PET project: Imaging modality offers new insights into neurodegenerative disease

Gary Boas
March 25, 2015
Martinos Center investigator Jacob Hooker has been awarded a grant that will help to advance important work exploring the processes underlying schizophrenia and Alzheimer’s among other diseases. (Image courtesy of Jacob Hooker.)

Positron emission tomography – more commonly known as PET – offers researchers and clinicians a means to peer into the human body, to gain better understandings of the chemical and biochemical interactions that occur there. Using the technology, investigators have been able to glean new insights about the underpinnings of disease, improve diagnosis and prognosis, and accelerate the development of new therapies.

All of this is made possible by chemical compounds known as radiotracers, the imaging agents used with PET. This is where Jacob Hooker comes in. The Director of Radiochemistry at the MGH Martinos Center for Biomedical Imaging and an Associate Professor at Harvard Medical School, Hooker leads a research group at the Center widely known for its development of novel methodologies to produce PET agents, as well as for its ability to perform innovative and challenging radiochemistry and multimodal imaging.

Now he is being honored with a NARSAD Independent Investigator grant from the Brain & Behavior Research Foundation. This grant, one of the highest distinctions in mental health research, will play an important role in advancing his group’s work.

“The award comes at a critical transition in our research,” he says, “where we are moving from imaging agent development to applications aimed at relating a particular class of enzyme to brain function in disease,” for example in developing new therapies for neuropsychiatric and neurodegenerative diseases.

In awarding the grant, the Brain & Behavior Research Foundation recognizes an already impactful career in biomedical imaging. Hooker’s involvement in the field dates back to his graduate school days at the University of California, Berkeley, where he enrolled after receiving an undergraduate degree in Chemistry and Textile Chemistry from North Carolina State University. While at a conference, he stumbled upon a drug abuse lecture by Joanna Fowler, in which she demonstrated the use of carbon-11 cocaine with PET to study the brain dopamine system.

“I had some familiarity with imaging from my PhD work,” he says, “but Joanna's lecture opened my eyes to new possibilities for applying physical organic chemistry concepts to neuroscience.” He turned his attention to this exciting field of study and, in his PhD work with Professor Matthew Francis, developed new technologies for the construction of biomedical imaging agents using nanometer-sized viruses.

The exhilaration he felt during those early days, the wonderment at what can be accomplished with imaging and chemistry, remains even now. “I am still drawn in by the seductive nature of our work,” he says. “How many other people get to make new molecules and see them moving in and interacting with the human brain?”

After finishing his doctoral work, in 2007, Hooker moved to Brookhaven National Laboratory in Long Island, N.Y., to work under Fowler (who would be awarded a National Medal of Science in 2009). There, as a Goldhaber Distinguished Fellow and a Ruth L. Kirschstein NIH Fellow, he developed new chemical strategies for the synthesis of positron emission tomography imaging (PET) agents. And quite successfully at that. In 2009, Battelle named him “Inventor of the Year” for this work. The following year, he received a Presidential Early Career award from President Obama for research and student mentorship.

He was recruited by the Martinos Center at Massachusetts General Hospital in 2009 and quickly discovered what a unique and remarkable environment it is.

“In my lab and through collaborations I work with some of the most talented and brilliant people,” he says. “Doors are always opening at the Martinos Center and research evolves incredibly fast. In the five and a half years I have been here, I can honestly say I've never had a boring day.”

Today, Hooker and his group are pursuing a range of projects helping to answer a number of critical questions about brain health. They are making considerable headway, for example, in understanding neuroinflammation in brain diseases including autism, amyotrophic lateral sclerosis (ALS), and Huntington’s disease.

Notably, they are also studying epigenetic regulation in the living human brain – in biology, “epigenetics” refers to processes that are not the result of changes in the DNA sequence. Last year they reported a new PET imaging probe that targets a set of enzymes called histone deacetylases (HDACs), opening up important new avenues of investigation.

“Research has shown that changes in the amount of HDAC in brain tissue may be an important feature of normal brain function as well as in the changes that result from aging, neuropsychiatric and neurodegenerative diseases,” said Frederick “Al” Schroeder, a researcher in Hooker’s lab, when the first papers describing the probe were published. "If we understand more about HDAC expression and function, we could develop new treatments to improve patient health.”

In fact, Hooker says, the NARSAD grant will support some of the first studies of an epigenetic process in the living human brain. He and his group are initially exploring epigenetic regulation in schizophrenia and Alzheimer’s disease but they plan to extend their work to other diseases as they progress.


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