Contact Information
Professor and Founding Director, The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC
Email: pera@usc.edu
Office Phone: 323-442-4366
Lab Phone: 323-442-2997
Fax: 323-442-1368
Office location: 1501 San Pablo St, ZNI-543
Lab location: 1501 San Pablo St, ZNI-501
Education
College of William and Mary, Williamsburg, VA., U.S.A., B.A., English Language and Literature (1972)
George Washington University, Washington, D.C., U.S.A., Ph.D., Pharmacology (1979)
Oxford University, Oxford, U.K., M.A. (1990)
Recent Publications
Pera MF. Stem cells. A new year and a new era. Nature. 2008 Jan 10;451(7175):135-6.
The International Stem Cell Initiative. Characteristics of Human Embryonic Stem Cells Lines: Results from the International Stem Cell Initiative. Nature Biotechnology, in press. (Pera is on the Steering Committee of ISCI) Nat Biotechnol. 2007 Jul;25(7):803-16. Epub 2007 Jun 17.
Andrew L. Laslett, Sean Grimmond, Brooke Gardiner, Lincon Stamp, Adelia Lin, Susan M. Hawes, Sam Wormald, David Nikolic-Paterson, David Haylock, and Martin F. Pera. Transcriptional Analysis of Early Lineage Commitment In Human Embryonic Stem Cells. BMC Developmental Biology, Mar 2; 7:12, 2007.
Daniella Herszfeld, Emma Langton -Bunker, Benjamin E. Reubinoff, Souheir Houssami, Leendert H.J. Looijenga, and Pera, M.F. - CD30 is a survival factor and a biomarker for transformed human pluripotent stem cells. Nat Biotechnol. 2006 Mar;24(3):351-7.
Research Description
Beginning with our work on human teratocarcinomas over 20 years ago, research in the Pera laboratory has always been focused on the biology of human pluripotent stem cells: their isolation and characterization, and the extrinsic factors that govern stem cell renewal and early lineage specification. Today, we work mainly with human embryonic stem cells, though we still study human embryonal carcinoma, and have begun to derive human induced pluripotent stem cells. Our current activities are summarized in the description of the research projects below.
Research Projects
1. What is a stem cell and what happens when it embarks on the pathway to lineage commitment?
Embryonic stem cells are characterized by expression of cell surface markers, their transcriptional profile and the expression of genes characteristic of pluripotent populations in the developing embryo, and by biological assay of their differentiation potential. The conventional view depicts stemness (defined by the features above) versus commitment as a binary choice between two alternate cellular states. However, stem cell cultures are heterogeneous. It turns out there is a gradient of expression of pluripotency genes in the population, and lineage specific transcription factors are often co-expressed with pluripotency genes. In other words, what is depicted as a binary choice is in fact a continuum of cell states. In this project, we are isolating stem cells at different stages in this hierarchy and analyzing their properties and differentiation potential, to better understand mechanisms of renewal and lineage commitment.
2. How do the growth properties of stem cells change during propagation in vitro, and how does this relate to genetic and epigenetic change seen during long term culture?
The maintenance of the pluripotent state requires conditions that not only suppress commitment but also allow survival of undifferentiated cells. Human ES cells can adapt to suboptimal conditions during cultivation in vitro. This process of adaptation can result in chromosomal changes similar to those seen in human cancers, changes that must be avoided if we are to use stem cells in therapy. We are investigating the role of NF-kB signaling in the epigenetic adaptation of human ES cells to survival in vitro. The activation of autocrine signaling through the CD30 receptor seems to play a key role in this process.
3. What is a human liver stem cell and can we isolate this cell from human embryonic stem cell cultures?
The study of human ES cell differentiation helps to inform work on tissue stem cells, and vice versa. We discovered a monoclonal antibody that reacts with ES cells undergoing hepatic differentiation in vitro. This antibody also appears to identify a novel putative stem cell population recently identified in the bile ducts of the adult human liver. We are using this reagent to enable the isolation of hepatic progenitors from human ES cultures or from fetal or adult liver.
Lab staff
- Shelley Hough: Research Scientist
- Kouichi Hasegawa: Senior Research Associate
- David Braxton- Visiting Medical student
- Veronika Akopian: Research Lab Technician II
- Crystal Sengstaken: PhD Student
Awarded Grants
ARC & Biotechnology of Australia (Commonwealth Government) - Biotechnology Centre of Excellence Award (2002-2006, total A$43.5M) $500K per annum July 2004-June 2006 to our laboratory
Juvenile Diabetes Research Foundation "Characterisation of novel embryonic stem cell lines" (2005-2006) US$125,248 p.a.
CIRM Shared Research Laboratory and Course in Current Protocols in Human Embryonic Stem Cell Research US$2,346,100/3 years
NIH USC Center for Liver Disease US$93,309/2 year