Molecular Recognition in Biological Systems and Bioinformatics

Immune cell function in cancer; cytokine therapy of tumors; cancer stem cells; flow cytometry.

My recent research has involved studies on the lymphocytes found in the microenvironment of tumors obtained from human patients with lung cancer or ovarian cancer. The primary goal of these studies is to identify the phenotype of these cells and to understand why the T-cells, although present within the tumor microenvironment, fail to suppress tumor growth. A variety of flow cytometric and microscopic approaches to studying the nature and function of these cells, as well as attempts to reverse their hypo-responsiveness in vitro, are coupled with in vivo studies attempting to alter the function of these cells in xenografts of human tumor pieces in immuno-compromised scid mice.

Another area of study has involved the identification of peptide epitopes in the immunoglobulin molecules produced by human lymphoma cells, as an approach to the development of dendritic cell-based vaccines designed to be effective against individual patient lymphomas.

A third related area is the identification and analysis from tumors of so-called "side-population" cells which are purported to be cancer stem cells.

I also am administrator of Flow Cytometry in the Confocal Microscopy and Flow Cytometry Facility. In this capacity, I perform all cell sorting in the Facility, perform multiplex cytokine assays using the cytometric bead array, train new users of the data acquisition instruments, and consult with researchers regarding their flow cytometry applications.

Flow Cytometer, Confocal Microscope

Analysis of flow cytometry data

Human, mouse

Cytokines, Signal transduction proteins

Study of immune regulation of tumor growth

Flow cytometry, Confocal microscopy, ELISA, ELIspot

Fluorescently labeled antibodies, cytometric beads for cytokine analysis

Primary cell cultures derived from human tumors, primary dendritic cells

Protein purification

Cancer

Lung, ovary, lymphoid cells

Sugano, M., Conway, T.F., Jr., Kelleher, R.J., Jr., Sugiyama, Y., Chen, F-A, Bankert, R.B., and Bernstein, S.H. 2001. Human Dendritic Cells Pulsed with Autologous Epstein-Barr Virus Transformed Cell (BCL) Lysate Elicit a BCL Specific MHC-Class II Restricted T-Cell Response. J. Exp. & Clin. Cancer Res. 20:175-82.

Lou, Q., Kelleher, R.J, Jr., Sette, A., Loyall, J., Southwood, S., Bankert, R.B., and Bernstein, S.H. 2004. Germline Tumor-Associated Immunoglobulin V_H Regon Peptides Provoke a Tumor Specific Immune Response Without Altering the Response Potential of Normal B Cells. Blood 104:752-759.

Broderick, L, Yokota, S.J., Reineke, J., Mathiowitz, E., Stewart, C.C., Barcos, M., Kelleher, R.J., Jr. and Bankert, R.B. 2005. Human CD4 Effector Memory T Cells Persisting in the Microenvironment of Lung Cancer Xenografts Are Activated by Local Delivery of IL-12 to Proliferate, Produce IFN-γ, and Eradicate Tumor Cells. J. Immunol. 174:898-906.

Lou, Q., Conway, T.F. Jr., Egilmez, N.K., Loyall, J.L., Bernstein, S.H., Kelleher, R.J., Jr., and Bankert, R.B. 2006. B Cell Tumor Vaccine Enhanced by Covalent Attachment of Immunoglobulin to Surface Proteins on Dendritic cells. Clinical Immunology 118:66-76.

Nazareth, M.R., Broderick, L., Simpson-Abelson, M.R., Kelleher, R.J., Jr., Yokota, S.J., and Bankert, R.B., 2007. Characterization of Human Lung Tumor-Associated Fibroblasts and Their Ability to Modulate the Activation of Tumor-Associated T Cells. J. Immunol. 178: 5552 - 5562.