by Roberta Nichols and Alicia Di Rado

Are blood cancer stem cells born “bad,” or does something in the environment around them make them take a turn to the dark side?

That is just one question that Ching-Cheng Chen, Ph.D., is exploring. Chen, who recently joined City of Hope as assistant professor in the Division of Hematopoietic Stem Cell and Leukemia Research, searches through hematopoietic stem cells’ developmental tree to understand what pushes these cells to differentiate the way they do.

Ching-Cheng Chen (Photo by p.cunningham)

Specifically, he is particularly interested in what scientists call the stem cell niche: the microenvironment in which stem cells live and mature. Factors such as proteins or other cells in this environment help determine stem cell fate, encouraging the cells to stay dormant when unneeded or to differentiate or proliferate when the body needs new tissues. Sometimes, though, factors in the niche can push cells to go wrong.

Chen studies the niche in both healthy and diseased conditions, such as leukemia.

In postdoctoral work at the Stanford University School of Medicine — where he had worked since 2003 before joining City of Hope — he and his colleagues created a special assay to discover a key player in creating the hematopoietic stem cell niche: a specific, primitive type of bone cell. The group published its work in Nature.

Chen also has shed light on how hematopoietic stem cells make the jump to create mast cells, immune cells involved in allergic responses, tissue repair and protection from disease. He identified the adult mouse mast cell progenitor in 2005.

And by studying small numbers of progenitor cells individually, he demonstrated how powerful this single-cell strategy can be and found that cells are fated to become mast cells significantly earlier in the hematopoietic stem cell differentiation process than previously thought. These findings were published in Cell Stem Cell in April.

He also discovered certain important molecules, called paired immunoglobulin receptors, on the surface of hematopoietic stem cells. That earned him a K99/R00 grant from the National Institutes of Health to study how these receptors affect the fate and survival of hematopoietic stem cells.

Chen and his colleagues plan to continue to study the hematopoietic stem cell niche in mouse models, while also working with tissue samples from human patients to study the difference between normal hematopoietic bone marrow environment and the environment when a patient has leukemia.

“We have a long way to go, but by studying this bone marrow environment, at least we can understand how the hematopoietic stem cell is regulated,” Chen said.

That work may not only shine light on leukemia stem cells, but also help scientists reach a major goal: generating hematopoietic stem cells that can then be manipulated into other important cells of blood lineage.

By understanding how to regulate hematopoietic stem cells, he said, “we may have some clue in how to produce or try to influence an embryonic stem cell to become a hematopoietic cell.”

He added: “If we can replicate the bone marrow environment in vitro, perhaps we can differentiate these cells into the hematopoietic cells we want with high frequency and purity.”

Chen received his doctoral degree in cellular and molecular biology at the University of Alabama at Birmingham and was an instructor in the Department of Pathology at Stanford University before joining City of Hope. He now works in the Arnold and Mabel Beckman Center for Cancer Immunotherapeutics & Tumor Immunology.