Karen Duff, Ph.D.

Dept of Pathology and Cell Biology, Dept of Psychiatry, Taub Institute at Columbia University/ NYSPI, New York

Dr. Duff joined Columbia University with a joint appointment at the NYS Psychiatric Institute in 2006, and she currently holds appointments in the depts. of Pathology and Cell Biology, Psychiatry and the Taub Institute for research on Alzheimer’s, and the aging brain. In the last 20 years, Dr. Duff has genetically engineered several widely used mouse models for AD, tauopathies and synucleinopathies. These mice have been used in studies ranging from MRI and PET for diagnostics development, to proof-of-concept testing of therapeutic targets. Currently, her main interests are fourfold - studying how AD related pathology and dysfunction propagates though the brain and from cell to cell as the disease worsens; using multi-omics platforms (transcriptomics, lipidomics and metabolomics) to study the role of aging and inheritance of the AD risk variant APOE4 as an initiating factor in AD; the role and therapeutic potential of protein clearance pathways in tauopathies and the basis and manipulation of memory deficits using optogenetic and brain stimulation techniques. Dr. Duff received her Ph.D from Sydney Brenner’s dept at the University of Cambridge (UK) in 1991, then moved to London to work briefly with Alison Goate before moving to the US with John Hardy in 1992 to a position at the University of South Florida. In 1996, she moved her lab to the Mayo Clinic Florida and in 1998 to the Nathan Kline Institute/New York University. She has published over 140 peer reviewed papers and has received several awards, the most prestigious being the Potamkin Prize in 2006. 

Funded Research

Project Description Researchers Funding
Propagation of Tauopathy and Ubiquitin Proteasome System Dysfunction: Impact and Rescue with a UPS Activator

The brain of a patient with Alzheimer’s disease shows two abnormalities: clumps of a protein called amyloid into what is known as amyloid plaques, and clumps of a protein called tau into what is known as neurofibrillary tangles. One of the features of Alzheimer’s disease is that the tangles start in one part of the brain (areas involved in memory and learning), but they infect new regions and spread through the brain, contributing to the worsening of the disease.

Investigating the Mechanism of Entorhinal Cortex Hypermetabolism in APOE4 Targeted Replacement Mice

Carriers of the APOE4 gene are at significantly increased risk for developing Alzheimer’s disease. We have discovered that aging mice that express the APOE4 gene possess increased activity in a region of the brain that is implicated in the development of Alzheimer’s disease, and we think this increased activity may be an important link between APOE4 and Alzheimer’s disease pathology. In order to understand the cause of this increased brain activity, we will utilize sophisticated techniques to measure important genes and proteins known to increase brain activity.