Research Faculty

Molecular Immunology
201 Bard Hall
Mail Code: 50 Haven Avenue
New York NY 10032
United States

Phone: 212-305-4721
Fax: 212-305-4722
Education and Training
M.D. 1983 Columbia University
Seth Lederman, M.D.
Director, Laboratory of Molecular Immunology,
Associate Professor
Research Summary

Our laboratory was chartered to continue investigating the function of the immune system at a fundamental level and to developing therapeutics for autoimmune diseases and HIV. Our fundamental research on the CD40-Ligand (CD154) elucidated the molecular basis of T cell helper function and led to the development of therapeutic candidates for autoimmune diseases and organ transplant rejection in collaboration with Biogen-IDEC and CellTech/UCB. The successful defense of our CD154 patents established precedents defining the relationship between therapeutics and molecular targets. In collaboration with Prof. David Baltimore (then at Rockefeller University and later MIT), we identified and functionally characterized the CD40 signaling molecule, TRAF-3. Our earlier research efforts in HIV contributed to understanding how the V3 loop of HIV gp120 affected fusion with CD4 cell membranes, an early and essential event in viral entry and infection.

Selected Publications
  1. Gamper C, Omene CO, van Eyndhoven WG, Glassman GD, Lederman S. Expression and function of TRAF-3 splice-variant isoforms in human lymphoma cell lines. Hum Immunol. 2001. 62(10):1167-77. PMID: 11600226
  2. Gamper C, van Eyndhoven WG, Schweiger E, Mossbacher M, Koo B, Lederman S. TRAF-3 interacts with p62 nucleoporin, a component of the nuclear pore central plug that binds classical NLS-containing import complexes. Mol Immunol. 2000. 37(1-2):73-84. PMID: 10781837
  3. van Eyndhoven WG, Gamper CJ, Cho E, Mackus WJ, Lederman S. TRAF-3 mRNA splice-deletion variants encode isoforms that induce NF-kappaB activation. Mol Immunol. 1999. 36(10):647-58. PMID:10509816
  4. van Eyndhoven WG, Frank D, Kalachikov S, Cleary AM, Hong DI, Cho E, Nasr S, Perez AJ, Mackus WJ, Cayanis E, Wellington S, Fischer SG, Warburton D, Lederman S. A single gene for human TRAF-3 at chromosome 14q32.3 encodes a variety of mRNA species by alternative polyadenylation, mRNA splicing and transcription initiation. Mol Immunol. 1998. 35(18):1189-206. PMID: 10199393
  5. Liu QY, Rubin MA, Omene C, Lederman S, Stein CA. Fas ligand is constitutively secreted by prostate cancer cells in vitro. Clin Cancer Res. 1998. 4(7):1803-11. PMID: 9676859
  6. Sullivan GM, Canfield SM, Lederman S, Xiao E, Ferin M, Wardlaw SL. Intracerebroventricular injection of interleukin-1 suppresses peripheral lymphocyte function in the primate. Neuroimmunomodulation. 1997 . 4(1):12-8. PMID: 9326740
  7. Lederman S, Sullivan G, Benimetskaya L, Lowy I, Land K, Khaled Z, Cleary AM, Yakubov L, Stein CA. Polydeoxyguanine motifs in a 12-mer phosphorothioate oligodeoxynucleotide augment binding to the v3 loop of HIV-1 gp120 and potency of HIV-1 inhibition independency of G-tetrad formation. Antisense Nucleic Acid Drug Dev. 1996. 6(4):281-9. Erratum in: Antisense Nucleic Acid Drug Dev 1997. 7(2):131. PMID: 9012864
  8. Karpusas M, Hsu YM, Wang JH, Thompson J, Lederman S, Chess L, Thomas D. 2 A crystal structure of an extracellular fragment of human CD40 ligand. Structure. 1995. 3(12):1426. PMID: 8747468 Erratum in: Structure. 1995. 3(12):1426. PMID: 8589998
  9. Cleary AM, Fortune SM, Yellin MJ, Chess L, Lederman S. Opposing roles of CD95 (Fas/APO-1) and CD40 in the death and rescue of human low density tonsillar B cells. J Immunol. 1995. 155(7):3329-37. PMID: 7561026
  10. Cheng G, Cleary AM, Ye ZS, Hong DI, Lederman S, Baltimore D. Involvement of CRAF1, a relative of TRAF, in CD40 signaling. Science. 1995. 267(5203):1494-8. PMID: 7533327
  11. Covey LR, Cleary AM, Yellin MJ, Ware R, Sullivan G, Belko J, Parker M, Rothman P, Chess L, Lederman S. Isolation of cDNAs encoding T-BAM, a surface glycoprotein on CD4+ T cells mediating contact-dependent helper function for B cells: identity with the CD40-ligand.Mol Immunol. 1994. 31(6):471-84. PMID: 7514269
  12. Lederman S, Yellin MJ, Cleary AM, Pernis A, Inghirami G, Cohn LE, Covey LR, Lee JJ, Rothman P, Chess L. T-BAM/CD40-L on helper T lymphocytes augments lymphokine-induced B cell Ig isotype switch recombination and rescues B cells from programmed cell death. J Immunol. 1994. 152(5):2163-71. PMID: 7907632
  13. Yellin MJ, Sippel K, Inghirami G, Covey LR, Lee JJ, Sinning J, Clark EA, Chess L, Lederman S. CD40 molecules induce down-modulation and endocytosis of T cell surface T cell-B cell activating molecule/CD40-L. Potential role in regulating helper effector function. J Immunol. 1994. 152(2):598-608. PMID: 7506727
  14. Yellin MJ, Sinning J, Covey LR, Sherman W, Lee JJ, Glickman-Nir E, Sippel KC, Rogers J, Cleary AM, Parker M, Chess L, Lederman S.T lymphocyte T cell-B cell-activating molecule/CD40-L molecules induce normal B cells or chronic lymphocytic leukemia B cells to express CD80 (B7/BB-1) and enhance their costimulatory activity. J Immunol. 1994. 153(2):666-74. PMID: 7517421
  15. Ramesh N, Fuleihan R, Ramesh V, Lederman S, Yellin MJ, Sharma S, Chess L, Rosen FS, Geha RS. Deletions in the ligand for CD40 in X-linked immunoglobulin deficiency with normal or elevated IgM (HIGMX-1). Int Immunol. 1993. 5(7):769-73. PMID: 8103673
  16. Stein CA, Cleary AM, Yakubov L, Lederman S. Phosphorothioate oligodeoxynucleotides bind to the third variable loop domain (v3) of human immunodeficiency virus type 1 gp120. Antisense Res Dev. 1993. 3(1):19-31. PMID: 8495104
  17. Lederman S, Yellin MJ, Inghirami G, Lee JJ, Knowles DM, Chess L. Molecular interactions mediating T-B lymphocyte collaboration in human lymphoid follicles. Roles of T cell-B-cell-activating molecule (5c8 antigen) and CD40 in contact-dependent help. J Immunol. 1992. 149(12):3817-26. PMID: 1281189
  18. Lederman S, Bergmann JE, Cleary AM, Yellin MJ, Fusco PJ, Chess L. Sulfated polyester interactions with the CD4 molecule and with the third variable loop domain (v3) of gp120 are chemically distinct. AIDS Res Hum Retroviruses. 1992. 8(9):1599-610. PMID: 1457206
  19. Lederman S, Yellin MJ, Krichevsky A, Belko J, Lee JJ, Chess L. Identification of a novel surface protein on activated CD4+ T cells that induces contact-dependent B cell differentiation (help). J Exp Med. 1992. 175(4):1091-101. PMID: 1348081.
  20. Yellin MJ, Lee JJ, Chess L, Lederman S. A human CD4- T cell leukemia subclone with contact-dependent helper function. J Immunol. 1991. 15;147(10):3389-95. PMID: 1834738
  21. Lederman S, DeMartino JA, Daugherty BL, Foeldvari I, Yellin MJ, Cleary AM, Berkowitz N, Lowy I, Braunstein NS, Mark GE, Chess L. A single amino acid substitution in a common African allele of the CD4 molecule ablates binding of the monoclonal antibody, OKT4. Mol Immunol. 1991. 28(11):1171-81. PMID: 1961196
  22. Reddy MM, Goetz RR, Gorman JM, Grieco MH, Chess L, Lederman S. Human immunodeficiency virus type-1 infection of homosexual men is accompanied by a decrease in circulating B cells. J Acquir Immune Defic Syndr. 1991;4(4):428-34. PMID: 1706770
  23. Lederman S, Gulick R, Chess L. Dextran sulfate and heparin interact with CD4 molecules to inhibit the binding of coat protein (gp120) of HIV. J Immunol. 1989. 15;143(4):1149-54. PMID: 2545782.

Honors and Awards
  • 1985-1990 National Institutes of Health, Physician Scientist
  • 1992-1994 Arthritis Investigator, Arthritis Foundation (National)
  • 1992-1995 "Differentiation and Function of Human Helper T cells", RO-1 (rank 8.1 percentile), P.I., Seth Lederman.
  • 1992-1995 "Differentiation and Function of Human Helper T cells", American Cancer Society (Declined).
  • 1993 Dr. Harold and Golden Lamport Award for Excellence in Clinical Science Research
  • 1993 Columbia Presbyterian Medical Center, Clinical Research Development Grant, "Preclinical Studies of the mAb 5c8", P.I., Seth Lederman.
  • 1996-1999 "Molecular Analysis of Helper T cells Function", American Cancer Society (rank, top 10%. (Declined).
  • 1996-2001 "Differentiation and Function of Human Helper T cells", RO-1 (rank 7.3 percentile), P.I., Seth Lederman, Competitive renewal.
Committees , Council, and Professional Society Memberships
  • 1990- American College of Rheumatology
  • 1990- American Federation for Medical Research (formerly, the American Federation for Clinical Research
  • 1990-1992 Faculty Council, College of Physicians and Surgeons, Columbia University, NY, NY
  • 1991- American Association of Immunologists
  • 1992- American Chemical Society - Medicinal Chemistry Division
  • 1993 New York Arthritis Foundation Grant Reviewer
  • 1993 Ad Hoc Reviewer; Immunochemical Sciences Study Section, N.I.H.
  • 1993 Ad Hoc Reviewer; Aids and Related Research Study Section (1), N.I.H.
  • 1994-1996 Medical and Scientific Committee, N.Y. Chapter of the Arthritis Foundation
  • 1994-1995 Scientific Program Abstract Reviewer - Am. College of Rheumatology Nat'l Meeting
  • 1996 Ad Hoc Reviewer, American Cancer Society, Immunology Study Section
  • 1998- American Academy of Pharmaceutical Physicians
  • 1998-2001 Grant Review Committee – Nat’l Arthritis Foundation, Cellular Immunology
  • 1999 Scientific Program Abstract Reviewer - Am. College of Rheumatology Nat'l Meeting
  • 1999-2001 Department of Medicine, Institutional Review Board for use of Human Subjects
  • 2000- Clinical Immunology Society
  • 2000-2005 American Editor – Human Immunology
  • 2003- American Society of Clinical Oncology
  • 2005- American Academy of Dermatology (Adjunct)

T cell help, Helper function, CD154, CD40-ligand; CD40-L, CD40, TRAF-3, CD40 signaling, lupus erythematous, rheumatoid arthritis, HIV, AIDS