Jessica Tyler, PhD
Dr. Jessica Tyler is a molecular biologist who uses a wide array of technical approaches to uncover how packaging of our genetic material into chromosomes influences normal cellular functions and how their dysfunction leads to cancer and aging. She was recruited from the University of Colorado School of Medicine in May 2010 to the Department of Biochemistry and Molecular Biology at The University of Texas MD Anderson Cancer Center at Houston.
Dr. Tyler, born in England in 1969, always had a fascination for molecules, leading her to pursue her Bachelors Degree in Biochemistry at the University of Sheffield. She graduated in 1990 with a first class honors degree and the Hans Krebs Prize in Biochemistry. Having performed her undergraduate research on transcriptional regulation, she was fascinated to learn more and performed her PhD studies on a herpes virus transcriptional activator at the MRC Virology Unit in Glasgow, mentored by Dr. Roger Everett. In 1994, she moved to work with Dr. James Kadonaga the University of California San Diego to explore how chromatin structure regulates transcription. While there, she identified the key chromatin assembly factors Chromatin Assembly Factor 1 (CAF-1) and Anti-silencing Function 1 (Asf1) from Drosophila. In 2000, Dr. Tyler and her husband moved to Denver for faculty positions in the Department of Biochemistry and Molecular Genetics at the University of Colorado School of Medicine. While in Denver, they were very successful both professionally and personally – they have 5 year old triplets.
Her research focuses on understanding how all the fundamental activities of the Eukaryotic genome, including DNA repair, gene expression, and DNA replication are tightly regulated by packaging the DNA together with histones into chromatin and by dynamic alterations to this chromatin structure. Dr. Tyler utilizes her expertise to discover novel ways in which the chromatin structure is altered during gene expression and double-strand DNA repair, and to understand how these chromatin dynamics regulate these key nuclear processes. For example, her group discovered that histones are acetylated and then deacetylated during the process of double-strand DNA repair via homologous recombination. They also discovered that chromatin is reassembled following double-strand DNA repair and that this is essential for survival after DNA repair. Their molecular structure of a histone chaperone bound to histones was paradigm shifting for our understanding of how chromatin is assembled and disassembled. Dr. Tyler’s group has also uncovered novel mechanisms of transcriptional regulation, whereby the removal of histones from promoter regions is essential for transcriptional activation, while the replacement of histones onto promoter regions is essential for transcriptional repression.
Her studies use a combination of molecular genetic in budding yeast, tissue culture studies, biochemistry, biophysics and structural approaches. The proteins and processes that they study are so highly conserved through eukaryotic evolution, that what they learn in the highly genetically malleable yeast system is directly relevant to the situation in humans. As such, they are uniquely able to gain rapid insight into their research problem in budding yeast, and use their findings to inform their analyses in higher eukaryotic organisms. The success of this approach is apparent from their recent discovery of novel post-translational modifications or “epigenetic marks” on human histone proteins that are linked to cancer. Her research achievements were funded by multiple grants from the National Institutes of Health. Dr. Tyler was a Leukemia and Lymphoma Society Scholar from 2003-2008 and was awarded the prestigious Charlotte Friend Woman in Cancer Research Award for 2009 from the American Association of Cancer Research. She was also the Program Leader for the Molecular Oncology Program of the University of Colorado Cancer Center. In 2009 she was promoted to full professor and in 2010 she was awarded the Tenovus medal in Biology.
Now that she has moved to The University of Texas MD Anderson Cancer Center as a CPRIT rising star, Dr. Tyler’s goal is define how the novel chromatin changes that her group has uncovered actually occur in the cell and the molecular mechanisms by which they regulate normal gene expression patterns, double-strand DNA repair and cell survival after DNA repair. Understanding these processes should identify novel targets for therapeutic intervention. In addition to learning how chromatin regulates fundamental processes in the cell, their studies will help us to understand how defects in the chromatin structure lead to gene dysfunction and genomic instability, in turn causing cancer and leukemia. For example, they have recently uncovered a novel way to dramatically extend the lifespan and healthspan of budding yeast by altering the chromatin structure, and would like to apply this discovery to mammals given that age is the highest risk factor for most cancers.