Barbara Timmermann Research

  • B.S., Universidad Nacional de Cordoba, Argentina Biology, 1970
  • M.S., University of Texas, Austin, Botany (Phytochemistry), 1977
  • Ph.D., University of Texas, Austin, Botany (Phytochemistry), 1980
  • Research Associate, University of Arizona, 1981-1985
  • Assistant Professor, Associate Professor and Professor, University of Arizona, Department of Pharmacology and Toxicology, 1985-2000
  • Regents Professor, University of Arizona, Department of Pharmacology and Toxicology, 2000- 2005
  • Distinguished Professor and Chair, University of Kansas, Department of Medicinal Chemistry, August 2005-present

Awards/Honors/Activities

  • Woman of Distinction, University of Kansas, August 2006
  • University Distinguished Professor, University of Kansas, May 2005-present
  • Chair, Department of Medicinal Chemistry, University of Kansas, 2005-present
  • Member, International Organization for Chemical Sciences in Development (IOCD), Biotic Exploration Fund, 2005-present
  • Director:
    • NIH Center of Biomedical Research Excellence (COBRE) Center for Cancer Experimental Therapeutics (CCET), 2005-present
    • NIH International Cooperative Biodiversity Groups (ICBG) Program, 1993-2005
    • NIH Botanical Research Center, Arizona Center for Phytomedicine Research, 2000-2005
    • NIH Minority International Research Training (MIRT) Project, 2000-2005
    • USAID University Development Linkages Program USA-Chile ,1993-2000
  • Member, Editorial Board, Journal of Natural Products, 2002-present
  • National Institutes of Health (NIH/NCCAM), National Advisory Council Member, 2001-2005
  • Regents Professor, University of Arizona, February 2000
  • Fellow, American Association for the Advancement of Science (AAAS), February 2000
  • Member, Executive and Scientific Advisory Committees: AAAS Western Hemisphere Cooperation Program, 1992-2002
  • Research Support as PI: National Institutes of Health (NIH); National Science Foundation (NSF); US Department of Agriculture (USDA); US Agency for International Development (USAID); The John D. and Catherine T. MacArthur Foundation; Tinker Foundation; Arizona Disease Control Research Commission; Kansas Bioscience Authority; various pharmaceutical and chemical corporate grants.

Instruction

Arizona

  • PCOL 837 A, Medicinal Chemistry and Pharmacognosy
  • PCOL 837 B, Medicinal Chemistry and Pharmacognosy
  • PCOL 870, Phytomedicine
  • PCOL 820, Case Studies in Pharmacology
  • PCOL 821, Case Studies in Pharmacology
  • PHSC 632, Natural Medicinal Products
  • PLS 541, Economic Botany of Arid Lands
  • PCOL 195, Of People Plants and Medicine

Kansas

  • MDCM 626, Medicinal Chemistry II: Homeostatic Agents
  • MDCM 605, Phytomedicinal Agents I
  • MDCM 606, Phytomedicinal Agents II
  • MDCM 607, Clinical Pharmacognosy
  • MDCM 785, Natural Products of Medicinal Significance

COBRE CCET

Natural Product Chemistry Research


Garden to cultivate medicinal potential of plants.

Native medicinal plant project wins Kansas Bioscience Authority funding.


COBRE Center for Cancer Experimental Therapeutics

Dr. Barbara Timmermann also leads the COBRE initiative for the Center for Cancer Experimental Therapeutics (CCET). Scientific projects at the cutting edge of cancer research, interactions among researchers at the interface of chemistry and biology, and the strong mentoring of junior faculty toward independent careers will contribute to the application for the establishment of a Comprehensive Cancer Center by the National Cancer Institute (NCI) at the University of Kansas Medical Center. The CCET has two scientific Cores.

Core B - High Throughput Screening

The High Throughput Screening (Core B) provides high throughput screening and target identification technology. Using state-of-the-art, automated equipment and a drug-like compound collection of synthetic and natural products, the lab provides a vital tool for biomedical research. The facility is dedicated to providing researchers with high throughput technologies and chemical libraries to assist in identifying biological probes/chemical leads for drug discovery.

Core C - Medicinal Chemistry

The Medicinal Chemistry (Core C) supports the research of all COBRE projects and the High Throughput Screening (HTS) laboratory. Its main role is the design and synthesis of chemical libraries, and large scale production of compounds for screening by the HTS core. The laboratory also conducts the preparation of natural product libraries in appropriate formats for biological screening in cell-free HTS assays. In addition, short courses, workshops and support seminars are conducted for COBRE clients and the core provides in silico guidance to the HTS core.


Natural Product Chemistry Research

Dr. Timmermann's primary research interests focus on the discovery and biological investigation of novel drug lead compounds from plant and microbial biodiversity, including phenolics, terpenoids, alkaloids, phytoestrogens, and other natural products. Her studies involve evaluating the medicinal importance of these various classes of compounds, including estrogenic, anticancer, anti-oxidant, anti-inflammatory, anti-microbial, and anti-tuberculosis properties. Additionally, the research in her laboratory involves identification of enzymes in the biosynthetic pathway leading to the production of important metabolites; chemical and molecular phylogeny; chemosystematics; chemical ecology; biodiversity prospecting for drug lead discovery, and safety and efficacy studies of botanical dietary supplements with anti-inflammatory activity.

Advanced analytical and medicinal chemistry techniques are employed for drug lead discovery in the Timmermann laboratories, which are housed in the modern Multidisciplinary Resource Building (MRB) on KU's West Campus. Laboratory members employ NMR, MS, and UV spectroscopic techniques, as well as HPLC, GC/MS, LC/MS/MS and other chromatographic methods, for characterization, identification, and purification of novel natural products. Additionally, as part of the KU Medicinal Chemistry Department, Dr. Timmermann's laboratory has access to the state-of-the-art High-Throughput Screening (HTS) laboratory and its expert staff members, who are able to aid in the bioassay-guided isolation of active compounds from natural products.

 

Dr. Timmermann's interests in botanical dietary supplements and functional foods include the chemical and biological standardization and evaluation of natural product-based botanical medicines. With Complementary and Alternative Medicine (CAM) therapy becoming increasingly popular in the United States and abroad, it is more critical than ever that to evaluate and validate the benefits of supplements and other natural medicines, as well as to provide methods for their standardization. Completed studies include analysis of the anti-cancer effects of catechins from green tea (Camellia sinensis), particularly epigallocatechin gallate (EGCG).

 

Research by the Timmermann group, in conjunction with the Arizona Center for Phytomedicine Research, includes studies of the anti-inflammatory effects of ginger (Zingiber officinale) and turmeric (Curcuma longa) for the treatment of arthritis, colitis, and other inflammatory diseases. Studies of the characterization, identification, and quantification of constituents within the rhizomes, and the composition of marketed ginger- and turmeric-based dietary supplements, provided standardized material for pre-clinical studies. Further work continues to involve the elucidation of biosynthetic pathways for the gingerols and curcuminoids and both in vitro and in vivo studies of these natural products in models of inflammatory diseases.

 

Another of Dr. Timmermann's research interests, biodiversity prospecting, offers a valuable opportunity to directly address one of the most important relationships between biodiversity and human health: our dependence on Nature for medicine. Drug lead discovery from natural products, if appropriately designed and carried out, can provide economic incentives for the conservation of the diversity of plants, animals, and microorganisms on Earth. While natural products drug discovery has a long history, the idea that this process could yield conservation and development benefits is relatively new. Dr. Timmermann's research in this area has included bioprospecting in Chile, Argentina, and Mexico through an International Cooperative Biodiversity Group (ICBG) program, where her multidisciplinary and international team of researchers identified a number of novel natural products including the anti-tuberculosis compound saringosterol from Lessonia nigrescens, antibacterial diterpenoid acids from Azorella compacta, and a number of cytotoxic lignans from Larrea tridentata. Future work is projected to include prospecting in other parts of the world, where biodiversity- including a number of species with potential medicinal benefits- is quickly being lost to deforestation and other ecological problems. These projects will continue to focus on drug discovery and conservation of existing biodiversity.

 

Another area of interest in the Timmermann laboratory is chemical ecology. The viceroy-monarch and viceroy-queen butterfly associations are classic examples of mimicry. These relationships were originally classified as Batesian, or parasitic, but were later reclassified as Mullerian, or mutualistic, based on predator bioassays. The Mullerian reclassification implies that viceroy is unpalatable because it too is chemically defended like the queen and the monarch. However, unlike the queen and the monarch, the viceroy defensive chemistry has remained uncharacterized. We demonstrated that the viceroy butterfly (Limenitis archippus) not only sequesters nonvolatile defensive compounds from its larval host-plant, Carolina willow (Salix caroliniana), but also secretes volatile defensive compounds when disturbed. Our chemical results are consistent with other researchers&#rsquo; reclassification of the viceroy-queen and viceroy-monarch butterfly as Mullerian. The viceroy butterfly possesses chemical defenses different from its monarch and queen butterfly counterparts (phenolic glycosides vs. cardiac glycosides, respectively), an unusual phenomenon in mimicry warranting future study.

Selected Publications (from more than 180)

Books (from 9)

Books (co-authored)

  • Yoshioka, H., T.J. Mabry and B.N. Timmermann. Sesquiterpene Lactones, Nuclear Magnetic Resonance, Chemistry and Distribution. The University of Tokyo Press, Tokyo, 1972, 544 pp.
  • Montenegro, G. and B.N. Timmermann. Chile, Nuestra Flora Util. Especies de uso Apicola, Alimentario en Medicina Folclorica, Artesanal y Ornamental. Abaco Press, Santiago, Chile, 2000, 284 pp.

Books (co-edited)

  • Timmermann, B.N., C. Steelink and F.A. Loewus. Recent Advances in Phytochemistry, Vol. 18. Phytochemical Adaptations to Stress. Plenum Press, New York, 1984, 334 pp.
  • Whitehead, E.E., C.F. Hutchinson, B.N. Timmermann and R.G. Varady. 1987. Arid Lands: Today and Tomorrow. Proceedings of an International Research and Development Conference. October 20-25, 1985. Westview Press, Boulder, Colorado. 1435 pp.

Chapters (from 18)

  • Timmermann, B.N. Biodiversity Prospecting in Drylands of Latin America in Combating Desertification with Plants, D. Pasternak and A. Schliessel (Eds.), pp 97-111, Kluwer Academic/Plenum Publishers, NY (2001).
  • Montenegro, G., Gomez, M.,Mujica, A.M., and Timmermann B.N. Theoretical Models for Regeneration of Medicinal Plants and Their Application in Sustainable Wild Harvesting. Pp 275-290 in: Lemons, J., R. Victor, and D. Schaffer (eds.), Conserving Biodiversity in Drylands: Best Practices in Developing Nations. Kluwer Academic Publishers, Norwell, MA 513 pgs. (2003).
  • Pfeiffer, E., H. Esch, S. Hohle, A. Solyom, B.N. Timmermann and M. Metzler. In vitro studies on the estrogenic activity and the metabolism of curcumin. In: Functional Foods: Safety Aspects (G. Eisenbrand, Ed). Deutsche Forschungsgemeinschaft, Senate Commission on Food Safety, Wiley-VCH Verlag, Weinheim, pp. 325-329 (2003).
  • Timmermann, B.N. Chemistry and Mechanisms of Action of Anti-Inflammatory Botanicals. Pp.95-102 in: Proceedings from the Eighth Shizuoka Forum on Health and Longevity, Biomedical and Sociological Approaches toward a Healthy Longevity-Society, Shizuoka, Japan, 175 pgs. (2004)
  • Timmermann, B.N. 2005. Biodiversity Prospecting in Drylands of Latin America. In Biodiversity & Health: Focusing Research to Policy. Proceedings of the International Symposium, held in Ottawa, Canada, October 25-28. Edited by J.T. Arnason, P.M. Catling, E. Small, P.T. Dang, and J.D.H. Lambert. NRC Research Press, Ottawa, Ontario. pp. 79-84. (2003).
  • Timmermann, B.N.; and Funk, J.L. Multidisciplinary Studies of Anti-Inflammatory Botanicals: Ginger and Turmeric, in Phytochemicals: Health Promotion and Therapeutic Potential. Proceedings of the Seventh International Phytochemical Conference, held in Buena Park, California, October 20-21, 2008. Edited by M.S. Meskin. CRC Press, Boca Raton, FL. (in press).

Peer-reviewed Publications (selected from a total of ca. 150 publications, ca. 50 within the last five years)

  • Valcic, S., B.N.Timmermann, D.S. Alberts, G.A. Wächter, M. Krutzsch, J. Wymer and J. Guillen. 1996. Inhibitory Effect of Six Green Tea Catechins and Caffeine on the Growth of Four Selected Human Tumor Cell Lines. Anti Cancer Drugs 7: 461-468. PMID: 8826614.
  • Gensler, H., B.N. Timmermann, S. Valcic and G. Wächter. 1996. Prevention of Photo-carcinogenesis by Topical Administration of Pure Epigallocatechin Gallate Isolated from Green Tea. Nutrition and Cancer 26(3): 325-335. PMID: 8910914.
  • Barthelman, M., W.B. Bair III, K.K. Stickland, W. Chen, B.N. Timmermann, S. Valcic, Z. Dong and G.T. Bowden. 1998. (-)-Epigallocatechin-3-gallate inhibition of ultraviolet B-induced AP-1 activity. Carcinogenesis. 19(12): 2201-2204. PMID: 9886579.
  • Chen, W., Z. Dong, S. Valcic, B.N. Timmermann and G.T. Bowden. 1999. Inhibition of Ultraviolet B-induced c-fos Gene Expression and p38 Mitogen-Activated Protein Kinase Activation by (-)-Epigallocatechin Gallate in a Human Keratinocyte Cell Line. Molecular Carcinogenesis 24(2): 79-84. PMID: 10078934.
  • Dvorakova, K., R.T. Dorr, S. Valcic, B.N.Timmermann and D.S. Alberts. 1999. Pharmacokinetics of the green tea derivative, EGCG, by the topical route of administration in mouse and human skin. Cancer Chemotherapy and Pharmacology 43: 331-335. PMID: 10071985.
  • Valcic, S., A. Muders, N.E. Jacobsen, D.L. Liebler, and B.N. Timmermann. 1999. Antioxidant chemistry of green tea catechins. Identification of products of EGCG reaction with peroxyl radicals. Chem. Res. in Toxicol. 12(4): 382 386. PMID: 10207128.
  • Waechter, G., S. Valcic, M.L. Flagg, S.G. Franzblau, G. Montenegro, E. Suarez and B.N. Timmermann. 1999. Antitubercular activity of pentacyclic triterpenoids from plants of Argentina and Chile. Phytomedicine 6(5): 341-345. PMID: 11962541.
  • Timmermann, B.N., G. Wachter, S. Valcic, B. Hutchinson, J. Henzel, C. Casler, S. Ram, F. Currim, R. Manak, S. Franzblau, W. Maiese, D. Galinis, E. Suarez, R. Fortunato, E. Saavedra, R. Bye, R. Mata and G. Montenegro. 1999.The Latin American ICBG: The First Five Years. Pharm. Biol. 37, Supplement, 35-54.
  • Valcic, S., J.A. Burr, B.N. Timmermann and D.C. Liebler. 2000. Antioxidant Chemistry of Green Tea Catechins. New oxidation products of (-)- epigallocatechin gallate and (-)- epigallocatechin from their reactions with peroxyl radicals. Chem. Res. Toxicol.13(A): 801-810. PMID: 10995252.
  • Gezginci, M.H. and B.N. Timmermann. 2001. A short synthetic route to nordihydroguaiaretic acid (NDGA) and its stereoisomer using Ti-induced carbonyl-coupling reaction.Tetrahedron Letters 42: 6083-6085.
  • Wachter, G., S.G. Franzblau, G. Montenegro, J.J. Hoffmann, W.M. Maiese and B.N. Timmermann. 2001. Inhibition of Mycobacterium tuberculosis growth by saringosterol from Lessonia nigrescens. J. Nat. Prod. 64 (11): 1463-1464. PMID: 11720535.
  • Whitman, S., M. Gezginci, B.N. Timmermann & T.R. Holman. 2002. Structure-Activity Relationship Studies of Nordihydroguaiaretic Acid Inhibitors toward Soybean, 12-Human, and 15-Human Lipoxygenase. J. Med. Chem. 45(12), 2659-2661. PMID: 12036375.
  • Lambert, J.D., D. Zhao, R.O. Meyers, R.K. Kuester, B.N. Timmermann and R.T. Dorr. 2002. Nordihydroguaiaretic acid: hepatotoxicity and detoxification in the mouse. Toxicon 40: 1701-1708. PMID: 12457882.
  • Jolad, S., L.C. Lantz, A. M. Solyom, G.J. Chen, R.B. Bates, and B.N. Timmermann. 2004. Fresh organically grown ginger (Zingiber officinale): composition and effects on LPS-induced PGE2 production Phytochemistry 65:1937-1954. PMID: 15280001.
  • Lambert, J.D., Dorr, R.T., and Timmermann, B.N. 2004. Nordihydroguaiaretic Acid: A Review of its Numerous and Varied Biological Activities. Pharmaceutical Biology. 42(2): 149-158. PMID: 12457882.
  • Khera, S., Carducci, M., Michael, D., Gu, J Q., and Timmermann, B.N. 2004. (4R,5R,7S,8S,9S) 7 hydroxy 8 hydroxymethyl 4 methyl perhydrocyclopenta[c]pyran 1 one from Valeriana laxiflora. Acta Cryst.C60, o773 o775. PMID: 15528817.
  • Kiela, P.R., Midura, A.J., Kuscuoglu, N., Jolad, S.D., Solyom, A.M., Besselsen, D.G., Timmermann, B.N., and Ghishan, F.K. 2004. Boswellia serrata does not offer protection and is potentially hepatotoxic in mouse models of chemically induced colitis. Am J Physiol Gastrointest 288:G798-G808.
  • Mata, R., Morales, I., Perez, O., Rivero-Cruz, I., Acevedo, L., Enriquez-Mendoza, I., Bye, R., Franzblau, S.G., and Timmermann, B.N. 2004. Antimicrobacterial Compounds from Piper sanctum. J. Nat Prod 67(12): 1961-1968. PMID: 15620234.
  • Gu, J-Q., Wang, Y., Franzblau, S., and Timmermann, B.N. 2004. Constituents of Quinchamalium majus with Potential Antitubercular Activity. Z. Naturforsch 59(c), 797-802. PMID: 15666537.
  • Lambert, J.D., Sang, S., Dougherty, A., Caldwell, C.G., Meyers, R.O., Dorr, R.T., and Timmermann, B.N. 2005. Cytotoxic lignans from Larrea tridentata. Phytochemistry 66(7), 811-815. PMID: 15797607.
  • Jolad, S.D., Lantz, R.C., Solyom, A.M., Chen, C.J., Bates, R.B. and Timmermann, B.N. 2005.Commercially processed dry ginger (Zingiber officinale): Composition and effects on LPS-induced PGE2 production. Phytochemistry 66(13), 1614-1635. PMID: 15996695.
  • Jiang, H., A. Solyom, B. N. Timmermann, D. Gang. 2005. Characterization of gingerol-related compounds in ginger rhizome (Zingiber officinale Rosc.) by high performance liquid chromatography/electrospray ionization mass spectrometry. Rapid Commun.Mass Spectrom. 19, 2957-2964. PMID: 16189817.
  • Gutierrez-Lugo, M.T., Y. Wang, S. G. Franzblau, E. Suarez and B. N. Timmermann. 2005. Antitubercular sterols from Thalia multiflora Horkel ex Koernicke. Phytother. Res. 19, 876-880. PMID: 16261518.
  • Jiang, H., B. N. Timmermann and D. R. Gang. 2006. Use of liquid chromatography-electrospray ionization tandem mass spectrometry to identify diarylheptanoids in turmeric (Curcuma longa L.) rhizome. J Chromat. A 1111, 21-31. PMID: 16490201.
  • Jiang, H., A. Somogyi, N.E. Jacobsen, B.N. Timmermann and D.R. Gang. 2006. Analysis of curcuminoids by positive and negative electrospray ionization and tandem mass spectrometry. 2006. Rapid Comm. Mass. Spectrom. 20, 1001-1012. PMID: 16479557.
  • Johnson, L., H. Strich, A. Taylor, B. Timmermann, D. Malone, N. Teufel-Shone, R. Drummond, R. Woosley, E. Pereira and A. Martinez. 2006. Use of herbal remedies by diabetic Hispanic women in the southwestern United States. Phytother. Res. 20, 250-255. PMID: 16557605.
  • Gu, J.-Q., Y. Wang, S.G. Franzblau, G. Montenegro and B. N. Timmermann. 2006. Dereplication of pentacyclic triterpenoids in plants by GC/MS. Phytochem. Anal. 17 (2), 102-106. PMID: 16634286.
  • Funk, J. L., J. N. Oyarzo, J. B. Frye, G. Chen, R. C. Lantz, S. D. Jolad, A. M. Solyom and B. N. Timmermann. 2006. Turmeric extracts containing curcuminoids prevent experimental rheumatoid arthritis. J. Nat. Prod. 69 (3), 351-355. PMID: 16562833.
  • Ramirez-Ahumada, M.C., B.N.Timmermann and D. R. Gang. 2006. Biosynthesis of curcuminoids and gingerols in turmeric (Curcuma longa) and ginger (Zingiber officinale): identification of curcuminoid synthase and hydroxycinnamoyl-CoA thioesterases. Phytochemistry 67 (18), 2017-2029. PMID: 16890967.
  • Jiang, H., A. Somogyi, B.N. Timmermann and D.R. Gang. 2006. Instrument dependence of ESI ionization and MS/MS fragmentation of the gingerols. Rapid Comm. Mass Spectrom. 20 (20), 3089-3100. PMID: 16991102.
  • Uno, J.K., O.I. Kolek, E.R. Hines, H. Xu, B.N. Timmermann, P.R. Kiela and F. K. Ghishan. 2006. The role of tumor necrosis factor a in down-regulation of osteoblast Phex gene expression in experimental murine cholitis. Gastroenterology 131 (2), 497-509. PMID: 16890604.
  • Prudic, K. L.; Khera, S.; Solyom, A.; Timmermann, B. N. 2007. Isolation, identification, and quantification of potential defensive compounds in the viceroy butterfly and its larval host plant, Carolina willow. J. Chem. Ecol. 33(6): 1149-1159. PMID: 17431749.
  • Lantz, R. C.; Chen, G. J.; Sarihan, M.; Solyom, A. M.; Jolad, S. D.; Timmermann, B. N. 2007. The effect of extracts from ginger rhizhome on inflammatory mediator production. Phytomedicine 14: 123-128. PMID: 16709450.
  • Jiang, H.; Timmermann, B. N.; Gang, D. R. 2007. Characterization and identification of diarylheptanoids in ginger (Zingiber officinale Rosc.) using high-performance liquid chromatography/electrospray ionization mass spectrometry. Rapid. Commun. Mass. Spectrom. 21(4): 509-518. PMID: 17238228.
  • Billerey-Larmonier, C.; Uno, J. K.; Larmonier, N.; Midura, A. J.; Timmermann, B. N.; Ghishan, F. K.; Kiela, P. R. 2008. Protective effects of dietary curcumin in mouse model of chemically-induced colitis are strain dependent. J. Inflamm. Bowel Dis. 14(6): 780-793. PMID: 18200517
  • Funk, J. L.; Frye, J. B.; Oyarzo, J. N.; Timmermann, B. N. 2009. Comparative effects of two gingerol-containing Zingiber officinale extracts on experimental rheumatoid arthritis. J. Nat. Prod. 72: 403-407. PMID: 1921655

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