Richard J. Ford, M.D., Ph.D., Associate Professor. Case Western Reserve University, 1974 (M.D.), Washington University, 1971 (Ph.D.).

The Role of Cytokine Growth Factors in Normal and Neoplastic Human Lymphocytes

The major interest of our research laboratory is the control of cell growth in normal and neoplastic human B lymphocytes. For neoplastic B cells, our studies focus on control of cell growth in human non-Hodgkin's lymphoma (NHL), mediated through autocrine cytokine growth factors, similar to those described for normal human B lymphocytes (BCGF, 12, 60kd). We have purified and characterized these cytokines and demonstrated that they stimulate cell growth not only in normal, activated human B lymphocytes but also in a wide variety of B-cell NHLs and in chronic B-cell leukemias such as hairy cell leukemia and chronic lymphocytic leukemia. We have recently cloned the gene for high molecular weight B cell growth factor. Now referred to as IL14, so we now have molecular probes and recombinant growth factor obtained from the BCGF gene, that will allow for understanding human B cell growth control in normal humoral immune responses, as well as in dysregulated pathologic conditions such as B cell lymphoma. We are now cloning the IL-14 receptor (IL14R), and studying its expression as part of the autocrine growth process. In addition, we are devising strategies for biologic therapies for the lymphomas through selective interdiction of neoplastic cell growth pathways with novel inhibitors.

Other studies, involve murine lymphomas including Severe Combined Immune Deficient (SCID) mice to develop model systems for the in vivo growth of human lymphomas, that will allow for studies on both therapeutics as well as immune modulation/regulation of human lymphoma cell growth.

Recent References:

Robertson, L.E., S. Chubb, R.E. Meyn, M. Story, R. Ford, W.N. Hittelman and W. Plunkett: Induction of apoptotic cell death in chronic lymphocytic leukemia by 2-chloro-2'-deoxyadenosine and 9- -D-arabinosyl-2-fluoroadenine. Blood 81: 143-150, 1993.

Ford, R.J., A. Tamayo, D. Li and F. Cabanillas: Human B cell lymphomas: In vitro and in vivo studies on growth factors and cell growth. Leukemia & Lymphoma 10: 51-56, 1993.

Ambrus, J.L., J. Pippin, A. Joseph, X. Chenguang, D. Blumenthal, A. Tamayo, K. Claypool, D. McCourt, A. Srikiatchatochorn and R.J. Ford: Identification of a CDNA for a human high molecular weight B cell growth factor (HWF-BCGF). Proceed for The National Academy of Science U.S.A. 90: 6330-6334, 1993.

Giglio A.d., S. O'Brien, R.J. Ford, Jr., J. Manning, H. Saya, M. Keating, D. Johnston, D.F. Chamone and A.B. Deisseroth: Proliferating cell nuclear antigen (pcna) expression in chronic lymphocytic leukemia (CLL). Leukemia & Lymphoma 10: 265-271, 1993.

Owen-Schaub, L., Meterissin, S. and Ford, R.J.: Fas/APO-1 expression and function on malignant cells of hematologic and non-hematologic origin. J. Immunother. 14: 234-241, 1993.

Younes, A., Drach, J., Katz, R., Jendiroba, D., Sabourian, M.H., Sarris, A.H., Swan, Jr., F., Hill, D., Cabanillas, F., Ford, R. and Andreeff, M.: Growth inhibition of follicular small cleaved cell lymphoma cells in short-term culture by interleukin-3. Annals of Oncology 5: 265-268, 1994.