochemical system changes. Based on these visuals, Dr. Hooker hopes to generate “rules” or theories for how neurochemicals interact with each other and modulate brain activity at the whole brain system level.
• New Radiotracer Development: Dr. Hooker and his team are developing the next generation of probes that will allow us to see new things occurring within the brain, whether they be neurochemical interactions or structural processes like myelination or neuroinflammation. Findings from these studies can yield crucial insights for developing novel therapeutics.