Daniel Conrad received a B.Sc. from W.Va Wesleyan College in 1970 and a Ph.D. in Biochemistry from W.Va. University (Go Mountaineers) in 1973.  His postdoctoral studies were at the Department of Immunology, University of Manitoba, from 1973 to 1977, and his mentor there was Dr. Arnold Froese.  While there, he first started allergic studies and his postdoctoral research published the first description of what is now known as the alpha chain of the high affinity IgE receptor.  Dr. Conrad then moved to Virginia Commonwealth University and had a one year postdoc with Dr. Shaun Ruddy.  He then joined the faculty of the Department of Microbiology and Immunology as an Assistant Professor.  In 1981, he moved to The Johns Hopkins University, initially as an Assistant Professor and then Associate in the Subdepartment of Immunology, headed by Dr. Kimishige Ishizaka.  In 1989, Dr. Conrad returned to Va Commonwealth Univ. as a Professor of Microbiology and Immunology.  He has been funded by NIH continuously, starting in 1978, for his research on IgE receptors.

Daniel H. Conrad

Professor

Microbiology and Immunology

dconrad@vcu.edu

Virginia Commonwealth University School of Medicine

Department of Microbiology and Immunology


Medical Sciences Bldg
Office phone: (804) 828-2311

BOX 980678

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. The protease that cleaves CD23 was recently identified by this lab as ADAM10 and this discovery has led to new directions for the laboratory. 

We have prepared B cell ADAM10 knockouts (global knockouts are lethal) as well as B cell transgenics that overexpress ADAM10.  The B cell ADAM10 knockouts had greatly increased CD23 cell surface expression and decreased IgE (as well as IgG) production and the mechanisms for this suppression are being investigated.  One possibility is decreased Notch2 signaling as this was shown to be defective in the ADAM10 knockouts.  The ADAM10 transgenics are also being studied and these mice have an almost complete block in B cell development as well as a strong enhancement of myeloid cell production.  Mechanisms of these changes are under investigation and the mice represent a potential new model system for studying myeloid derived suppressor cell formation and action.  Finally, one agent that increases ADAM10 activity is the kainate receptor.  This was originally described in the CNS, but we have found also true in B lymphocytes. Kainate receptor stimulation inhibits Ig formation and the mechanism for this effect is being studied.  Overall, the main objective of the laboratory continues to be directed at developing new mechanisms to control IgE synthesis and thereby help control IgE-mediated allergic disease.

About the Lab

Members

Jamie Sturgill

Ph.D. Candidate

Department of Microbiology and Immunology


Education:

  1. University of Kentucky, Biology, 1998-2002

 

Research:

My project deals with neuro-immune aspects of immune regulation. We have recently identified the presence of a specific type of glutamate receptor in both the human and murine immune system. When this receptor is stimulated, we see a pronounced increase in cellular proliferation and antibody production. Currently, we are investigating this mechanism and how this receptor could be targeted for therapeutic potential.

David Gibb

MD/PhD Student


Education:

  1. University of Virginia, School of Engineering and Applied Science, 2000-04
      Major: Engineering Sciences, Minor: Biomedical Engineering


Research:

By generating B cell-specific ADAM10 knockout and transgenic mice, we have learned that ADAM10 is a prominent regulator of B cell development and antibody production. Analysis of knockout mice revealed that ADAM10 is required to activate Notch2 signaling and marginal zone B cell development (J. Exp. Med., 2010). Additionally, transgenic mice have taught us that ADAM10 may regulate the myeloid cell vs. B cell fate decision in early bone marrow precursors. As a result, we are currently examining the effect of multiple ADAM10-mediated cleavage events on antibody production, germinal center formation, and hematopoietic stem cell differentiation. 

Sarah Norton

Ph.D. Candidate

Department of Microbiology and Immunology


Education:

  1.  University of Virginia, BS in Biology, 2003

  2.  Virginia Commonwealth University, MS in Biology, 2007

  

Research: 

Fullerenes are carbon spheres that can act as powerful anti-oxidants.  While insoluble in their native state, fullerenes can be derivatized with polar chemical groups that affect both localization and biological activity of the molecule.  We have published previously that specifically derivatized fullerenes can inhibit mast cell degranulation and cytokine production in vitro.  Additionally, we find these compounds are co-localized with mast cells in murine lung tissues in vivo.  Thus we are examining their efficacy in murine models of allergic asthma.  We have found that these compounds significantly inhibit both airway inflammation and bronchoconstriction associated with asthma.  Thus, there is potential for these molecules as novel therapeutics for asthma and other mast cell driven diseases.

Joel Mathews

Ph.D. Candidate

Department of Microbiology and Immunology


Education:

  1. Brigham Young University,  B.Sc. in Molecular Biology, 2006


Research:

  I joined the laboratory of Daniel Conrad in the Spring of 2006.  Dr. Conrad laboratory is known for its studies on CD23 and its control of IgE and allergies.  Just before I joined the laboratory, we published that ADAM10 is the sheddase responsible for the release of CD23 from the cell.  Since joining the laboratory my work has been focused on trying to decipher the mechanism of this release as well as ADAM10 role in antibody production in the human system and the mouse system.  In the mouse system we have also expanded these studies to look at an IgE dependent disease, asthma.  Through these studies we have discovered that blocking ADAM10 does decrease IgE and IgE related diseases, similar to what was seen in mice overexpressing CD23 on B-cells.

Natalia Chaimowitz

MD/PhD Student


Education:

  1. Broward Community College, AA in Biology, 2004

  2. Florida Gulf Coast University, BS in Biotechnology, 2007

    Research:

I study the effects of glutamate, an excitatory neurotransmitter, on mouse B cell function. I also want to determine  if these effects are mediated by adam10, a member of disentegrins and metalloproteases protein family, that has been implicated in regulation IgE production and B cell development.


Sheinei Saleem

Ph.D. Student

Department of Microbiology and Immunology


Education:

  1. James Madison University, BS in biology, 2007

  2. INOVA Fairfax Hospital- Clinical Laboratory Sciences, MT (ASCP)-2008


Research:

I joined the Conrad laboratory in the Spring of 2009 and I am utilizing the ADAM10 transgenic animal as a novel model to study myeloid derived suppressor cell development and function. 

Dae-Joong Kang

Mouse Core C technician


Education:

  1. SungKyunKwan University, Seoul, Korea, MS in Microbiology, 1994

  2. University of Tokyo, Ph.D student in Molecluar Biology & Cellular Bioscience, 1995,  Tokyo, Japan.


  1.       Gibb DR, El SM, Kang DJ, Rowe WJ, El SR, Cichy J, Yagita H, Tew JG, Dempsey PJ, Crawford HC, et al. ADAM10 is essential for Notch2-dependent marginal zone B cell development and CD23 cleavage in vivo. J Exp.Med. 2010 Feb 15;

  2.       Ford JW, Sturgill JL, Conrad DH. 129/SvJ mice have mutated CD23 and hyper IgE. Cell Immunol 2009;254(2):124-34. PMCID:PMC2643045

  3.     Le Gall SM, Bobe P, Reiss K, Horiuchi K, Niu XD, Lundell D, Gibb DR, Conrad D, Saftig P, Blobel CP. ADAMs 10 and 17 Represent Differentially Regulated Components of a General Shedding Machinery for Membrane Proteins such as TGF{alpha}, L-Selectin and TNF{alpha}. Mol.Biol.Cell 2009 Jan 21;

  4.     Ford JW, Kilmon MA, Haas KM, Shelburne AE, Chan-Li Y, Conrad DH. In vivo murine CD23 destabilization enhances CD23 shedding and IgE synthesis. Cell Immunol. 2006 Oct;243(2):107-17

  5.     Sukumar S, Conrad DH, Szakal AK, Tew JG. Differential T cell-mediated regulation of CD23 (Fc epsilonRII) in B cells and follicular dendritic cells. J.Immunol. 2006 Apr 15;176(8):4811-7

  6.     Weskamp G, Ford JW, Sturgill J, Martin S, Docherty AJ, Swendeman S, Broadway N, Hartmann D, Saftig P, Umland S, et al. ADAM10 is a principal 'sheddase' of the low-affinity immunoglobulin E receptor CD23. Nat.Immunol. 2006 Dec;7(12):1293-8

  7.     Caven TH, Shelburne A, Sato J, Chan-Li Y, Becker S, Conrad DH. 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. 2005 Dec;238(2):123-34

  8.     Kilmon MA, Shelburne AE, Chan-Li Y, Holmes KL, Conrad DH. CD23 trimers are preassociated on the cell surface even in the absence of its ligand, IgE. J Immunol. 2004 Jan 15;172(2):1065-73

  9.     Conrad DH, Ford JW, Sturgill JL, Gibb DR. CD23: an overlooked regulator of allergic disease. Curr.Allergy Asthma Rep. 2007 Sep;7(5):331-7

Selected Publications

Education and Professional Experience

John Ryan, Ph.D.John_Ryan.htmlshapeimage_2_link_0
Sarah Spiegel, Ph.D.Sarah_Spiegel.htmlshapeimage_3_link_0
Lawrence Schwartz, MD/Ph.DLawrence_Schwartz.htmlshapeimage_7_link_0
Daniel Conrad, Ph.D.shapeimage_8_link_0
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