Partners MS Center

David E. Anderson, Ph.D.

Instructor in Neurology

Center for Neurologic Diseases
Brigham and Women's Hospital
Harvard Institutes of Medicine, HIM-641
77 Avenue Louis Pasteur
Boston, MA 02115

Tel: (617) 525-5330
Fax: (617) 525-5333

Email: danderson@rics.bwh.harvard.edu

Education & Training

1992 B.S., University of California, Davis
1993-1999 Ph.D. , Immunology, Harvard University
1999-2003 Postdoctoral Fellow, Immunology, University of California, Davis

Research & Professional Experience

2002-2003 Assistant Research Immunologist, University of California, Davis
2004-Present Instructor, Department of Neurology, Brigham & Women's Hospital and Harvard Medical School

Professional Society Involvement

1994-Present American Association of Immunologists, member
1999-Present Clinical Immunology Society, member
2004-Present International Society of Neuroimmunology, member

Research Interests

My research interests are focused on elucidating mechanisms by which inflammation is regulated within the CNS. My research approach utilizes human ex vivo brain tumor specimens as a means of studying tumor cells, glial cells, and populations of lymphocytes that migrate into the CNS to modulate an inflammatory response directed against the tumor cells. To date, most investigations of human immunity directed against tumors have utilized peripheral tumors, while research on malignant gliomas has overwhelmingly focused on issues related to tumor cell biology. My research targets a fundamental yet poorly understood interface between human immunity and CNS tumor cell biology.

I have established a strong and productive collaboration with colleagues at Columbia University, which provides me with unique access to large numbers of human CNS tumor specimens. Detailed functional and molecular analysis of these specimens allows me to pose and answer novel and important questions that have long gone unaddressed.

The current goals of my research are to elucidate the mechanisms by which the tumor microenvironment of malignant gliomas hinders tumor-specific immunity. More specifically, I am studying the TIM-3:Galectin-9 pathway and three different mechanisms by which it may influence CNS immunity directed against human gliomas: 1) the influence of tumor cell expression of galectin-9 on infiltrating TIM-3+ T cells, 2) the influence of tumor cell expression of galectin-9 on TIM-3+ microglia, and 3) the influence of galectin-9 expression on tumor cell invasion/metastasis.  To answer these questions, it is necessary to isolate and examine small numbers of defined cells of interest using multiparameter fluorescence activated cell sorting (FACS) and/or laser capture microdissection (LCM). Use of ex vivo cell populations isolated by FACS allows me to performed functional assays on defined cell populations, while use of LCM allows me to evaluate the gene expression profile of cell populations of interest while cognizant of their functional biology. The use of these two approaches affords me the opportunity to ask more precise questions and to better define mechanisms at both cellular and molecular levels.

These current research objectives represent the departure point for my long-term desire to better understand the molecular mechanisms by which inflammation is regulated within the CNS, and how these mechanisms influence a variety of human neurodegenerative diseases influenced by inflammation, including brain tumors, multiple sclerosis, and Alzheimer’s disease among others. I envision future investigations that will focus on distinct mechanisms by which glial cells, including boh astrocytes and microglia, contribute to the regulation of CNS inflammation.

Publications

Original Articles

1. Torres, J.V., Anderson, D.E., Malley, A., Banapour, B., Axthelm, M.K., Benjamini, E., Gardner, M.B. SIV envelope glycoprotein epitopes recognized by antibodies from infected or vaccinated rhesus macaques. J Med Primatol 1993; 22:129-137.

2. Torres, J.V., Malley, A., Banapour, B., Anderson, D.E., Axthelm, M.K., Gardner, M.B., Benjamini, E. An epitope on the surface envelope glycoprotein (gp130) of simian immunodeficiency virus (SIVmac) involved in viral neutralization and T cell activation. AIDS Res Hum Retroviruses 1993; 9:423-430.

3. Anderson, D.E., Malley, A., Benjamini, E., Gardner, M.B., Torres, J.V. Hypervariable epitope constructs as a means of accounting for epitope variability. Vaccine 1994; 12:736-740.

4. Windhagen, A., Anderson, D.E., Carrizosa, A., Williams, R.E., Hafler, D.A. IL-12 induces human T cells secreting IL-10 with IFN g. J Immunol 1996; 157:1127-1131.

5. Anderson, D.E., Ausubel, L.J., Krieger, J., Höllsberg, P., Freeman, G.J., Hafler, D.A. Weak peptide agonists reveal functional differences in B7-1 and B7-2 costimulation of human T cell clones. J Immunol 1997; 159:1669-1675.

6. Höllsberg, P., Scholz, C., Anderson, D.E., Greenfield, E.A., Kuchroo, V.K., Freeman, G.J., Hafler, D.A. Expression of a hypoglycosylated form of CD86 (B7-2) on human T cells and altered binding properties to CD28 and CTLA-4. J Immunol 1997; 159:4799-4805.

7. Scholz, C., Patton, K.T., Anderson, D.E., Freeman, G.J., Hafler, D.A. Expansion of autoreactive myelin basic protein reactive T cells in multiple sclerosis is independent of exogenous B7 costimulation. J Immunol 1997; 160:1532-1538.

8. Meyer, D., Anderson, D.E., Gardner, M.B., Torres, J.V. Hypervariable epitope constructs representing variability in envelope glycoprotein of SIV induce a broad humoral immune response in rabbits and rhesus macaques. AIDS Res Hum Retroviruses 1998; 14:751-760.

9. Windhagen, A., Anderson, D.E., Carrizosa, A., Balashov, K., Weiner, H.L., Hafler, D.A. Cytokine secretion of myelin basic protein reactive T cells in patients with multiple sclerosis. J Neuroimmunol 1998; 91:1-9.

10. Anderson, D.E., Torres, J.V. SRV receptor and neutralization mechanism by antibodies to the envelope glycoprotein. Viral Immunol 1999; 12:47-56.

11. Anderson, D.E.,Bieganowska, K.D., Bar-Or, A., DeOliveira, E., Carreno, B., Collins, M., Hafler, D.A. Paradoxical inhibition of T-cell function in response to CTLA-4 blockade; heterogeneity within the human T-cell population. Nature Med 2000; 6:211-214.

12. Carlos, M.P., Anderson, D.E., Gardner, M.B., Torres, J.V. Immunogenicity of a vaccine preparation representing the variable regions of the HIV-1 envelope glycoprotein. AIDS Res Hum Retroviruses 2000; 16:153-161.

13. Leung, N.J., Aldovini, A., Young, R., Jarvis, M.A., Smith, J.M., Meyer, D., Anderson, D.E., Carlos, M.P., Gardner, M.B., Torres, J.V. The kinetics of specific immune responses in rhesus macaques inoculated with live recombinant BCG expressing SIV Gag, Pol, Env, and Nef proteins. Virology 2000; 268:94-103.

14. Anderson, D.E., Carlos, M.P., Nguyen, L.N., Torres, J.V. Overcoming original (antigenic) sin. Clin Immunol 2001; 101:152-157.

15. Bar-Or, A., Oliveira, E.M.L., Anderson, D.E., Krieger, J.I., Duddy, M., O’Connor, K.C., Hafler, D.A. Immunological memory: contribution of memory B cells expressing costimulatory molecules in the resting state. J Immunol 2001; 167:5669-5677.

16. Anderson, R.C., Elder, J.B., Brown, M.D., Mandigo, C.E., Parsa, A.T., Kim, P.D., Senatus, P., Anderson, D.E., Bruce, J.N. Changes in the immunologic phenotype of human malignant glioma cells after passaging in vitro. Clin Immunol 2002; 102:84-95.

17. Oliveira, E.M.L., Bar-Or, A., Waliszewska, A.I., Cai, G., Anderson, D.E., Krieger, J.I., Hafler, D.A. CTLA-4 dysregulation in the activation of myelin basic protein reactive T cells may distinguish patients with multiple sclerosis from healthy controls. J Autoimm 2003; 20:71-81.

18. Carlos, M.P., Yamamura, Y., Yu, Q., Conzen, K., Anderson, D.E., and Torres, J.V. Humoral immunity to immunodominant epitopes of Hepatitis C virus in individuals infected with genotypes 1a or 1b. Clin Immunol 2004; 111:22-27.

19. Reddy, K.J., Banapour, B., Anderson, D.E., Lee, S.H., Marquez, J.P., Carlos, M.P., and Torres, J.V. Induction of immune responses against human papilloma viruses by hypervariable epitope constructs. Immunology 2004; 112:321-327.

20. Anderson, D.E., Llenado, R.A., and Torres, J.V. Humoral immunity and the evolution of HIV-2. Viral Immunol 2004; 17:436-439.

21. Mycko, M.P., Walder, H., Anderson, D.E., Bourcier, K.D., Wucherpfennig, K.W., Kuchroo, V.K., and Hafler, D.A. Cross-reactive TCR responses to self antigens presented by different MHC class II molecules. J Immunol 2004; 173:1689-1698.

22. Ghorbani M, Nass T, Azizi A, Soare C, Aucoin S, Giulivi A, Anderson DE, Diaz-Mitoma F. Comparison of antibody- and cell-mediated immune responses after intramuscular hepatitis C immunizations of BALB/c mice. Viral Immunol. 2005;18(4):637-48.

23. Anderson DE, Singapuri A, Kang KH, Montefiori DC, Torres JV. Timing of retroviral infection influences anamnestic immune response in vaccinated primates. Viral Immunol. 2005;18(4):689-94.

24. Koguchi K*, Anderson DE*, Yang L, O'Connor KC, Kuchroo VK, Hafler DA. Dysregulated T cell expression of TIM3 in multiple sclerosis. J Exp Med. 2006;203(6):1413-8. *These authors share first authorship

Reviews/Chapters/Editorials

1. Bar-Or A, Oliveira EM, Anderson DE, Hafler DA. Molecular pathogenesis of multiple sclerosis. J Neuroimmunol. 1999;100(1-2):252-9.

2. Anderson DE, Sharpe AH, Hafler DA. The B7-CD28/CTLA-4 costimulatory pathways in autoimmune disease of the central nervous system. Curr Opin Immunol. 1999;11(6):677-83.

3. Anderson, DE and Hafler, DA. Immune Tolerance. In: Textbook of the Autoimmune Diseases (Lahita, RG, ed.). Philadelphia: Lippincott Williams & Wilkins;2000.

4. Anderson DE, Hafler DA. Immune tolerance and the nervous system. Adv Exp Med Biol. 2001;490:79-98.

5. Anderson, DE, Bar-Or, A, and Hafler, DA. Molecular Pathology of Multiple Sclerosis. In: Molecular Pathology of Autoimmune Diseases (Theofilopoulos, AN and Bona, CA, eds.). Abingdon (UK): Taylor and Francis Publishers;2002.

6. Hafler DA, Slavik JM, Anderson DE, O'Connor KC, De Jager P, Baecher-Allan C. Multiple sclerosis. Immunol Rev. 2005;204:208-31.

7. Baecher-Allan C, Anderson DE. Regulatory cells and human cancer. Semin Cancer Biol. 2006;16(2):98-105.

8. Baecher-Allan C, Anderson DE. Immune regulation in tumor-bearing hosts. Curr Opin Immunol. 2006;18(2):214-9.

 
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