F. David Horgen PH.D.
College of Natural and Computational Sciences - Department of Natural Science
PROFESSOR OF CHEMISTRY
CHAIR, DIVE CONTROL BOARD
HEAD, SHARED INSTRUMENTATION FACILITY
FACULTY ATHLETICS REPRESENTATIVE
PRINCIPLE INVESTIGATOR, LABORATORY OF MARINE BIOLOGICAL CHEMISTRY
Education:
- Post-doctoral Fellowship, Marine Natural Products Chemistry, Department of Chemistry, University of Hawaii at Manoa
- Ph.D., Pharmacognosy, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago
- B.S., Biology, Florida International University
Courses Taught:
- CHEM 3030 Organic Chemistry I
- CHEM 3031 Organic Chemistry I Lab
- CHEM 3032 Organic Chemistry II
- CHEM 3033 Organic Chemistry II Lab
- CHEM 6310 Marine Natural Products Chemistry
- CHEM 2052 General Chemistry II
- CHEM 4030 Biochemistry I
- CHEM 4031 Biochemistry I Laboratory
Awards:
2017 HPU Teacher of the Year, 2014 HPU Golden Apple Award for Scholarship, 2011 Visiting Professor (honorary), Tongji Medical College, Huazhong University of Science and Technology; 2011 Weinman Innovator Award for Translational Research, Weinman Foundation/ University of Hawaii Cancer Center (Co-investigator; funded by the Weinman Foundation fund to support the development of cutting-edge cancer research); 2009 Jack L. Beal Award, American Chemical Society/American Society of Pharmacognosy (Best paper of 2008 in the Journal of Natural Products among early-career investigators); 2004 Presidents Award for Outstanding Service by a Faculty Member, Hawaii Pacific University; 2002 AFPE Fellow, American Foundation for Pharmaceutical Education, Rockville, MD; 1996 Van Dorens Scholars Scholarship, University of Illinois at Chicago; 1993-1997 Graduate College University Fellowship, University of Illinois at Chicago; 1993-1996 Graduate Fellowship, American Foundation for Pharmaceutical Education, Rockville, MD; 1992 Graduate Fellowship, Honorable Mention, National Science Foundation, Arlington, VA.
Professional Interests:
Marine natural products chemistry, bioanalytical chemistry, biological screening, and chemical ecology
Personal Interests/Biography:
Fishing, spearfishing, hunting, hiking, scuba diving
Teaching Interests/Research:
Dr. Horgen’s major research interest is marine natural products chemistry. This field focuses on molecules that are produced by plants, animals and microbes in the marine environment and the manner in which these substances affect other organisms. For example, these compounds (known as marine natural products) are produced by organisms to protect them from being eaten, to kill or immobilize their prey, to defend their territories, or to communicate. At the same time, marine natural products have high structural diversity and possess chemical properties that allow them to act as drugs in the human body, which makes them a valuable resource for finding new therapies for a wide range of diseases, especially cancer. The focus in Dr. Horgen’s lab is the discovery of marine natural products that can interact with proteins involved in human diseases and switch these proteins on and off as needed to prevent or stop the progress of disease.
Publications:
Hoelting, K.; Madlmayr, A.; Hoeger, B.; Lewitz, D.; Weng, M.; Haider, T.; Duggan, M.; Ross, R.; Horgen, F. D.; Sperandio, M.; Dietrich, A.; Gudermann, T.; Zierler, S. TRPM7 Activity Drives Human CD4 T-Cell Activation and Differentiation in a Magnesium Dependent Manner. bioRxiv 2024, 2024.12.04.626765. PMID: 39677770. PMCID: PMC11643021. DOI: 10.1101/2024.12.04.626765.
Yao, G.; Parris, M. R.; Kuo, W. C.*; Pörzgen, P.; Castillo, B.*; Mason, E. S.; Chinchilla, A.; Huang, J.; Suzuki, S.; Ross, R.*; Akana, E.; Vander Schuit, S.*; Miller, S. P.; Penner, R.; Sun, H.-S.; Feng, Z.-P.; Hull, K. G.; Romo, D.; Fleig, A.; Horgen, F. D. Transient Receptor Potential Melastatin 7 (TRPM7) Ion Channel Inhibitors: Preliminary SAR and Conformational Studies of Xenicane Diterpenoids from the Hawaiian Soft Coral Sarcothelia edmondsoni. J Nat Prod 2024, 87 (4), 783–797. PMID: 38537009. https://doi.org/10.1021/acs.jnatprod.3c00942.
Luo, Z.; Zhang, X.; Fleig, A.; Romo, D.; Hull, K. G.; Horgen, F. D.; Sun, H.-S.; Feng, Z.-P. TRPM7 in Neurodevelopment and Therapeutic Prospects for Neurodegenerative Disease. Cell Calcium 2024, 120, 102886. PMID: 38631163. https://doi.org/10.1016/j.ceca.2024.102886.
Phan, N.; Vizza, C.; Lim, E.; Dorsey Elson, L.; Jackson, A.; Kaumatule, B.; Horgen, F. D.; Vakalahi, H.; Shekhattari, P.; Okamoto, S. Mentorship Interventions Creating a Mentoring Community through Faculty Writing Retreats at a Teaching Intensive, Minority Serving University: The HUI Scholars Program. The Chronicle of Mentoring & Coaching 2024, 8 (2), 45–52. https://doi.org/10.62935/pj96169.
Vakalahi, H. O., Okamoto, S. K., Horgen, F. D., Lim, E., Phan, N., Kaumatule, B. S., & Sheikhattari, P. Promoting health research among underrepresented students through the HUI SRC. Hawai‘i Journal of Health and Social Welfare 2023; 82, 36-43. PMID: 37901664. PMCID: PMC10612418.
Zheng, G.; Lv, K.; Wang, H.; Huang, L.; Feng, Y.; Gao, B.; Sun, Y.; Li, Y.; Huang, J.; Jin, P.; Xu, X.; Horgen, F. D.; Fang, C.; Yao, G. Piericones A and B as Potent Antithrombotics: Nanomolar Noncompetitive Protein Disulfide Isomerase Inhibitors with an Unexpected Chemical Architecture. J Am Chem Soc 2023. PMID: 36696679. https://doi.org/10.1021/jacs.2c12963.
Khalil, A.; Shekh‐Ahmad, T.; Kovac, S.; Wykes, R. C.; Horgen, F. D.; Fleig, A.; Walker, M. C. Drugs Acting at TRPM7 Channels Inhibit Seizure‐like Activity. Epilepsia Open 2023, epi4.12773. https://doi.org/10.1002/epi4.12773. PMID: 37328275 PMCID: PMC10472385.
Hammad, A. S.; Yu, F.; Al-Hamaq, J.; Horgen, F. D.; Machaca, K. STIM1 Signals through NFAT1 Independently of Orai1 and SOCE to Regulate Breast Cancer Cell Migration. Cell Calcium 2023, 114, 102779. https://doi.org/10.1016/j.ceca.2023.102779. PMID: 37399784.
Turlova, E.; Ji, D.; Deurloo, M.; Wong, R.; Fleig, A.; Horgen, F. D.; Sun, H.-S.; Feng, Z.-P. Hypoxia-Induced Neurite Outgrowth Involves Regulation Through TRPM7. Mol Neurobiol 2023, 60 (2), 836–850. PMID: 36378470. https://doi.org/10.1007/s12035-022-03114-9.
Zeitlmayr, S.; Zierler, S.; Staab-Weijnitz, C. A.; Dietrich, A.; Geiger, F.; Horgen, F. D.; Gudermann, T.; Breit, A. TRPM7 Restrains Plasmin Activity and Promotes Transforming Growth Factor-Β1 Signaling in Primary Human Lung Fibroblasts. Arch Toxicol 2022, 96 (10), 2767–2783. PMID: 35864199. PMCID: PMC9302958. https://doi.org/10.1007/s00204-022-03342-x.
Ji, D.; Fleig, A.; Horgen, F.D.; Feng, Z.-P.; Sun, H.-S. Modulators of TRPM7 and its potential as a drug target for brain tumours. Cell Calcium 2022, 101, 102521. PMID: 34953296. DOI: 10.1016/j.ceca.2021.102521.
Hyrenbach, K. D.; McGinnis, Z.*; Page, K.*; Rapp, D.; Horgen, F. D.; Lynch, J. M. Assessment of Plastic Ingestion by Pole‐caught Pelagic Predatory Fish from O’ahu, Hawai’i. Aquatic Conserv: Mar Freshw Ecosyst 2021, 31 (2), 408–419. PMID: 34334992. PMCID: PMC8323999. https://doi.org/10.1002/aqc.3507.
Ma, C.; Hoffmann, F. W.; Marciel, M. P.; Page, K. E.*; Williams-Aduja, M. A.*; Akana, E. N. L.; Gojanovich, G. S.; Gerschenson, M.; Urschitz, J.; Moisyadi, S.; Khadka, V. S.; Rozovsky, S.; Deng, Y.; Horgen, F. D.; Hoffmann, P. R. Upregulated ethanolamine phospholipid synthesis by selenoprotein I is required for effective metabolic reprogramming during T cell activation. Molecular Metabolism 2021, 101170. PMID: 33484950. PMCID: PMC7881273.
Turlova, E.; Wong, R.; Xu, B.; Li, F.; Du, L.; Habbous, S.; Horgen, F. D.; Fleig, A.; Feng, Z.-P.; Sun, H.-S. TRPM7 mediates neuronal cell death upstream of calcium/calmodulin-dependent protein kinase II and calcineurin mechanism in neonatal hypoxic-ischemic brain injury. Transl. Stroke Res. 2021, 12, 164-184. https://doi.org/10.1007/s12975-020-00810-3. PMID: 32430797.
Sun, H.-S.; Horgen, F. D.; Romo, D.; Hull, K. G.; Kiledal, S. A.; Fleig, A.; Feng, Z.-P. Waixenicin A, a marine-derived TRPM7 inhibitor: a promising CNS drug lead. Acta Pharmacol. Sin. 2020, 41, 1519–1524. PMID: 32994545. PMCID: PMC7921126. https://doi.org/10.1038/s41401-020-00512-4.
Wong, R.; Gong, H.; Alanazi, R.; Bondoc, A.; Luck, A.; Sabha, N.; Horgen, F. D.; Fleig, A.; Rutka, J. T.; Feng, Z.-P.; Sun, H.-S. Inhibition of TRPM7 with waixenicin A reduces glioblastoma cellular functions. Cell Calcium 2020, 92, 102307. https://doi.org/10.1016/j.ceca.2020.102307. PMID: 33080445.
Ardestani, G.; Mehregan, A.; Fleig, A.; Horgen, F. D.; Carvacho, I.; Fissore, R. A. Divalent cation influx and calcium homeostasis in germinal vesicle mouse oocytes. Cell Calcium 2020, 87, 102181. https://doi.org/10.1016/j.ceca.2020.102181. PMID: 32097818. PMCID: PMC7153984.
Reinicke, J.*; Kitatani, R.; Masoud, S.S.; Galbraith, K.K.*; Yoshida, W.; Igarashi, A.; Nagasawa, K.; Berger, G.; Yanagihara, A.; Nagai, H.; Horgen, F.D. Isolation, structure determination, and synthesis of cyclic tetraglutamic acids from box jellyfish species Alatina alata and Chironex yamaguchii. Molecules 2020, 25, 883. PMID: 32079282. PMCID: PMC707061.
Huang, Y.; Leng, T.-D.; Inoue, K.; Yang, T.; Liu, M.; Horgen, F. D.; Fleig, A.; Li, J.; Xiong, Z.-G. TRPM7 channels play a role in high glucose–induced endoplasmic reticulum stress and neuronal cell apoptosis. J. Biol. Chem. 2018, 293 (37), 14393–14406. PMID: 30076216. PMCID: PMC6139551.
Jung, M.R.*, Horgen, F.D., Orski, S.V., Rodriguez C., V., Beers, K.L., Balazs, G.H., Jones, T.T., Work, T.M., Brignac, K.C., Royer, S.-J., Hyrenbach, K.D., Jensen, B.A., Lynch, J.M. Validation of ATR FT-IR to identify polymers of plastic marine debris, including those ingested by marine organisms. Marine Pollution Bulletin 2018, 127, 704-716. PMID: 29475714.
Starkus, J.G.; Poerzgen, P.; Layugan, K.*; Kawabata, K.G.*; Goto, J.I.; Suzuki, S.; Myers, G.; Kelly, M.; Penner, R.; Fleig, A.; Horgen, F.D. Scalaradial is a potent inhibitor of transient receptor potential melastatin 2 (TRPM2) ion channels. Journal of Natural Products 2017, 80, 2741-2750. PMID: 29019677. PMCID: PMC6687308.
Anderson, B.*; Zhang, L.; Wang, H.; Lu, T.; Horgen, F.D.; Culliney, J.; Fang, J. Sedimentary carbon and nitrogen dynamics reveal impact of human land-use change on Kawainui Marsh, O'ahu, Hawai'i. Pacific Science 2017, 71, 17-27. https://doi.org/10.2984/71.1.2.
Huang, J.; Furuya, H.; Faouzi, M.; Zhang, Z.; Monteilh-Zoller, M.; Kawabata, K.G.*; Horgen, F.D.; Kawamori, T.; Penner, R.; Fleig, A. Inhibition of TRPM7 suppresses cell proliferation of colon adenocarcinoma in vitro and induces hypomagnesemia in vivo without affecting azoxymethane-induced early colon cancer in mice. Cell Communication and Signaling 2017, 15, 30. PMID: 28810912. PMCID: PMC5558780.
Sisquella, X.; Nebl, T.; Thompson, J.; Whitehead, L.; Malpede, B.M.; Salinas, N.D.; Rogers, K.; Tolia, N.H.; Fleig, A.; Tham, W.-H.; Horgen, F.D.; Cowman, A. Plasmodium falciparum ligand binding to erythrocytes induce alterations in deformability essential for invasion. eLife 2017, 6:e21083. PMID: 28226242. PMCID: PMC5333951.
Faouzi, M.; Kilch, T.; Horgen, F. D.; Fleig, A.; Penner, R. The TRPM7 channel kinase regulates store-operated calcium entry. Journal of Physiology 2017, 595, 3165-3180. PMID: 28130783. PMCID: PMC5430208.
Jansen, C; Sahni, J.; Suzuki, S.; Horgen, F.D.; Penner, R.; Fleig, A. The coiled coil domain of zebrafish TRPM7 is essential for Mg·nucleotide binding. Scientific Reports 2016, 6, 33459. PMID: 27628598. PMCID: PMC5024298.
Dussault, D.; Vua, K.D.; Vansach, T.*; Horgen, F.D.; Lacroix, M. Antimicrobial effects of marine algal extracts and cyanobacterial pure compounds against 5 foodborne pathogens. Food Chemistry 2016, 199, 114–118. PMID: 26775951.
Turlova, E.; Bae, C.J.; Deurloo, M.; Chen, W.; Barszczyk, A.; Horgen, F.D.; Fleig, A.; Feng, Z.-P.; Sun, H.-S. TRPM7 Regulates axonal outgrowth and maturation of primary hippocampal neurons. Molecular Neurobiology 2016, 53, 595-610. PMID: 25502295. PMCID: PMC4820394.
Huguet, F.; Calvez, M.L.; Benz, N.; Le Hir, S.; Mignen, O.; Buscaglia, P.; Horgen, F.D.; Férec , C.; Kerbiriou, M.; Trouvé P. Function and regulation of TRPM7, as well as intracellular magnesium content, are altered in cells expressing ΔF508-CFTR and G551D-CFTR. Cellular and Molecular Life Sciences 2016, 73, 3351-3373. doi: 10.1007/s00018-016-2149-6. PMID: 26874684.
Ju, Z.Y.; Viljoen, C.; Hutchinson, P.; Reinicke*, J.; Horgen, F.D.; Howard, L.; Lee, C.-S. Effects of diets on the growth performance and shell pigmentation of Pacific abalone. Aquaculture Research 2016, 47, 4004-4014. doi:10.1111/are.12851.
Mori, S.; Williams, H.; Cagle,* D.; Karanovich*, K.; Horgen, F.D.†; Smith III, R.; Watanabe, C.M.H. † Macrolactone nuiapolide, isolated from a Hawaiian marine cyanobacterium, exhibits anti-chemotactic activity. Marine Drugs 2015, 13, 6274-6290. PMID: 26473885. PMCID: PMC4626689. († corresponding authors)
Visser, D.; Langeslag, M.; Kedziora, K.M.; Klarenbeek, J.; Kamermans, A.; Horgen, F.D.; Fleig, A.; van Leeuwen, F.N.; Jalink, K. 2013. TRPM7 triggers Ca2+ sparks and invadosome formation in neuroblastoma cells. Cell Calcium 2013, 54, 404−415. PMID: 24176224. PMCID: PMC4912378.
Luo, L.; Wang, F.; Zhang, J.; Li, X.; Zhang, M.; Hao, X.; Xue, Y.; Li, Y.; Horgen, F.D.; Yao, G.; Zhang, Y. Cytotoxic alkaloids from the whole plants of Zephyranthes candida. Journal of Natural Products 2012, 75, 2113−2120. PMID: 23190013. PMCID: PMC3580115.
Zierler, S., Yao, G., Zhang, Z., Kuo*, C.W., Pörzgen, P., Penner, R., Horgen, F.D., and Fleig, F.: Waixenicin A inhibits cell proliferation through magnesium-dependent block of transient receptor potential melastatin 7 (TRPM7) channels. Journal of Biological Chemistry 2011, 286, 39328-39335. PMID: 21926172. PMCID: PMC3234757.
Castillo*, B., Porzgen, P., Penner, R., Horgen, F.D. and Fleig, A.: Development and optimization of a highthroughput bioassay for TRPM7 ion channel inhibitors. Journal of Biomolecular Screening 2010, 15, 498-507. PMID: 20413646. PMCID: PMC4725312.
Jiménez, J.I. ‡; Vansach, T. ‡,*; Yoshida, W.Y.; Sakamoto, B.; Redwine, J.; Horgen, F.D.: Halogenated fatty acid amides and cyclic depsipeptides from an eastern Caribbean collection of the cyanobacterium Lyngbya majuscula. Journal of Natural Products 2009, 72, 1573-1578. (‡ contributed equally) PMID: 19739598. PMCID: PMC3510382.
Adams, B.*; Pörzgen, P.; Yoshida, W. Y.; Westenburg, H. E.; Horgen, F. D.: Isolation and structure determination of malevamide E, a new dolastatin 14 analogue, from the marine cyanobacterium Symploca laete-viridis. Journal of Natural Products 2008, 71, 750-754. PMID: 18361518.
Ju, Z.Y.; Forster, I.; Conquest, L.; Dominy, W.; Kuo, W.C.*; Horgen, F.D.: Microbial community structures of shrimp floc cultures determined by biomarkers and their amino acid profiles. Aquaculture Nutrition 2008, 39,118-133. https://doi.org/10.1111/j.1365-2109.2007.01856.x.
Sata, N.; Abinsay, H.; Yoshida, W.; Horgen, F.D.; Sitachitta, N.; Kelly, M.; Scheuer, P.J.: Lehualides A-D, new metabolites from a Hawaiian sponge of the genus Plakortis (Homosclerophorida: Plakinidae). Journal of Natural Products 2005, 68, 1400-1403. PMID: 16180823.
Horgen, F.D.; Kazmierski, E.B.*; Westenburg, H.E.; Yoshida, W.Y.; Scheuer, P.J.: Malevamide D: isolation and structure determination of an isodolastatin H analog from the marine cyanobacterium Symploca hydnoides. Journal of Natural Products 2002, 65, 487-491. PMID: 11975485.
Luesch, H.; Harrigan, G.G.; Goetz, G.; Horgen, F.D.: The cyanobacterial origin of potent anticancer agents originally isolated from sea hares. Current Medicinal Chemistry 2002, 9, 1791-1806. PMID: 12369878.
Horgen, F.D.; Edrada, R.A.; de los Reyes, G.; Agcaoili, F.; Madulid, D.A.; Wongpanich, V.; Angerhofer, C.K.; Pezzuto, J.M.; Soejarto, D.D.; Farnsworth, N.R.: Biological screening of rain forest plot trees from Palawan Island (Philippines). Phytomedicine 2001, 8, 71-81. PMID: 11292242.
Horgen, F.D.; Yoshida, W.Y.; Scheuer, P.J.: Malevamides A-C, new depsipeptides from the marine cyanobacterium Symploca laete-viridis. Journal of Natural Products 2000, 63, 461-467. PMID: 10785414.
Horgen, F.D.; Sakamoto, B.; Scheuer, P.J.: New triterpenoid sulfates from the red alga Tricleocarpa fragilis. Journal of Natural Products 2000, 63, 210-216. PMID: 10691711.
Horgen, F.D.; delos Santos, D.B.; Goetz, G.; Sakamoto, B.; Kan, Y.; Nagai, H.; Scheuer, P.J.: A new depsipeptide from the sacoglossan mollusk Elysia ornata and the green alga Bryopsis sp. Journal of Natural Products 2000, 63, 152-154. PMID: 10650101.
Sakamoto, B.; Hokama, Y.; Horgen, F.D.; Scheuer, P.J.; Kan, Y.; Nagai, H.: Isolation of a sulfoquinovosyl monoacylglycerol from Bryopsis sp. (Chlorophyta): identification of a factor causing a possible species-specific ecdysis response in Gambierdiscus toxicus (Dinophyceae) Journal of Phycology 2000, 36, 924-931. https://doi.org/10.1046/j.1529-8817.2000.00006.x.
Cui, B.L.; Chai, H.B.; Dong, Y.M.; Horgen, F.D.; Hansen, B.; Madulid, D.A.; Soejarto, D.D.; Farnsworth, N.R.; Cordell, G.A.; Pezzuto, J.M.; Kinghorn, A.D.: Quinoline alkaloids from Acronychia laurifolia. Phytochemistry 1999, 52, 95-98. PMID: 10466225.
Horgen, F.D.; Guinaudeau, H.; Pezzuto, J.M.; Soejarto, D.D.; Farnsworth, N.R.; Agcaoili, F.; de los Reyes, G.; Edrada, R.: Isolation and structure elucidation of ardisenone: a new, cytotoxic alkenylphenol from Ardisia iwahigensis. Journal of Natural Products 1997, 60, 533-535. PMID: 9170297.
Horgen, F.D.; Madulid, D.A.; Angerhofer, C.K.; Pezzuto, J.M.; Soejarto, D.D.; Farnsworth, N.R.: Isolation of gallic acid esters as antiplasmodial constituents of Swintonia foxworthyi (Anacardiaceae). Phytomedicine 1997, 4, 353-356. https://doi.org/10.1016/S0944-7113(97)80046-3.
