Welcome to the Lab
We hope you find something interesting as you look around. And please don’t hesitate to contact us if there is something interesting you wish to learn more about or if there is something we can improve.
We are an eclectic group interested in a wide variety of problems in biomedical research. One of the primary interests of the group is to develop homologous recombination as a method of gene therapy for genetic diseases. We are particularly interested in the genetic diseases of the blood such as sickle cell disease, thalassemia, primary immunodeficiencies including severe combined immunodeficiency and hemophilia. We believe that ultimately the safest and most robust cure for these diseases will be to utilize a genome editing approach where we precisely modify the target gene of interest by homologous recombination while leaving the rest of genome unperturbed.
In this strategy we engineer nucleases to make a specific DNA double-strand break in our gene of interest. We simultaneously provide a piece of “donor” DNA that the cell’s endogenous homologous recombination machinery uses as a template to repair the induced double-strand break. By designing the donor DNA correctly we can introduce precise sequence changes into the gene we want to modify. This method of genome modification is a specific way of performing precise genome editing.
From these studies we have developed expertise in multiple aspects of genome editing and are now applying our expertise to other important biomedical problems. These include using genome editing to better understand and develop genetic therapies for triplet repeat expansion diseases (such as Huntington’s disease, myotonic dystrophy, and spinal-cerebellar ataxia), engineering the immune system to become HIV resistant, engineering cells to secrete therapeutic proteins (a form of synthetic biology), and using genome editing to better understand the genesis of pediatric leukemias. Finally, we have begun to use genome editing as a research tool to create reporter cell lines that can be screened for differential effects of small molecules and lines in which proteins can be analyzed at a single molecule, single cell level by tagging the endogenous loci with fluorescent or other tags.
A relatively new interest in the lab is to understand how single cells behave in large populations of cells. We have developed a molecular barcode tracking system that allows us to simultaneously track tens of thousands to millions of cells and their progeny. We are applying this relatively new system in our own lab and with our collaborators to better understand the population dynamics of cells grown in culture, the process of transformation in culture, the development of chemotherapy resistance in leukemia, the clonal dynamics of tumor recurrence and metastasis, and to the question of the efficiency of hematopoietic stem cell engraftment following transplantation.
We hope this overview of the different projects gives you a good sense of the activities of the Porteus lab. If you are particularly more interested in a specific project, please contact us directly. Finally we like to collaborate, so if that is something you like as well, please contact us. Thanks!
Matt Porteus, MD, PhD
Dr. Porteus' research program focuses on developing genome editing by homologous recombination as curative therapy for children with genetic diseases but also has interests in the clonal dynamics of heterogeneous populations and the use of genome editing to better understand diseases that affect children including infant leukemias and genetic diseases that affect the muscle. Clinically, Dr. Porteus attends at the Lucille Packard Children’s Hospital where he takes care of pediatric patients undergoing hematopoietic stem cell transplantation.