Doris Kretzschmar Lab

Doris Kretzschmar Lab March 2019
Kretzschmar lab group, L to R: Doris Kretzschmar, Dani Long, Alex Law (Mar 2019)

Research interests

The focus of Dr. Kretzschmar’s work is to identify genetic factors and mechanisms that lead to progressive degeneration of the adult nervous system using Drosophila as a model for human diseases.

Current projects

Currently, we are focusing on Alzheimer’s disease (AD) using transgenic flies that express the Amyloid Precursor Protein or Tau, which are both key factors in the pathogenesis of AD. We are using these flies to study the toxic function of these proteins and to identify genes and genetic pathways that interfere with their toxicity. In one project, we investigate the functions of the different fragments generated from the Amyloid Precursor Protein and the consequences changes in their production has for the nervous system. In another project, we investigate effects that are caused by the loss or mutation of Tau, a microtubule-associated protein that is accumulating in the neurofibrillary tangles found in AD patients but also in other neurodegenerative diseases.

Amyloid Precursor Protein Localization
Confocal image showing the localization of the Amyloid Precursor Protein and its proteolytic fragments (with green and red fluorescence tags at both ends) within an intact Drosophila brain.
wild type fly and a transgenic fly
Brain sections from a wild type fly and a transgenic fly expressing human Tau with a disease-associated mutation. In contrast to wild type, vacuoles, revealing cell death, have formed in these flies (arrows).

Postdoctoral researcher

Dani Long, PhD
Dani Long, PhD

Sleep and other circadian disruptions occur during normal aging but are also a hallmark of several neurodegenerative diseases, including Alzheimer’s Disease (AD). It was originally assumed that this may be a side effect of AD however, circadian disruptions can be detected very early in the disease and recently it has been suggested that they may actively contribute to AD. Although many studies have correlated circadian disruptions with memory decline and AD, how they are functionally linked remains elusive. We are therefore investigating how proteins involved in AD may cause circadian disruptions using the Drosophila model. We are focusing on the Amyloid Precursor Protein (APP) and the fragments that are produced from it, which include the Amyloid ß fragment that accumulates in the plaques that are characteristic for AD. We are testing whether APP is found in the master clock neurons that regulate circadian rhythms and that are responsible for synchronizing the rhythms in clocks found throughout the body and we are investigating how disease-associated changes in APP affect these neurons.

email Dani