Bookmark and Share

Tonya J Webb
 

Tonya J Webb Ph.D.

Academic Title: Assistant Professor
Primary Appointment: Microbiology and Immunology
twebb@som.umaryland.edu
Location: HSF-I, 380
Phone: 410-706-4109
Fax: 410-706-6970
Lab: 410-706-3140

Personal History:

Dr. Webb graduated cum laude from Prairie View A&M University with a major in Biology and a minor in Chemistry. Her first research opportunity was as a Leadership Alliance/ Howard Hughes fellow at Dartmouth College. She performed her doctoral studies at Indiana University, under the direction of Randy Brutkiewicz, PhD, a leader in the field of NKT cell biology. She was postdoctoral fellow in the laboratory of David Wilkes, MD, and worked on mechanisms regulating immune tolerance. Her second postdoctoral fellowship focused on cancer immunology at Johns Hopkins with Jonathan Schneck, MD, PhD and Mathias Oelke, PhD. She joined the faculty as a tenure track Assistant Professor in 2009. Her laboratory investigates the role of Natural killer T (NKT) cells in cancer immunotherapy.

Research Interests:

aAPC-Mediated NKT cell Modulation to Enhance Cancer Immunotherapy

Natural killer T (NKT) cells comprise a specialized subset of T lymphocytes that express cell surface markers characteristic of NK cells. The ability of these cells to produce cytokines, activate cells of both the innate and adaptive immune responses, and recognize antigen in the context of CD1d molecules strongly suggest that NKT cells play a pivotal role in anti-tumor immunity. However, anti-tumor effects mediated by these cells may be compromised because cancer patients have a reduction in both NKT cell number and function. Therefore, we hypothesize that adoptive transfer of effector NKT cells will be an effective therapeutic strategy to enhance cancer immunotherapy. Our lab has developed CD1d-lg-based artificial Antigen Presenting Cells (aAPC), which can facilitate the induction and expansion of primary T and NKT cells. Research efforts are focused on modifying these CD1d-lg based aAPC to stimulate and analyze different NKT cell subsets in vitro and in vivo.

Restoring NKT cell function: a novel immunotherapeutic strategy for Breast Cancer

Preclinical studies and clinical trials have demonstrated that immunotherapy can effectively treat cancer; however, breast cancer immunotherapy needs to also focus on removing negative factors that could inhibit the immune response in order to maximize its therapeutic effects. The mechanisms by which NKT cells are functionally reduced in cancer patients has yet to be identified. It is known that lipids are frequently shed by tumors and can block immune responses. In fact, lipid levels are higher in the mammary tissue and sera of breast cancer patients compared to healthy controls. Thus, we hypothesize that lipid shedding by breast cancers cells is a mechanism used to inhibit NKT cell activation and possibly cause their death. Current studies are focused on investigating whether blocking breast cancer-associated ganglioside biosynthesis can restore NKT cell function.

Alterations in cellular bioenergetics influences NKT cell mediated responses to Lymphoma

In these studies we are focusing on a specific type of non-Hodgkin Lymphoma, Mantle Cell Lymphoma (MCL), for which there is currently no curative treatment option available. MCL is characterized by the chromosomal translocation and nuclear overexpression of cyclin D1. Secondary chromosomal abnormalities and dysregulation of cell cycle machinery also contribute to MCL pathogenesis, such as aberrant activation of phosphoinositide-3 kinase/Akt (PI3K/Akt) and mammalian target of rapamycin (mTOR) signaling. Two well-established targets of PI3K/Akt and mTOR signaling pathways are hypoxia inducible factors (HIF) 1 and 2. HIF-1 plays a role in the reprogramming of cancer metabolism by activating the transcription of genes encoding glucose transporters and glycolytic enzymes. As NKT cells are activated by glycolipid antigens, it is likely that overexpression of HIF-1 alters the repertoire of glycolipid antigens. Thus, we hypothesize that the overexpression of HIF-1α modulates CD1d-mediated NKT responses to MCL. We are testing our hypothesis with in vitro and in vivo studies to identify the mechanism by which HIF-1α regulates NKT cell function and ex vivo studies using clinical samples to discern whether the expression of HIF-1α correlates with the number and/or the function of NKT cells in the blood of lymphoma patients.

Lab Techniques and Equipment:

The research in my lab is focused on CD1d-mediated NKT cell activation and the assays used to monitor this interaction are typically ELISA and flow cytometry. A variety of molecular techniques are also used to measure downstream signaling events and to modulate the function of proteins of interest.


Publications:

Webb TJ, Li X, Giuntoli RL 2nd, Lopez PH, Heuser C, Schnaar RL, Tsuji M, Kurts C, Oelke M, Schneck JP. Molecular identification of GD3 as a suppressor of the innate immune response in ovarian cancer (2012) Cancer Res. 72:3744-52.

Sun W, Subrahmanyam PB, East JE, Webb TJ (2012) Connecting the Dots: Artificial Antigen Presenting Cell-Mediated Modulation of Natural Killer T Cells. J Interferon Cytokine Res. 32(11):505-16.

Subrahmanyam, P.B., Webb, TJ (2012) Boosting the immune response: the use of iNKT cell ligands as vaccine adjuvants. Frontiers in Biology. 7(5):436-444.

East JE, Kennedy AJ, Webb TJ (2012) Raising the Roof: The Preferential Pharmacological Stimulation of Th1 and Th2 Responses Mediated by NKT Cells. Med Res Rev. doi: 10.1002/med.21276. in press

East JE, Sun W, Webb TJ (2012) Artificial Antigen Presenting Cell (aAPC) Mediated Activation and Expansion of Natural Killer T Cells. J. Vis. Exp. (70), e4333, doi:10.3791/4333

Hua J, Liang S, Ma X, Webb TJ, Potter JP, Li Z. (2011) The Interaction between Regulatory T Cells and NKT Cells in the Liver: A CD1d Bridge Links Innate and Adaptive Immunity. PLoS One. 6(11):e27038.

Hua, J., Ma, X., Webb, T., Potter, J.J., Oelke, M., Li, Z. (2010) Dietary fatty acids modulate antigen presentation to hepatic NKT Cells in non-alcoholic fatty liver disease. J Lipid Res. 51(7):1696-703.

Webb, TJ, Bieler, J.G. Schneck, J., Oelke, M. (2009) Ex vivo induction and expansion of Natural Killer T cells by CD1d1-Ig coated artificial antigen presenting cells. J Immunol Methods 346: 38-44. PMC2810536

Giuntoli, R.L.II, Webb, TJ, Zoso, A., Rogers, O. Diaz-Montes, T.P., Bristow, R.E. Oelke, M. (2009) Ovarian Cancer Associated Ascites Demonstrates Altered Immune Environment: Implications for Anti-tumor Immunity. Anticancer Res 29:2875-84.

Webb, TJ, Giuntoli, R.L.II, Rogers, O., Schneck, J., Oelke, M. (2008) Ascites specific inhibition of CD1d-mediated activation of natural killer T cells. Clin Can Res. 14: 7652-7658. PMC2676584

Hong, L., Webb, T.J., Wilkes, D.S. (2007) Dendritic Cell - T Cell Interactions: CD8αα Expressed on Dendritic Cells Regulates T Cell Proliferation. Immunology Letters. 108:174-178.

Choi KS, Webb T, Oelke M, Scorpio DG, Dumler JS. (2007) Differential Innate Immune Cell Activation and Proinflammatory Response in Anaplasma phagocytophilum Infection. Infect Immun. 75(6):3124-30.

Webb T.J., Litavecz R.A., Khan M.A., Du W., Gervay-Hague J., Renukaradhya G.J., Brutkiewicz R.R. (2006) Inhibition of CD1d1-mediated antigen presentation by the vaccinia virus B1R and H5R molecules. Eur J Immunol. 36(10): 2595-2600.

Webb, T.J., Sumpter, T.L., Thiele, A.T., Swanson, K.A., and Wilkes, D.S. (2005) The Phenotype and Function of Lung DCs. Crit Rev Immunol 25(6):465-91.