Steve Kornblau, M.D.
Associate Professor

Research Interests: Leukemia; apoptosis; cell cycle; graft-versus-host disease, proteomics

Medical School: Doctor of Medicine, U.T. Medical Branch at Galveston, Galveston, TX, 1985

Residency: Baylor College of Medicine, Affiliated Hospitals, Houston, TX, 1986-88

Fellowship: Hematology/Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 1988-91

Board Certification: Internal Medicine, 1988; Medical Oncology  1991; Hematology, 1992

Clinical & Research Summary
I have two areas of research interest. In the first, I am evaluating the expression and prognostic importance of cell cycle- and apoptosis-regulating genes in adult hematologic malignancies. Work done by my group and in collaborations with others has characterized the expression patterns and clinical relevance of the following proteins in AML: Rb, BCL2, Bax, BCL-X, XIAP, ERK, PKCa, Waf1, caspase-2, caspase-3, proliferating cell nuclear antigen (PCNA), AML2 and CBFB-MYH11 (inv[16] fusion protein). The expression of these proteins in ALL, myelodysplasia (MDS) and chronic lymphocytic leukemia (CLL) are also currently under investigation.

In addition to studying entire populations we have developed new techniques to study expression in the rare cells that survive exposure to chemotherapy. By doing so, we hope to determine if cells that survive chemotherapy do so because of preexisting tendencies or through “luck”. We are also performing proteomics to simultaneously investigate the expression patterns of many proteins. Early data suggests that we can classify AML based on the expression and activation patterns of key signal transduction pathway and apoptosis regulating proteins and that within these clusters different proteins are prognostic. Ultimately this knowledge will be utilized to tailor targeted therapies to the patients most likely to benefit from them, thereby increasing the efficacy of therapy and decreasing the toxicity.

The second area of research interest involves studies to evaluate the function and use of suicidal lymphocytes as a means of controlling GVHD. This severe or even fatal complication of allogeneic transplantation markedly limits the number of patients that can benefit from transplantation. We are using a modified retrovirus to introduce a suicide gene into the lymphocytes that cause GVHD so that we can control their fate after infusion into a patient. The concept is that if GVHD arises, a prodrug is given to the patient; only the GVHD-causing lymphocytes with the suicide gene will convert the prodrug into a toxic compound, which kills them, thereby stopping GVHD. If successful, this technology would permit us to remove many of the traditional barriers to transplantation, thereby allowing more patients to benefit from a graft-versus-leukemia effect.

We are the only group in the world to develop a murine model to test the function and optimize the use of suicidal lymphocytes. Determining the best way to use suicidal lymphocytes and investigating novel applications of them will be a major focus of our research over the next few years. Two clinical trials using testing this hypothesis should open this year.