Anne Davidson, MBBS
Investigator, Center for Autoimmunity and Musculoskeletal Diseases
Adjunct Professor Microbiology and Immunology
Albert Einstein College of Medicine
350 Community Drive, Manhasset, NY 11030
Phone: (516) 562-3840
Fax: (516) 562-2953
E-mail: adavidson1@nshs.edu

MBBS, 1978, Melbourne University
FRACP, 1985, Royal Australasian College of Physicians
Board Certified Medicine, 1990
Rheumatology, 1992

The current interests of the laboratory are focused on pathogenesis and therapy of SLE, an autoimmune disease affecting women of childbearing years. Production of autoantibodies directed against ubiquitous cellular components, such as DNA and other nuclear antigens, results in formation of immune complexes that can deposit in target tissues, such as skin, joints, kidney and brain, and initiate an inflammatory process that causes organ damage.  Other immune cells also become activated and contribute to the inflammatory process. SLE is currently treated with immune suppressing drugs that are themselves toxic. In addition, these drugs are not sufficiently efficacious at inducing long-term disease remission, and disease often recurs once the drugs are withdrawn.

The first goal of the laboratory is to understand more about the regulation of auto-antibody producing B cells and to use newly-discovered pathways of immune activation to design and test novel therapies for SLE. New therapies for SLE have become possible with the discovery that the activation of T cells requires two signals. The first signal is based on recognition of a specific antigen. The second signal is based on a conserved set of molecules on the surface of T cells called co-stimulatory receptors. When these are engaged by the appropriate co-stimulatory ligand in the presence of signal 1, cell activation proceeds. B cells also receive co-stimulatory or survival signals that synergize with signals received through the B cell receptor. Drugs based on modulating the effects of co-stimulation can therefore prevent or alter activation of both T and B cells. Several co-stimulatory agents are being used in the laboratory in three different mouse models of SLE, including one model of proliferative nephritis, one model of sclerosing kidney disease and a model of anti-phospholipid syndrome. Mice with knock-in of anti-DNA and anti-cardiolipin heavy chains have been bred into these models to allow study of the effects of treatment on B cell selection. 

The second goal of the laboratory is to understand the role of co-stimulatory molecules in target organ inflammation. Co-stimulatory receptors are involved in trafficking of immune cells to target organs. Normally, immune cells are sequestered in the lymphoid organs, such as the spleen and lymph nodes. When they traffic to a non-lymphoid organ, such as the kidney, they can induce inflammation. Recent work therefore focuses on lupus nephritis and the role of immune cell activation in kidney damage so as to understand the molecular basis for cell migration to the kidney and for resolution of inflammation after remission inducing therapies. In collaboration with Nephrologists at Mount Sinai and University of Michigan, the laboratory has constructed a molecular profile of renal inflammation and remission that has generated several testable hypotheses. Further studies will address whether similar profiles are found in human SLE. 

Finally, translational studies are being performed in the setting of clinical trials to determine the efficacy and mechanism of action of new biologic agents that target immune activation in humans.
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Lab Members:

Name:   Ioana Moisini, MD, PhD
Position:   Postdoctoral Research Fellow
Education:   MD, University of Medicine and Pharmacy “Gr. T. Popa” Iasi, Romania;
PhD, University of Tennessee Health Science Center / St. Jude Children’s Research Hospital, Memphis, TN
Research:   My projects are focused on elucidating the mechanisms of selection of autoreactive B cells using the 3H9 and D42 site-directed transgenic models and the study of the effects of various therapeutic agents on B cell tolerance and repertoire in these models.
E-mail:   imoisini@nshs.edu
    
Name:   Weiqing Huang, MD
Position:   Research Associate
Education:   Beijing Medical University, Beijing China. MD; Beijing Medical University, Beijing China. MS
Research:   My research work focuses on the pathogenesis of SLE, and the mechanism of action of novel co-stimulatory molecules on the immune system both in murine models and patients with SLE.
E-mail:   whuang@nshs.edu
    
Name:   Ramalingam Bethunaickan, PhD
Position:   Postdoctoral Research Fellow
Education:   Ph.D. in Biomedical Science 2003 from Tuberculosis Research Center (ICMR), and MGR Medical University, Chennai, India.
Research:   Mechanism of Remission of Lupus Nephritis. Stage-Specific Molecular profiling for Lupus Nephritis among different murine models of SLE.
Understanding pathogenesis of SLE nephritis, improved therapeutic strategies and identification of potential biomarkers within these models. Studies remission mechanisms in lupus nephritis, and works on renal inflammation in lupus.
E-mail:   rbethuna@nshs.edu
    
Name:   Haiou Tao
Position:   Research Assistant
E-mail:   htao@nshs.edu
    
Name:   Mark Cintron
Position:   Research Assistant
E-mail:   mcintron@nshs.edu
    
Name:   Ingrid Solano
Position:   Research Assistant
E-mail:   isolano@nshs.edu
    
Name:   Zheng (Steve) Liu
Position:   Graduate Student
E-mail:   zliu@nshs.edu

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Selected Publications:

Davidson, A., Lopez, J., Prus, D. and Sun, D.  A monoclonal anti-idiotype specific for human polyclonal IgM rheumatoid factor. J Immunol 148:3873 1992.

Youngblood, K., Fruchter, L., Ding, G., Lopez, J., Bonagura, V., and A. Davidson. Rheumatoid factors from the peripheral blood of patients with rheumatoid arthritis are genetically heterogeneous and somatically mutated.  J Clin Invest 93:852 1994.

Zhang, M., Spey, D., Ackerman, S., Majid A., and A. Davidson.  Rheumatoid factor idiotypic and antigenic specificity is strongly influenced by the light chain VJ junction. J. Imm. 156:3570 1996.

K. Teller, L Budhai, M Zhang, M.D., N Haramati,  H D. Keiser, and A Davidson. HLA DRB1 and DQB typing of Hispanic-American patients with rheumatoid arthritis: the "shared epitope" hypothesis may not apply. J. Rheumatol 23:1363-68  1996.

Budhai, L., Oh, K. and A. Davidson.  An in vitro assay for detection of glomerular binding IgG autoantibodies in patients with SLE. J. Clin. Invest. 98:1585-93 1996.

Ilan, Y., Prakash, R., Davidson, A., Jona, V., Droguett, G., Horwitz, M., Roy Chowdhury, N., and J. Roy Chowdhury. Oral tolerization to adenoviral antigens permits long term gene expression using recombinant adenoviral vectors. J. Clin. Invest. 98:2640-47 1997.

Y. Ilan, G. Droguett, N. Roy-Chowdhury, Y. Li, K. Sengupta, NR Thumalla, A. Davidson, J. Roy-Chowdhury, and MS Horwitz. Insertion of the adenoviral E3 region into a recombinant viral vector prevents anti-viral humoral and cellular immune responses and permits longterm gene expression. Proc Natl Acad Sci 94:2587-92 1997.

Zhang, M., Majid, A., Bardwell, P., Vee, C., and A. Davidson. Rheumatoid factor specificity of a VH3 encoded antibody is dependent on the heavy chain CDR3 region and is independent of protein A binding. J. Immunol. 161:2284-9 1998

Zhang, M. and A. Davidson.  A rheumatoid factor specific mimotope identified by a peptide display library. Autoimmunity 30:131-42 1999.

Mihara, M., I.Tan, Y. Chuzhin, B. Reddy, L. Budhai, A. Holzer and A. Davidson. CTLA4Ig interferes with T cell-dependent B cell maturation in murine SLE J. Clin. Invest. 106:91-101 2000.

B. Reddy, S. Gupta Y. Chuzhin, A. Kalergis, L. Budhai, M. Zhang, G. Droguett, M. Horwitz, J. Roy Chowdhury, S. G. Nathenson and A. Davidson. The effect of CD28/B7 blockade on alloreactive T and B cells after liver cell transplantation. Transplantation 71:801-11 2001.

A. Davidson and B. Diamond. Autoimmune diseases.  New Engl. J. Med. 345:340-350 2001.

X Wang, W. Huang, M.Mihara, J Sinha, and A Davidson. Mechanism of action of combined short term CTLA4Ig and anti-CD40L in murine SLE. J. Immunol. 168:2046-53 2002.

W. Huang, J. Sinha, J. Newman, B. Reddy, L. Budhai, R. Furie, A. Vaishnaw and A. Davidson. The effect of anti-CD40 ligand antibody on B cells in human SLE. Arthritis Rheum. 46:1554-62 2002.

X. Wang, W. Huang, M. Mihara, L. Schiffer and A. Davidson. Effects of anti-CD154 treatment on B cells in murine SLE Arthritis Rheum 48:495-506 2003.

A. Davidson, X. Wang, M. Mihara, M. Ramanujam, W. Huang, L. E. Schiffer, A. Akkerman and J. Sinha. Costimulatory blockade in the treatment of murine SLE. Ann. NY. Acad. Sci 987:188-198 2003.

L. Schiffer, J. Sinha, X. Wang, W. Huang, G. von Gersdorff, M. Schiffer, M.P. Madaio and A. Davidson. Short term administration of costimulatory blockade and cyclophosphamide induces remission of SLE nephritis in NZB/W F1 mice by a mechanism downstream of renal immune complex deposition. J. Immunol 171:489-97 2003.

J Reiser, M Loos, G von Gersdorff, H Watanabe, K Schwarz, C Faul, A Weins, T P DiLorenzo, M Kretzler, M Simons, Wang, J-C Schwartz, S G Nathenson, A Davidson, J A Kreidberg, P Mundel. Promotion of cell matrix adhesion and orchestration of cell-cell contacts define novel roles of B7-1 in podocytes and proteinuric kidney diseases. J. Clin. Invest. 113: 1390-7 2004.

Ramanujam. M and A. Davidson. The current status of targeting BAFF/BLyS for autoimmune diseases. Arthritis Research and Therapy 6:197-202 2004.

Ramanujam M, Wang X, Huang W, Schiffer L. Grimaldi C, Akkerman A, B. Diamond, M. Madaio and A. Davidson. The mechanism of action of TACI-Ig in murine SLE. J. Immunol 173:3524-34 2004.

A. Akkerman, W. Huang, X. Wang, M. Ramanujam, L. Schiffer, M. Madaio, S M. Factor and A.
Davidson. CTLA4Ig Prevents Initiation But Not Evolution Of Anti-Phospholipid Syndrome In NZW/BXSB Mice. Autoimmunity 2004 Oct-Nov;37:445-51.

Ye Q, Wang L, Wells AD, Tao R, Han R, Davidson A, Scott ML, Hancock WW. BAFF binding to T cell-expressed BAFF-R costimulates T cell proliferation and alloresponses. Eur J Immunol. 2004 34:2750-9. Zeguo Zhao, Elena Weinstein, Marina Tuzova, Anne Davidson, Peter Mundel, Paola Marambio, Chaim Putterman. Human lupus anti-DNA antibodies cross-react with a-actinin and induce renal disease Arthritis Rheum 2005 52:522-30.

Davidson A, Diamond B, Wofsy D and Daikh D. Block and tackle: CTLA4Ig takes on lupus. Lupus 14:197-203 2005.

Forestier C, Molano A, Im JS, Dutronc Y, Diamond B, Davidson A, Illarionov PA, Besra GS, Porcelli SA. Expansion and Hyperactivity of CD1d-Restricted NKT Cells during the Progression of Systemic Lupus Erythematosus in (New Zealand Black x New Zealand White) F1 Mice. J Immunol. 2005. 175(2):763-70.

Ramanujam M, Wang X, Huang W, Liu Z, Schiffer L, Tao H, Frank D, Rice J, Diamond B, Yu K, Porcelli S, and A Davidson. Similarities and differences between selective and non-selective BAFF blockade in murine SLE: J. Clin. Invest. 2006.116:724-34.

Davidson A and Aranow C. SLE nephritis. New mechanisms and therapies. Curr Op Rheumatology 2006 Sep;18(5):468-75.

Tomczak MF, Erdman SE, Davidson  A, Wang YY, Nambiar PR, Rogers AB, Rickman B, Luchetti D, Fox JG and Horwitz BH. Inhibition of H. hepaticus-induced colitis by IL-10 requires the presence of the p50/p105 subunit of NFkB. J. Immunol. 2006, 177: 7332-7339.

Poutahidis T, Haigis KM, Rao VP, Nambiar PR, Taylor CL, Ge Z, Watanabe K, Davidson  A, Horwitz BH, Fox JG, Erdman SE. Cytokine mediated rapid reversal of epithelial invasion in a mouse model of microbially-induced colon carcinoma. Carcinogenesis 28(12):2614-23 2007.

Martin DA, Zhang K, Kenkel J, Hughes G, Clark E, Davidson A and KB Elkon. Autoimmunity from adoptively transferred dendritic cells is initiated by both αβ and γδ T-cells but does not require MyD88 signaling. J. Immunol. 2007 179:5819-28. 2007.

Schiffer L, Bethunaickan R, Ramanujam M, Huang W, Schiffer M, Tao H, Madaio MM, Bottinger EP and A Davidson. Activated renal macrophages are markers of disease onset and disease remission in lupus nephritis J. Immunol 2008 180: 1938-1947. PMC2587994.

Ramanujam M and A Davidson. Targeting of the immune system in systemic lupus Erythematosus. Exp. Rev. Mol. Med 2008 Jan 21;10:e2.

Ramanujam M and A Davidson. BAFF blockade for SLE – will the promise be fulfilled? Immunological Reviews 2008 223:156-74.

Kahn P, Ramanujam M, Bethunaickan R, Huang W, Tao H, Madaio MP, Factor SM and A Davidson. Prevention of murine anti-phospholipid syndrome by BAFF blockade. Arthritis and Rheumatism 2008 58:2824-34. PMC2596604

Ramanujam M, Kahn P, Huang W, Tao H, Tepas M, Alpoge E, Factor SM, Madaio MP and A Davidson. Interferon alpha treatment of NZN/BXSB F1 females mimics some but not all features associated with the Yaa mutation. Arthritis and Rheumatism (in press).