Research Interest:

My laboratory's current research efforts are focused on 2 related themes in tumor biology: 1) identifying molecular protein profiles of tumor initiation and progression; and 2) understanding the function of epithelial membrane protein-2 (EMP2) in tumor progressive and escape from immune surveillance.

UCLA EDRN. The first project is the UCLA Early Detection Research Network of which I am the co-Director. The Early Detection Research Network (EDRN) is a consortium launched by the NCI approximately 5 years ago. The EDRN is a main flagship of the NCI's war on cancer, and thus is a major focus of the NCI's strategic game plan. This program is focused on identifying viable strategies for detecting cancer. One of the missions of the UCLA EDRN is to evaluate / validate new tumor markers. Our vision is to discover molecular signatures of tumor development. In this regard, our research is almost directly analogous to tumor profiling using DNA arrays; our approach falls under the category of "proteomics". Our profiling effort is based on the hypotheses that: i) there are fundamental pathways common to most, if not all cancers (e.g., life-death decision, cell cycle control, DNA repair, etc.); ii) disruption of one or more of these pathways is caused by, and/or results in altered protein expression, modification, localization, and/or activity; iii) determination of these protein changes on a population basis would define statistical clinical relevance, and mechanistically, would help define the molecular / protein 'circuitry' of a tumor cell. One experimental approach we have used is to examine the expression of multiple protein within a given pathway using high density tissue microarrays. Tissue microarrays are "chips" with hundreds or thousands of individual tissue "spots" representing hundreds of different patients. Together, these samples can be tested for protein express, activation, and / or chromosomal abnormalities. There are many interesting implications to studying "molecular circuitry" in tumors. First, we will define protein profiles that are diagnostic for subsets of cancers and/or prognostic for outcomes. As such, our focused 'deliverable' is to define markers that will have clinically utility. Second, as we expand our protein profile database, multivariate and cluster-type analyses will suggest novel, previously unappreciated, protein interactions. The mechanism of interaction will be testable experimentally.

The Molecular Mechanism of Tumor Progression: Evasion of host immune surveillance and resistance to therapeutic treatment. My second research focus is on the mechanism of tumor progression, specifically the mechanism by which tumor cells become resistance to immune surveillance and/or therapeutic treatment. Through a productive collaboration with Dr. Jonathan Braun, we have identified a GAS3 family member, Epithelial Membrane Protein-2 (EMP2), in a screen for functional tumor suppressor genes. Reduced expression of EMP2 ehanced tumorigenicity in vivo, and profoundly decreased cell susceptibility to cytotoxic lymphocyte (CTL)-mediated killing in vitro. Biochemical studies indicated that EMP2 may play an important and previously unappreciated role in trafficking of surface proteins to specific lipid raft domains. Accordingly, the focus of our research is to define the biochemical role of EMP2 on subcellular trafficking of surface proteins; its mechanism in cytotoxic cell targeting and immunogenicity; and, its use in disease stratification of a native human cancer.

 Current Publications

1.    Berberian, L., Goodglick, L., Kipps, T., and Braun, J. Immunoglobulin VH3 Gene Products: Natural Ligands for HIV gp120.  Science, 261:1588-1591, 1993.

2.    Goodglick, L. and Braun, J. Revenge of the Microbes: Superantigens of the T and B Cell Lineage.  Am. J. Pathol., 144:623-636, 1994.

3.    Goodglick, L., Felsher, D.W., Neshat, M.S., and Braun, J. A Novel Octamer Regulatory Element in the VH11 Leader Exon of B-1 Cells. J. Immunol., 154:4546-4556, 1995.

4.    Goodglick, L., Zevit, N., Neshat, M.S., and Braun, J.  Mapping the Ig Superantigen Binding Site of HIV-1 gp120. J. Immunol., 155, 5151-5159, 1995.

5.    Townsley-Fuchs, J., Kam, L., Fairhurst, R., Gange, S.J., Goodglick, L., Giorgi, J.V., Sidell, N., Detels, R., and Braun, J. HIV-1 gp120 Superantigen- Binding Serum Antibodies.  A Host Factor in Homosexual HIV-1 Transmission. J. Clin. Invest., 98:1794-1801, 1996.

6.    Goodglick, L., Aldrovandi, G.M., Zack, J.A., and Braun, J. HIV-1 gp120: An Immunoglobulin Superantigen.  In: K. Tomonari, (ed.), Viral Superantigens.  CRC Press, Inc., 1997.

7.    Goodglick, L., Vaslet, C.A., Messier, N.J., and Kane, A.B. Growth Factor Responses and Protooncogene Expression of Murine Mesothelial Cell Lines Derived from Asbestos-Induced Mesotheliomas. Toxicol. Pathol., 25: 565-573, 1997.

8.    Chatterjee, D., Han, Z., Mendoza, J., Goodglick, L., Hendrickson, E. A., Pantazis, P., and Wyche, J. H.  Monocytic Differentiation of HL-60 Promyelocytic Leukemia Cells Correlates with the Induction of Bcl-X_L. Cell Growth Differen., 8: 1083-1089, 1997.

Goodglick, Lee, Ph.D.

Assistant Professor