Richard J. Ford, M.D., Ph.D.

Professor of Pathology, Department of Hematopathology at the M.D. Anderson Cancer Center in Houston, Texas, and member of the Lymphoma Research Foundation Mantle Cell Lymphoma Consortium Cell Bank Working Group

Richard J. Ford, M.D., Ph.D., has been drawn to the biology of B-cells and what makes B-cells grow since he began his medical career over 30 years ago, when very little was known about the biology of B-cells. After being exposed to the spectrum of hematological cancers in his work as a pathologist, Dr. Ford became particularly interested in the pathogenesis of non-Hodgkin lymphoma (NHL).

"There were a lot of interesting things about NHLs, particularly B-cell NHLs that were very different from normal B-cells," says Dr. Ford. "I was also interested as to why B-cell lymphomas, at least over the last three decades, where showing a continuing rate of incidence, while most other human cancers were not increasing or in some cases, were decreasing."

The combination of his interest in basic science research in B-cell cancers and his clinical work with blood cancer patients led Dr. Ford to concentrate his efforts in mantle cell lymphoma (MCL) and diffuse large B-cell lymphomas (DLBCL), the two types of lymphoma studied in Dr. Ford's laboratory at M.D. Anderson Cancer Center in Houston. "The focus of our work is to understand the physiologic mechanisms that are involved in tumor cell growth in MCL and DLBCL. We're primarily studying a group of tumor necrosis factor family receptors, particularly CD40 and BLyS/BAFF bath receptor BR3, which are involved in B lymphoid cell survival mechanisms," says Dr. Ford.

With three-year funding from the Lymphoma Research Foundation (LRF), which began in 2003, Dr. Ford has been developing cell cultures and animal models that reflect the unique characteristics of mantle cell lymphoma, particularly the blastoid variant of MCL, in the hope of devising more effective and less toxic treatments against the disease. "Blastoid MCL has an even worse prognosis than classic MCL and nobody really understands the biologic aspects of the disease. By understanding the pathophysiology of MCL, we can discover where the vulnerable points for therapy will be and how to develop specific agents to target the tumor cells," says Dr. Ford.

Dr. Ford's work in growing patient cell cultures in his laboratory has resulted in the development of a substantial number of cell lines representing MCL and DLBCL. In 2007, Dr. Ford's laboratory contributed a patient cell line from classic MCL, called MINO, to the LRF's MCL Cell Bank, which is a repository of MCL cell lines created by scientists from around the world.

"There are various cell lines available now both of the typical type of MCL like MINO and the blastoid variant. MINO has all of the characteristics both morphologic and immunophenotypic of classic MCL, and for that reason it is of particular interest to investigators worldwide," says Dr. Ford.

Making a Personal Contribution to Research

The creation of MCL cell lines is important because it gives all investigators, especially those who don't have access to patient material or who don't have experience in generating cell lines, the opportunity to study the molecular biology of MCL. Capturing DNA with characteristic abnormalities from the genetic material of both new patients who haven't been previously treated as well as from relapsing or refractory patients is equally important to research, says Dr. Ford.

"Much of our current effort is involved in trying to understand what it is about refractory or relapsing patients that may be different from primary (therapy sensitive) patients who are treated quite successfully," says Dr. Ford.

In fact, collecting the genetic material from MCL patients is so important to research, Dr. Ford stops whatever he's doing to get the sample. "If a patient is willing to give us a blood sample to make sure that we get the tumor cells, my rule of thumb is that whatever I'm doing, day or night or on weekends, I drop and come running to get the specimen, process the specimen and get it to the incubator. To us, these patient specimens are the most valuable [research] samples we can obtain," says Dr. Ford.

"We're making significant progress in mantle cell lymphoma and in other NHLs, but what is needed now is more money for research. A major stumbling block to the work we're doing right now is the fact that government funding in cancer research is currently way down. The result is that laboratories like mine are facing a funding crisis of a magnitude not previously seen in cancer research. And that is particularly unfortunate, because I think this is the most exciting time in the post-Genome era, where I think that the continuing increases in our understanding of disease processes in difficult to understand tumors like MCL is likely to translate into more effective therapies," says Dr. Ford.

By Jo Cavallo