Francesca Cole, PhD

  • Recruited to: The University of Texas MD Anderson Cancer Center
  • Recruited from: Memorial Sloan-Kettering Cancer Center
  • Award: First-Time, Tenure-Track Faculty Member

Dr. Francesca Cole received her Ph.D. at The Mount Sinai School of Medicine of New York University and her postdoctoral training at Memorial Sloan-Kettering Cancer Center. In September 2012 she joined the Department of Molecular Carcinogenesis at The University of Texas MD Anderson Cancer Center at Science Park, Smithville.Her research focuses on mechanisms of homologous recombination in mammalian cells, with the goal of identifying targets for improved cancer therapies.

Dr. Cole started her scientific career as an undergraduate Sigma Xi Summer Research Fellow in the laboratory of D. Stave Kohtz at The Mount Sinai School of Medicine, where she studied factors regulating mouse and human muscle cell differentiation. She received her Ph.D. in 2004 under the mentorship of Robert S. Krauss and was supported by a Howard Hughes Medical Institute Predoctoral Fellowship. Dr. Cole’s doctoral research focused on the role of an Ig superfamily protein, CDO, in mammalian muscle development. This work led to the discovery that CDO promotes myogenic transcription factors by a unique mechanism that targets their obligate binding partners to favor formation of the active complex. She also generated two mutant alleles of Cdo in the mouse to discern that CDO promotes skeletal muscle development during embryogenesis. Intriguingly, mice lacking CDO showed the hallmark features of holoprosencephaly, a tragic and common developmental defect of midline designation in humans that is most often associated with mutation in Sonic hedgehog (SHH) pathway components. This work was the first to implicate that CDO acts to regulate the SHH pathway and laid the groundwork for pioneering studies identifying CDO and its related family member, BOC, as SHH co-receptors.

Dr. Cole’s training as a developmental biologist and work on developmental defects led to a strong interest in the mechanisms of chromosome segregation during meiosis, a specialized cell division program that generates haploid gametes. Errors in the repair of programmed DNA double-strand breaks – required for accurate chromosome segregation – lead to aneuploidies such as Down Syndrome and are a major cause of developmental disability in humans. For her postdoctoral research, supported by a Ruth L. Kirschstein National Research Service Award fellowship, Dr. Cole joined the laboratory of Maria Jasin at Memorial Sloan-Kettering Cancer Center to study mechanisms of DNA repair by homologous recombination in meiosis, defects in which lead to loss of genome integrity and cancer.

Using cytological and genetic analysis, Dr. Cole’s research revealed that mammals have a homeostatic mechanism capable of robustly buffering large cell-to-cell variability in early meiotic recombination events to suppress formation of aneuploid gametes. Overcoming the lack of molecular tools available to study mammalian recombination, Dr. Cole developed innovative technologies and systems to probe homologous recombination at an unprecedented level of resolution. This work now enables the sophisticated analysis of recombination within the complex mammalian genome, previously enjoyed only by more genetically tractable organisms such as budding yeast.

At the UT MD Anderson Cancer Center, Dr. Cole will take advantage of these new assay systems to mechanistically dissect the actions of homologous recombination pathways and their function in the protection and disruption of genome integrity. Ultimately, by determining how these pathways compensate and collaborate with one another, this work should lead to the identification of targets for improved cancer therapeutics.