The research interests of Zhenkun Lou, Ph.D., center on the DNA damage response pathway, which is critical for maintaining genomic stability. Dysfunction of this pathway results in genomic instability and cancer predisposition. Therefore, many components of the DNA damage response pathway are identified as tumor suppressors. By focusing on several key regulators in this pathway and using biochemical and genetic approaches, Dr. Lou attempts to elucidate the roles of this DNA damage pathway in tumorigenesis.
Dr. Lou's research team is also interested in molecular mechanisms of aging. The team uses biochemical and genetic approaches to investigate the cellular function and regulation of specific proteins that regulate longevity.
Regulators in the DNA damage response pathway. Similar to mitogenic signaling pathways, the DNA damage-induced signaling pathway consists of kinase-dependent signaling cascades that regulate cell cycle progression, DNA repair and apoptosis following DNA damage, collectively called the DNA damage response pathway.
Ataxia telangiectasia mutated (ATM) protein and ataxia telangiectasia-related (ATR) protein are upstream kinases in this DNA damage response pathway. ATM and ATR activate the downstream checkpoint kinases Chk1 and Chk2 (Cds1). These four protein kinases, with the help of mediator proteins, phosphorylate a number of downstream effector proteins, including tumor suppressors p53 and BRCA1. Dr. Lou studies the role of each of these regulators in the DNA damage response pathway.
- Molecular mechanisms of aging. The Sir2 family of protein deacetylases has been shown to regulate longevity in multiple organisms. Overexpression or activation of SIR2 results in extended life span in yeast, Caenorhabditis elegans and drosophila. Dr. Lou is investigating the cellular function and regulation of the mammalian ortholog of SIR2, SIRT1.
Significance to patient care
Dr. Lou is working to improve understanding of the causes and mechanisms of aging and tumor development, thereby contributing to strategies for cancer prevention as well as better methods for diagnosis and treatment.