Ohno Lab
Masuo Ohno, Ph.D.
Head of Lab

Research Scientist, Center for Dementia Research

Ohno Lab

Molecular and Cellular Cognition for Alzheimer’s Disease Therapy
The Ohno lab studies molecular and cellular mechanisms of Alzheimer’s disease (AD) and related cognitive disorders by applying multidisciplinary approaches to transgenic mouse models. We focus on the β-secretase enzyme called BACE1, which initiates the production of amyloid-β (Aβ) peptides from their parent molecule APP, since the genetics indicates that Aβ is the key driver of disease progression.

By evaluating gene knockout and small-molecule inhibitors in AD mouse models (e.g., 5XFAD), we have demonstrated that successful therapeutic BACE1 inhibition for cognitive benefits needs to start during very early or asymptomatic disease stages. Importantly, recent failure of BACE1 inhibitor clinical trials (especially, cognitive worsening in early or prodromal AD cases including MCI) brings up the issue of critical physiological function of BACE1 (most likely through regulating signaling pathways via substrates other than APP). Our research goal is to develop therapeutic interventions for AD that can increase BACE1 inhibition efficacy in ameliorating cognitive symptoms, while avoiding potential adverse effects associated with direct over-inhibition. Our work will have important implications for designing safe and practical BACE1 inhibitor trials ranging from combination or multi-targeted therapy for symptomatic AD to preventive BACE1 inhibitor monotherapy in a preclinical stage of AD.

Research Interests

The major focus of my research is on (1) understanding molecular, cellular, and systems foundations of learning & memory and (2) establishing the therapeutic strategies to improve and/or prevent the progression of cognitive disorders associated with Alzheimer’s disease or normal aging. With the aging of our population, therapeutic interventions of cognitive disorders or dementia are becoming one of the most crucial facets of public health. Elucidating mechanisms by which information is encoded, stored and recalled in normal brain and understanding how these processes are impaired in disease conditions work cooperatively like the two wheels in order to unequivocally validate potential therapeutic approaches for the treatment of human cognitive impairments. Modern behavioral, biophysical and molecular genetics of the mouse provides a powerful tool to address these problems. In our laboratory, we apply a combination of molecular biology, biochemistry, electrophysiology, pharmacology and behavioral assays to genetically engineered mouse models that lack or overexpress specific genes. These multidisciplinary analyses of mutant mice synergistically favor our tackling divergent aspects of learning & memory and their impairments.


B.A. (Pharmacology) Gifu Pharmaceutical University, Gifu, JAPAN
Ph.D. (Pharmacology) Kyushu University, Fukuoka, JAPAN
Postdoctoral Training
Postdoctoral Fellow, Cold Spring Harbor Laboratory, Cold Spring Harbor , NY (PI: Dr. Alcino J. Silva)
Visiting Assistant Researcher, Department of Neurobiology and Brain Research Institute, UCLA, Los Angeles, CA (PI: Dr. Alcino J. Silva)

Awards and Honors

1989-1991 Research Award from the Japan Society for the Promotion of Science (JSPS)
1992 Mochida Memorial Foundation Research Fellowship Award
1998 Uehara Memorial Foundation Research Fellowship Award