Ph.D. (1997-2003) – University of Western Ontario, Dept. of Physiology & Pharmacology; Supervised by Dr. Andrew Watson, with a focus on mammalian preimplantation development.
Post-doctoral training (2003-2008) - University of Calgary, Dept. of Biochemistry and Molecular Biology; Supervised by Dr. Jay Cross, with a focus on placental development.
Assistant Professor (2008-2013) - University of Calgary, Faculty of Medicine, Dept. of Comparative Biology & Experimental Medicine with a focus on trophoblast stem cell biology and placental development. Funding support from CIHR; NIH/NICHD
Assistant Professor (2013-2019) - University of California San Diego, Faculty of Health Sciences, Dept. of Obstetrics, Gynecology & Reproductive Sciences with a focus on trophoblast stem cell biology and placental development in the context of placental insufficiency. Funding support from CIHR; NIH/NICHD; UCSD/UCLA Diabetes Research Center
Our laboratory investigates the development of the placenta in pregnancies that result in fetal growth restriction, many of which are complicated by maternal disease, such as pre-eclampsia or diabetes or by maternal exposure to substances, such as marijuana. We study placenta-specific trophoblast cells from their stem cell state, through differentiation as well as their interactions with other placental cell types. Our use of mouse/rat in vivo and in vitro models of fetal growth restriction as well as a collaboration with the human placenta group allows us to focus on how trophoblast populations and/or their interactions are altered in the compromised placental environment.
Stress-mediated trophoblast proliferation: adaptation or pathology? For many pregnancies, there are few effective ways to treat placental diseases that result in fetal demise, poor fetal outcome and/or increased risk of fetal programing of adult onset disease. Poor placental function is a contributing cause of pregnancy related diseases, and despite decades of research there is limited understanding of how the basic biological processes involved in placental development fail. Aberrant trophoblast cell proliferation and differentiation have been considered responsible. Although persistent proliferation of trophoblast cells occurs throughout gestation in both the human and mouse placentae, human Trophoblast Stem (TS) cells, which have just recently been identified, are not thought to persist beyond early development. This leaves a gap in our understanding of the mechanisms that support placental homeostasis and regenerative potential, later in pregnancy. Mouse TS cells are better characterized and have been used as an investigational model of the molecular mechanisms supporting trophoblast proliferation and differentiation. In many organs, tissue-specific stem/progenitor cells underlie homeostasis and provide an ability to adapt to stress and injury. Our lab identified increased trophoblast proliferation and expression of the TS marker, Eomes, beyond early development and have found a population of proliferative, multipotent TS-like cells using Sca-1 as a cell surface marker, in the late gestation mouse placenta. Our governing hypothesis is that placental stress confers proliferative potential to a sub-population of trophoblast, and we propose this population is critical to fetal health. The objectives of this project are to use genetic and genomic techniques to study persistent TS and Sca-1+ trophoblast populations in the context of placental insufficiency and assess whether they provide the mouse placenta an adaptive mechanism. We will investigate the function of Sca-1(Ly6A) in mouse trophoblast to provide insight into the adaptive response. Additionally, we will compare the transcriptomes of mouse TS to the novel human TS cells. Ultimately, our work will determine the regenerative capacity of the placenta and aid in identifying the role human TS cells in this process. Funded by NIH/NICHD; 2019-2024
Prospective Research Students:
For inquires regarding research in the Natale Lab, please email both Dr. David Natale at firstname.lastname@example.org and our research associate Bryony Natale at email@example.com. We are currently seeking 499 students and Graduate students to join our lab.
- Albers RE, Kaufman M, Natale BV, Keoni C, Kulkarni-Datar K, Min S, Natale DRC* and Brown TL*. Trophoblast-Specific Expression of HIF-1a Results in Preeclampsia-like Symptoms and Fetal Growth Restriction. (2019) Scientific Reports, 9(1):2742. PMID: 30808910 * corresponding, co-senior authors.
- Llurba OE, Xiao E, Natale DR, Fisher SA. Oxygen and lack of oxygen in fetal and placental development, feto-placental coupling and congenital heart defects. (2018). Birth Defects Res Dec 1;110(20):1517-1530. doi: 10.1002/bdr2.1430. PMID: 30576091
- Natale BV, Mehta P, Vu P, Schweitzer C, Gustin K, Kotadia R, Natale DRC. Reduced Uteroplacental Perfusion Pressure (RUPP) causes altered trophoblast differentiation and pericyte reduction in the mouse placenta labyrinth. (2018) Scientific Reports, 8(1):17162. PMID 30464252
- Natale BV and Natale DRC. Placentation in the mouse. (2018). Encycolpedia of Reproduction, 2nd edition, Volume 2; (eds. Tom Spencer and Jodi Flaws) p440-447. Elsevier. ISBN 9780128118993
- Langford M, Outhwaite JE, Hughes M, Natale DRC and Simmons DG. Deletion of the Syncytin A receptor Ly6e impairs syncytiotrophoblast fusion and placental morphogenesis causing embryonic lethality in mice. (2018) Scientific Reports, 8 (1): doi:10.1038/s41598-018-22040-2
- Soncin F, Khater M, To C, Pizzo D, Farah O, Wakeland A, Rajan KAN, Nelson KK, Chang CW, Moretto-Zita M, Natale DR, Laurent LC and Parast MM. Comparative analysis of mouse placentae across gestation reveals species-specific regulators of placental development. (2018). Development Jan 22. [Epub ahead of print]. PMID:29361559
- Natale BV, Schweitzer C, Hughes M, Globisch MA, Kotadia R, Tremblay E, Vu P, Cross JC, Natale DRC. Sca-1 identifies a trophoblast population with multipotent potential in the mid-gestation mouse placenta. (2017). Scientific Reports July 17;7(1):5575. Doi: 10.1038/s441598-017-06008-2. PMID: 28717241.
- Min S, Natale BV and Natale DRC. Temporal and Spatial Expression of Glyceraldehyde 3-Phosphate Dehydrogenase (Gapdh) in the Mouse Placenta. (2017). Placenta, September 57:170-74. DOI: http://dx.doi.org/10.1016/j.placenta.2017.06.343.
- Kenchegowda D, Natale B, Lemus MA, Steven A. Fisher* and Natale DR*. Inactivation of maternal HIF-1α at mid-pregnancy causes placental defects and deficits in oxygen delivery to the fetal organs under hypoxic stress. (2017). Developmental Biology Feb 15;422(2):171-185. doi: 10.1016/j.ydbio.2016.12.013. Epub 2016 Dec 9. PMID: 27940158. * corresponding authors
- Ulrich V, Gelber SE, Vukelic M, Sacharidou A, Herz J, Urbanus RT, de Groot PG, Natale DR, Harihara A, Redecha P, Abrahams VM, Shaul PW, Salmon JE, Mineo C. (2016). ApoE Recpetor 2 mediates trophoblast dysfunction and pregnancy complications induced by antiphospholipid antibodies in mice. Arthritis & Rheumatology 68(3) 730-739.
- Zita MM, Soncin F, Natale D, Pizzo D, Parast M. (2015). Gene Expression Profiling Reveals a Novel Regulatory Role for Sox21 Protein in Mouse Trophoblast Stem Cell Differentiation. Journal of Biological Chemistry 290 (50), 30152-30162.
- Outhwaite J, Natale BV, Natale DRC and Simmons DG. (2015) Expression of aldehyde dehydrogenase family 1, member A3 in glycogen trophoblast cells of the murine placenta. Placenta Mar;36(3):304-11.
- Soncin F, Natale D, Parast MM. (2015). Signaling pathways in mouse and human trophoblast differentiation: a comparative review. Cell Mol Life Sci. Apr;72(7):1291-302. PMID 25430479.
- Kaufman MR, Albers RE, Keoni C, Kulkarni-Datar K, Brown TL* and Natale DRC*. (2014). Important Aspects of Placental-Specific Gene Transfer. Theriogenology. Oct 82(7):1043-1048. PMID: 25110063. PMC4167466. * co-anchor authors.
- Hughes M, Natale BV, Simmons DG and Natale DRC. (2013). Ly6E is expressed in a subset of trophoblast cells in the chorion and labyrinth of the mouse placenta. Placenta, 34(9):831-835.
- Gasperowicz M and Natale DRC. (2011). Establishing three blastocyst lineages – Then what? Biology of Reproduction, 84(4):621-630.
- Natale DRC, Hemberger M, Hughes, M and Cross JC. (2009). Activin promotes differentiation of cultured trophoblast stem cells towards a labyrinth cell fate. Developmental Biology 335:120-131.
- Natale DRC*, Simmons DG*, Begay V, Hughes M and Cross JC. (2008). Early patterning of cells that comprise the three trophoblast cell layers of the labyrinth layer of the mouse placenta. Development 135(12):2083-1091. * co-first author.
- Natale DRC, Starovic M and Cross JC. (2006). Phenotypic Analysis of the Mouse Placenta. In: Methods in Molecular Medicine, Vol. 121: Placenta and Trophoblast: Methods and Protocols Vol. I, (eds. Soares MJ and Hunt JS). pp 275-293. Humana Press.
- Natale DR, Paliga A, Beier F, D’Souza SJA and Watson AJ. (2004). p38 MAPK signaling during murine pre-implantation development. Developmental Biology 268(1):76-88.
Complete list of publications is available at: