Dr. Maya Koronyo-Hamaoui PhD

In the past 20 years, I have been driven by a desire to uncover the role of innate immune cells – especially peripheral monocytes and macrophages – in CNS repair and regeneration, ultimately leading to the development of immunomodulation-based therapies for AD. This approach presents a paradigm shift away from the common view that any involvement of peripheral immune cells in the brain is a sign of pathology. My team discovered that instead of being detrimental, recruitment of a subset of bone marrow (BM)-derived monocytes into the brain resulted in a marked attenuation of disease progression, as well as synaptic and cognitive preservation in transgenic murine models of AD. This effect was achieved by either adoptive transfer of BM-derived CD115⁺LyC6^hi monocytes from young donors to the peripheral blood of symptomatic transgenic AD mice, or immunization with altered myelin-derived antigens (such as MOG45D or glatiramer acetate). These multifaceted immunomodulation strategies were found to substantially regulate neuroinflammation and diminish various aspects of AD neuropathology and dysfunction. To further enhance the capacity of innate immune cells, my lab has successfully combined monocytes with enhanced angiotensin-converting enzyme, an amyloid β-protein (Aβ) degrading enzyme, identifying molecular pathways to create a highly neuroprotective monocytic phenotype to resist AD pathology.

Another major focus of my research is exploring AD-specific pathology in the neurosensory retina, an accessible CNS organ for noninvasive imaging. My team was a pioneer in the discovery of pathological hallmarks of AD, Aβ plaques, in the human AD retina, including at early disease stages. We further developed an innovative methodology for noninvasive detection of retinal Aβ deposits in live rodent models, allowing for highly specific and detailed monitoring of individual Aβ plaques during disease progression and in response to therapy. Our novel imaging technology has been translated to humans and was successfully tested in proof-of-concept clinical trials. This approach is currently undergoing further validation in several large-scale cohorts.  My investigations into neuroimmunology and as it relates to AD therapy and the discovery of pathological hallmarks of AD in the retina with the development of retinal imaging technology have garnered multiple awards.

Ongoing projects that I would like to highlight include the following:

NIA R01 AG055865               
Koronyo-Hamaoui (PI)
04/01/18 – 12/31/23
Alzheimer’s Disease Hallmark Pathology and Associated Inflammation in the Retina

NIA R01 AG056478
Koronyo-Hamaoui (PI)
09/15/17 – 05/31/23
Retinal Imaging of Alzheimer’s Disease Pathology

NIA R01 AG075998
Crother, Koronyo-Hamaoui (Co-PI)
9/1/21 – 8/31/26
Chlamydia pneumoniae in Alzheimer’s Disease

NIH AI134714-04S1
Bernstein (PI); Role: Co-Investigator
9/1/21 – 8/31/22
Increased neutrophil function in Alzheimer’s disease

NIA RF1AG074365
Tourtellotte (PI); Role: Co-Investigator
9/1/21 – 8/31/24
Modulating Microglia Function to Restore Amyloid-beta Proteostasis in Alzheimer’s Disease