Diana Laird, PhD

Associate Professor
Department of Obstetrics Gynecology & Reproductive Sciences; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research
+1 415 476-5471
Research Overview: 

We are interested in heterogeneity, selection, and interactions with the environment at the cellular level. Our crucible is the developing germline, the precursors of the egg and sperm. We use quantitative imaging and genomic approaches in mouse models, naked mole rats, and human stem cells. Our work is motivated by solving infertility, reproductive aging, and understanding the effects of prenatal exposures to endocrine-disrupting chemicals and psychosocial stressors. Main research themes include:

The selection or elimination of germ cells during development. A small number of primordial germ cells established during early mammalian development supply all of the eggs or sperm for the reproductive lifespan. This process appears to be surprisingly inefficient, with germ cells lost at multiple steps: some fail to migrate through the embryo, some proliferate less, some fail to undergo differentiation, and many are eliminated by programmed cell death. In mice, we use lineage tracing together with single cell analysis to understand the clonal dynamics of primordial germ cells as they relate to behaviors such as migration, proliferation, differentiation and apoptosis. We ask parallel questions in humans using stem cells and organoids. Understanding the basis for success or failure of nascent germ cells and the relationship to quality of the resulting egg or sperm has important implications for birth defects and inherited diseases such as Fragile X, infertility, and for the increasingly realistic prospect of growing gametes in a dish.

Aging and the ovarian reserve. Female reproductive lifespan is determined by the number of non-growing eggs in her ovary as well as the rate of loss during growth. A critical social and health issue is predicting a woman’s remaining period of fertility, but current practices measure only maturing eggs rather than the most critical reserve population. Further, a link between ovary function and systemic health is suggested by the increased risk for many diseases of aging after menopause. For insight into fertility as well as the role of the ovary in aging, we are studying the establishment of the ovarian reserve during fetal life and its maintenance during adulthood. We are using mouse genetics, stem cells, as well as a rodent model of extreme aging, the naked mole rat, which is capable of reproducing for nearly 3 decades.

Epigenetics and Environment in germ cell development. Distinct from changes to the genetic code, epigenetic mechanisms are important for coordinating rapid cell fate changes, particularly in periods of transcriptional quiescence or meiosis and meiotic arrest. As germ cell development also involves resetting of epigenetic marks as a way to wipe the slate clean for the next generation, interference with this process can potentially wield effects across generations. A current project in the lab concerns the effects of common chemicals and prenatal stress on developing germ cells and their ‘memories’ of exposures.
 

Primary Thematic Area: 
Developmental & Stem Cell Biology
Secondary Thematic Area: 
Cancer Biology & Cell Signaling
Research Summary: 
Genetic and environmental mechanisms of germline development

Websites

Featured Publications: 

Heterogeneity of transposon expression and activation of the repressive network in human fetal germ cells.

Development (Cambridge, England)

Reznik B, Cincotta SA, Jaszczak RG, Mateo LJ, Shen J, Cao M, Baskin L, Ye P, An W, Laird DJ

Heterogeneity of primordial germ cells.

Current topics in developmental biology

Nguyen DH, Jaszczak RG, Laird DJ