University of Rochester School of Medicine
Department of Microbiology & Immunology 
Faculty Profile

Portrait of David Topham, Ph.D.

Ph.D. (1994)
University of Vermont

David Topham
Associate Professor of Microbiology & Immunology

Primary Academic Appointment:
  Dept. of Microbiology and Immunology

Center Affiliation:
  Center for Vaccine Biology and Immunology
  Environmental Health Sciences Center

GEBS Cluster Affiliations:
  IMV - Immunology, Microbiology, and Virology
Contact Information
University of Rochester
School of Medicine and Dentistry
601 Elmwood Ave, Box 609
Rochester, New York 14642
 Medical Center
KMRB 3-9631
Phone: (585) 273-1403
Fax: (585) 273-2452
E-Mail: david_topham@urmc.rochester.edu
Research Focus
T Cell Immunity Against Respiratory Viruses
Research Overview
Virus infections of the respiratory tract are responsible for a great deal of illness and even death among the world's human population. Influenza, in particular, has a history of causing deadly pandemics and the continuing emergence of highly pathogenic H5 influenzas around the world is reason for concern. It is essential to understand how the immune system clears a virus infection and provides long term immunity if we are to design more rational vaccination and treatment strategies. The lab has a combined program in basic research using animal models of influenza infection and immunity, as well as a translational research program to study human immune responses to influenza infection and vaccination.  Within these programs we are investigating the mechanisms that provide optimal immune protection against influenza virus.  One particular focus is to understand how T cells are regulated in the environment of the lung tissue and airways.  We believe this is the key to generating long-lived protective immunity against diverse influenza viruses, including potential pandemic strains.  The concepts and information we gather from the animal models are being directly translated into the human situation.  To this end, we have established the New York Influenza Center of Excellence, a robust, collaborative program for basic and translational investigation of influenza virology, pathogenesis, immunology, and vaccines.
Recent Publications
Lee HY, Topham DJ, Park SY, Hollenbaugh J, Treanor J, Mosmann TR, Jin X, Ward B, Miao H, Holden-Wiltse J, Perelson AS, Zand M, Wu H Simulation and Prediction of the Adaptive Immune Response to Influenza A Virus Infection. J Virol. 2009 May 13;

Bancos S, Bernard MP, Topham DJ, Phipps RP Ibuprofen and other widely used non-steroidal anti-inflammatory drugs inhibit antibody production in human cells. Cell Immunol. 2009 Apr 3;

Klein I, Cornejo JC, Polakos NK, John B, Wuensch SA, Topham DJ, Pierce RH, Crispe IN "Kupffer cell heterogeneity: functional properties of bone marrow derived and sessile hepatic macrophages." Blood. 2007 Dec 1;110(12):4077-85
Richter MV, Topham DJ "The {alpha}1beta1 Integrin and TNF Receptor II Protect Airway CD8+ Effector T Cells from Apoptosis during Influenza Infection." J Immunol. 2007 Oct 15;179(8):5054-63
Klein I, Cornejo JC, Polakos NK, John B, Wuensch SA, Topham DJ, Pierce RH, Crispe IN "Kupffer cell heterogeneity: functional properties of bone marrow-derived and sessile hepatic macrophages." Blood. 2007 Aug 9;
Polakos NK, Klein I, Richter MV, Zaiss DM, Giannandrea M, Crispe IN, Topham DJ "Early Intrahepatic Accumulation of CD8+ T Cells Provides a Source of Effectors for Nonhepatic Immune Responses." J Immunol. 2007 Jul 1;179(1):201-10
Richards KA, Chaves FA, Krafcik F, Topham DJ, Lazarski CA, Sant AJ "Direct ex vivo analyses in HLA-DR1 transgenic mice reveal an exceptionally broad pattern of immunodominance in the primary HLA-DR1 restricted CD4 T cell response to influenza hemagglutinin." J Virol. 2007 May 16;
Richter M, Ray SJ, Chapman TJ, Austin SJ, Rebhahn J, Mosmann TR, Gardner H, Kotelianski V, Defougerolles AR, Topham DJ.  "Collagen Distribution and Expression of Collagen-Binding {alpha}1beta1 (VLA-1) and {alpha}2beta1 (VLA-2) Integrins on CD4 and CD8 T Cells during Influenza Infection." J Immunol. 2007 Apr 1;178(7):4506-16.
Treanor J, Wu H, Liang H, Topham DJ "Immune responses to vaccinia and influenza elicited during primary versus recent or distant secondary smallpox vaccination of adults." Vaccine. 2006 Nov 17;24(47-48):6913-23
Polakos NK, Cornejo JC, Murray DA, Wright KO, Treanor JJ, Crispe IN, Topham DJ, Pierce RH.  "Kupffer cell-dependent hepatitis occurs during influenza infection." Am J Pathol. 2006 Apr;168(4):1169-78; quiz 1404-5.
Divekar AA, Zaiss DM, Lee FE, Liu D, Topham DJ, Sijts AJ, Mosmann TR.  "Protein vaccines induce uncommitted IL-2-secreting human and mouse CD4 T cells, whereas infections induce more IFN-gamma-secreting cells."  J Immunol. 2006 Feb 1;176(3):1465-73.
Chapman, T. J, Castrucci, M. R, Padrick, R. C, Bradley, L. M. Topham, D. J.  "Antigen-specific and non-specific CD4(+) T cell recruitment and proliferation during influenza infection." Virology (in press)
Ray SJ, Franki SN, Pierce RH, Dimitrova S, Koteliansky V, Sprague AG, Doherty PC, de Fougerolles AR, Topham DJ. The collagen binding alpha1beta1 integrin VLA-1 regulates CD8 T cell-mediated immune protection against heterologous influenza infection. Immunity 20:167-79, 2004.
Sangster MY, Riberdy JM, Gonzalez M, Topham DJ, Baumgarth N, Doherty PC. An Early CD4+ T Cell-dependent Immunoglobulin A Response to Influenza Infection in the Absence of Key Cognate T-B Interactions. J. Exp. Med. 198 1011-1021, 2003.
Topham DJ, Crispe IN. Contrasting urban and rural lifestyles of memory CD8+ T cells. Immunity 18:584-6, 2003.
Topham DJ, Castrucci MR, Wingo FS, Belz GT, Doherty PC. The Role of Antigen in the Localization of Naive, Acutely Activated, and Memory CD8(+) T Cells to the Lung During Influenza Pneumonia. J Immunol. 167:6983-6990, 2001.
Topham DJ, Cardin RC, Christensen JP, Brooks JW, Belz GT, Doherty PC. Perforin and Fas in murine gammaherpesvirus-specific CD8(+) T cell control and morbidity. J Gen Virol. 82:1971-81, 2001.
Sangster MY, Topham DJ, D'Costa S, Cardin RD, Marion TN, Myers LK, Doherty PC. Analysis of the virus-specific and nonspecific B cell response to a persistent B-lymphotropic gammaherpesvirus. J Immunol. 164:1820-8, 2000.
Marine JC, McKay C, Wang D, Topham DJ, Parganas E, Nakajima H, Pendeville H, Yasukawa H, Sasaki A, Yoshimura A, Ihle JN. SOCS3 is essential in the regulation of fetal liver erythropoiesis. Cell 98:617-27, 1999.
Marine JC, Topham DJ, McKay C, Wang D, Parganas E, Stravopodis D, Yoshimura A, Ihle JN. SOCS1 deficiency causes a lymphocyte-dependent perinatal lethality. Cell 98:609-16, 1999.
Moriggl R, Topham DJ, Teglund S, Sexl V, McKay C, Wang D, Hoffmeyer A, van Deursen J, Sangster MY, Bunting KD, Grosveld GC, Ihle JN. Stat5 is required for IL-2-induced cell cycle progression of peripheral T cells. Immunity 10:249-59, 1999.

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