Anatomical and functional imaging of the marmoset brain.
Mechanisms of cerebrovascular dysfunction in stroke and Alzheimer’s disease.
Genetically engineered marmoset models of brain function and neurological disorders.

We are interested in using a combination of behavioral, electrophysiological and imaging techniques to understand the mechanisms of neurovascular coupling that maintain a tight relationship between neuronal activity and cerebral blood flow. This relationship is crucial for the brain, and its disruption leads to dysfunction and disease. Our main research interests are in understanding mechanisms of cerebrovascular dysfunction as a common cause of several neurodegenerative diseases. We have extensive experience in the development and application of multimodal neuroimaging methods to study the brain’s anatomy and function, and our laboratory works with genetically engineered marmoset models of brain diseases, including stroke, Alzheimer’s disease and multiple sclerosis.

Our expertise is in the development of functional neuroimaging methods to understand:

1. how the cerebral microvasculature reacts, in space and in time, to changes in neuronal activity. 
2. how the mechanisms of neurovascular coupling are disrupted in neurological disorders.

On theme 1, we focus on understanding how the spatial localization and temporal evolution of the hemodynamic response to functional brain stimulation relate to the cortical cytoarchitecture. We use fMRI and optical imaging methods to probe the functional response to focal neuronal activity. Much of this was initiated in rodents, but has been ported to marmosets, a nonhuman primate with great promise as an animal model in biomedical research. We have been extremely productive in our work with marmosets (34 manuscripts published in the past 10 years), spanning from fMRI, to two-photon optical microscopy, to detailed MRI description of the rich anatomical details of the marmoset brain, to manuscripts on marmoset models of multiple sclerosis and transgenic and genetically engineered marmosets. We developed transgenic marmosets that express the genetically encoded calcium indicator molecule GCaMP6 that will constitute a much-improved animal model for studying neurovascular coupling in relevant conditions. These animals are the first transgenic marmosets produced outside Japan, the only transgenic marmosets present in the USA, and are currently in F1 generation and ready to be studied with two-photon laser scanning microscopy.

On theme 2, we are interested in understanding how the mechanisms of CBF regulation are altered by pathological brain states, including stroke and Alzheimer’s disease. We developed a genetically engineered marmoset model of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), the most frequent of the genetic small vessel diseases. Data obtained from marmosets are likely to offer new insights into the molecular and genetic mechanisms of neurological disorders, and potentially contribute to the development of novel biomarkers and therapeutical approaches with higher translational impact.