Department of Cell Biology

Carl Schildkraut, PhD

carl01 


Professor, Department of Cell Biology
Chanin Bldg., Room 416
718.430.2097

carl.schildkraut@einsteinmed.org

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The Centromere and alpha satellite DNA and the tau protein
Genomic Instability
Initiation Of DNA Replication
Study Replication Initiation and Fork Progression
Recent Publications 
Biosketch 
Lab Members 
Collaborators
 

  

Our laboratory is a part of the Institute for Aging Research, the Einstein Stem Cell Institute Center and the Cancer Center.

A major interest of our lab is the organization and regulation of the DNA replication program in mammalian cells and its effect on gene expression. One area we have been concentrating on the role of DNA replication in neuronal diseases such as Alzheimer's. Alzheimer’s disease (AD) is a neuro-degenerative disease that has been studied for more than three decades. Surprisingly after all this effort, there is still no unequivocal treatment and the cause is not known.

We are also focused on understanding the role of genomic instability at human chromosomal fragile sites in cancer and aging.

Genome instability occurs in the early development of many cancers and other diseases and is thought to be caused by replication fork stalling. This is clinically relevant since most current cancer therapies are based on radiation or chemotherapeutic agents that stall or block forks. Manipulating cellular responses to fork stalling may therefore prove crucial in improving effectiveness of current chemotherapies.

Long-term interests:

• Difficult to replicate regions accumulate secondary structures which, if not properly resolved, may block DNA replication fork movement and lead to genome instability. We are studying mechanisms to resolve these barriers for efficient and faithful DNA replication.
• The role of DNA replication of genes involved in neurological diseases such as Alzheimer's. We will examine critical genes in the brain that undergo mutations with aging.
• Genome protection by telomeres.
• Regulation and reprogramming of DNA replication of human embryonic stem (ES) cells and induced pluripotent stem cells (iPS).
• Mechanisms leading to breaks at sites that result in chromosomal rearrangements frequently detected in cancer cells.

Current projects include a wide range of interests:

• The replication of two repeated sequence DNAs that are involved in Alzheimer's disease: alpha satellite DNA and the ribosomal DNA genes .
• The DNA2 nuclease/helicase can cleave G-quadruplex structures which are one of the most common non-B structures present in DNA. We study the effect on the deletion of DNA2 on DNA replication.
• Replication of the alpha satellite DNA at centromeres of specific human chromosomes. These include chromosome 21 and the Y chromosome. The Y chromosome is lost with aging and we are studying the replication of this chromosome to understand more about this loss. Chr 21 undergoes trisomy in Down syndrome and people with Down syndrome have a higher risk of getting Alzheimer's symptoms.
 

 
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