Miriam das Dores Mendes Fonseca, MSc, PhD

Miriam Fonseca
Senior Research Associate

Contact Information:

919-681-4710
miriam.mendesfonseca@duke.edu

Background and Research Interests

I am a pharmacist and scientist with a diverse background encompassing molecular biology, neuropharmacology, immunology, and pain research. My passion lies in understanding the underlying pathways of conditions such as chronic pain, inflammation, cancer and neuro-immune-related diseases such as multiple sclerosis. My educational journey includes completing a master's and PhD degree from the University of Sao Paulo, Brazil, and conducting my dissertation research under the guidance of Dr. Thiago Cunha. During my master's studies, I focused on elucidating the signaling pathways of kynurenine metabolism involving neuroimmune glia in the development of neuropathic pain. For my PhD, I investigated the role of IL-27 in neuropathic pain, which led to the discovery that microglial-induced release of anti-inflammatory cytokine IL-10 can help alleviate neuropathic pain. My time in Dr. Cunha's lab also allowed me to collaborate with various researchers and contribute to numerous publications addressing the neuro-immune mechanisms underlying pain and others immune disorders.

In an effort to enhance my skill set, I relocated to the United States to join Dr. Romero-Sandoval’s lab as a Postdoctoral Researcher. Under his mentorship, I focused on investigating the role of endoplasmic reticulum stress through the IRE1α/XBP1s pathway in an acute pain model. Our findings revealed that this pathway plays a crucial role in regulating eicosanoid metabolism in myeloid immune cells. By targeting IRE1α-XBP1 signaling, it may be possible to improve analgesia and reduce the use of opioids. In addition, I also explored the impact of the IRE1α-XBP1 pathway in chemotherapy-induced peripheral neuropathy (CIPN). Through our investigations, we identified a potential blood biomarker that can predict the development of CIPN during chemotherapy treatment. This offers the potential for personalized dosing, decreasing the risk of adverse effects and ensuring effective treatment without long-term consequences for patients.

Currently, I am a Research Associate Senior in Donnelly’s lab where I am involved in several meaningful projects with emphasis on clinical application. Our team is particularly focused on unraveling the molecular crosstalk between sensory neurons and non-neuronal cell types, such as immune cells, glial cells, cancer cells, and microorganisms influence the relationship between pain and inflammation, with the goal of developing novel therapeutic approaches and biomarkers for the management of pain and inflammatory conditions. 

Publications

  1. Rangel L. Silva, Alexandre H. Lopes, Amanda Becerra, Miriam M. Fonseca, Alexandre Maganin, Andre L.L. Saraiva, Fernando Q. Cunha, Jose C. Alves-Filho, Dario S. Zamboni, Thiago M. Cunha. Molecular mechanisms of zymosan-induced inflammasome activation in macrophages. Cell Signal. 2024 Sep 18;124:111418. doi: 10.1016/j.cellsig.2024.111418
  2. Rafaela M Guimarães, Conceição E Aníbal-Silva, Marcela Davoli-Ferreira , Francisco Isaac F Gomes, Atlante Mendes, Maria C M Cavallini, Miriam M Fonseca, Samara Damasceno, Larissa P Andrade , Marco Colonna, Cyril Rivat, Fernando Q Cunha, José C Alves-Filho, Thiago M Cunha. Neuron-associated macrophage proliferation in the sensory ganglia is associated with peripheral nerve injury-induced neuropathic pain involving CX3CR1 signaling Elife. 2023 May 31;12:e78515. doi: 10.7554/eLife.78515.
  3. Alexandre G Maganin*, Guilherme R Souza*, Miriam D Fonseca*, Alexandre H Lopes, Rafaela M Guimarães, André Dagostin, Nerry T Cecilio, Atlante S Mendes, William A Gonçalves, Conceição Ea Silva, Francisco Isaac Fernandes Gomes, Lucas M Mauriz Marques, Rangel L Silva, Letícia M Arruda, Denis A Santana, Henrique Lemos, Lei Huang, Marcela Davoli-Ferreira, Danielle Santana-Coelho, Morena B Sant'Anna, Ricardo Kusuda, Jhimmy Talbot, Gabriela Pacholczyk, Gabriela A Buqui, Norberto P Lopes, Jose C Alves-Filho, Ricardo M Leão, Jason C O'Connor, Fernando Q Cunha, Andrew Mellor, Thiago M Cunha. Meningeal dendritic cells drive neuropathic pain through elevation of the kynurenine metabolic pathway in mice. J Clin Invest. 2022 Dec 1;132(23):e153805. doi: 10.1172/JCI153805. PMCID: PMC9711882. *The three authors share the first authorship.
  4. Park SH, Eber MR, Fonseca MM, Patel CM, Cunnane KA, Ding H, Hsu FC, Peters CM, Ko MC, Strowd RE, Wilson JA, Hsu W, Romero-Sandoval EA, Shiozawa Y. Usefulness of the measurement of neurite outgrowth of primary sensory neurons to study cancer-related painful complications. Biochem Pharmacol. 2021 Jun;188:114520. doi: 10.1016/j.bcp.2021.114520. Epub 2021 Mar 17. PubMed PMID: 33741328; PubMed Central PMCID: PMC8154668.
  5. Uhelski ML, Li Y, Fonseca MM, Romero-Sandoval EA, Dougherty PM. Role of innate immunity in chemotherapy-induced peripheral neuropathy. Neurosci Lett. 2021 Jun 11;755:135941. doi: 10.1016/j.neulet.2021.135941. Epub 2021 May 4. PubMed PMID: 33961945; PubMed Central PMCID: PMC8190706.
  6. Prado DS, Damasceno LEA, Sonego AB, Rosa MH, Martins TV, Fonseca MDM, Cunha TM, Cunha FQ, Alves-Filho JC. Pitavastatin ameliorates autoimmune neuroinflammation by regulating the Treg/Th17 cell balance through inhibition of mevalonate metabolism. Int Immunopharmacol. 2021 Feb;91:107278. doi: 10.1016/j.intimp.2020.107278. Epub 2020 Dec 17. PubMed PMID: 33341737.
  7. Elisson Meireles Lamim Jerônimo, André Luiz Machado Viana, Miriam das Dores Mendes Fonseca, Marilene Lopes Ângelo, Bruno Cesar Correa Salles, Stella Maris da Silveira Duarte, Sônia Aparecida Figueiredo, Maria Rita Rodrigues, Fernanda Borges de Araújo Paula. Caffeinated instant coffee prevents an increase in exercise-mediated superoxide anion production in rat peritoneal neutrophils. December, 2020 in Revista de Ciencias Farmaceuticas Basica 41 e Aplicada. doi: 10.4322/2179-443X.0673.
  8. Damasceno LEA, Prado DS, Veras FP, Fonseca MM, Toller-Kawahisa JE, Rosa MH, Públio GA, Martins TV, Ramalho FS, Waisman A, Cunha FQ, Cunha TM, Alves-Filho JC. PKM2 promotes Th17 cell differentiation and autoimmune inflammation by fine-tuning STAT3 activation. J Exp Med. 2020 Oct 5;217(10). doi: 10.1084/jem.20190613. PubMed PMID: 32697823; PubMed Central PMCID: PMC7537396.
  9. James W Morgan, Sarah D Pennypacker,E Alfonso Romero-Sandoval, Miriam M Fonseca. Methods and protocols for translatable rodent models of postsurgical pain. Methods Cell Biol. 2022;168:249-276. doi: 10.1016/bs.mcb.2021.12.018. Epub 2022 Jan 20.
  10. Sarah D Pennypacker, Miriam M Fonseca, James W Morgan, Patrick M Dougherty, Juan R Cubillos-Ruiz, Roy E Strowd, E Alfonso Romero-Sandoval. Methods and protocols for chemotherapy-induced peripheral neuropathy (CIPN) mouse models using paclitaxel. Methods Cell Biol. 2022;168:277-298. doi: 10.1016/bs.mcb.2021.12.019. Epub 2022 Jan 10.
  11. Kanashiro A, Hiroki CH, Fonseca DM, Birbrair A, Ferreira RG, Bassi GS, Fonseca MD, Kusuda R, Cebinelli GCM, da Silva KP, Wanderley CW, Menezes GB, Alves-Fiho JC, Oliveira AG, Cunha TM, Pupo AS, Ulloa L, Cunha FQ. The role of neutrophils in neuroimmune modulation. Pharmacol Res. 2020 Jan;151:104580. doi: 10.1016/j.phrs.2019.104580. Epub 2019 Nov 28. Review. PubMed PMID: 31786317; PubMed Central PMCID: PMC7023896.
  12. Chopra S, Giovanelli P, Alvarado-Vazquez PA, Alonso S, Song M, Sandoval TA, Chae CS, Tan C, Fonseca MM, Gutierrez S, Jimenez L, Subbaramaiah K, Iwawaki T, Kingsley PJ, Marnett LJ, Kossenkov AV, Crespo MS, Dannenberg AJ, Glimcher LH, Romero-Sandoval EA, Cubillos-Ruiz JR. IRE1α-XBP1 signaling in leukocytes controls prostaglandin biosynthesis and pain. Science. 2019 Jul 19;365(6450). doi: 10.1126/science.aau6499. PubMed PMID: 31320508.
  13. Piñeros AR, de Lima MHF, Rodrigues T, Gembre AF, Bertolini TB, Fonseca MD, Berretta AA, Ramalho LNZ, Cunha FQ, Hori JI, Bonato VLD. Green propolis increases myeloid suppressor cells and CD4+Foxp3+ cells and reduces Th2 inflammation in the lungs after allergen exposure. J Ethnopharmacol. 2020 Apr 24;252:112496. doi: 10.1016/j.jep.2019.112496. Epub 2019 Dec 21. PubMed PMID: 31870795.
  14. Lopes AH, Silva RL, Fonseca MD, Gomes FI, Maganin AG, Ribeiro LS, Marques LMM, Cunha FQ, Alves-Filho JC, Zamboni DS, Lopes NP, Franklin BS, Gombault A, Ramalho FS, Quesniaux VFJ, Couillin I, Ryffel B, Cunha TM. Molecular basis of carrageenan induced cytokines production in macrophages. Cell Commun Signal. 2020 Sep 7;18(1):141. doi: 10.1186/s12964-020-00621-x. PubMed PMID: 32894139; PubMed Central PMCID: PMC7487827.
  15. Davoli-Ferreira M, de Lima KA, Fonseca MM, Guimarães RM, Gomes FI, Cavallini MC, Quadros AU, Kusuda R, Cunha FQ, Alves-Filho JC, Cunha TM. Regulatory T cells counteract neuropathic pain through inhibition of the Th1 response at the site of peripheral nerve injury. Pain. 2020 Aug;161(8):1730-1743. doi: 10.1097/j.pain.0000000000001879. Epub 2020 Mar 26.PubMed PMID: 32701834.
  16. Fonseca MM, Davoli-Ferreira M, Santa-Cecília F, Guimarães RM, Oliveira FFB, Kusuda R, Ferreira DW, Alves-Filho JC, Cunha FQ, Cunha TM. IL-27 Counteracts Neuropathic Pain Development Through Induction of IL-10. Front Immunol. 2019;10:3059. doi: 10.3389/fimmu.2019.03059. eCollection 2019. PubMed PMID: 32047492; PubMed Central PMCID: PMC6997342.
  17. Guimarães RM, Davoli-Ferreira M, Fonseca MM, Damasceno LEA, Santa-Cecilia FV, Kusuda R, Menezes GB, Cunha FQ, Alves-Filho JC, Cunha TM. Frontline Science: Blood circulating leukocytes fail to infiltrate the spinal cord parenchyma after spared nerve injury. J Leukoc Biol. 2019 Sep;106(3):541-551. doi: 10.1002/JLB.HI1118-458R. Epub 2019 May 31. PubMed PMID: 31150565.
  18. Santa-Cecília FV, Ferreira DW, Guimaraes RM, Cecilio NT, Fonseca MM, Lopes AH, Davoli-Ferreira M, Kusuda R, Souza GR, Nachbur U, Alves-Filho JC, Teixeira MM, Zamboni DS, Cunha FQ, Cunha TM. The NOD2 signaling in peripheral macrophages contributes to neuropathic pain development. Pain. 2019 Jan;160(1):102-116. doi: 10.1097/j.pain.0000000000001383. PubMed PMID: 30169421.
  19. Silva NR, Gomes FV, Fonseca MD, Mechoulam R, Breuer A, Cunha TM, Guimarães FS. Antinociceptive effects of HUF-101, a fluorinated cannabidiol derivative. Prog Neuropsychopharmacol Biol Psychiatry. 2017 Oct 3;79(Pt B):369-377. doi: 10.1016/j.pnpbp.2017.07.012. Epub 2017 Jul 15. PubMed PMID: 28720466.
  20. Quadros AU, Pinto LG, Fonseca MM, Kusuda R, Cunha FQ, Cunha TM. Dynamic weight bearing is an efficient and predictable method for evaluation of arthritic nociception and its pathophysiological mechanisms in mice. Sci Rep. 2015 Oct 29;5:14648. doi: 10.1038/srep14648. PubMed PMID: 26511791; PubMed Central PMCID: PMC4625149.
  21. Fonseca MD, Cunha FQ, Kashfi K, Cunha TM. NOSH-aspirin (NBS-1120), a dual nitric oxide and hydrogen sulfide-releasing hybrid, reduces inflammatory pain. Pharmacol Res Perspect. 2015 Jun;3(3):e00133. doi: 10.1002/prp2.133. Epub 2015 May 8. PubMed PMID: 2623648. PubMed Central PMCID: PMC4492749.
  22. Viana AL, Fonseca MD, Meireles EL, Duarte SM, Rodrigues MR, Paula FB. Effects of the consumption of caffeinated and decaffeinated instant coffee beverages on oxidative stress induced by strenuous exercise in rats. Plant Foods Hum Nutr. 2012 Mar;67(1):82-7. doi: 10.1007/s11130-011-0267-8. PubMed PMID: 22173821.