2003 Fifth Annual Beckman Scholars Symposium
Arnold and Mabel Beckman Foundation

Stem Cell Research Panel
A National Research Perspective

Meri Firpo, Ph.D.
Assistant Research Geneticist
Department of Obstetrics, Gynecology and Reproductive Sciences
University of California San Francisco

The focus of the Firpo lab is the regulation of stem cell growth, both from the perspective of the maintenance of stem cell potential, and the regulated differentiation to functional tissues. We are interested in embryonic, fetal and adult stem cells. Our lab has two areas of active research. First, we have developed a model of in utero hematopoietic transplantation in mice. For this model, we isolate populations of cells containing hematopoietic stem cells from adult and fetal mice and embryonic stem cells using specific antibodies. The cells are then injected into fetal mice through the uterine wall. At various times after birth, the injected mice are analyzed to determine whether engraftment has occurred, and the degree of contribution of donor cells in hematopoietic tissues, including peripheral blood, bone marrow and spleen.

The remaining two projects are part of our human embryonic stem (hES) program. This project covers the distribution of hES cells to other labs, both at UCSF, and to academic institutions throughout the world. As part of the characterization of the cell lines, we will determine what is required to maintain human ES cells in an undifferentiated state. We also have established a training program to help establish hES culture techniques in other labs by hands-on training of individuals visiting our lab. The second project involving hES cells explores the regulation of differentiation of hES cells into mature cells of several tissues. At the current time, we are actively differentiating hematopoietic, hepatocytes, pancreatic, and neural cells. Ultimately, development of methods of genetic alteration will allow us to regulate differentiation, isolate populations that may be suitable for transplantation therapies, and to follow the engraftment of embryonic stem cells-derived tissues. In addition to monitoring the differentiation and genetic status of subclones, we assay the differentiation to the various cell lineages through assessment of expression of tissue-specific cell-surface markers.

In summary, This lab is studying two questions related to stem cell biology. First, what is required to keep a stem cell a stem cell, while allowing it to proliferate? Second, what signals regulate the steps of stem cells take after they become committed to differentiate?

Meri Firpo is an Assistant Research Professor in the Center for Reproductive Sciences at the University of California San Francisco, where she directs the Human Embryonic Stem Cell Laboratory. She received her Ph.D. in 1992 from the Cornell University Medical College Graduate School of Medical Sciences after completing a research project in the Developmental Hematopoiesis Laboratory at the Sloan Kettering Institute. Her research at the Sloan Kettering Institute was focused on adult bone marrow stem cells. She then did a postdoctoral fellowship at the National Jewish Institute for Immunology and Respiratory Medicine in Denver, Colorado, where she completed a research project on generating hematopoietic stem cells from mouse embryonic stem (ES) cells in culture. After returning to the Bay Area in 1995, Dr. Firpo did a second postdoctoral fellowship at the DNAX Research Institute for Molecular and Cellular Biology in Palo Alto, California, where she studied the development of the human hematopoietic system and human models of leukemia.

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In 1997, Dr. Firpo came to the University of California San Francisco, where she directed the derivation of two of the human ES cell lines included in the National Institutes of Health Registry of Human Embryonic Stem Cells. She is currently working on using human ES cells as a model of human development, and differentiating human ES cells into functional tissues for transplantation. She is also deriving new lines suitable for transplantation therapies.