Renee Reijo Pera, Ph.D.
Principal Investigator
reneer@stanford.edu

Dr. Reijo Pera is the Director of the Human Embryonic Stem Cell Research and Education and a Professor of Obstetrics and Gynecology at Stanford University. Her research is aimed at understanding the genetics of human embryo growth and development and in characterizing the basic properties of human embryonic stem cells, especially their ability to differentiate to all cell types including germ cells. She has received numerous awards throughout her career and most recently was named Outstanding Faculty Mentor at UCSF in 2005 and one of the twenty Top Women On Leadership featured in Newsweek 2006. She received her Bachelor of Science degree from the University of Wisconsin (Superior), her doctoral degree from Cornell University in Ithaca, New York, and her postdoctoral training at the Whitehead Institute for BioMedical Research at the Massachusetts Institute of Technology in Cambridge, Massachusetts.

Click here to see Dr. Reijo Pera's scientific publications

James Byrne, Ph.D.
Postdoctoral Fellow
byrnej@stanford.edu

Embryonic stem cells (ESCs) can proliferate indefinitely, maintain an undifferentiated pluripotent state and differentiate into any cell type.  The ability of ESCs to differentiate into any cell type means we may be able to utilize these cells to cure or alleviate the symptoms of many degenerative diseases.  However, allogenic human ESCs (ESCs derived from spare IVF embryos) are genetically divergent from the host/patient, this means that transplantation of allogenic ESC-derived cell-types into a patient (without immunosuppressive drugs) will incite an immune response and result in the rejection of the transplanted ESCs.  A solution to the immune rejection problem would be to generate isogenic ESCs from somatic cell nuclear transfer (SCNT) embryos derived from the patients own cells, a concept commonly referred to as "therapeutic cloning".  However, the feasibility of human therapeutic cloning is severely limited by both the low blastocyst production efficiency observed following human SCNT and the fact that to date, no primate SCNT ESC line has been produced.  Recently, in collaboration with Dr. Shoukhrat Mitalipov, I have pioneered a number of improvements to the SCNT procedure which have resulted in a significant increase in the efficiency of SCNT blastocyst production in the rhesus monkey and I have derived two rhesus SCNT ESC lines.  My current goals are to investigate if the therapeutic cloning protocols I have successfully used in the non-human primate will work with human oocytes, to understand the underlying mechanisms of SCNT-based reprogramming and to develop basic research and clinical applications based on the SCNT-reprogrammed cell lines.

Publications

• Byrne, J. A., Simonsson, S. and Gurdon, J. B. (2002).  From intestine to muscle: nuclear reprogramming through defective cloned embryos.  Proceedings of the National Academy of Sciences. 99(9):6059-6063.
• Byrne, J. A. and Gurdon, J. B. (2002).  Commentary on human cloning. Differentiation. 69:154-157.
• Gurdon, J. B. and Byrne, J. A. (2002).  The history of cloning. Ethical eye: cloning. Council of Europe Publishing. ISBN: 92-971-4702-7.
• Gurdon, J. B. and Byrne, J. A. (2002). Chapter 14: Cloning of Amphibians. Principles of Cloning. Editors: Cibelli, J., Lanza, R. P., Campbell, K. H. S. and West, M. D.  ISBN: 0-12-174597-X.
• Byrne, J. A., Simonsson, S., Western, P. S. and Gurdon, J. B. (2003).  Nuclei of adult mammalian somatic cells are directly reprogrammed to Oct-4 stem cell gene expression by amphibian oocytes.  Current Biology. 13(14):1206-1213.
• Gurdon, J. B., Byrne, J. A. and Simonsson, S. (2003).  Nuclear reprogramming and stem cell creation.  Proceedings of the National Academy of Sciences. Colloquium. August 14, 2003. 10.1073/pnas.1834207100.
• Gurdon, J. B. and Byrne, J. A. (2003).  The first half-century of nuclear transplantation.  Proceedings of the National Academy of Sciences.  100(14):8048-8052.
• Gurdon, J. B., Byrne, J. A. and Simonsson, S. (2005).  Nuclear reprogramming by Xenopus oocytes. Novartis Found Symp. 265:129-36.
• Byrne, J. A., Mitalipov, S. M. and Wolf, D.P. (2006). Current Progress with Primate Embryonic Stem Cells. Current Stem Cell Research & Therapy. 1:127-138.
• Mitalipov, S. M., Kuo, H. C., Byrne, J. A., Fujimoto, A, Clepper, L, Meisner, L. F., Johnson, J., Zeir, R and Wolf, D. P. (2006). Isolation and characterization of novel rhesus monkey embryonic stem cell lines. Stem Cells. 24: 2177-2186.
• Byrne, J. A., Mitalipov, S. M., Clepper, L. and Wolf, D. P. (2006). Transcriptional profiling of rhesus monkey embryonic stem cells. Biology of Reproduction. 75: 908-915.
• Sugihara, K., Sugiyama, D., Byrne, J., Wolf, D., Lowitz, K., Kobayashi, Y., Kabir-Salmani, M., Nadano, D., Aoki, D., Nozawa, S., Nakayama, J., Mustelin, T., Ruoslahti, E., Yamaguchi, N., and Fukuda, M. (2007).  Trophoblast cell activation by trophinin ligation is implicated in human embryo implantation. Proceedings of the National Academy of Sciences. 104:3799-3804.
• Mitalipov, S. M., Zhou, Q., Byrne, J. A., Ji, W. Z., Norgren, R. B. and Wolf, D. P. (2007).  Reprogramming following somatic cell nuclear transfer in primates is dependent upon nuclear remodeling.  Human Reproduction. June 11; [Epub ahead of print]
  

Shawn Chavez, Ph.D.
Postdoctoral Fellow
chavezs@stanford.edu

During my graduate studies, my research concentrated on identifying and characterizing novel regulators of apoptosis in trophoblast cells and elucidating the molecular mechanisms mediating trophoblast apoptosis.  My current work is focused on the role of DNA Methyltransferases (DNMTs) in human germ cell differentiation and imprinting.  Recent studies in mice suggest that the expression of germ cell specific genes may be sensitive to changes in DNA methylation and that DNA methylation may contribute to the regulation of germ cell differentiation.  Therefore, we are evaluating the expression and function of DNMTs in hESC-derived germ cells throughout development and determining their importance for normal germ cell differentiation and imprinting.

Publications

• Aschkenazi, S., Straszewski, S., Verwer, K., Foellmer, H., Rutherford, T., Mor, G. Differential Regulation and Function of the Fas/FasL System in Human Trophoblast Cells. Biology of Reproduction 2002; 66: 1853-186.
• Mor, G., Straszewski, S., Kamsteeg, M. The Role of the Fas/FasL System in Female Reproductive Organs: Survival and Apoptosis. Biochemical Pharmacology 2002; 64: 1305-1315.
• Mor, G., Straszewski, S., Kamsteeg, M. The Fas/FasL System in Reproduction: Survival and Apoptosis. Scientific World Journal 2002; 2: 1828-1842.
• Abrahams, V.M., Straszewski, S.L., Kamsteeg, M., Hanczaruk, B., Rutherford, T.J., Schwartz, P.E., Mor, G. Epithelial Ovarian Cancer Cells Secrete Functional Fas Ligand. Cancer Research 2003; 63: 5573-5581.
• Abrahams, V.M., Straszewski, S.L., Kim Y.M., Romero R., Mor, G. Macrophages and apoptotic cell clearance during pregnancy. American Journal of Reproductive Immunology 2004; 51(4): 275–282.
• Straszewski-Chavez, S.L., Abrahams, V.M., Funai, E.F., Mor, G. X-linked Inhibitor of Apoptosis (XIAP) Confers Human Trophoblast Cell Resistance to Fas-Mediated Apoptosis. Molecular Human Reproduction 2004; 10(1): 33-41.
• Abrahams, V.M., Straszewski-Chavez, S.L., Guller, S., Mor, G. First trimester trophoblast cells secrete Fas ligand which induces immune cell apoptosis. Molecular Human Reproduction 2004; 10(1): 55-63.
• Abrahams, V.M., Bole-Aldo, P., Kim, Y.M., Straszewski-Chavez, S.L., Chaiworapongsa, T., Romero, R., Mor, G. Divergent Trophoblast Responses to Bacterial Products Mediated by Toll-Like Receptors. Journal of Immunology 2004; 173: 4286-4296.
• Straszewski-Chavez, S.L., Abrahams, V.M., Mor, G. The Role of Apoptosis in Trophoblast Survival and Differentiation During Pregnancy. Endocrine Reviews 2005 26(7): 877-897.
• Aplin, J.D., Straszewski-Chavez, S.L., Kalionis, B., Dunk, C., Morrish, D., Forbes, K., Baczyk, D., Rote, N., Malassine, A., and Knöfler, M. Trophoblast differentiation: progenitor cells, fusion and migration-A Workshop Report. Placenta 2006 27 (Supplement A): 1-3.
• Straszewski-Chavez, S.L., Visintin, I.P., Karassina, N., Los, G., Liston, P., Halaban, R., Mor, G.  XAF1 mediates TNF-a-induced apoptosis and XIAP cleavage by acting through the mitochondrial pathway. Journal of Biological Chemistry 2007 282(17): 13059-13072.
• Fest, S., Aldo, P.B., Abrahams, V. M., Visintin, I., Alvero, A., Chen, R., Chavez, S.L., Romero, R., and Mor, G. Trophoblast–Macrophage Interactions: a Regulatory Network for the Protection of Pregnancy. American Journal of Reproductive Immunology 2007 57: 55–66.
• Chavez, S.L.*, Meneses, J.J.*, Nguyen, H.N., Kim, S.K. and Reijo Pera, R.A. Characterization of Six New Human Embryonic Stem Cell Lines (HSF-7, -8, -9. -10, -12 and -13) Derived Under Minimal-Animal Component Conditions. Stem Cells and Development 2008 17(3): 535-546.  *Contributed equally

Kelly Haston, M.S.
Graduate Student
khaston@stanford.edu

My previous research involved investigating the effects of pesticides on gonad development in leopard frogs. This research was performed in the laboratory of Dr. Tyrone Hayes at UC Berkeley. My current research interests lies in understanding how the erasure and establishment of sex specific methylation on imprinted genes is carried out during mouse germ cell development. Of particular interest is whether mice with disruptions in germ cell specific genes are maintaining wild type imprinting status or showing aberrant epigenetic patterns.

Kehkooi Kee, Ph.D.
Postdoctoral Fellow
kkee@stanford.edu

I have been very interested in genetics and molecular mechanisms of germ cell progression, especially meiotic recombination and human genetics. My current projects are: dissecting the molecular mechanisms of human germ cell progression, in vitro differentiation of hESCs to germ cells, and studying effects of environmental toxins on human germ cell development

Nina Kossack
Ph.D. Candidate
nkossack@stanford.edu

My previous research involved investigating mutations in the luteinizing hormone/chorionic gonadotropin receptor (LHCGR) gene that are resulting in Leydig cell hypoplasia. This research was performed at the Institute of Reproductive Medicine of the University in Muenster, Germany. My current research goals are the isolation and characterization of spermatogonial stem cells.

So Hyun Lee, Ph.D.
Postdoctoral Fellow
sohyun@stanford.edu

My previous research during my tenure in graduate school, involved understanding the mechanisms necessary for somatic cell nuclear transfer and in vitro fertilization in the hDAF transgenic pig. My current research goals are to understand the mechanism of early germ cell specification and differentiation in humans. More specifically, I'm interested in the differentiation of human embryonic stem cells to oocytes and how somatic cell nuclear transfer can be utilized to progress the field of stem cell biology.

Ha Nam Nguyen, M.S.
LS Research Assistant
hanam@stanford.edu

My current work revolves around deriving induced pluripotent stem (iPS) cells from adult human skin fibroblasts and assessing their potential to differentiate into other cell types. In addition, I am investigating the developmental processes of the early human embryos.

Publications

• Weier, J.F., Ferlatte, C., Baumgartner, A., Jung, C.J., Nguyen, H.N., Chu, L.W., Pedersen, R.A., Fisher, S.J., and Weier, H.U. (2006). Molecular cytogenetic studies towards the full karyotype analysis of human blastocysts and cytotrophoblasts. Cytogenetic and genome research 114, 302-311.

• Privette, L. M., Weier, J. F., Nguyen, H. N., Yu, X. and Petty, E. M. (2008). Loss of CHFR in human mammary epithelial cells causes genomic instability by disrupting the mitotic spindle assembly checkpoint. Neoplasia 10, 643-52.

• Chavez, S. L., Meneses, J. J., Nguyen, H. N., Kim, S. K. and Pera, R. A. (2008). Characterization of Six New Human Embryonic Stem Cell Lines (HSF7, -8, -9, -10, -12, and -13) Derived Under Minimal-Animal Component Conditions. Stem Cells Dev 17, 535-546.

Cory Nicholas
Ph.D. Candidate
cory2007@stanford.edu

Human and Mouse in vitro Germ Cell Differentiation from Embryonic Stem Cells

I hypothesize that mature, functional human and mouse oocytes can differentiate from embryonic stem cells in vitro and progress through a sequence of required genetic and epigenetic events that recapitulate in vivo germ cell differentiation. My specific aims are to:

Sonya Schuh-Huerta, Ph.D.                                                    
Postdoctoral Fellow
sonyas1@stanford.edu

I have great interests in the genes and proteins involved in gamete development, reproduction, and fertility.  My graduate work focused on mammalian sperm motility and the molecular signaling pathways and processes that prepare sperm for fertilization.  During my postdoctoral position I am focusing on the “female side” of reproductive research.  A woman is born with approximately one million eggs (oocytes).  Throughout life oocytes are recruited to resume meiosis, mature and be ovulated, or they undergo apoptosis and die.  With no oogonial stem cells, over time the oocyte/follicle population is eventually depleted, menstrual cycling ceases, and menopause ensues.  Coinciding with this decline in oocyte number is a decline in fertility, typically beginning in the early 30’s and becoming more significant around age 37.  However, there is great variability between women.  My current work aims to elucidate the genes and chromosomes that are involved in establishing a woman’s oocyte endowment and associated with ovarian aging or follicle loss, and the environmental and ethnic factors that may modify these effects.  I am using a genome-wide microarray scanning approach to analyze the DNA of a large sample of women of 5 major ethnic groups, who are also examined by ultrasound for the number of remaining follicles they have.  Currently, there are no good predictors of declining fertility or menopause, and therefore an underlying objective of this work is to translate our findings into clinical applications; to use follicle count and genetic testing as a way to prospectively identify women at risk for premature and natural decline in ovarian function and fertility.

Publications

• Krasnow, S.M., Fraley, G.S., Schuh, S.M., Baumgartner, J.W., Clifton, D.K., Steiner, R.A. (2003).  A role for galanin-like peptide in the integration of feeding, body weight regulation, and reproduction in the mouse.Endocrinology, 144(3):813-822.
• Carlson, A.E, Quill, T.A., Westenbroek, R.E., Schuh, S.M., Hille, B., Babcock, D.F. (2005).  Identical phenotypes of CatSper1 and CatSper2 null sperm. J Biol Chem, 280(37):32238-44.
• Xie, F., Garcia, M.A., Carlson, A.E., Schuh, S.M., Babcock, D.F., Jaiswal, B.S., Gossen, J., Esposito, G., van Duin, M., Conti, M. (2006).  Soluble adenylyl cyclase (sAC) is indispensable for sperm function and fertilization.  Dev Biol, 396(2):353-62.
• Schuh, S.M., Carlson, A.E., McKnight, G.S., Conti, M., Hille, B., Babcock, D.F. (2006).  Signaling pathways for modulation of mouse sperm motility by adenosine and catecholamine agonists.  Biol Reprod, 74:492-500.
• Schuh, S.M., Hille, B., Babcock, D.F. (2007).  Adenosine and catecholamine agonists speed the flagellar beat of mammalian sperm by a non-receptor-mediated mechanism.  Biol Reprod, 77(6):960-9.
  
  
  

Henrike Siemen, M.S.
Ph.D. Candidate
hsiemen@stanford.edu

My current research interest is to understanding the roles of the PUMILIO genes, PUM1 and PUM2, in mammals. My aim is to utilize knockout and silencing approaches, to examine the function of Pumilio in human and mouse embryonic stem (ES) cells, as well as in ES cell derived cells. My focus lies in understanding the function of these genes in neurons and germ cells, as data from lower organisms suggests that Pumilio plays an important role in those cell types.

Connie Wong, Ph.D.
Postdoctoral Fellow
conniewg@stanford.edu

MicroRNAs (miRNAs) are small RNA molecules that regulate many developmental processes in diverse animals. Human embryonic stem cells (hESCs) express a unique set of miRNAs, and many hESC-specific miRNAs change in expression level upon differentiation. Mouse embryonic stem cells defective in miRNAs biogenesis failed to differentiate both in vivo and in vitro. Thus, it is likely that hESC-specific miRNAs also function in differentiation. I am interested in studying the role of miRNAs in the differentiation of germ cells from hESCs. I also plan to identify miRNAs that function specifically in germ cell development using a combination of genetics and cell biology approaches.