Renee A. Reijo Pera, Ph.D.

Current Research Interests

Our laboratory is focused on three inter-related areas of research: 1) Understanding early decisions in human development, 2) examining genetic and epigenetic requirements for formation of the germ cells that give rise to each generation, and 3) understanding the basis for sporadic diseases such as Parkinson's Disease that may be linked to complex genetic and/or epigenetic and developmental errors.

Human embryo development begins with the fusion of egg and sperm, a remodeling of the maternal and paternal pronuclei and a series of cleavage divisions. Subsequently, on Day 3, the embryonic genome is activated and the stage is set for a series of cell fate decisions that lead to formation of the distinct tissues of the blastocyst, the primary germ layers and the germ cell lineage. Our recent findings indicate that human embryo development is characterized by a complex pattern of gene expression with the vast majority of genes that are modulated being down-regulated. Moreover, we observed that the majority of genes that are expressed in early human preimplantation development are of unknown function/identity. Thus, to probe function, we developed the tools necessary to examine one of the earliest decisions in human embryo development, namely the allocation of cells to the germ cell lineage. We have found that both human embryonic stem cells and human adult- and fetal-derived induced pluripotent stem cells can form both primordial germ cells and meiotic germ cells. Moreover, the use of hESCs and iPSCs allows the genetic dissection of human germ cell and somatic cell formation; we have found that a family of translational factors regulates germ cell formation, maintenance and differentiation.

Our understanding of the origins of common sporadic or idiopathic diseases in the human population is very limited. Often, genetically-defined etiologies represent a small subpopulation of affected individuals. Our long term goal is to combine modern technologies of human genetics and epigenetics, human embryology, stem cell biology and neurobiology, through a unique group of collaborators, in order to understand the etiology of sporadic PD. Our hypothesis is that we can distinguish sporadic PD that is genetically-based (hard-wired) from that which is epigenetic in origins (able to be erased), prior to transplantation of iPSC-derived neurons, based on recapitulation of cardinal features of PD in vitro following reprogramming. This hypothesis allows us to address a larger concept for long-term study and that is whether embryonic epigenetic errors that are observed at human imprinted loci are just a visible subset of a much larger set of errors that can present as common sporadic neurodegenerative disorders that arise later in life. We chose to focus on PD because of a unique set of observations that we believe makes PD ideal for inquiries into sporadic disease, in general, and neurodegenerative disease specifically.