Office for People With Developmental Disabilities

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Cellular Pathology Laboratory

07/11/12

Janusz Frackowiak, MD, PhD, Head

[email protected]

The goal of the research conducted in the Cellular Pathology Laboratory is identification of the pathomechanisms of developmental disabilities in Down syndrome and autism that could become targets of specific treatments. The pathomechanisms of altered brain development and functions that are studied in Down syndrome are those associated with the presence of three copies of the genes coding for amyloid-β precursor protein (APP), an evolutionally conserved protein with multiple functions, and DYRK1A, a kinase that regulates activities of numerous enzymes. The studies are concentrated on the mechanisms of accumulation of distinct APP fragments known as β-amyloid peptide (Aβ) species, and their biological effects. The experiments on pharmacological normalization of DYRK1A activity in cultured cells and animal models provide clues on strategies to normalize brain development.

Our research on autism focuses on the mechanisms and biological consequences of deposition of Aβ fragments in the brain. We found that accumulation of truncated Aβ in neurons leads to oxidative stress, which led us to propose the hypothesis of a self-enhancing pathological process in autism initiated in childhood by intraneuronal deposition of truncated Aβ. The responsible mechanisms are the subject of further studies, as they have the potential to become targets of treatment and prevention.

The research studies of the Cellular Pathology Laboratory apply human brain tissue obtained from the IBR Brain and Tissue Bank for Research in Developmental Disabilities and Aging, as well as cell culture models and transgenic mouse models. New research tools—monoclonal and polyclonal antibodies—are being developed and characterized in cooperation with the Humoral Immunology Laboratory.