Education

Biography

Dr. Nagle is a Professor of Pharmacognosy in the UM Department of Bio Molecular Sciences. His research program focuses on the discovery and molecular pharmacology of natural product-based molecular-targeted antitumor agents. His group has discovered hundreds of antitumor plant and marine secondary metabolites, many that have undergone preclinical evaluation at the University of California at San Diego, St. Jude Children's Research Hospital, and the US National Cancer Institute. Dr. Nagle has extensive experience in the discovery of unique natural products that inhibit hypoxia-inducible factor (HIF)-regulated hypoxic signaling in cancer. Dr. Nagle’s team has discovered dozens of natural products that inhibit HIF-1 in breast tumor models. Currently, his program focuses on agents that interfere with the organ-specific genetic pre-programming of aggressive “triple-negative” breast tumor cells. His group is working to assess the anti-metastatic breast cancer potential of natural products, including Traditional Chinese Medicine (TCM) products. He has co-authored nearly 90 peer-reviewed publications, including eight book chapters and an invited seminal chapter on “Natural Products as Probes of Selected Targets in Tumor Cell Biology and Hypoxic Signaling” and another on “Mechanism-Based Screening for Cancer Therapeutics.”

Research Interests

• Discovery of natural products that inhibit HIF-regulated hypoxic signaling in breast cancer.
• Discovery of antitumor natural products from marine organisms and plants.
• Molecular pharmacology and target identification though the discovery and use of natural products as probes of tumor cell biology
• Discovery and development of natural products in Traditional Chinese Medicines that interfere with organotropic “triple-negative” breast tumor metastases.

Scientific Activities

Teaching Experience

Honors & Awards

Publications

1. Dewitz, C.; McEachern, E.; Shin, S.; Akong, K.; Nagle, D.G.; Broide, D.H.; Akuthota, P.; Crotty Alexander, L.E. “Hypoxia inducible factor-1α inhibition modulates airway hyperresponsiveness         and nitric oxide levels in a BALB/c mouse model of asthma.” Clin. Immunol. 2017, 176, 94-99.
2. Nagle, D.G. “A perspective on natural products in breast cancer carcinogenesis and chemoprevention” Ann. Carcinog. 2016, 1, 1002.
3. Mahdi, F.; Morgan, J.B.; Liu, W.; Agarwal, A.K.; Jekabsons, M.B.; Liu, Y.; Zhou, Y.-D.; Nagle, D.G. “Sampangine (a copyrine alkaloid) exerts biological activities through cellular redox cycling of its quinone and semiquinone intermediates” J. Nat. Prod., 2015, 78, 3018-3023.
4. Morgan, J.B.; Liu, Y.; Coothankandaswamy, V.; Mahdi, F.; Jekabsons, M.B.; Gerwick, W.H.; Valeriote, F.A.; Zhou, Y.-D.; Nagle, D.G. “Kalkitoxin inhibits angiogenesis, disrupts cellular hypoxic signaling, and blocks mitochondrial electron transport in tumor cells” Mar. Drugs 2015, 13, 1552-1568. PMC4377999
5. Datta, S.; Mahdi, F.; Ali, Z.; Jekabsons, M.B.; Khan, I.H.; Nagle, D.G.; Zhou, Y.-Z. “Toxins in botanical dietary supplements: Blue cohosh components disrupt cellular respiration and mitochondrial membrane potential” J. Nat. Prod., 2014, 77, 111–117.
6. Li, J.; Du, L.; Kelly, M.; Zhou, Y.-D.; Nagle, D.G. "Structures and potential antitumor activity of sesterterpenes from the marine sponge Hyrtios communis" J. Nat. Prod., 2013, 76, 1492–1497.
7. Du, L.; Zhou, Y.-D.; Nagle, D.G. "Inducers of hypoxic response: Marine sesquiterpene quinones activate HIF-1." J. Nat. Prod., 2013, 76, 1175–1181.
8. Datta, S.; Zhou, Y.-D.; Nagle, D.G. “Comparative study of chromatographic medium-associated mass and potential antitumor activity loss with bioactive extracts” J. Nat. Prod., 2013, 76, 642–647.  
9. Li, J.; Mahdi, F.; Du, L.; Jekabsons, M.B.; Zhou, Y.-D.; Nagle, D.G. “Semisynthetic studies identify mitochondria poisons from botanical dietary supplements - geranyloxycoumarins from Aegle marmelos” Bioorg. Med. Chem., 2013, 21, 1795–1803.
10. Datta, S.; Li, J.; Mahdi, F.; Jekabsons, M.B.; Nagle, D.G.; Zhou, Y.-D. “Glycolysis inhibitor screening identifies the bis-geranylacylphloroglucinol protonophore moronone from Moronobea coccinea” J. Nat. Prod., 2012, 75, 2216–2222.
11. Du, L.; Mahdi, F.; Jekabsons, M.B.; Nagle, D.G.; Zhou, Y.-D. “Structures and mechanisms of antitumor agents - Xestoquinones uncouple cellular respiration and disrupt HIF signaling in human breast tumor cells” J. Nat. Prod., 2012, 75, 1553–1559.
12. Li, J.; Mahdi, F.; Du, L.; Datta, S.; Nagle, D.G.; Zhou, Y.-D. “Mitochondrial respiration inhibitors suppress protein translation and hypoxic signaling via the hyperphosphorylation and inactivation of translation initiation factor eIF2a and elongation factor eEF2.” J. Nat. Prod., 2011, 74, 1894–1901.
13. Mahdi, F.; Falkenberg, M.; Ioannou, E.; Roussis, V.; Zhou, Y.-D.; Nagle, D.G. “Thyrsiferol inhibits mitochondrial respiration and HIF-1 activation” Phytochem. Lett., 2011, 4, 75–78.
14. Du, L.; Mahdi, F.; Jekabsons, M.B.; Nagle, D.G.; Zhou, Y.-D. “Natural and semisynthetic Mammea-type isoprenylated dihydroxycoumarins uncouple cellular respiration” J. Nat. Prod., 2011, 74, 240–248.
15. Du, L.; Mahdi, F.; Jekabsons, M.B.; Nagle, D.G.; Zhou, Y.-D. “Mammea E/BB, An isoprenylated dihydroxycoumarin protonophore that potently uncouples mitochondrial electron transport disrupts 14 hypoxic signaling in tumor cells” J. Nat. Prod., 2010, 73, 1868–1872.
16. Morgan, J.B; Mahdi, F.; Liu, Y.; Coothankandaswamy, V.; Jekabsons, M.B.; Johnson, T.A.; Sashidhara, K.V.; Crews, P.; Nagle, D.G.; Zhou, Y.-D. “The marine sponge metabolite mycothiazole: A novel prototype mitochondrial complex I inhibitor” Bioorg. Med. Chem., 2010, 18, 5988–5994. BMC-D-10- 00755R1.
17. Veena, C.K.: Liu, Y.; Mao, S.-C.; Morgan, J.B.; Mahdi, F.; Jekabsons, M.; Nagle, D.G.; Zhou, Y.-D. “The alternative medicine pawpaw and its acetogenin constituents inhibit hypoxic activation of hypoxiainducible factor-1” J. Nat. Prod., 2010, 73, 956–961. (ACS Statistic: Among the top 20 most accessed manuscripts for May 2010 in J. Nat. Prod.)