Cancer metabolic reprogramming is an important hallmark of cancer. It relies of the fact that cancer tissue possesses several important metabolic features, such as differential utilization of many essential metabolites. Cancer metabolic reprogramming is required for malignant transformation, tumor development, invasion and metastasis. Its complex and dynamic nature has been recognized as one of the major challenges for effective cancer treatment. Therefore, a better understanding of metabolic dependencies in specific tumor types can provide a path for improved cancer treatments.
However, no efficient methodologies currently exist that allow noninvasive imaging and quantification of the uptake of essential metabolites in animal models of disease. To address the unmet need for nutrient uptake imaging tools, we decided to develop a novel platform based on a combination of versatile “click” chemistry reactions with noninvasive, ultrasensitive bioluminescent imaging techniques.
The results will lead to the generation of novel, effective treatments; therefore, this novel platform has high clinical applicability. Due to its versatile nature, application of the platform can be expended to studies of many other important human pathologies in which changes in metabolism play a key role, such as diabetes, neurodegenerative diseases, nonalcoholic steatohepatitis, and many others. Please see the first demonstration of the platform recently published in Nature Methods (2019).
Cancer metabolic reprogramming is an important hallmark of cancer. It relies of the fact that cancer tissue possesses several important metabolic features, such as differential utilization of many essential metabolites. Cancer metabolic reprogramming is required for malignant transformation, tumor development, invasion and metastasis. Its complex and dynamic nature has been recognized as one of the major challenges for effective cancer treatment. Therefore, a better understanding of metabolic dependencies in specific tumor types can provide a path for improved cancer treatments.
However, no efficient methodologies currently exist that allow noninvasive imaging and quantification of the uptake of essential metabolites in animal models of disease. To address the unmet need for nutrient uptake imaging tools, we decided to develop a novel platform based on a combination of versatile “click” chemistry reactions with noninvasive, ultrasensitive bioluminescent imaging techniques.
The results will lead to the generation of novel, effective treatments; therefore, this novel platform has high clinical applicability. Due to its versatile nature, application of the platform can be expended to studies of many other important human pathologies in which changes in metabolism play a key role, such as diabetes, neurodegenerative diseases, nonalcoholic steatohepatitis, and many others. Please see the first demonstration of the platform recently published in Nature Methods (2019).
Cancer metabolic reprogramming is an important hallmark of cancer. It relies of the fact that cancer tissue possesses several important metabolic features, such as differential utilization of many essential metabolites. Cancer metabolic reprogramming is required for malignant transformation, tumor development, invasion and metastasis. Its complex and dynamic nature has been recognized as one of the major challenges for effective cancer treatment. Therefore, a better understanding of metabolic dependencies in specific tumor types can provide a path for improved cancer treatments.
However, no efficient methodologies currently exist that allow noninvasive imaging and quantification of the uptake of essential metabolites in animal models of disease. To address the unmet need for nutrient uptake imaging tools, we decided to develop a novel platform based on a combination of versatile “click” chemistry reactions with noninvasive, ultrasensitive bioluminescent imaging techniques.
The results will lead to the generation of novel, effective treatments; therefore, this novel platform has high clinical applicability. Due to its versatile nature, application of the platform can be expended to studies of many other important human pathologies in which changes in metabolism play a key role, such as diabetes, neurodegenerative diseases, nonalcoholic steatohepatitis, and many others. Please see the first demonstration of the platform recently published in Nature Methods (2019).
Elena Goun received her MSc degree from the University of Central Florida (USA) in the field of medicinal chemistry under supervision of Professor Howard Miles. She then continued her PhD studies in the field of medicinal chemistry and drug delivery in the group of Professor Paul Wender at Stanford University (USA), where she received extensive training in the field of organic synthetic chemistry and in methods for the development of novel drug delivery. After earning her PhD in 2008, Elena moved to the University of California at Berkeley (USA), where she performed her postdoctoral studies in the field of chemical biology in the group of Carolyn Bertozzi. In September 2011, Elena Goun was appointed at École Polytechnique Fédérale de Lausanne (EPFL, Switzerland), where for the first 3 years, she was responsible for running an academic exchange program for Russian students and faculty, which was the biggest international program in Switzerland (total funding of 8 million CHF). In August 2014, Elena launched her independent career as a Tenure-Track Assistant Professor at the Institute of Chemical Sciences and Engineering, EPFL. Elena is an advocate for interdisciplinary approaches to research, combining organic synthetic chemistry and optical imaging to find solutions to fundamental problems in biology and medicine.
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2023
46. Shihadih, D.; Wang, X.; Zushin, P.; Khodakivskyi, P.; Park, H.M.; Nomura, D.; Goun, E.; Calvisi, D.; Chen, X; Stahl, A. FATP5 is indispensable for the growth of intrahepatic cholangiocarcinoma. Accepted to Molecular Cancer Research
45. Kozak, A; Mikhaylov, G.; Khodakivskyi, P.; Goun, E.; Turk, B.; Vasiljeva, O. A New Cathepsin D Targeting Drug Delivery System Based on Immunoliposomes Functionalized with Lipidated Pepstatin A. Accepted to Pharmaceutics.
44. Maric, T.; Bazhin, A.; Khodakivskyi, P.; Mikhaylov, G.; Solodnikova, E.; Yevtodiyenko, A.; Paola Attianese, G.; Coukos, G.; Irving, M.; Joffraud, M.; Cantó, C.; Goun, E.* A bioluminescent-based probe for in vivo non-invasive monitoring of nicotinamide riboside uptake reveals a link between metastasis and NAD+ metabolism. Biosens. Bioelectron. 2023 Jan 15; 220:114826. DOI: 10.1016/j.bios.2022.114826.
2021
43. Yevtodiyenko, A.; Bazhin, A.; Khodakivskyi, P.; Godinat, A.; Budin, G.; Maric, T.; Pietramaggiori, G.; Scherer, S.; Kunchulia, M.; Eppeldauer, G.; Polyakov, S.V.; Francis, K.P.; Bryan, J.N.; Goun, E.* Portable bioluminescent platform for in vivo monitoring of biological processes in non-transgenic animals. Nat. Commun. 2021, 12(1):2680. doi: 10.1038/s41467-021-22892-9 (link)
42. Khodakivskyi, P.V.; Lauber, C.L.; Yevtodiyenko, A.; Bazhin, A.A.; Bruce, S.; Ringel-Kulka, T.; Ringel, Y; Betrisey, B.; Torres, J.; Hu, J.; Chou, C.J.; Goun E.A.*, Noninvasive imaging and quantification of bile salt hydrolase activity: from bacteria to humans. Sci. Adv. 2021, 7(6), eaaz9857, DOI: 10.1126/sciadv.aaz9857 (link)
41. Cui, L.; Gouw, A.M.; LaGory, E.L.; Guo, S.; Attarwala, N.; Tang, Y.; Qi, J.; Chen, Y.S.; Gao, Z.; Casey, K.M.; Bazhin, A.A.; Chen, M.; Hu, L.; Xie, J.; Fang, M.; Zhang, C.; Zhu.; Wang, Z.; Giaccia, A.J.; Gambhir, S.S.; Zhu, W.; Felsher, D.W.; Pegram, M.D.; Goun, E.A.; Le, A.; Rao, J., Mitochondrial copper depletion suppresses triple-negative breast cancer in mice. Nat. Biotechnol. 2021, 39(3), 357-367. doi: 10.1038/s41587-020-0707-9 (link)
2020
40. Bazhin, A.A.; Sinisi, R.; De Marchi, U.; Hermant, A.; Sambiagio, N.; Maric, T.; Budin, G.; Goun, E.A.*, A bioluminescent probe for longitudinal monitoring of mitochondrial membrane potential. Nat. Chem. Biol. 2020,16(12),1385-1393. (link)
This paper was highlighted in:
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Chemical & Engineering News, August 14, 2020;
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ScienceDaily, August 12, 2020.
2019
39. Karatas, H.; Maric, T.; D’Alessandro, P. L.; Yevtodiyenko, A.; Vorherr, T.; Hollingworth, G.; Goun, E.A.*, Real-time imaging and quantification of peptide uptake in vitro and in vivo. ACS Chem Biol. 2019, 14, 2197-2205. (link)
38. Maric, T.; Mikhaylov, G.; Khodakivskyi, P.; Bazhin, A.; Sinisi R.; Bonhoure, N.; Yevtodiyenko, A.; Jones, A.; Muhunthan, V.; Abdelhady, G.; Shackelford, D.; Goun, E.* Bioluminescent-based imaging and quantification of glucose uptake in vivo. Nat. Methods 2019, 16(6):526-532. (link)
This paper was highlighted* in:
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Springer Nature, May 16, 2019;
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Chemical & Engineering News, May 18, 2019;
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ScienceDaily, May 20th, 2019.
37. Bazhin, A.A.; Chambon, M.; Vesin, J.; Bortoli, J.; Collins, J.W.; Turcatti, G.; Chou, C.J.; Goun, E.A.* A Universal Assay for Aminopeptidase Activity and Its Application for Dipeptidyl Peptidase-4 Drug Discovery. Anal. Chem. 2019, 91, 1098-1104. (link)
36. Miyazaki, T.; Gharib, S.A.; Hsu, Y.A.; Xu, K., Khodakivskyi, P.; Kobayashi, A.; Paragas, J.; Klose, A.D.; Francis, K.P.; Dubikovskaya, E.; Page-McCaw, P.S.; Barasch, J.; Paragas, N. Cell-specific image-guided transcriptomics identifies complex injuries caused by ischemic acute kidney injury in mice. Commun Biol. 2019, 2, 326. (link)
35. Mermod, M.; Bongiovanni, M.; Petrova, T.; Goun, E.; Simon, C.; Tolstonog, G.; Monnier, Y. Prediction of Occult Lymph Node Metastasis in Head and Neck Cancer with CD31 Vessel Quantification. Otolaryngol Head Neck Surg. 2019, 160, 277-283 (link).
2018
34. Godinat, A.; Bazhin.; Goun, E.* Bioorthogonal chemistry in bioluminescence imaging. Drug Discov. Today 2018, 9, 1584-1590. (link)
33. Reber, J.; Willershäuser, M.; Karlas, A.; Paul-Yuan, K.; Diot, G.; Franz, D.; Fromme, T.; Ovsepian, S. V.; Bézière, N.; Dubikovskaya, E.; Karampinos, D. C.; Holzapfel, C.; Hauner, H.; Klingenspor, M.; Ntziachristos, V. Non-invasive Measurement of Brown Fat Metabolism Based on Optoacoustic Imaging of Hemoglobin Gradients. Cell Metab. 2018, 27, 689-701. (link)
2017
32. Wang, Y.; Thompson, J. M.; Ashbaugh, A. G.; Khodakivskyi, P.; Budin, G.; Sinisi, R.; Heinmiller, A.; van Oosten, M.; van Dijl J. M.; van Dam, G. M.; Francis, K. P.; Bernthal, N. M.; Dubikovskaya, E. A.; Miller, L. S. Preclinical Evaluation of Photoacoustic Imaging as a Novel Noninvasive Approach to Detect an Orthopaedic Implant Infection. J Am Acad Orthop Surg. 2017, Suppl 1:S7-S12. (link)
31. Mermod, M.; Bongiovanni, M.; Petrova, T. V.; Dubikovskaya, E. A.; Simon, C.; Tolstonog, G.; Monnier, Y. Correlation between podoplanin expression and extracapsular spread in squamous cell carcinoma of the oral cavity using subjective immunoreactivity scores and semiquantitative image analysis. Head Neck 2017, 39, 98-108. (link)
30. Mezzanotte, L.; van Root, M.; Karatas, H.; Goun, E.A.; Löwik, C.W.G.M. In Vivo Molecular Bioluminescence Imaging: New Tools and Applications. Trends Biotechnol. 2017, 35, 640-652. (link)
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29. Godinat, A.; Karatas, H.; Budin, G.; Dubikovskaya, E.* Chemical ligation for molecular imaging. In Chemical Ligation: Tools for Biomolecule Synthesis and Modification. John Wiley & Sons, 2017.
28. Park, H. M.; Russo, K. A.; Karateev, G.; Park, M.; Dubikovskaya, E.; Kriegsfeld, L. J.; Stahl, A. A system for in vivo imaging of hepatic free fatty acid uptake Gastroenterology 2017, 152, 78-81. (link)
2016
27. Mermod, M.; Bongiovanni, M.; Petrova, T. V.; Dubikovskaya, E. A.; Simon, C.; Tolstonog, G.; Monnier, Y. Prediction of occult lymph node metastasis in squamous cell carcinoma of the oral cavity and the oropharynx using peritumoral Prospero homeobox protein 1 lymphatic nuclear quantification. Head Neck. 2016, 38, 1407-1415. (link)
26. Stammes, M. A.; Maeda, A.; Bu, J.; Scollard, D. A.; Kulbatski, I.; Medeiros, P. J.; Sinisi, R.; Dubikovskaya, E. A.; Snoeks, T. J.; van Beek, E. R.; Chan, A. B.; Löwik, C. W.; DaCosta, R.S. The Necrosis-Avid Small Molecule HQ4-DTPA as a Multimodal Imaging Agent for Monitoring Radiation Therapy-Induced Tumor Cell Death. Front Oncol. 2016, 6, 221. (link)
25. Stammes, M. A.; Knol-Blankevoort, V. T.; Cruz, L. J.; Feitsma, H. R.; Mezzanotte, L.; Cordfunke, R. A.; Sinisi, R.; Dubikovskaya, E. A.; Maeda, A.; DaCosta, R. S.; Bierau, K.; Chan, A.; Kaijzel, E. L.; Snoeks, T. J.; van Beek, E. R.; Löwik, C. W. Pre-clinical Evaluation of a Cyanine-Based SPECT Probe for Multimodal Tumor Necrosis Imaging. Mol Imaging Biol. 2016, 18, 905-915. (link)
24. Homulle, H. A.; Powolny, F.; Stegehuis, P. L.; Dijkstra, J.; Li, D. U.; Homicsko, K.; Rimoldi, D.; Muehlethaler, K.; Prior, J.O.; Sinisi, R.; Dubikovskaya, E.; Charbon, E.; Bruschini, C. Compact solid-state CMOS single-photon detector array for in vivo NIR fluorescence lifetime oncology measurements. Biomed Opt Express 2016, 7, 1797-1814. (link)
2015
23. Vorobyeva, A.G.; Stanton, M.; Godinat, A.; Lund, K.B.; Karateev, G.G.; Francis, K.P.; Allen, E.; Gelovani, J.G.; McCormack, E.; Tangney, M.; Dubikovskaya, E.A.* Development of a Bioluminescent Nitroreductase Probe for Preclinical Imaging. PLoS One. 2015, 10(6): e0131037. (link)
22. Tharp, K.M.; Jha, A. K.; Kraiczy, J.; Yesian, A.; Karateev, G.; Sinisi, R.; Dubikovskaya, E. A.; Healy, K. E.; Stahl, A. Matrix-Assisted Transplantation of Functional Beige Adipose Tissue. Diabetes 2015, 64, 3713-3724. (link)
“Copyright: Clearance Center, Inc. Publisher: Elsevier ”
2014-2013
21. Godinat, A.; Budin, G.; Morales, A.; Park, H.; Sanman, L.; Bogyo, M.; Yu, A.; Stahl, A.; Dubikovskaya, E. A.* A biocompatible “split luciferin” reaction and its application for non-invasive bioluminescent imaging of protease activity in living animals. Curr Protoc Chem Biol. 2014, 6,169-189. (link)
20. Geissbuehler, S.; Sharipov, A.; Godinat, A.; Bocchio, N. L.; Sandoz, P. A.; Huss, A.; Jensen, N. A.; Jakobs, S.; Enderlein, J.; van der Goot, F. G.; Dubikovskaya, E. A.; Lasser, T.; Leutenegger, M. Live-cell multiplane three-dimensional super-resolution optical fluctuation imaging. Nat Commun. 2014, 5, 5830. (link)
19. Dubikovskaya, E.; Chudnovskiy, R.; Karateev, G.; Park, H. M.; Stahl, A. Measurement of long-chain fatty acid uptake into adipocytes. In Methods in enzymology. Elsevier, 2014.
18. Godinat, A.; Park, H. M.; Miller, S. C.; Cheng, K.; Hanahan, D.; Sanman, L. E.; Bogyo, M.; Yu, A.; Nikitin, G. F.; Stahl, A.; Dubikovskaya, E. A.* A Biocompatible In Vivo Ligation Reaction and its Application for Non-Invasive Bioluminescent Imaging of Protease Activity in Living Mice. ACS Chem Biol. 2013, 8, 987-999.
Publications prior to independent career
17. Henkin, A.H.; Cohen, A.S.; Dubikovskaya, E.A.; Park, H.M.; Nikitin, G.F.; Auzias, M.G.; Kazantzis, M.; Bertozzi, C.R.; Stahl, A. Real-time noninvasive imaging of fatty acid uptake in vivo. ACS Chem Biol. 2012, 7, 1884-1891.
16. Van de Bittner, G.C.; Dubikovskaya,A.; Bertozzi, C.R.; Chang, C.J. In vivo imaging of hydrogen peroxide production in a murine tumor model with a chemoselective bioluminescent reporter. Proc Natl Acad Sci U S A. 2010, 107, 21316-321.
15. Cohen, A.S.; Dubikovskaya,A.; Rush, J.S.; Bertozzi, C.R. Real-Time Bioluminescence Imaging of Glycans on Live Cells. J Am Chem Soc. 2010, 132, 8563-8365.
14. Lee, H.L.; Dubikovskaya,A.; Hwang, H.; Semyonov, A.N.; Wang, H.; Jones, L.R.; Twieg, R.J.; Moerner, W.E.; Wender, P.A. Single-molecule motions of oligoarginine transporter conjugates on the plasma membrane of Chinese hamster ovary cells. J Am Chem Soc. 2008, 130, 9364-9370.
13. Dubikovskaya,A.; Thorne, S.H.; Pillow, T.H.; Contag, C.H.; Wender, P.A. Overcoming multidrug resistance of small-molecule therapeutics through conjugation with releasable octaarginine transporters. Proc Natl Acad Sci U S A. 2008, 105, 12128-33.
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This paper was highlighted in Nature Biotechnology 2008, 26, 1095, Medical News Today ( 20th, 2008), ScienceDaily (Aug. 19th, 2008), Science News, Washington (Aug. 19, 2008), and SciBX on Science (Aug. 28th, 2008).
12. Wender, P. A.; Galliher, W. C.; Goun, E. A.; Jones, L. R.; Pillow, T. H. The Design of Guanidinium-Rich Transporters and Their Internalization Mechanisms. Advanced Drug Delivery Reviews 2008, 60, 452-472.
11. Wender, P. A.; Goun, E. A.; Jones, L. R.; Pillow, T. H.; Rothbard, J. B.; Shinde, R.; Contag, C. H. Real-time Analysis of Uptake and Bioactivatable Cleavage of Luciferin-Transporter Conjugates in Transgenic Reporter Mice. Proc Natl Acad Sci U S A. 2007, 104, 10340-10345.
10. Jones, L. R.; Goun, E. A.; Shinde, R.; Rothbard, J. B.; Contag, C. H.; Wender, P. A. Releasable Luciferin-Transporter Conjugates: Tools for the Real-Time Analysis of Cellular Uptake and Release. J Am Chem Soc. 2006, 128, 6526-6527.
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This paper was highlighted in Nature Methods, 2006, 3, 498.
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9. Goun, E. A.; Pillow, T. H.; Jones, L. R.; Rothbard, J. B.; Wender, P. A. Molecular Transporters: Synthesis of Oligoguanidinium Transporters and their Application to Drug Delivery and Real Time Imaging. ChemBiochem 2006, 7, 1497-1515.
8. Goun, E. A.; Shinde, R.; Dehnert, K. W.; Adams-Bond, A.; Wender, P. A.; Contag, C. H.; Franc, B. L. Intracellular Cargo Delivery by an Octaarginine Transporter Adapted to Target Prostate Cancer Cells through Cell Surface Protease Activation. Bioconjugate Chemistry 2006, 17, 787-796.
7. Osintsev, A. V.; Levit, G. L.; Krasnov, V. P.; Miles, D. H.; Solodnikov, S. Yu.; Goun, E. A. Synthesis and Antileukemic Activity of N-Phthaloyl-2-amino alcohols. Pharmaceutical Chemistry Journal 2004, 38, 120-122.
6. Pimenova, E. V.; Krasnych, O. P.; Goun, E. A.; Miles, D. H. Synthesis and Reactions of 2-Hydroxy-4-oxo-4-(2,3,5,6-tetrafluoro-4-methoxyphenyl)-but-2-enoic Acid Methyl Ester. Journal of Fluorine Chemistry 2003, 121, 201-204.
5. Goun, E. A.; Cunningham, G.; Chu, D.; Nguyen, C.; Miles, D. H. Antibacterial and Antifungal Activity of Indonesian Ethnomedical Plants. Fitoterapia 2003, 74, 592-596.
4. Solodnikov, S. Yu.; Miles, D. H.; Krasnych, O. P.; Goun, E. A.; Naser, S. A.; Konyukhova, N. A.; Denisov, V. E.; Shilov, Yu. I. Synthesis, Antithrombin and Antituberculous Activity of 2-Hydrazino Derivatives of Acyl Pyruvic Acid Methyl Esters. Pharmaceutical Chemistry Journal, 2002, 36, 229-231.
3. Goun, E. A.; Petrichenko, V. M.; Solodnikov, S. Yu.; Suhinina, T. V.; Kline, M. A.; Cunningham, G.; Nguyen, C.; Miles, D. H. Anticancer and Antithrombin Activity of Russian Plants. Journal of Ethnopharmacology 2002, 81, 337-342.
2. Goun, E. A.; Cunningham, G.; Solodnikov, S. Yu.; Krasnykch, O. P.; Miles, D. H. Antithrombin Activity of Some Constituents from Origanum vulgare. Fitoterapia 2002, 73, 692-694.
1. Porrata, P.; Goun, E. A.; Matsui, H. Size-Controlled Self-Assembly of Peptide Nanotubes Using Polycarbonate Membranes as Templates. Chemistry of Materials 2002, 14, 4378-4381.
ngineering, EPFL. Elena is an advocate for interdisciplinary approaches to research, combining organic synthetic chemistry and optical imaging to find solutions to fundamental problems in biology and medicine.
