Faculty Profile

As a full time teaching faculty, Dr. Mancia's current research collaboration has focused upon the characterization of the phytochemical profiles of various licorice root forms including commercially extracts containing DBM (dibenzoylmethane). Their investigations aim to identify novel reagents for prostate cancer therapeutics. The project involves development of analytical techniques, for the separation, quantification and characterization of active components in G. glabra.  Dr. Mancia's prior post doctoral and dissertation experience on the roles of glycolipids in B and T cell functions, and tumor cell death serves her current work on a cancer research program, which blends separation science, natural products and medicinal chemistry for the advancement of cancer therapeutics.

Dr. Mancia is delighted being a part of the Department of Chemistry & Biochemistry at Spelman.  She can think of no better environment in which to grow as an educator and scholar. She enjoys the atmosphere and the commitment of the students, faculty and administration to excellence.  She looks forward to the day to start working, one long time research question on membrane biochemistry: to examine if T cell mediated cytotoxicity immune response modulation by tumor-secretedgangliosides is related to lipid raft synthesis/rearrangement during the T cell response, specifically during the T-cell receptor (TCR)-induced lytic granule release. Dr. Mancia foresees good chemistry!

College Service

First Year advisor, FYE 2010-present
Health Careers Council, 2011-present
Women's Center LGBTQ Faculty Curriculum Committee Member, 2013-present
Ida B. Wells-Barnett Collaborative Member, Spring 2014-present

Department Service

General Chemistry Laboratory Coordinator, 2008-present
Student research co-mentor (2008-present)

T-Cell Mediated Cytotoxicity Modulation by Tumor –Secreted Gangliosides: Lipid Raft’s as Membrane Protection Mechanism.

Gangliosides, although originally were consider merely structural components of cellular membranes, now are recognized as having critical effects on cellular interactions, including proliferation, differentiation, and viral transformation.  Tumors present high levels of gangliosides in comparison to normal cells, including cytotoxic T lymphocytes (CTLs).  But most relevant, gangliosides are actively shed from the membranes of these tumor cells, modulating the immune response in cancer; causing immunosuppresion, and allowing tumor immune escape.  One of my long time research questions is to examine if T cell mediated cytotoxicity immune response modulation by tumor-secreted gangliosides is related to lipid raft synthesis/rearrangement during the T cell response, specifically during the T-cell receptor (TCR)-induced lytic granule release.  Raft-like microdomains are detected at the synaptic interface between CTL and the targets.  Thus, the surface of the CTL likely to encounter high concentrations of granule content pore forming protein perforin, will be enriched in glycolipids.  Therefore, if T cell activation is dependent in lipid raft synthesis, then is possible when CTLs attack their targets, synthesis of lipids rafts and rearrangement is upregulated. The result is a less fluid and tighter membrane, refractory to perforin lesions.  Confirming how gangliosides modulate T cell mediated cytotoxicity will advance the development of new ganglioside-like inhibitors for: (1) impairing anti tumor immunity, which will modulate ganglioside shedding, lessening its immunomodulatory effects; (2) enhancing the anti-tumoral activity of immune cells with the purpose of developing novel immunotherapies and/or vaccines to prevent and/or treat cancer.

Techniques

• Apoptosis/necrosis, caspases assays by Flow cytometry and Western blots
• Cell culture techniques, Cytotoxicity (chromium release), cell proliferations, and hemolytic assays.
• TL granules isolation, gangliosides isolation and purification, TLC, HPTLC, HPLC, radioisotope assays, electrophoresis.
• Techniques to further develop for ganglisodes membrane analysis: LC-MS

Isolation and Identification of Bioactive Compounds from Natural Products as Potential Chemotherapeutic Agents for Advanced Prostate Cancer- (Collaboration)

Licorice root (Glycyrrhiza glabra), a herbal Chinese medicine, has shown medicinal utility in cancer prevention and other therapeutic modalities. The small β-diketone Dibenzoylmethane (DBM) is a minor constituent of licorice.  It has been shown to deregulate the cell cycle of human prostate cancer cells; to decrease expression and function of an important prostatic protein, the androgen receptor.  Characterization of the phytochemical profiles of various licorice root forms including commercially available DBM will advance our search in identifying novel reagents for prostate cancer therapeutics. We have confirmed by GC/MS analysis, DBM as a minor constituent of G. glabra (Mancia, MD and et al, 2014). Other metabolites and related structures are also of interest. Future studies aim to quantify and characterize DBM in licorice root and powder forms by GC/MS and NMR.  In addition, we aim to determine if there are other compounds that are more bioactive than DBM in the licorice extracts.  Bioactivity will be examined by cell culture proliferation assays and flow cytometry and active compounds will be characterized by HPLC, GC/MS, LC/MS and NMR. These studies will potentially lead to the development of new therapeutic products for prostate cancer.  It will also, serve to clarify the mode of action of these bioactive compounds by the identification of cellular targets.

Techniques

• Bioassay- guided fractionation methods will be explored for the isolation of bioactive components within the licorice root extracts, by cell culture antiproliferative activity assays in prostate cancer cells.
• The development of various chromatographic techniques coupled with mass spectrometry and NMR will be used to (1) isolate components of the licorice root fractions and (2) characterize bioactive compounds showing the greatest antiproliferative activity in prostate cancer cells.
• Identification of cellular targets for bioactive constituents, by protein binding techniques and protein arrays.

Mancia, M.D., M.E. Reid*, E.S. DuBose*, J.A. Campbell, and K.M. Jackson; Qualitative Identification of Dibenzoylmethane in Licorice Root (Glycyrrhiza glabra) using Gas Chromatography-Triple Quadrupole Mass Spectrometry. Natural Product Communications 9(1): 91-94; 2014. 

Lee, M.E., D Martin, T King, L Brown, M De Leon, K.M. Jackson, CM Woods.  Gene-Silencing of Reversion-induced  LIM Protein Compromises Responses to Interleukin-16 in Jurkat T-cells, Proceedings of the International Society for Interferon and Cytokine Research and International Cytokine Society, 7:49-54; 2008.

M. Maloney, S. Bishop, G. Torrence and M. De Leon. Comparison of Total Lipid Composition in Gb3-Positive andGb3-  Deficient Burkitt’s Lymphoma Cells. Journal of Liquid Chromatography & Related Technologies. 28: 2571-2580; 2005.

Jackson KM, DeLeon M, Verret CR, Harris WB. Dibenzoylmethane induces cell cycle deregulation in human prostate cancer cells. Cancer Lett; Apr 25; 178(2): 161-5; 2002.

Johnson KP, Rowe GC, Jackson BA, D'Agustino JL, Campbell PE, Guillory BO, Williams MV, Matthews QL, McKayJ, Charles GM, Verret CR, DeLeon M, Johnson DE, Cooke DB. Novel antineoplastic isochalcones inhibit the expression of cyclooxygenase 1, 2 and EGF in human prostate cancer cell line LNCaP. Cell Mol Biol (Noisy-le-grand); Sep; 47(6):1039-45; 2001.

Jackson, K.M., M. De Leon, L. Sistonen., and C.R.Verret Heat Shocked A20 Lymphoma Cells Fail to Induce Degranulation of Cytotoxic T Lymphocytes: Possible Mechanism of Resistance. Cellular Immunology 203: 12-18; 2000.

De Leon, M., K.M. Jackson, J.R. Cavanaugh, D. Mbangkollo and C.R. Verret.  Arrest of the Cell Cycle Reduces Susceptibility of Target Cells to Perforin-Mediated Lysis. Journal of Cellular Biochemistry 69: 425-435; 1998.