Massachusetts General Hospital

Research Investigator Profile

Mark W. Albers, MD, PhD

• Assistant Professor of Neurology,
  Harvard Medical School
• Assistant in Neurology,
  Department of Neurology

Research Description

The goal of the research in the Albers lab is to elucidate the pathogenic actions and physiological functions of genes implicated in neurodegenerative disease. Our principal hypothesis is that these genes confer vulnerability to neurons by disrupting the integrity of neurons and neural circuits. The questions addressed by these studies intersect with fundamental questions in neuroscience, including how are connections in the nervous system formed, how are these connections modified by experience, and how is the communication across these connections disrupted by disease mechanisms. We address these issues in the peripheral olfactory neural circuit of the mouse and human, a circuit that is evolutionarily conserved. The mouse circuit is genetically tractable, and the human circuit is vulnerable to neurodegenerative disease. We combine novel mouse models that express pathogenic and normal isoforms of the human amyloid precursor protein solely in  a subset of olfactory neurons with multiphoton in vivo imaging, fluorescence activated cell sorting, deep sequencing, and other basic techniques of investigation. Examination of these lines has revealed miswiring of the olfactory neural circuit and profound changes in gene expression in neurons not expressing the disease gene, associated with accelerated neuronal turnover in vivo. A second focus of the laboratory is to elucidate the physiological function of these genes by generating and examining cell-specific knockouts of the gene family in specific classes of neurons in this circuit. We believe that some of the insights revealed in these investigations will provide clues to understanding the actions of these disease genes in other vulnerable, plastic circuits in the brain, such as the entorhinal cortex and the hippocampus.  Read more.