Michael Dyer Lab

As progenitor cells exit the cell cycle and differentiate, thousands of genes turn on and off in precisely orchestrated programs. Changes in chromatin structure and genome accessibility accompany those changes in gene expression. Many in the field studied chromatin modifications in embryonic stem cells or cancer cell lines because they are tractable and scalable experimental systems with extensive reference databases. Instead of pursuing this established area of study, we chose to focus on patient tumors and normal-developing human and murine retinae.

The unique research environment at St. Jude allows us to invest the time and effort to overcome the technical hurdles required to develop a map of the chromatin landscape during retinogenesis and in childhood cancers such as retinoblastoma. That investment now yields important new insights into the biology of retinal development and disease.

As retinal cells differentiate, they must maintain a group of genes in a state of readiness to turn on at a moment’s notice in response to stress, injury or disease. In mammals, retinal neurons do not regenerate, so they must maintain this state of readiness over their lifetime. The remarkable feature of those rapid-response genes is that they are not normally expressed during retinal development, nor are they required for cellular homeostasis. In normal healthy individuals, they may never activate.

However, if the neurons encounter changes in their environment, toxins, or disease-related stressors, they rapidly activate those transcriptional programs. The particular way that individual cells organize their chromatin during development to respond to stress, injury, or disease later in life is a concept we call cellular pliancy. Looking ahead, we are excited about the new opportunities to manipulate the chromatin landscape in order to alter cellular pliancy in vivo and to visualize the changes in response of individual neurons to stress, injury, or disease.

Our studies on retinal development and disease give us a deep appreciation of the interplay between normal developmental processes and childhood cancer. We extend our studies to include diverse pediatric solid tumors, such as neuroblastoma, osteosarcoma, rhabdomyosarcoma, Ewing sarcoma, and others. Recently, we discovered individual tumor cells can transition through their normal developmental hierarchy, but the process attenuates. These developmental transitions are important because they contribute to disease recurrence after treatment. 

In all our efforts, our lab strives to connect the science to the patient. To achieve this, our diverse and inclusive team of experts guide our multidisciplinary approach. Our diversity drives discovery at every level, and we take pride in this strategy.