Description:

The Department of Biochemistry and Molecular Genetics Departmental Seminar Series presents:

Michael Dyer, PhD
Investigator, HHMI
Richard C. Shadyac Endowed Chair in Pediatric Cancer Research
Member, Department of Developmental Neurobiology
Co-Leader, Developmental Biology and Solid Tumor Progression
Head, Division of Developmental Biology

My lab is interested in understanding how proliferation and differentiation are coordinated in the developing retina and how those processes become uncoupled in retinoblastoma. Recently, we made a discovery that has fundamentally altered our understanding of the molecular and cellular mechanisms of retinal development and may also have a major impact on efforts to restore vision in some patients with retinal degeneration. We discovered that individual retinoblastoma tumor cells express multiple developmental programs simultaneously. This occurs through deregulation of the epigenetic programs that are directly or indirectly regulated by the RB1 protein. To explore this finding further, we developed a novel experimental system to quantify the epigenetic reprogramming of individual retinal neurons by using 4 factors (Oct4, Klf4, Sox2, and Myc) and somatic cell nuclear transfer. We discovered that the epigenetic barriers to reprogramming dramatically differ across retinal cell types, and they are developmental stage–specific. Moreover, we have used a 3-dimensional culture system to show for the first time that mouse iPSCs can form the optic cup and differentiated retinae. One of the most exciting results from these experiments is that our iPSC lines derived from retinal neurons are more efficient at differentiate into laminated retinae than fibroblast derived iPSCs or embryonic stem cells. Our current research is focused on elucidating the underlying molecular mechanisms that contribute to this epigenetic memory of retinal derived iPSCs. It may also provide crucial preclinical data on the use of retinal-derived iPSCs for future clinical trials of photoreceptor-replacement therapy to treat retinal degeneration.