Bruce Yankner, M.D., Ph.D.


Professor of Genetics and Neurology

Harvard Medical School
Dept. of Pathology, NRB-858C
77 Avenue Louis Pasteur
Boston, MA 02115
Tel: 617-432-6800
Fax: 617-432-6825
Email: bruce_yankner@hms.harvard.edu
Visit my lab page here.




The overall goal of our research is to achieve a greater understanding of the molecular basis of brain aging and how normal aging transitions to pathological aging, giving rise to neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease.

The ongoing projects fall into 2 major areas: 1) The role of DNA damage and altered gene expression in the aging process, and in particular the aging of the brain; and 2. Biological and pathological functions of genes that cause Alzheimer’s and Parkinson’s disease.

Our laboratory investigates the systems biology of the aging human brain by defining transcriptional changes and sites of age-related DNA damage on a genome-wide scale, and by modeling aspects of these processes in cultured cells and mice. Four related studies are ongoing: 1. We have developed a method for generating genomic maps that locate sites of DNA damage across entire chromosomes. By generating these maps, we can then ask: Is there a relationship between sites of DNA damage and changes in the expression of specific genes during aging? And does this relationship change in the genomes of individuals with cognitive decline, both at early stages and at the more severe stage we call Alzheimer’s disease? By analyzing genomes of individuals who had rigorous cognitive function testing, we hope to achieve a greater understanding of age-related cognitive decline. 2. Why are some individuals able to live past 100 and remain cognitively intact? The molecular basis of extreme longevity in the human population is poorly understood. To address this intriguing issue, we have also taken a systems biology approach by generating transcriptional profiles and DNA damage maps from individuals who lived to be greater than 100 years of age. 3. Can we model human aging in mice? To begin to address this question, we are studying gene knockout mouse models with genomic instability to determine whether they recapitulate aspects of normal brain aging. 4. Only aging humans develop the pathology of Alzheimer’s disease, raising the question of what is unique about the aging human brain. To obtain greater insight into the evolution of the aging process, we are identifying the age-regulated genes in several mammalian species ranging from mouse to man.

A complementary area of interest is how known genetic causes of Alzheimer’s and Parkinson’s disease relate to mechanisms of aging. Previous work from this laboratory showed that the amyloid precursor protein (APP) and presenilins, which are involved in Alzheimer’s disease, and alpha synuclein, which is involved Parkinson’s disease, participate in signal transduction pathways that affect neuronal vulnerability. Ongoing studies are focused on understanding the normal biological functions of these proteins and how they cause disease in the setting of an aging brain.

The studies in this laboratory frequently involve interdisciplinary approaches with collaborations between computational biologists, molecular biologists and neurobiologists, both within the lab and with other labs. The methodology ranges from molecular interaction and signaling studies in cultured cells to the analysis of genetically engineered mice and the human brain.


For a complete listing of publications click here.



Last Update: 10/30/2013