Columbia University

College of Physicians & Surgeons

Division of Pulmonary, Allergy & Critical Care

Divisional Faculty

Paul B. Rothman, M.D.

Chief, Division of Pulmonary, Allergy & Critical Care
Richard J. Stock Professor of Medicine (Immunology) and Microbiology

Mailing Address:

Columbia Univeristy
630 West 168th Street
PH 8 East Room 101
New York, MY 10032

Biography:

B.S., Massachusetts Institute of Technology, 1980
M.D., Yale University School of Medicine, 1984
Residency, The Presbyterian Hospital in the City of New York
Clinical Fellowship, Division of Rheumatology , Columbia University
Research Fellowship, Department of Biochemistry (Dr. F. Alt), Columbia University

Honors:

1980 Phi Beta Kappa, MIT
1980 John Asinari Research Award, Honorable Mention, MIT
1984 Alpha Omega Alpha, Yale
1984 Merck Manual Award for Outstanding Scholastic Achievement, Yale School of Medicine
1986 NIH Physician Scientist Award
1989 James S. McDonnell Foundation Career Development Award in Molecular Medicine and Oncology
1990 American College of Rheumatology Senior Rheumatology Scholar Award
1991 Pfizer Scholars Award for New Faculty
1992 Pew Scholar in the Biomedical Sciences
1994 Pharmacia Allergy Research Foundation Fellowship Award
1995 Leukemia Society of America Scholar Award
1996 Cancer Research Institute/Partridge Foundation Clinical Investigator Award
1996 Asthma and Allergy Foundation of America Investigator Award
1997 Member, American Society for Clinical Investigation
1997 Pharmacia Allergy Research Foundation International Award
1998 Member, Collegium Internationale Allergologicum
2000 Pfizer Visiting Professor on Allergic Diseases and Asthma, University of Cincinnati

Clinical and Research Interests:

Dr. Rothman's work centers on understanding the role cytokines and cytokine signaling plays in both normal lymphocyte development and leukemic transformation. He investigates the role of cytokine signaling ina asthma and allergic immune responses, mechanisms underlying the ability of the v-abl oncogene to transform pre-B cells, how cytokines signal cells to activate transcription, and how the BCL-6 oncoprotein regulates cytokine signal transduction.

Publications:

Thomas, Y., Rogozinski, L., Rothman, P., Rabbani, L., Andrews, J., Irigoyen, O., and Chess, L. (1982). Further dissection of the funtional heterogeneity within the OKT4 and OKT8 human T cell subsets. J. Clin. Immunol. 2:85-145.

Lutzker, S., Rothman, P., Pollock, R., Coffman, R., and Alt, F. (1988). Regulation of the expression of germline immunoglobulin gamma 2b transcripts by LPS and IL-4: evidence for directed heavy chain class switching. Cell. 53:177-184.

Rothman, P., Lutzker, S., Cook, W., Coffman, R., and Alt, F. (1988). Interleukin 4 induction of C epsilon transcripts in B lymphoid cells. J. Exp. Med. 168:2385-2390.

Alt, F.W., Ferrier, P., Malynn, B., Lutzker, S., Rothman, P., Berman, J., Blackwell, K., Mellis, S., Pollock, R., Furley, A., Rathbun, G., Yancopoulos, G., Logtenberg, T., Morrow, M., Cook, W., Heinke, B., and Suh, H. (1988). Control of recombination events during lymphocyte differentiation: heavy chain variable region gene assembly and heavy chain class-switching. Ann. N.Y. Acad. Sci. Vol. 556:9-24.

Rothman, P., Li, S.C., and Alt, F. (1989). Molecular mechanism of isotype class-switching. Sem. in Immunol. Vol. 1(1):65-77.

Rothman, P., Chen, Y., Lutzker, S., Li, S., Coffman, R., and Alt, F. (1990). Structure and expression of germline Ig heavy chain epsilon transcripts: IL-4 plus LPS-directed switching to C-epsilon. Mol. and Cell. Biol. 10:11672-1679.

Rothman, P., Lutzker, S., Gorham, B., Stewart, V., and Alt, F.W. (1990). Mitogen and lymphokine regulation a germline gamma3 transcription unit: regulation of heavy chain class switching. Int. Immunol. 2:621-627.

Yancopoulos, G.D., Oltz, E., Rathbun, G., Smith, R., Lansford, R., Rothman, P., Kaplan, K., Procop, S., and Alt, F.W. (1990). Isolation and characterization of genes specifically and differentially expressed during the pre-B or pre-B plus B cell differentiation stages. Proc. Natl. Acad. Sci. USA 87:5759-5763.

Li, S.C., Rothman, P., Boothby, M., Ferrier, P., Glimcher, L., and Alt, F.W. (1991). Control of immunoglobulin heavy chain constant region gene expression. Advances in Experimental Medicine and Biology: Mechanisms of Lymphocyte Activation and Immune Regulation III. Vol. 292:245-251.

Rothman, P., Li, S., Glimcher, L., Alt, F.W., and Boothby, M. (1991). Identification of an IL-4/LPS responsive element at the germline epsilon promoter. Mol. Cell. Biol. 11:5551-5561.

Schultz, C.L., Rothman, P., Kühn, R., Kehry, M., Müller, W., Rajewsky, K., Alt, F., Coffman, R.L. (1992). T helper cell membranes promote IL-4-independent expression of germ-line Cgamma1 transcripts in B cells. J. Immunol. 149:60-64.

Coffman, R.L., Lebman, D.A., and P. Rothman (1993). The mechanism and regulation of immunoglobulin isotype switching. Advances in Immunology. 54:229-270.

McIntyre, T.M., Klinman, D.R., Rothman, P., Lugo, M., Dasch, J.R., Mond, J.J., and C. Snapper. (1993). Transforming growth factor ß1 selectively stimulates IgG2b secretion by LPS-activated murine B cells. J. Exp. Med. 177:1031-1038.

Rothman, P. (1993). Interleukin-4 targeting of immunoglobulin heavy chain class-switch recombination. Research in Immunology. 144:579-583.

Xu, L., Gorham, B., Li, S.C., Bottaro, A., Alt, F.W., and P. Rothman. (1993). Replacement of germline epsilon promoter by gene targeting alters control of immunoglobulin heavy chain class-switching. Proc. Natl. Acad. Sci. USA. 90:3705-3709.

Bottaro, A., Lansford, R., Xu, L., Zhang, J., Rothman, P., Alt, F.W. (1994). S region transcription per se promotes basal IgE class switch recombination but additional factors regulate the efficiency of the process. EMBO J. 13:665-674.

Covey, L.R., Cleary, A.M., Yellin, M.J., Ware, R.W., Sullivan, G., Belko, J., Parker, M., Lee, J.J., Rothman, P., Chess, L., and S. Lederman. (1994). Isolation of cDNAs encoding T-BAM, a surface protein on T lymphocytes mediating contract-dependent helper function for B cells: identity with the CD40-ligand. Mol. Immunol. 31:471-484.

Lederman, S., Yellin, M.J., Cleary, A.M., Pernis, A., Inghirami, G., Cohn, L.E., Covey, L., Lee, J.J., Rothman, P., and L. Chess. (1994). The T-BAM/CD40-L molecule on T lymphocytes augments lymphokine-induced B cell immunoglobulin isotype switch recombination and rescues B cells from programmed cell death. J. Immunol. 152:2163-2171.

Liao, F., Birshtein, B., and Rothman, P. (1994). The transcription factor BSAP (NF-HB) is essential for immunoglobulin germline epsilon transcription. J. Immunol. 6:491-498.

Li, S.C., Rothman, P., Zhang, J., Hirsh, D., and F. Alt. (1994). Germline µ expression during immunoglobulin heavy chain class switching. Int. Immunol. 6:491-498.

Rothman, P., B. Kreider, D. Levy, U. Wegenka, A. Eilers, T. Decker, F. Horn, H. Kashleva, J. Ihle, and C. Schindler. Cytokines signal through tyrosine phosphorylation of a family of related transcription factor. Immunity. 1:457-468.

Schindler, C., H. Kashleva, A. Pernis, R. Pine, and P. Rothman. (1994). STF-IL4: A novel IL-4 induced signal transducing factor. EMBO J. 13:1350-1356.

Xu, L., and P. Rothman. (1994). IFN-gamma represses epsilon germ-line transcription and subsequently down-regulates switch recombination to epsilon. Int. Immunol. 6:515-522.

Danial, N., Pernis, A., and P. Rothman. (1995). v-abl activates JAK-STAT signaling in pre-B cells. Science. 269:1875-1877.

Kim, J., R. Reeves, P. Rothman, and M. Boothby. (1995). The non-histone chromosomal protein HMG-I (Y) regulates the immunoglobulin epsilon germline RNA promoter. Europ. J. Immunol. 25:798-808.

Pernis, A., Golub, K., Garfeind, E., Coffman, R.L., Schindler, C., and P. Rothman. (1995). Differential STAT1 activation among T helper cell populations. Science. 269:245-248.

Pernis, A., Witthuhn, B., Keegan, A., Garfein, E., Ihle, J., Paul, W., Pierce, J., and P. Rothman. (1995). IL-4 signals through two related pathways. Proc. Natl. Acad. Sci. USA. 92:7971-7975.

Pernis, A., J. Yopp, S. Gupta, E. Garfein, H. Kashleva, C., Schindler, and P. Rothman. (1995). Gamma chain-associated cytokine receptors signal through distinct transducing factors. J. Biol. Chem. 270:14517-14522.

Rothman, P., and R.L. Coffman. (1996). Ig Heavy Chain Class-Switching. In Handbook of Experimental Immunology, 5th Edition (Blackwell Sci. Pub.: Cambridge). Chapter 5, Section 2.

Ryan, J.J., McReynolds, L.J., Wang, L-H., Keegan, A., Garfein, E., Rothman, P., Nelms, K., Paul, W.E. (1996). IL-4 induced growth and gene expression are predominately controlled by distinct regions of the human IL-4 receptor. Immunity. 4:123-132.

Chai, S. and P. Rothman. (1997). Activation of Variable JAKs and STATs in cells expressing BCR-abl. J. Immunol. 158:4720-4728.

Dorsch, M., Fan, P.-D., Danial, N., Rothman, P., and S. Goff. (1997). The thrombopoietin receptor can mediate proliferation without activation of the Jak-STAT pathway. J.Exp. Med. 186:1947-1955.

Lu, B., Reichel, M., Fisher, D.A., Smith, J.F. and Rothman, P. (1997). Carboxy terminus of Stat6 is required for IL-4 induced transcription. J. Immunol. 159:1255-1264.

Miller, R.L. and Rothman, P.B. (1997). Molecular mechanisms controlling IgE responses. In Handbook of immune modulating agents. T.F. Kresina, editor (Marcel Dekker Inc.). Chap. 2.

Reichel, M., B. Nelson, P. Greenberg, and P. Rothman. (1997). Homodimerization of the interleukin-4 receptor alpha chain cytoplasmic domain is sufficient for activation of
Stat6 and induction of IL-4-specific gene expression. J. Immunol. 158:5860-5867.

Ye, B.H., Cattoretti, G., Zhang, J., Hawe, N., Shen, Q., de Waard, R., Orazi, A., Nouri-Shrazi, M., Chaganti, R.S.K., Rothman, P., Stall, A., Pandolfi, P.P., and R. Dalla-Favera. (1997). The BCL-6 proto-oncogene controls germinal center formation and TH2-type inflammation. Nature Genetics. 16:161-170.

Banerjee, A. and P. Rothman. (1998). IL-7 Reconstitutes Multiple Aspects of v-Abl Mediated Signaling. J. Immunol. 161:4611-4617.

Danial, N., Losman, J. A., Lu, T., Yip, N., Krishnan, K., Krolewski, J., Goff, S.P., Wang, J.Y.J., and P.Rothman. (1998). Direct interaction of Jak 1 and v-Abl is required for v-Abl induced activation of STATs and proliferation. Mol. Cell. Biol. 18:6795-6804.

Lu, B., Ebensperger, C., Dembic, A., Wang, Y., Kuehner, D., Kvatyuk, M., Lu, T.,Ng, D., Stall, A., Coffman, R.L., S. Pestka, and P. Rothman. (1998). Targeted disruption of the IFN receptor gene results in severe immune defects in mice. Proc. Natl. Acad. Sci. USA 95:8233-8238.

Miller, R.L. and P. Rothman. (1998). Analysis of cytokine-mediated immunoglobulin E pathway in asthma and hyperimmunoglobulin E syndrome. J. Allergy Clin. Immunol. 102:503-511.

Morawetz, R.A., Giese, N.A., Gabriele, L., Rothman, P., Horak, I., Ozato, K., and H.C. Morse III. (1998). Relationship of cytokines and cytokine signaling to immunodeficiency disorders in the mouse. Brazilian Journal of Medical and Biological Research. 31:61-67.

Pan, P.-Y. and P. Rothman IL-4 Receptor Mutations. Current Opinions in Immunology (1999) 11:615-620.

Tau, G. and P. Rothman, Biological functions of IFN-? Receptors. Allergy (1999) 54:1233-1251.

Losman, J., Chen, P., Hilton, D., and P. Rothman. SOCS 1 Inhibits IL-4 Signal Transduction. (1999) J. Immunol. 162:3770-3774

Harris, M., Chang,C.-C., Berton, M.T., Danial, N., Zhang, J., Kuehner, D., Ye, B. H., Cattoretti, G., Kvatyuk, M., Pandolfi, P. P., Dalla-Favera, R., and P. Rothman. Transcriptional Repression of Stat 6-Dependent IL-4 Induced Genes by BCL-6: Specific Regulation of I? Transcription and IgE Switching. (1999) Mol Cell Biol, 19:7264-7275.

Dorsch, M., N. Danial, P. Rothman, and S.P. Goff A Thrombopoietin Receptor Mutant Deficient in Jak-STAT Activation Mediates Proliferation but nit Differentiation in UT-7 cells. (1999) Blood,94:2676-2685.

Tau, G., von der Weid, T.,. Wang, Y., Lu, B.,Cowan, S., Kvatyuk, M., Pernis, A., Cattoretti, G. Braunstein, N., Coffman, R.L., and P. Rothman. IFN-g Signaling Alters the Function of TH1 Cells (2000) J. Exp. Med. 977-986.

Giallourakis, C., Kashiwada, M., Pan, P.Y., Danial, N., Jiang, H., Coggeshall, K. M., Cambier, J. and P. Rothman. Positive Regulation of IL-4 Mediated Proliferation by the SH2-Containing Inositol 5'-Phosphatase (SHIP) (2000) J. Biol. Chem. 29275-29282.

Serreze, D.V., Post, C.M., Chapman, H.D., Ellis, E.A., Lu, B, Rothman, P. Interferon-gamma Receptor Signaling is Dispensable for the Development of Autoimmune type I Diabetes in NOD mice. (2000) Diabetes 49:2007-2011

Losman, J., P. Chen, H. Jiang, P.Y. Pan, M. Kashiwada, C. Giallourakis, K. Foltenyi, and Paul Rothman IL-4 Signaling is Regulated Through the Recruitment of Phosphatases, Kinases, and SOCS Proteins to the Receptor Complex. (2000) Cold Spring Harbor Symposia, CSH Press, Vol LXIV:405-416.

Danial, N. and P. Rothman. JAK-STAT Signaling Activated by Abl Oncogenes, Oncogene. (2000) 19:2523-2531.

Jiang, H, Harris, M.B., and P. Rothman. IL-4/13 Signaling, Beyond JAK/STAT. Journal of Allergy and Clinical Immunology, (2000) 105(6 Pt 1):1063-70.

Canfield, S. and P. Rothman, TH2 Inflammation Repressed by Chemokines. (2000) invited News and Views, Nature Immunology. 1:189-190.

Chen , P.X, Losman, J.A., P. Rothman, (2000) SOCS Proteins, Regulators of Intracellular Signaling, Immunity. 13:287-290

Kashiwada, M., Giallourakis, C.G., Pan, P.Y., and P. Rothman. Immunoreceptor-based Inhibitory (ITIM) of IL-4 Receptor Associates with SH2-containing Phosphatases and Regulates IL-4 Induced Proliferation. (2001) (J. Immunol.167:6382-7)

Jiang, H., Kashiwada, M., Foltenyi, K., Vuong, B., Donahue, L., Hehn, B., and P. Rothman. Protein tyrosine kinase Fes mediates the Jak-dependent activation of IRS in interleukin-4 signaling. (2001) J. Immunol. 166:2627-2634

Tau, G., Weisberg, J., Cowan, S., Braunstein, N. and P. Rothman Regulation of IFN-? Signaling is Essential for the Cytotoxic Activity of CD8+ T Cells (2001) (J. Immunol., 167:5574-5582)

American Lung Association Asthma Clinical Research Centers (P. Rothman Principal Investigator, New York Consortium). The Safety of Inactivated Influenza Vaccine in Adults and Childen with Asthma (2001). New England Journal of Medicine. 345:1529-1536.

Chen, X. P.; Losman, J. A.; Cowan, S.; Donahue, E.; Fay, S.; Vuong, B. Q.; Nawijn, M. C.; Capece, D.; Cohan, V. L.; Rothman, P. Pim serine/threonine kinases regulate the stability of Socs-1 protein. (2002) Proc Natl Acad Sci U S A 99: 2175-2180.

Schroeder, A.J., Arimura, A., Pavlidis, P., Capece, D., and Paul B. Rothman STAT6 Serves as a Positive and Negative Regulator of Gene Expression in IL-4-stimulated B lymphocytes.(2002) J. Immunol., Cutting Edge. 168:996-1000

Banerjee, A., Banks, A.S., Nawijn,, M.C., Chen, X.P., and P. Rothman. Suppressor of Cytokine Signaling (SOCS)-3 Inhibits Activation of Nuclear Factor of Activated T Cells (NFAT)p (2002) J. Immunol., Cutting Edge. 168:4277-4281.

Toniato, E., Chen, P., Losman, J., Donahue,L., and P. Rothman. TRIM8/GERP RING Finger Protein Interacts with SOCS-1 (2002). J. Biol. Chem. 277: 37315-37322.

Oki, S., Limander, A., Danial, N., and P. Rothman. Functional involvement of Akt signaling downstream of Jak1 in v-Abl-induced activation of hematopoietic cells (2002) Blood, 100:966-973.

Banerjee, A, Harris, M.B. and P. Rothman, (2002) Inhibition of Cytokine Signaling Therapeutic Targets of Airway Inflammation. Marcel Dekker, Inc. in press

Pernis, A.B. and P. Rothman, JAK-STAT Signaling in Asthma, JCI, (2002) 109:1279-1283

Losman, J.A., X.P. Chen , B.Q. Vuong, and P.Rothman. PP2A Regulates the Stability of Pim Protein Kinases. (in press, JBC)

Serreze, D.V., Pierce, M.A., Post, C.M., Chapman, H.D., Savage, H., Bronson, R.T., Rothman, P., and G.A.Cox. Paralytic autoimmune myositis develops in NOD mice made Th1 cytokine deficient by expression of an IFN-g receptor b chain transgene. (2003)J. Immunol. in press.