Diana Laird, PhD

Professor
Department of Obstetrics Gynecology & Reproductive Sciences
+1 415 476-5471

Germ cells have the unique property of being dispensable for survival of the individual yet essential for the species. The germline is established during early development as a small population of primordial germ cells that give rise to the adult gametes following sex differentiation during late fetal life. This segregation from somatic lineages for all but the very first cell divisions in the embryo places an evolutionary premium on the germline.  Study of the fetal germline provides a window into the fundamental mechanisms of pluripotency as well as cell fate decisions, migration, and natural selection. In further, the roots of conditions such as infertility and chromosomal abnormalities can be found in fetal germ cell development. We are using mouse models in the following areas:

  1. Primordial germ cell migration: How and why do germ cells migrate? Is migration perfunctory, or does it serve as a filter for fitness? We are studying the role of the non-canonical Wnt pathway in primordial germ cell migration as well as interrogating the role of the niche.
  2. Clonal dynamics of germ cell development: Do all primordial germ cells contribute equally to the pool of gametes? How does migration as well as the developmentally programmed wave of apoptosis affect the clonal composition of the germline? We are using genetic lineage tracing and mouse mutants to understand the basis of germ cell selection and elimination during development.
  3. Environmental influences on germ cell development: Do germ cells carry memories of their environment to the next generation? Studies in animals suggest that nutritional information or chemical exposures during development can wield transgenerational changes through epigenetic mechanisms. We are studying the effects of common plasticizing agents on fetal germ cell development and epigenetic reprogramming.
  4. Quantitative imaging and mathematical modeling: We develop methods for imaging whole organs, embryos and cells. Our research increasingly calls for more sophisticated algorithms for quantifying structures, tissue organization and phenotypes.
Research Summary: 
Genetic and environmental mechanisms of germline development
Mentorship Development: 

4/30/20    Mental Health in a Pandemic: Q&A for Faculty
5/26/20    Effective Strategies for IDPs for Partial Resumption of Lab Research
11/10/20    Optimizing the Efficiency of Your Lab

Websites

Publications: 

Iterative oxidation by TET1 is required for reprogramming of imprinting control regions and patterning of mouse sperm hypomethylated regions.

Developmental cell

Prasasya RD, Caldwell BA, Liu Z, Wu S, Leu NA, Fowler JM, Cincotta SA, Laird DJ, Kohli RM, Bartolomei MS

Differential susceptibility of male and female germ cells to glucocorticoid-mediated signaling.

eLife

Steven A Cincotta, Nainoa Richardson, Mariko H Foecke, Diana J Laird

Differential susceptibility of male and female germ cells to glucocorticoid-mediated signaling.

bioRxiv : the preprint server for biology

Cincotta SA, Richardson N, Foecke MH, Laird DJ

Transcriptional repression upon S phase entry protects genome integrity in pluripotent cells.

Nature structural & molecular biology

Gökbuget D, Lenshoek K, Boileau RM, Bayerl J, Huang H, Wiita AP, Laird DJ, Blelloch R

Generation of Schwann cell derived melanocytes from hPSCs identifies pro-metastatic factors in melanoma.

bioRxiv : the preprint server for biology

Samuel RM, Navickas A, Maynard A, Gaylord EA, Garcia K, Bhat S, Majd H, Richter MN, Elder N, Le D, Nguyen P, Shibata B, Llabata ML, Selleri L, Laird DJ, Darmanis S, Goodarzi H, Fattahi F

Postnatal oogenesis leads to an exceptionally large ovarian reserve in naked mole-rats.

Nature communications

Brie?o-Enr?quez MA, Faykoo-Martinez M, Goben M, Grenier JK, McGrath A, Prado AM, Sinopoli J, Wagner K, Walsh PT, Lopa SH, Laird DJ, Cohen PE, Wilson MD, Holmes MM, Place NJ

TET1 Catalytic Activity is Required for Reprogramming of Imprinting Control Regions and Patterning of Sperm-Specific Hypomethylated Regions.

bioRxiv : the preprint server for biology

Prasasya RD, Caldwell BA, Liu Z, Wu S, Leu NA, Fowler JM, Cincotta SA, Laird DJ, Kohli RM, Bartolomei MS

A Roadmap for Three-Dimensional Analysis of the Intact Mouse Ovary.

Methods in molecular biology (Clifton, N.J.)

Soygur B, Foecke MH, Gaylord EA, Fries A, Li J, Arora R, Laird DJ

Ovary Development: Insights From a Three-Dimensional Imaging Revolution.

Frontiers in cell and developmental biology

Soygur B, Laird DJ

Apoptosis in the fetal testis eliminates developmentally defective germ cell clones.

Nature cell biology

Nguyen DH, Soygur B, Peng SP, Malki S, Hu G, Laird DJ

MON-LB130 Glucocorticoid Receptor Signaling and Stress in the Developing Mammalian Germline.

Journal of the Endocrine Society

Steven Anthony Cincotta, Diana Laird

The UCSF Mouse Inventory Database Application, an Open Source Web App for Sharing Mutant Mice within a Research Community.

G3 (Bethesda, Md.)

Wall E, Scoles J, Joo A, Klein O, Quinonez C, Bush JO, Martin GR, Laird DJ

Maternal vitamin C regulates reprogramming of DNA methylation and germline development.

Nature

DiTroia SP, Percharde M, Guerquin MJ, Wall E, Collignon E, Ebata KT, Mesh K, Mahesula S, Agathocleous M, Laird DJ, Livera G, Ramalho-Santos M

Heterogeneity of primordial germ cells.

Current topics in developmental biology

Nguyen DH, Jaszczak RG, Laird DJ

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

Kinesin superfamily protein Kif26b links Wnt5a-Ror signaling to the control of cell and tissue behaviors in vertebrates.

eLife

Susman MW, Karuna EP, Kunz RC, Gujral TS, Cantú AV, Choi SS, Jong BY, Okada K, Scales MK, Hum J, Hu LS, Kirschner MW, Nishinakamura R, Yamada S, Laird DJ, Jao LE, Gygi SP, Greenberg ME, Ho HH

Smad4 regulates growth plate matrix production and chondrocyte polarity.

Biology open

Whitaker AT, Berthet E, Cantu A, Laird DJ, Alliston T

Patterning of sharp cellular interfaces with a reconfigurable elastic substrate.

Integrative biology : quantitative biosciences from nano to macro

Curtis A, Li DJ, DeVeale B, Onishi K, Kim MY, Blelloch R, Laird DJ, Hui EE

Insights from imaging the implanting embryo and the uterine environment in three dimensions.

Development (Cambridge, England)

Arora R, Fries A, Oelerich K, Marchuk K, Sabeur K, Giudice LC, Laird DJ

ROR2 in the adult mouse testis.

Molecular reproduction and development

Arora R, Laird DJ

Meiotic onset is reliant on spatial distribution but independent of germ cell number in the mouse ovary.

Journal of cell science

Arora R, Abby E, Ross AD, Cantu AV, Kissner MD, Castro V, Ho HY, Livera G, Laird DJ

A miR-372/let-7 Axis Regulates Human Germ Versus Somatic Cell Fates.

Stem cells (Dayton, Ohio)

Tran ND, Kissner M, Subramanyam D, Parchem RJ, Laird DJ, Blelloch RH

DAZL and CPEB1 regulate mRNA translation synergistically during oocyte maturation.

Journal of cell science

Sousa Martins JP, Liu X, Oke A, Arora R, Franciosi F, Viville S, Laird DJ, Fung JC, Conti M

Cryopreservation and recovery of human endometrial epithelial cells with high viability, purity, and functional fidelity.

Fertility and sterility

Chen JC, Hoffman JR, Arora R, Perrone LA, Gonzalez-Gomez CJ, Vo KC, Laird DJ, Irwin JC, Giudice LC

Follicle dynamics and global organization in the intact mouse ovary.

Developmental biology

Faire M, Skillern A, Arora R, Nguyen DH, Wang J, Chamberlain C, German MS, Fung JC, Laird DJ

Novel domains of expression for orphan receptor tyrosine kinase Ror2 in the human and mouse reproductive system.

Developmental dynamics : an official publication of the American Association of Anatomists

Arora R, Altman E, Tran ND, Laird DJ

Wnt and Bmp fit germ cells to a T.

Developmental cell

Cantú AV, Laird DJ

Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells.

Nature

Blaschke K, Ebata KT, Karimi MM, Zepeda-Martínez JA, Goyal P, Mahapatra S, Tam A, Laird DJ, Hirst M, Rao A, Lorincz MC, Ramalho-Santos M

Ror2 enhances polarity and directional migration of primordial germ cells.

PLoS genetics

Laird DJ, Altshuler-Keylin S, Kissner MD, Zhou X, Anderson KV

Induced pluripotent stem cell-derived hepatocytes have the functional and proliferative capabilities needed for liver regeneration in mice.

The Journal of clinical investigation

Espejel S, Roll GR, McLaughlin KJ, Lee AY, Zhang JY, Laird DJ, Okita K, Yamanaka S, Willenbring H

Identification of a novel gene involved in asexual organogenesis in the budding ascidian Botryllus schlosseri.

Developmental dynamics : an official publication of the American Association of Anatomists

Laird DJ, Chang WT, Weissman IL, Lauzon RJ

Continuous development precludes radioprotection in a colonial ascidian.

Developmental and comparative immunology

Laird DJ, Weissman IL

50 million years of chordate evolution: seeking the origins of adaptive immunity.

Proceedings of the National Academy of Sciences of the United States of America

Laird DJ, De Tomaso AW, Cooper MD, Weissman IL