Kyle Miller, PhD

  • Recruited to: The University of Texas at Austin
  • Recruited from: College of London
  • Award: First-Time, Tenure-Track Faculty Member

Dr. Kyle Miller received his PhD in 2004 from the University College London in the lab of Dr. Julia Cooper at the London Research Institute in London, U.K. He then joined the lab of Dr. David Toczyski in the Department of Biochemistry and Biophysics at the University of California, San Francisco, UCSF Helen Diller Family Comprehensive Cancer Center for his first postdoctoral training. At the end of 2006, Dr. Miller went to work in the lab of Professor Stephen Jackson, FRS, at the Wellcome Trust/Cancer Research UK Gurdon Insitute of Cancer and Developmental Biology at the University of Cambridge, U.K. for a second postdoctoral training. In August 2011, he became an Assistant Professor in the Department of Molecular Genetics and Microbiology and is a member of the Institute of Cellular and Molecular Biology at the University of Texas at Austin.

Dr. Miller’s scientific interests and goals are to understand the pathways that contribute to genome stability in eukaryotic cells. To this end, he studied telomeres and how they function in genome maintenance during his graduate studies. Telomeres define the ends of eukaryotic chromosomes and their preservation is one of the hallmarks of cancer. Using fission yeast as a model system, he discovered an unanticipated role for telomere binding proteins in promoting semi-conservative replication through telomeres. Using biochemical and genetic analysis, he found that replication forks often pause and break within telomere sequences and that, Taz1, a telomere binding protein, is required to promote replication fork progression through telomeres. These findings defined a novel function for telomere binding proteins that is conserved in human cells and is important for maintaining genomic stability and averting cancer.

As a postdoctoral researcher with David Toczyski at UCSF, he analyzed the role of histone deacetylases (HDACs) in the DNA damage response (DDR) in the model organism, budding yeast. His work revealed that certain HDACs are cell-cycle regulated and targets of the DNA-damage checkpoint. These enzymes regulate the chromatin, specifically the histone modification H3K56Ac, whose regulation is essential for maintaining genome stability and promoting DNA repair. Thus, the DDR functions to regulate chromatin through histone acetylations that participate in genome stability. This work also led to the discovery of the novel histone acetyltransferase enzyme responsible for H3K56Ac that also participates in genome maintenance in yeast.

After becoming interested in studying human cells, Dr. Miller joined the lab of Stephen Jackson at the University of Cambridge, England where his research was supported by the Wellcome Trust to study chromatin and cellular responses to DNA damage. His work revealed that certain histone modifications are important targets upon DNA damage in human cells. His work showed that specific HDAC enzymes function in the DDR by localizing to DNA damage, deacetylating certain histone marks that collectively, participate in orchestrating efficient DNA repair. Inhibitors of HDACs represent a large class of anticancer drugs that have radio-sensitizing effects in patients. These studies helped define a novel mechanism of action for these drugs.

At the University of Texas at Austin, Dr. Miller aims to continue his work on the relationship between chromatin and DNA repair in human cells using multifaceted and diverse approaches to explore how these cellular pathways maintain genome integrity. Understanding these pathways and how they are connected will hopefully help researchers gain important insights into the mechanisms of cancer therapeutic drugs that act at the chromatin and DNA level.