Daniel H. Conrad , Ph.D.
Professor

Phone: (804) 828-2311
Dept. Fax: (804) 828-9946
e-mail: dconrad@vcu.edu

Address:
Department of Microbiology & Immunology
Virginia Commonwealth University
PO Box 980678
1217 E. Marshall St., 419 Medical Sciences Building 
Richmond, VA 23298-0678

Professional Experience

• B.S., 1970, W. Virginia Wesleyan College 
• Ph.D., 1973, W. Virginia University 
• Postdoctoral Studies: 1973-1976, University of Manitoba Winnipeg, Canada;  1977-1978, Medical College of Virginia

Research Interests:

Approximately one third of the U.S. population suffers from IgE-mediated allergic disease. The high incidence of IgE-mediated allergic disease in man has lead to a strong commitment to understanding the basic mechanisms involved in IgE-mediated conditions with the objective of developing new methods for alleviation or even elimination of human allergy.

My laboratory is involved in studies of the basic mechanisms of IgE-mediated allergic disease. Special attention is paid to cell surface receptors for IgE. Two general classes of these receptors are known to exist; the first, known as Fce RI, has a very high affinity for IgE and is found exclusively on mast cells and basophils. Crosslinking of FceRI causes these cells to release the mediators that cause allergy; however, the biochemical mechanisms of this mediator release process are poorly understood.
Additional studies have shown an additional class of IgE Fc receptors, known as FceRII. These receptors are present on a wide variety of hematopoietic cells. Recent molecular cloning studies FceRI and FceRII are completely unrelated proteins. FceRII receptors are thought to be important with regard to parasitic immunity and in regulating IgE synthesis. These receptors are also involved in the regulation of B cell activation and differentiation as evidenced by the finding that the FceRII was identical with the B cell activation antigen CD23.

The involvement of the FceRII in B cell activation and eventual immunoglobulin (especially IgE) synthesis is an area of great interest. The lymphokine known as interleukin 4 (IL-4) both "turns on" IgE synthesis, via a switching mechanism as well as increasing FceRII synthesis. We have established a correlation between high FceRII levels and decreased IgE synthesis and the mechanism for this inhibition is being studied. This involves both a transgenic CD23 overexpression models as well as in vitro developed models. This correlation is currently being studied with the objective of developing methodologies to regulate IgE synthesis. In addition, the manner of interaction of the Fce RII with IgE is being carefully studied, with the objective of developing reagents that will block this interaction and thus, help control IgE-mediated allergic disease. The potential involvement of CD23 in B cell apoptosis is also being investigated.  Other studies have shown that the FceRII is highly efficient in enhancing antigen presentation/ processing by B cells and the mechanism for that enhancement is being sought. Finally, recent studies have identified ADAM10 as the primary sheddase that cleaves CD23 from the membrane.  Since IgE production is inversely related to CD23 cleavage, this identification potentially provides a new mechanism to control IgE production.

Selected Publications:

Caven,T.H., A.Shelburne, J.Sato, Y.Chan-Li, S.Becker, and D.H.Conrad. 2005. IL-21 dependent IgE production in human and mouse in vitro culture systems is cell density and cell division dependent and is augmented by IL-10. Cell Immunol. 238:123-134.

Ford,J.W., M.A.Kilmon, K.M.Haas, A.E.Shelburne, Y.Chan-Li, and D.H.Conrad. 2006. In vivo murine CD23 destabilization enhances CD23 shedding and IgE synthesis. Cell Immunol. 243:107-117.

Pongratz,G., J.W.McAlees, D.H.Conrad, R.S.Erbe, K.M.Haas, and V.M.Sanders. 2006. The level of IgE produced by a B cell is regulated by Norepinephrine in a p38 MAPK- and CD23-dependent manner. J Immunol 177:2926-2938.

Sukumar,S., D.H.Conrad, A.K.Szakal, and J.G.Tew. 2006. Differential T cell-mediated regulation of CD23 (Fc epsilonRII) in B cells and follicular dendritic cells. J.Immunol. 176:4811-4817.

Weskamp,G., J.W.Ford, J.Sturgill, S.Martin, A.J.Docherty, S.Swendeman, N.Broadway, D.Hartmann, P.Saftig, S.Umland, A.Sehara-Fujisawa, R.A.Black, A.Ludwig, J.D.Becherer, D.H.Conrad, and C.P.Blobel. 2006. ADAM10 is a principal 'sheddase' of the low-affinity immunoglobulin E receptor CD23. Nat.Immunol. 7:1293-1298.

Kilmon,M.A., A.E.Shelburne, Y.Chan-Li, K.L.Holmes, and D.H.Conrad. 2004. CD23 trimers are preassociated on the cell surface even in the absence of its ligand, IgE. J.Immunol 172:1065-1073.

Chen,B.H., M.A.Kilmon, C.Ma, T.H.Caven, Y.Chan-Li, A.E.Shelburne, R.M.Tombes, E.Roush, and D.H.Conrad. 2003. Temperature effect on IgE binding to CD23 versus Fc epsilon RI. J.Immunol. 170:1839-1845.

Chen,B.H., C.Ma, T.H.Caven, Y.Chan-Li, A.Beavil, R.Beavil, H.Gould, and D.H.Conrad. 2002. Necessity of the stalk region for immunoglobulin E interaction with CD23. Immunology 107:373-381.

Rabah,D. and D.H.Conrad. 2002. Effect of cell density on in vitro mouse immunoglobulin E production. Immunology  106:503-510.

Kilmon,M.A., R.Ghirlando, M.P.Strub, R.L.Beavil, H.J.Gould, and D.H.Conrad. 2001. Regulation of IgE production requires oligomerization of CD23. J.Immunol. 167:3139-3145.

Payet-Jamroz,M., S.L.Helm, J.Wu, M.Kilmon, M.Fakher, A.Basalp, J.G.Tew, A.K.Szakal, N.Noben-Trauth, and D.H.Conrad. 2001. Suppression of IgE responses in CD23-transgenic animals is due to expression of CD23 on nonlymphoid cells. J Immunol 166:4863-4869.

Rabah,D., S.Grant, C.Ma, and D.H.Conrad. 2001. Bryostatin-1 specifically inhibits in vitro IgE synthesis. J.Immunol. 167:4910-4918.

Haczku,A., K.Takeda, E.Hamelmann, J.Loader, A.Joetham, I.Redai, C.G.Irvin, J.J.Lee, H.Kikutani, D.Conrad, and E.W.Gelfand. 2000. CD23 exhibits negative regulatory effects on allergic sensitization and airway hyperresponsiveness. Am.J.Respir.Crit Care Med. 161:952-960.

Wang,Z., Van Tuyle,G., Conrad,D., Fisher,P.B., Dent,P., and Grant,S. 1999. Dysregulation of the cyclin-dependent kinase inhibitor p21WAF1/CIP1/MDA6 increases the susceptibility of human leukemia cells (U937) to 1-beta-D-arabinofuranosylcytosine-mediated mitochondrial dysfunction and apoptosis [In Process Citation]. Cancer Res. 59:1259-1267.

Payet,M.E., Woodward,E.C., and Conrad,D.H. 1999. Humoral response suppression observed with CD23 transgenics. J.Immunol. 163:217-223.

Payet,M. and Conrad,D.H. 1999. IgE regulation in CD23 knockout and transgenic mice [In Process Citation]. Allergy 54:1125-1129.

Tinnell,S.B., Jacobs-Helber,S.M., Sterneck,E., Sawyer,S.T., and Conrad,D.H. 1998. STAT6, NF-kappaB and C/EBP in CD23 expression and IgE production. Int.Immunol. 10:1529-1538.

Conrad,D.H. 1998. Structure and function of CD23. In The Immmunoglobulin Receptors and their Physiological and Pathological Roles in Immunity. J.G.J.Van de Winkel and Hogarth,P.M., editors. Kluwer Academic Pub., Boston. 195-206.

Conrad,D.H., Tinnell,S.B., and Kelly,A.E. 1998. Immunoglobulin E. In Current Review of Allergic Disease. M.A.Kaliner, editor. Blackwell Science, Philadelphia. 39-50.

Conrad,D.H., Kilmon,M.A., Studer,E.J., and Cho,S.-W. 1997. The low affinity receptor for IgE as a therapeutic target. Biochem.Soc.Trans. 25:393-397.

Cho,S.W., Kilmon,M.A., Studer,E.J., Van der Putten,H., and Conrad,D.H. 1997. B cell activation and Ig, especially IgE, production is inhibited by high CD23 levels in vivo and in vitro . Cell.Immunol. 180:36-46.

Cho,S.-W. and Conrad,D.H. 1997. A new multivalent B cell activation model -- Anti-IgD bound to FctRI: Properties and comparison with CD40L-mediated activation. Int.Immunol. 9:239-248.

Campbell,K.A., Studer,E.J., Kilmon,M.A., Lees,A., Finkelman,F.D., and Conrad,D.H. 1997. Induction of B cell apoptosis by co-crosslinking CD23 and sIg involves aberrant regulation of c- myc and is inhibited by bcl -2. Int.Immunol. 9:1131-1140.

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Date Last Modified: 07/10/2008
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