Microbiology and Immunology
Assistant Director for Diversity, Equity and Inclusion
Education and Training
Prairie View A&M University, BS, Biology, 1998
Indiana University, PhD,Microbiology and Immunology, 2003
Indiana University School of Medicine, Postdoctoral fellow, Immunology, 2005
Johns Hopkins, Postdoctoral fellow, Cancer Immunology, 2009
Dr. Webb is a leading immunologist and research scientist who is recognized for her studies focused on the modulation of CD1d-mediated NKT cell activation for cancer immunotherapy using natural and artificial platforms.
NKT cells recognize lipid antigen presented in the context of CD1d molecules. Following activation, NKT cells rapidly secrete both Th1 and Th2 cytokines and can mediate cytolytic activity. Therefore, NKT cells can both directly, through cytotoxicity, and indirectly, through activation of other effector cells, mediate anti-tumor immunity. Consequently, NKT cells constitute an important subset of T cells that can play a critical role in regulating the host's anti-tumor immune response. However, cancer patients have a reduction in both NKT cell number and function, and these deficits currently limit the potential clinical application of NKT cells for cancer therapy. Building on previous studies, the overarching hypothesis to be tested in the Webb lab is that NKT cells play an important role in cancer immune surveillance and to address this hypothesis, her group aims to:
- Determine the mechanisms by which NKT cells are reduced in cancer patients.
- Design novel therapeutics to restore NKT cell number and function in cancer patients.
- Investigate the mechanisms by which NKT cells recognize and destroy tumors.
One of Dr. Webb's main career goals is to be able to provide exceptional trainees with the opportunity to perform cutting edge research in an outstanding academic environment. In addition, research areas championed by her group include the development of novel cancer immunotherapeutic strategies and research into cancer health disparities.
cancer immunology, cancer immunotherapy, CD1d-mediated NKT cell activation ELISA, flow cytometry, Western blotting, qPCR, lipidomics, proteomics spheroids, artificial antigen presenting cells
Shissler SC, Bates J, Hester D, Jones LP, Webb TJ. (2021) Inbred strain characteristics impact the NKT cell repertoire. ImmunoHorizons. 5(3):147-156
Shissler SC, Singh NJ, Webb TJ. (2020) Thymic resident NKT cell subsets show differential requirements for CD28 co-stimulation during antigenic activation. Sci Rep.10(1):8218.
Webb TJ, Carey GB, East JE, Sun W, Bollino DR, Kimball AS, Brutkiewicz RR. Alterations in cellular metabolism modulate CD1d-mediated NKT-cell responses. Pathog Dis. 2016 Aug;74(6).
Younis RH, Han KL, Webb TJ. Human Head and Neck Squamous Cell Carcinoma-Associated Semaphorin 4D Induces Expansion of Myeloid-Derived Suppressor Cells. J Immunol. 2016 Feb 1;196(3):1419-29.
Tiper IV, Temkin SM, Spiegel S, Goldblum SE, Giuntoli RL 2nd, Oelke M, Schneck JP, Webb TJ. VEGF Potentiates GD3-Mediated Immunosuppression by Human Ovarian Cancer Cells. Clin Cancer Res. 2016 Aug 15;22(16):4249-58.
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. Cancer Res. 2012 Aug 1;72(15):3744-52.
Webb TJ & Weinmann AS. (2019) Defining Barriers that Impede Choices. Immunity. 19;50(3):542- 544
Webb TJ (2021) Inclusion criteria: how NK cells gain access to T cells. J Clin Invest. 131(18):e152054. doi: 10.1172/JCI152054.
Webb TJ, Guerau-de-Arellano M, Jones HP, Butts CL, Sanchez-Perez L, Montaner LJ. (2022) The Minority Scientists' Experience: Challenging and Overcoming Barriers to Enhancing Diversity and Career Advancement. J Immunol. 208(2):197-202.
Cairo C & Webb TJ. (2022) Effective Barriers: The Role of NKT Cells and Innate Lymphoid Cells in the Gut. J Immunol. 208 (2):235-246.
Mechanisms by which ovarian cancers suppress CD1d-mediated NKT cell activation
Ovarian cancer is the fifth leading cause of cancer deaths among women, thereby accounting for more deaths than any other cancer of the female reproductive system. It is known that ovarian cancer tissue and ascites contain lymphocytic infiltrates, suggesting that immune cells traffic to tumors, but are then inhibited by immunosuppressive molecules within the tumor microenvironment. Moreover, vascular endothelial growth factor (VEGF) expression is inversely correlated with survival in ovarian cancer patients. Since avoiding detection by the host’s immune system is crucial for the growth and metastasis of cancer, we investigated the effects of ovarian cancer associated VEGF on CD1d-mediated antigen presentation to natural killer T (NKT) cells. Pretreatment of antigen presenting cells with ascites or conditioned medium from OV-CAR-3 and SK-OV-3 ovarian cancer cell lines suppressed CD1d-mediated NKT cell activation. Ovarian cancer-associated ascites and conditioned medium from ovarian cancer cell lines contain high levels of VEGF and ganglioside GD3. Importantly, inhibiting VEGF production by ovarian cancer cell lines led to a reduction in GD3 expression and restored NKT cell activation. Thus, we have identified a novel link between immunosuppressive ganglioside shedding and VEGF production by ovarian cancers. Current efforts are focused on determining the mechanisms by which VEGF signaling impairs CD1d mediated NKT cell responses, thus these studies have the potential to lead to the development of novel therapeutic targets for women with this disease.
The Role of Lipid Metabolism on CD1d-mediated NKT cell activation
Classically, two pathways are thought to exist for NKT cell activation. An antigen-dependent pathway by which NKT cells are activated through direct recognition of microbial glycolipid antigens via their TCR, and another cytokine dependent pathway due to the ability of NKT cells to respond to innate or inflammatory stimuli, that may be associated with self-Ag recognition. Given the important role that CD1d-specific NKT cells play in many different types of infections, autoimmunity and transplantation, we have investigated NKT cell responses during an acute viral infection and to malignant cells. These two divergent stimuli were potent inducers of cytokine production by NKT cells, and our studies revealed a novel role for the energy sensor AMP-activated protein kinase (AMPK) in regulating CD1d-mediated antigen processing and presentation. Current studies are focused on examining the role of lipogenesis on CD1d-dependent NKT cell responses to cancer.
American Cancer Society Diversity in Cancer Research Program
The ACS Diversity in Cancer Research Internship program, which began in 2021, targets talented, motivated URM undergraduate students to expose them to cancer research as a strategy to ultimately increase the number of URM people who enter the cancer research field.
Front Line News (August 26, 2022): Diversity in Cancer Research Internship Program
WBAL TV 11: University of Maryland School of Medicine program aims to improve diversity in biomedical science
The research in Dr. Webb's lab is focused on CD1d-mediated NKT cell activation and the assays used to monitor this interaction are typically qPCR, 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.