Assistant Director and Research Professor of the
National Center for Natural Product Research
Research Professor, Department of Pharmacognosy
Director, UMMC/NCNPR Cancer Drug Discovery Core
Dr. Pasco received his B.A. degree in Biology from Thiel College in 1974. He holds an M.S. in Natural Sciences and received a Ph.D. in Physiology in 1980 from the Roswell Park Cancer Research Institute, a graduate division of The University of Buffalo. He was a postdoctoral fellow in the Cancer Research Laboratory at the University of California at Berkeley for several years and was then appointed Assistant Professor of Biology at Maharishi International University in 1982 and Associate Professor and Co-director of the Ph.D. Program in Physiology, Cell and Molecular Biology in 1986. Dr. Pasco joined The University of Mississippi Department of Pharmacognosy and The National Center for the Development of Natural Products as Research Professor in 1995.
Click here to see Research in Progress and Publications
Research in Progress
Dr. Pasco's research interests include developing biological screens that use molecular tools to identify compounds within plants that contribute to their health benefits, especially those that exhibit immune enhancing and anti-cancer properties.
Research conducted under Dr. Pasco's supervision is focused on the detection of novel anticancer activities within natural products. These include compounds that exhibit anti-inflammatory and other activities that could impact tumor progression or target cancer stem cells.
His research also deals with the isolation and identification of innate immune enhancing components within natural products that have been used traditionally to enhance immune function. Some of this research has led to the development of two patented and commercialized botanical extracts, one for general enhancement of immune function (Spirulina extract-Immulina®) and the other for improving skin elasticity and wrinkle reduction (fraction from Aloe vera). Numerous clinical trials have been conducted using these products and several more are underway.
Dr. Pasco's long term research plans includes the search for more effective approaches for the treatment of cancer and other chronic disorders. These approaches will include both modern medical practices in addition to alternative or traditional therapies. One of the main areas of focus of this research group deals with the development of molecular biological based screens for the discovery of novel agents effective in the treatment of some types of cancer. These screens will be used to evaluate extracts from a wide range of natural products including plants, marine organisms as well as various micro organisms. In addition to this random screening program Dr. Pasco also uses clues from traditional medical systems of India, China, and others for identifying source materials that may yield anti cancer agents.
The laboratories directly under Dr. Pasco's supervision are focused on the detection of novel anticancer activities within natural products. Examples of these assays currently in use are listed below:
1. Antiinflammatory-Recent studies have demonstrated the importance of inflammation in various aspects of tumor progression. A battery of luciferase reporter gene constructs are introduced into the human chondrocyte cell line SW1353. Constructs contain either the promoter for the human cyclooxygenase-2 gene or binding sites for individual transcription factors important for mediating inflammatory signals such as NF-kappa B, AP-1 or Ets2. This assay has identified compounds that inhibit various aspects of transcription factor activation and have been isolated from plants with scientifically documented antiinflammatory properties.
2. Immune modulation-Luciferase reporter gene construct containing sites for NF-kappa B introduced into the human monocyte cell line THP-1. Most activators of monocytes /macrophages influence the activity of this transcription factor and therefore information regarding the activity of this factor is useful for detecting compounds from natural products that modulate macrophage function.
3. Prostate cancer-Luciferase reporter gene construct containing sites for the androgen receptor is introduced into the human prostate cancer cell line LNCaP. Cells are treated with dehydrotestosterone alone or in combination with plant extracts to detect the presence of compounds that inhibit androgen receptor function.
4. Antiangiogenesis-Screen designed to detect inhibitors of VEGF expression in liver tumors. The expression and secretion of VEGF by tumor cells is crucial for the development of the vascular system of the tumor. The Hep 3B cell line is transfected with a luciferase construct containing the promoter of the human VEGF gene. This screen will detect inhibitors of VEGF expression induced by a combination of hypoxia and cytokines.
Dr. Pasco's long term research plans includes the search for more effective approaches for the treatment of cancer and other chronic disorders. These approaches will include both modern medical practices in addition to alternative or traditional therapies. Through the balanced use of both approaches a new health care system can be developed that focuses on the health of the whole person, physical, mental and spiritual.
Nielsen CH, Balachandran P, Christensen O, Pugh ND, Tamta H, Sufka KJ, Wu X, Walsted A, Schjørring-Thyssen M, Enevold C, Pasco DS. Enhancement of natural killer cell activity in healthy subjects by Immulina®, A Spirulina extract enriched for Braun type lipoproteins. Planta Med. 76:1802-1808, 2010.
Pugh ND, Tamta H, Balachandran P, Wu X, Howell J, Dayan FE, Pasco DS. The majority of in vitro macrophage activation exhibited by extracts of some immune enhancing botanicals is due to bacterial lipoproteins and lipopolysaccharides. Int Immunopharmacol. 8(7):1023-1032, 2008.
Tamta H, Pugh ND, Balachandran P, Moraes R, Sumiyanto J, Pasco DS. Variability in in Vitro Macrophage Activation by Commercially Diverse Bulk Echinacea Plant Material Is Predominantly Due to Bacterial Lipoproteins and Lipopolysaccharides. J Agric Food Chem. 56:10552-10556, 2008.
Tabanca N, Ma G, Pasco DS, Bedir E, Kirimer N, Baser KH, Khan IA, Khan SI. Effect of essential oils and isolated compounds from Pimpinella species on NF-kappaB: a target for antiinflammatory therapy. Phytother Res.; 21(8):741-745, 2007.
Ma G, Khan SI, Benavides G, Schuhly W, Fischer NH, Khan IA, Pasco DS. Inhibition of NF-kappaB-mediated transcription and induction of apoptosis by melampolides and repandolides. Cancer Chemother Pharmacol. 60(1):35-43, 2007.
Balachandran, P., Pugh, N.D., Ma, G., Pasco, D.S. Toll-like receptor 2-dependent activation of monocytes by Spirulina polysaccharide and its immune enhancing action in mice. Int Immmunopharmacol. 6:1808-1814, 2006.
Pugh, N.D., Balachandran, P., Lata, H., Dayan, F.E., Joshi, V., Bedir, E., Makino, T., Moraes, R., Khan, I., Pasco, D.S. Melanin: dietary mucosal immune modulator from Echinacea and other botanical supplements. Int Immunopharmacol. 5:637-47, 2005.
Pugh, N., Ross, S.A., ElSohly, H.N., ElSohly, M.A., and Pasco, D.S. Isolation of Three New Polysaccharide Preparations With Potent Immunostimulatory Activity From Spirulina platensis, Aphanizomenon flos-aquae and Chlorella pyrenoidosa. Planta Medica 67:737-742, 2001.
Pugh, N. and Pasco, D.S. Characterization of Human Monocyte Activation By An Aqueous Extract of Aphanizomenon flos-aquae. Phytomedicine 8:445-453, 2001.
Pugh, N., Ross, S.A., ElSohly, M.A., and Pasco, D.S. Characterization of Aloeride, a New High Molecular Weight Polysaccharide from Aloe vera With Potent Immunostimulatory Activity. Journal of Agricultural and Food Chemistry 49: 1030-1034, 2001.
Subbaramaiah, K., Bulic, P., Lin, Y., Dannenberg, A.J., and Pasco, D.S. Development and Use of a Gene Promoter-Based Screen to Identify Novel Inhibitors of Cyclooxygenase-2 Transcription. Journal of Biomolecular Screening 6:101-110, 2001.
Ma G, Tabanca N, Husnu Can Baser K, Kirimer N, Pasco DS, Khan IA, Khan SI. Inhibition of NF-kappaB-mediated transcription and induction of apoptosis in human breast cancer cells by epoxypseudoisoeugenol-2-methyl butyrate. Cancer Chemother Pharmacol. 63(4):673-678, 2009.
Barker, C., Fagan, J. B. and Pasco, D. S., Interleukin-1 beta Suppresses the Induction of P4501A1 and P4501A2 mRNAs in Isolated Hepatocytes, Journal of Biological Chemistry, 267, 8050-8055, (1992).
Pasco, D.S., Boyum, K.W., Elbi, C., Siu, C. Fagan, J.B., Inducer-Dependent Transcriptional Activation of the P4501A2 Gene In Vivo and in Isolated Hepatocytes, Journal of Biological Chemistry, 268, 1053-1057, (1993).
Robertson, R.W., Zhang, L., Pasco, D.S. and Fagan, J. B., Aryl Hydrocarbon-induced Interactions at Multiple DNA Elements of Diverse Sequence-A Multicomponent Mechanism for Activation of Cytochrome P4501A1 (CYP1A1) Gene Transcription, Nucleic Acids Research, 22, 1741-1749, (1994).
Reich, M., Robertson, R.W., Pasco, D.S. and Fagan, J. B., Down-regulation of Nuclear Aryl Hydrocarbon Receptor DNA-Binding and Transactivation Functions: Requirement for a Labile or Inducible Factor, Molecular and Cellular Biology, 14, 5653-5660, (1994).
Barker, C., Fagan, J. B. and Pasco, D.S., Down-Regulation of P4501A1 and P4501A2 mRNA Expression in Isolated Hepatocytes by Oxidative Stress, Journal of Biological Chemistry, 269, 3985-3990, (1994).
Robinson, C. E., Keshavarzian, A., Pasco, D.S., Frommel, T.O., Winship, D.H., and Holmes, E.W: Determination of Protien Carbonyl Groups by Immunoblotting. Analytical Biochemistry 266: 48-57, (1999).
Bedir, E., Pugh, N., Calis, I., Pasco, D.S., Khan, I.A.: Immunostimulatory effects of cycloartane-type triterpene glycosides from Astragalus species. Biological and PharmaceuticalBulletin 266:(2000).
Nagle G.D., Zhou, Y.D., Park, P.U., Paul, V.J., Rajbhandari, I., Duncan, C.J.D., and Pasco, D.S. A New Indanone from the Marine Cyanobacterium Lyngbya majuscula That Inhibits Hypoxia-Induced Activation of the VEGF Promoter in Hep3B Cells. Journal of Natural Products 63:1431-1433, (2000).
Pugh, N., Ross, S.A., ElSohly, M.A., and Pasco, D.S. Characterization of Aloeride, a New High Molecular Weight Polysaccharide from Aloe vera With Potent Immunostimulatory Activity. Journal of Agricultural and Food Chemistry 49: 1030-1034, (2001).
Pugh, N., Khan, I.A., Moraes, R. M., and Pasco, D.S. Podophyllotoxin Lignans Enhance IL-1beta But Suppress TNF-alfa mRNA Expression in LPS-Treated Monocytes. Immunopharmacology and Immunotoxicology 23: 83-95, (2001).
Subbaramaiah, K., Bulic, P., Lin, Y., Dannenberg, A.J., and Pasco, D.S. Development and Use of a Gene Promoter-Based Screen to Identify Novel Inhibitors of Cyclooxygenase-2 Transcription. Journal of Biomolecular Screening 6:101-110, (2001).
Pugh, N., Ross, S.A., ElSohly, H.N., ElSohly, M.A., and Pasco, D.S. Isolation of Three New Polysaccharide Preparations With Potent Immunostimulatory Activity From Spirulina platensis, Aphanizomenon flos-aquae and Chlorella pyrenoidosa. Planta Medica 67:737-742, (2001).
Zhang, Z., ElSholy, H.N., Jacob, M.R., Pasco, D.S., Walker, L.A., Clark, A.M. Natural products inhibiting Candida albicans secreted aspartic proteases from Tovomita krukovii. Planta Medica 68:49-54, (2002).
Pasco, D.S. Using Transcription Factor Based Assays to Study Herbal Products. In Drug Discovery and Traditional Chinese Medicine:Science, Regulation, and Globalization (Ed. Yuan Lin) pp. 81-87. Kluwer Academic Publishers. Boston/Dordrecht/London, (2001)
Pasco, D.S., Dannenberg, A.J., and Subbaramaiah, K.J., Method of Screening Agents as Candidates for Drugs or Sources of Drugs March 13, 2001. (U.S. Patent No. 6,200,760).
Pasco, D.S., Pugh, N.D.C, Ross, S.A and ElSohly, M.A. High Molecular Weight Polysaccharide From Aloe vera With Immunostimulatory Activity. March 27, 2007 (U.S. Patent No. 7,196,072).
Pasco, D.S., Pugh, N.D.C, Ross, S.A., ElSohly, M.A., and ElSohly, H.N. Potent Immunostimulants From Microalgae. April 17, 2007 (U.S. Patent No. 7,205,284).
Pasco, D.S., Pugh, N.D.C, Ross, S.A and ElSohly, M.A. High Molecular Weight Polysaccharide From Aloe vera With Immunostimulatory Activity. August 3, 2010 (U.S. Patent No. 7,767,655 B2).
Pasco, D.S., Pugh, N.D.C Potent Immunostimulantory Extracts From Microalgae. Dec. 7, 2010 (U.S. Patent No. 7,846,452 B2