• Scholarly Materials and Research Equipment Award, Drexel University College of Medicine (2021)
• Society for Neuroscience poster selected as a Neuroscience “Hot Topic” (2016)
• International Brain Research Organization (IBRO) award to attend III Latin American School of Neuroscience (1998)

• Postdoctoral Fellowship in Neuroscience – Vollum Institute, Oregon Health and Sciences University
• Postdoctoral Associate in Neurobiology- University of Pittsburgh

Research in the A. Mortensen lab focuses on understanding mechanisms that regulate glutamate transporters, crucial proteins in the central nervous system (CNS) that modulate excitatory transmission. Our projects include basic research programs to further our knowledge of glutamate transporters regulation in physiological and disease states, and translational projects involving the development of small molecule allosteric modulators of these transporters. We use cell culture techniques, mutagenesis approaches, primary cultures of neurons and glia, pharmacology, in vitro models of stroke and epilepsy, and in vivo models of neuropathic pain and cocaine abuse disorder. We also collaborate with other labs to develop computational modelling, crystallography, and Cryo-EM approaches as well as medicinal chemistry to progress the development of our allosteric modulators to the clinic.

Visit the A. Mortensen Lab.

Excitatory amino acid transporters (EAATs) on the plasma membrane regulate and modulate glutamate neurotransmission by transporting synaptically released glutamate back into cells. This has a profound impact on the level of receptor activation and excitatory transmission.

The main goals of my research are twofold: to investigate the regulation of EAATs in physiological states and neurological disorders, and to progress the development of compounds that target these transporters for therapeutic purposes. Our interests include brain injury, ischemic stroke, epilepsy, substance use disorders and neuropathic pain, among others.

Secondary effects of brain trauma can be reduced by molecules that limit glutamate release, antagonists of ionotropic glutamate receptors, and compounds that target calcium influx. However, these compounds clinical use is limited by severe side effects. Other compounds that enhance the activity of EAAT2 (the main astrocytic transporter in the CNS) in pathological conditions, such as ß-lactam antibiotics, attenuate damage in both acute and chronic neurodegenerative disorders. Nevertheless, this approach is best administered prophylactically and could be associated with non-specific effects that limit their utility.

Previous studies in my lab have identified a unique natural compound from the spider Parawixia bistriata that increases the activity of glutamate transporter EAAT2 and has neuroprotective effects on retinal tissue under ischemia. Our follow up studies identified structural components of EAAT2 that are important for its interaction with the compound, which we subsequently used in virtual screening approaches to identify allosteric modulators of EAATs.

These novel allosteric modulators are currently being characterized in several in vitro and in vivo models, with a long-term goal to progress our preclinical studies into the clinic for relevant neurological disorders.

Commonwealth of Pennsylvania Announces Recent CURE Grant Recipients
(August 14, 2023)

Selected Publications

See a full list of publications here.

"Discovery of (R)-N-Benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide [(R)-AS-1], a Novel Orally Bioavailable EAAT2 Modulator with Drug-like Properties and Potent Antiseizure Activity In Vivo"
Abram M, Jakubiec M, Reeb K, Cheng MH, Gedschold R, Rapacz A, Mogilski S, Socała K, Nieoczym D, Szafarz M, Latacz G, Szulczyk B, Kalinowska-Tłuścik J, Gawel K, Esguerra CV, Wyska E, Müller CE, Bahar I, Fontana ACK, Wlaź P, Kamiński RM, Kamiński K
J Med Chem. 2022 Sep 8;65(17):11703-11725. doi: 10.1021/acs.jmedchem.2c00534. Epub 2022 Aug 19. PubMed PMID: 35984707; PubMed Central PMCID: PMC9469208

"Neuroprotective Properties of Chlorogenic Acid and 4,5-Caffeoylquinic Acid from Brazilian arnica (Lychnophora ericoides) after Acute Retinal Ischemia"
Liberato JL, Rosa MN, Miranda MCR, Lopes JLC, Lopes NP, Gobbo-Neto L, Fontana ACK, Dos Santos WF
Planta Med. 2022 Oct 11. doi: 10.1055/a-1903-2387. Epub ahead of print. PMID: 36220097

"Glutamatergic Neurons in Chronic Pain, and Emerging Non-opioid Therapies"
Temmermand R, Barret JE, Fontana ACK
Pharmacology Research, 185, 2022, 106492, ISSN 1043-6618

“Role of glutamate excitotoxicity and glutamate transporter EAAT2 in epilepsy: Opportunities for novel therapeutics development”
Green JL, Dos Santos WF, Fontana ACK
Biochemical Pharmacology. 2021 Sep 24; 193:114786. doi: 10.1016/j.bcp.2021.114786. PMID: 34571003. Review.

"Novel positive allosteric modulators of glutamate transport have in vitro neuroprotective properties in an in vitro excitotoxic model"
Falcucci RM, Wertz R, Green J, Salvino JM, Meucci O, Fontana AC
ACS Chem Neurosci.. doi: 10.1021/acschemneuro.9b00061. [Epub ahead of print]. PMID: 31257852, Jul 1, 2019

"Identification of a Novel Allosteric Modulator of the Human Dopamine Transporter"
Aggarwal S, Liu X, Rice C, Menell P, Clark PJ, Paparoidamis N, Xiao YC, Salvino JM, Fontana ACK, España RA, Kortagere S, Mortensen OV
ACS Chem Neurosci. doi: 10.1021/acschemneuro.9b00262. [Epub ahead of print]. PMID: 31184115, Jun 24, 2019

"Neuroprotective properties of RT10, a fraction isolated from Parawixia bistriata spider venom, against excitotoxicity injury in neuron-glia cultures"
Primini, EO, Liberato, JL, Fontana, ACK & Santos, WF
Journal of Venomous Animals and Toxins Including Tropical Diseases, 25, e148818, 2019

"Caffeic Acid Phenethyl Ester (CAPE) Protects PC12 Cells Against Cisplatin-Induced Neurotoxicity by Activating the AMPK/SIRT1, MAPK/Erk, and PI3k/Akt Signaling Pathways"
Ferreira RS, Dos Santos NAG, Bernardes CP, Sisti FM, Amaral L, Fontana ACK, Dos Santos AC
Neurotox Res. doi: 10.1007/s12640-019-00042-w. PubMed PMID: 31016689, Apr 23, 2019

"Parawixin2 Protects Hippocampal Cells in Experimental Temporal Lobe Epilepsy"
Liberato JL, Godoy LD, Cunha AOS, Mortari MR, de Oliveira Beleboni R, Fontana ACK, Lopes NP, Dos Santos WF
Toxins (Basel), 10(12). pii: E486. doi: 10.3390/toxins10120486, Nov 22, 2018 

"Protocols for Measuring Glutamate Uptake: Dose-Response and Kinetic Assays in In Vitro and Ex Vivo Systems"
Fontana ACK
Curr Protoc Pharmacol.;82(1):e45. doi: 10.1002/cpph.45. Epub 2018 Aug 27. PMID: 30152172, Sep 2018

"Identification of Novel Allosteric Modulators of Glutamate Transporter EAAT2"
Kortagere S, Mortensen OV, Xia J, Lester W, Fang Y, Srikanth Y, Salvino JM, Fontana ACK
ACS Chem Neurosci.;9(3):522-534. doi: 10.1021/acschemneuro.7b00308. Epub 2017 Nov 30.PMID: 29140675, Mar 21, 2018

"Drugs to alter extracellular concentration of glutamate: modulators of glutamate uptake systems"
Fontana, AC
Book: Biochemical Approaches for Glutamatergic Neurotransmission, ed. S. Parrot, Denoroy, Luc: Humana Press. ISBN: 978-1-4939-7228-9, doi: 10.1007/978-1-4939-7228-9, 2017

"Isolation and chemical characterization of agelaiatoxin8 (AvTx8) from Agelaia vicina wasp venom and its biological effects on GABA neurotransmission"
Pizzo AB, Beleboni RO, Gomes Carolino RO, de Oliveira L, Miranda A, Coutinho-Netto J, Fontana ACK, Dos Santos WF.
J Biochem Mol Toxicol. doi: 10.1002/jbt.21941, Jun 16, 2017

"Current approaches to enhance glutamate transporter function and expression"
Fontana AC
J Neurochem. doi: 10.1111/jnc.13200, Jun 20, 2015

"Neuroprotective effects of the glutamate transporter activator, MS-153, following traumatic brain injury in the adult rat"
Fontana AC, Fox DP, Zoubroulis A, Mortensen OV, Raghupathi R
J Neurotrauma, Jul 22, 2015

"Molecular determinants of transport stimulation of EAAT2 are located at interface between the trimerization and substrate transport domains"
Mortensen OV, Liberato JL, Coutinho-Netto J, Dos Santos WF, Fontana AC
J Neurochem; 133(2):199-210. doi: 10.1111/jnc.13047 (Epub 2015 Feb 26) PubMed PMID: 25626691, April 2015

"The lignan (-)-hinokinin displays modulatory effects on human monoamine and GABA transporter activities"
Timple JM, Magalhães LG, Souza Rezende KC, Pereira AC, Cunha WR, Andrade e Silva ML, Mortensen OV, Fontana AC
J Nat Prod.; 76(10):1889-95. doi: 10.1021/np400452n. (Epub 2013 Oct 10) Oct 25, 2013

"Identification of an allosteric modulator of the serotonin transporter with novel mechanism of action"
Kortagere S, Fontana AC, Rose DR, Mortensen OV
Neuropharmacology, 72:282-290. doi: 10.1016/j.neuropharm.2013.04.026, Sept 2013

"A catecholamine transporter from the human parasite Schistosoma mansoni with low affinity for psychostimulants"
Larsen MB, Fontana AC, Magallhães LG, Rodrigues V, Mortensen OV
Mol Biochem Parasitol. Jan 18, 2011

"Two allelic isoforms of the serotonin transporter from Schistosoma mansoni display electrogenic transport and high selectivity for serotonin"
Fontana AC, Sonders MS, Pereira-Junior OS, Knight M, Javitch JA, Rodrigues V, Amara SG, Mortensen OV
Eur J Pharmacol;616(1-3):48-57, Aug 15, 2009

"Enhancing glutamate transport: mechanism of action of Parawixin1, a neuroprotective compound from Parawixia bistriata spider venom"
Fontana AC, de Oliveira Beleboni R, Wojewodzic MW, Ferreira Dos Santos W, Coutinho-Netto J, Grutle NJ, Watts SD, Danbolt NC, Amara SG.
Mol Pharmacol. 2007 Nov;72(5):1228-37. Epub Jul 23, 2007

"Purification of a neuroprotective component of Parawixia bistriata spider venom that enhances glutamate uptake"
Fontana AC, Guizzo R, de Oliveira Beleboni R, Meirelles E Silva AR, Coimbra NC, Amara SG, dos Santos WF, Coutinho-Netto
J. Br J Pharmacol;139(7):1297-309, Aug 2003

"Excitatory amino acid transporters: keeping up with glutamate"
Amara SG, Fontana AC
Neurochem Int;41(5):313-8. Review, Nov 2002