Harvey Lodish Elected President of the American Society for Cell Biology

CAMBRIDGE, Mass. — Whitehead Member Harvey F. Lodish was elected President of the 10,000-member American Society for Cell Biology for the year 2004. Since its founding in 1960, the American Society for Cell Biology has brought together experts in the varied facets of cell biology to advance scientific knowledge, increase public awareness of the importance of biomedical research, and guide national policy on the education, training, and career development of biomedical researchers.

This honor is the latest in a long string of awards and appointments that have characterized Lodish’s distinguished career studying cell-surface proteins, key cogs in the communication between cells. His research on these membrane proteins has revealed molecular mechanisms underlying diseases such as diabetes, leukemia, and hypertension. More recently, the Lodish lab has branched out to study hematopoietic stem cells—very rare, adult stem cells capable of generating all the blood and immune cells of the body.

Hematopoietic Stem Cells

Hematopoietic stem cells provide a promising avenue to treat diseases such as cancer and other disorders of the blood and immune system, which are often treated with bone marrow transplants. But by using a patient’s own hematopoietic stem cells, doctors could avoid complications associated with transplanting foreign bone marrow.

In the future, researchers hope to selectively collect these stem cells from a patient, correct a faulty gene in the cells, and then reintroduce the cells into the patient to treat a disease like sickle cell anemia.

However, researchers are not able to generate the large numbers of hematopoietic stem cells needed for therapeutic use. Not only do they occur naturally in very small numbers and rarely reproduce in culture, but researchers don’t have direct ways to identify and purify individual hematopoietic stem cells. The key to overcoming these challenges is in understanding the underlying biology of stem cells, says Lodish.

"We are trying to make new markers, surface proteins that are unique to hematopoietic stem cells, that will enable us to quickly separate them from the plethora of other cells in the bone marrow and blood," says Lodish. On another front, the Lodish lab is collaborating with Linda Griffith’s lab at the Massachusetts Institute of Technology to develop a "bioreactor" to grow stem cells. This involves engineering the right kind of surface and supportive cells to mimic the three-dimensional architecture of the bone marrow.

The Lodish lab is also identifying new growth factors that will allow these stem cells to grow and reproduce in culture. "We would like to understand what controls the decision making process. For instance, what signals trigger these cells to divide into more stem cells or to turn into a progenitor of a specific cell type, such as a red blood cell or an antibody producing B cell? We have identified some candidate proteins, which may enable researchers to expand hematopoietic stem cell populations in the lab," says Lodish.

Erythropoietin Receptor

In another vein of research, the Lodish lab was the first to clone and identify the receptor for erythropoietin (Epo), a hormone produced by the kidneys that controls the production of red blood cells. Epo swings into action when a supply of red blood cells is needed in response to low oxygen pressure in the blood, for instance, when an individual suffers blood loss or climbs to a high altitude.

"Epo binds to receptors on the surface of specific red cell progenitors, activating many signaling pathways that prevent the progenitor cells from dying and instead cause them to divide. We have already defined one of these pathways, and now we are trying to build an integrated picture of how all the different signaling pathways activated by the Epo receptor act together to prevent the death of progenitor cells," explains Lodish.

Currently, Lodish and his colleagues are exploring how Epo signals in neuronal cells. Epo may act to protect certain neuronal cells from death after stroke.

Fat Cell Biology

The Lodish lab is also making inroads in fat cell biology. In 1995, the lab cloned adipocyte complement-related protein (ACRP30), a secreted protein made exclusively by fat cells. "We speculated that ACRP30 circulated in the blood as an inactive precursor of a hormone. While we suggested that ACRP30 had a role in energy storage or mobilization, its function was unknown until 1999," explains Lodish.

In collaboration with researchers at Genset, Inc., the Lodish lab recently showed that a fragment of ACRP30, called gACRP, circulates in human blood at low concentrations. They have discovered that the molecule can be administered in small doses to cause profound and sustained weight loss in chubby mice eating unlimited quantities of food high in fat and sugar. The gACRP causes muscle to burn fatty acids faster so they are not stored as fat and also increases the metabolism of the sugar glucose. "We are now trying to understand how the compound works by looking for the receptor it binds to and the cellular signals it induces," says Lodish.