Stephen E. Bloom - Cornell Veterinary Medicine

Dr. Bloom is a Professor in the Department of Microbiology and Immunology, and has been associated with the department since 1996. He received the BS degree in Biology from Long Island University in 1963, and then received his PhD degree in Genetics/Cell Biology from The Pennsylvania State University in 1968. Dr. Bloom has served as acting co-chair of the Dept. of Microbiology and Immunology (1999-2000), and Associate Director of the Institute for Comparative and Environmental Toxicology (1990-2004). He currently serves as Deputy Program Director for an NIH-supported training program in Environmental and Molecular Toxicology. His research program has been supported by the NIH, USDA/NRICGP, and the Johns Hopkins CAAT program.

Research Interests | Graduate Fields | Lab Members | Related Links | Selected References

Research Interests

Research in my laboratory is focused on the basis of acquired resistance of cancer cells to drugs, emphasizing studies of apoptotic signaling pathways. Furthermore, we are investigating novel approaches to bypassing drug resistance based on modulating apoptotic pathways. These studies are performed with an in vitro system consisting of a panel of B-lymphoma cell lines that differ in degree of sensitivity to drug-induced apoptotic cell death.

There are currently two main projects in the lab:

1. The roles of drug-induced signaling pathways in regulating the induction of apoptosis: We are studying the activation and roles of the JNK (c-Jun N-terminal kinase), p38, and p53 signaling pathways in regulating the sensitivity of B-lymphoma cells to anticancer drug-induced apoptosis. Recently, we found that the JNK pathway is differentially activated by exposure to drugs that inhibit mitochondrial function. Specifically, drug-mediated inhibition of complex III of the electron transport chain resulted in extensive and prolonged activation of the JNK pathway. In contrast, drug-mediated inhibition of complex I failed to activate JNK, but did activate the p38 pathway. We are currently examining the roles of these signaling pathways in modulating the induction of apoptosis using validated pharmacologic inhibitors of these pathways. Furthermore, we have found that some lymphoma cell lines are wild-type for the p53 tumor suppressor gene, and differential activation of this pathway could also contribute to modulation of drug sensitivity.

2. Reversal of drug resistance in Bcl-2 over-expressing lymphoma cells: B-lymphoma cell lines that over-express Bcl-2 protein are typically resistant to multiple drugs. This situation limits the effectiveness of current drug treatments for B-cell lymphoma. We are studying approaches for bypassing this type of drug resistance. First, we are investigating whether exposure of lymphoma cells to multiple drugs that inhibit mitochondrial function can bypass drug resistance. Second, we have recently developed a new B-lymphoma cell line that shows enhanced sensitivity, compared to the parental cell line, to drug-induced growth inhibition and apoptosis induction. Interestingly, the level of Bcl-2 protein is similar for the variant cell line and the parental cell line. Therefore, this variant cell line has acquired changes (e.g., mutations) that bypass Bcl-2-based drug resistance. We are presently investigating several candidate pathways that may be involved and that may provide targets to consider for new drug development.

Dr. Bloom is a member of the following Graduate Fields:

The Institute for Comparative and Environmental Toxicology (ICET) and Graduate Field of Environmental Toxicology

Selected References

Bloom, S.E., D.E. Muscarella, M.Y. Lee, and M. Rachlinski. (1998). Cell death in the avian blastoderm: resistance to stress-induced apoptosis and expression of anti-apoptotic genes. Cell Death Differentiation 5:529-538.

O'Brien, K.A., D. E. Muscarella, and S. E. Bloom. (2001). Differential induction of apoptosis and MAP kinase signaling by mitochondrial toxicants in drug sensitive compared to drug resistant B-lineage lymphoid cell lines. Tox. Appl. Pharmacol. 174:245-256.

Muscarella, D.E. and S. E. Bloom. (2002). Differential activation of the c-Jun N-Terminal kinase pathway in arsenite-induced apoptosis and sensitization of chemically-resistant compared to susceptible B-lymphoma cell lines. Tox. Sci. 68:82-92.

Muscarella, D. E. and S.E. Bloom. (2003). Cross-linking of surface IgM in the Burkitt's lymphoma cell line ST486 provides protection against aresnite- and stress-induced apoptosis that is mediated by ERK and phosphoinisotide 3-kinase signaling pathways. J. Biol. Chem. 278:4358-4367.

Muscarella, D. E., O'Brien, K.A., Lemley, A.T., and S.E. Bloom. (2003). Reversal of Bcl-2 mediated resistance of the EW36 human B-cell lymphoma cell line to aresnite and pesticide-induced apoptosis by PK11195, a ligand of the mitochondrial benzodiazepine receptor. Tox. Sci. 74:66-73.

Bloom, S.E., A.T. Lemley, and D.E. Muscarella. (2006). Potentiation of apoptosis by heat stress plus pesticide exposure in stress resistant human B-lymphoma cells and its attenuation through interaction with follicular dendritic cells. Role of c-Jun N-terminal kinase signaling. Toxicol. Sci. 89:214-223.