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Center for Regenerative Medicine - Dr. Jeanne F. Loring

Research

Harnessing the amazing power of human pluripotent stem cells

Human pluripotent stem cells have the remarkable abilities to expand indefinitely and develop into every cell type in the body. The mission of our research group is to advance human stem cell research efficiently by the application of powerful new cutting edge technologies. Collaboration is key to our success; the scientists in our group work together to develop and master complex techniques and they freely share their results and ideas.  We also have a large international group of trusted collaborators who strengthen our science by contributing their unique knowledge.

At the center of all of our research efforts is our unique database, called the Stem Cell Matrix.  The Matrix is the repository for comprehensive datasets of molecular information on human stem cells and tissues. It currently contains more than 5,000 samples, and we are integrating genomic and epigenomic data from each sample.  Our data include gene expression analysis, microRNA expression, SNP (single nucleotide polymorphism) genotyping, DNA methylation profiling, and genome and methylome sequencing, as well as phenotypic information about the cells and tissues. The data in the Stem Cell Matrix have taught us what makes a stem cell a stem cell, and the Matrix is the launching point for studies of genomic stability, epigenomic aberrations, differentiation, and the molecular basis of human disease.  At the heart of the Matrix is its role in improving quality control of human stem cells that are to be used for clinical applications.

Some of our stem cell projects:

Human disease:  We have basic and translational projects studying several human diseases, using technologies that range from making disease-specific induced pluripotent stem cells (iPSCs) from patient skin biopsies to experimental transplantation strategies.  Our active projects include Alzheimer disease, Fragile X, multiple sclerosis, and several others.  

Genomics:  When we look closely at the genomes of pluripotent cells, we see that they acquire changes in their DNA sequence during expansion and differentiation.  This is because some changes give cells a growth advantage, and it has raised concerns about the safety of cells used for transplantation.  However, it is important to note that changes like these also occur in FDA-approved "adult" stem cells, so it is not a problem specific to pluripotent cells.  We are determining what aberrations may cause problems in clinical applications.

Epigenomics:  Pluripotent stem cells are a great system to study control of gene expression. For example, we have completely sequenced the "methylomes" of undifferentiated and differentiated cells, to determine exactly what parts of genes are methylated and demethylated as the cells change.  This gives us awesome power to understand fundamental biology.

Single cell sequencing:  Currently methods for genomic analysis require large populations of cells.  We are developing methods to capture single cells (like cancer stem cells in the blood or cells within a differentiated population in a dish) in order to better characterize and understand them.

MicroRNAs:  MicroRNAs regulate the translation of mRNA transcripts. We are delivering microRNAs and microRNA inhibitors to cells to understand pluripotency, enhance reprogramming and direct cells along specific lineages.

Gene targeting:  We are incorporating methods for genetic engineering of human stem cells. These methods hold the key for correcting (or inducing) disease-causing mutations in pluripotent cells.  In theory, a patient's skin cells could be made into iPSCs, their genetic mutation corrected, the cells differentiated into an appropriate cell type, and then cell therapy used to ameliorate the disease.

Improved drug development:  One of the most important short-term applications for human iPSCs is in pharmaceutical drug development.  We are building a large bank of ethnically diverse iPSCs to screen for toxicity of drugs that is caused by genetic/ethnic background.  This would allow drugs to be tested on groups of people who would be least likely to have adverse side effects.

Conservation of endangered species:  We have initiated the production of a frozen bank of iPSCs from endangered species.  We have generated iPSCs from the drill monkey and the Northern White Rhino, and are in the process of adding more species.  The bank will preserve the unique genomic content of individual animals, and may eventually be used to generate gametes for assisted reproduction.

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