Dr. Adelfa E. Serrano

Professor
Dr. Adelfa E. Serrano Brizuela

Contact Info

  • Laboratory of Molecular and Cellular Biology of Parasites: Malaria
    Rm A-310, Rm A-346, Rm A-349
    Department of Microbiology and Medical Zoology,
    University of Puerto-Rico-School of Medicine
    Medical Sciences Campus
    P.O. Box 365067,
    San Juan, P.R. 00936-5067.
  • Phone Office:
    787) 758-2525 ext.: X-1313;
    (787) 751-9486
    Phone Lab:
    (787) 758-2525, X-2217, X-1314

Education

  • B.S. Biology , University of Puerto Rico, R.P., P.R. 1979
  • M.S. Biology/Parasite Immunology, University of Puerto Rico, R.P., P.R. 1981
  • Ph. D. Zoo/Immunoparasitology, University of Georgia, Dept. of Zoology 1987
  • Post-doc Molec. Biol. of Parasites, Harvard School of Public Health, Trop.Pub. Health 1991

Coordinator AIDS and Infectious Diseases Laboratory (Rm A-349), RCMI-Center for Molecular Genetics and Infectious Diseases Research (Serrano, Activity Coordinator)
Link: http://rcmi.rcm.upr.edu/research/molgencore.html

Malaria, caused by Plasmodium spp., remains as the most devastating parasitic disease affecting more than 225 million people worldwide. Nearly 1 million deaths are reported yearly, mostly children under the age of 5. Half of the world’s population is considered at risk of malaria. Despite of ongoing efforts to generate novel antimalarials, find alternate vector controlling strategies and develop of an effective vaccine, the emergence and rapid spread of multidrug resistant Plasmodium coupled to the insecticide-resistant Anopheles strains, has resulted in re-emergence of this disease. There are currently no new drugs available and resistance has been reported for all of the antimalarials currently in use. Our previous and current work focuses in understanding mechanisms of underlying the development of Plasmodium drug resistance. The long-term goal of our research is to fully understand oxidative stress coping mechanisms and the glutathione biosynthetic pathway in the rodent malaria model, P. berghei in order to identify potential targets and drug resistance mechanisms to control the spread of malaria.

RESEARCH INTEREST

Our research is focused on genes from the glutathione biosynthesis and recycling pathway and those encoding ABC transporter proteins. These genes were previously associated to antimalarial resistance. Our approach to study this phenomenon is a combination of molecular and cellular biology techniques using Plasmodium berghei, which is a powerful rodent model for in vivo analyses. Following disruption of the genes of interest, both individually and in combination (double knockouts), phenotypical analyses including parasite development within the vertebrate (mouse) and invertebrate (mosquito) hosts are performed. In addition, sensitivity profiles to various anti-malarial drugs are determined both in vitro and in vivo. These studies contribute to a more comprehensive understanding of the oxidative stress coping mechanisms mediated by GSH and the role of ABC transporter proteins in parasite development providing new avenues for the development of novel antimalarial intervention strategies.

Additional research interests include in vivo drug testing of antimalarial compounds as part of collaborative efforts.

PUBLICATIONS

  1. Rosado-Quiñones AM, Colón-Lorenzo EE, Pala ZR, Bosch J, Kudyba K, Kudyba H, Leed SE, Roncal N, Baerga-Ortiz A, Roche-Lima A, Gerena Y, Fidock DA, Roth A, Vega-Rodríguez J, Serrano AE. Novel hydrazone compounds with broad-spectrum antiplasmodial activity and synergistic interactions with antimalarial drugs. Antimicrob Agents Chemother. 2024 Apr 19:e0164323. doi: 10.1128/aac.01643-23. Epub ahead of print. PMID: 38639491.
  2. Amador, LA; Colón-Lorenzo, EE; Rodríguez, AD; Serrano, AE. Probing the Antiplasmodial Properties of Plakortinic Acids C and D: An Uncommon Pair of Marine Peroxide-Polyketides Isolated from a Two-Sponge Association of Plakortis symbiotica and Xetospongia deweerdtae Collected near Puerto Rico. 2024. Life14(6), 684; https://www.mdpi.com/2075-1729/14/6/684
  3. Amador, LA, Rodríguez, AD, Carmona-Sarabia, E, Colón-Lorenzo, EE and Serrano, AE. Two Gracilioethers Containing a [2(5H)-Furanylidene]ethano- 2 ate Moiety and 9,10-Dihydroplakortone G: New Polyketides 3 from the Caribbean Marine Sponge Plakortis halichondrioides. 2024. Sci., 13, x. https://www.mdpi.com/2076-3417/14/1/281
  4. Roche-Lima A, Rosado-Quiñones AM, Feliu-Maldonado RA, Figueroa-Gispert MDM, Díaz-Rivera J, Díaz-González RG, Carrasquillo-Carrion K, Nieves BG, Colón-Lorenzo EE, Serrano AE. Antimalarial Drug Combination Predictions Using the Machine Learning Synergy Predictor (MLSyPred©) tool. Acta Parasitol. 2024 Mar;69(1):415-425. doi: 10.1007/s11686-023-00765-z. Epub 2024 Jan 2. PMID: 38165555; PMCID: PMC11001753.
  5. Derilus D, Rahman MZ, Serrano AE, Massey SE. Proteome size reduction in Apicomplexans is linked with loss of DNA repair and host redundant pathways. Infect Genet Evol 2021 Jan; 87:104642. PMID: 33296723, PMCID: PMC7936648, doi: 10.1016/j.meegid.2020.104642.
  6. Colón-Lorenzo EE, Colón-López DD, Vega-Rodríguez J, Dupin A, Fidock DA, Baerga-Ortiz A, Ortiz JG, Bosch J and Serrano AE (2020). Structure-Based Screening of Plasmodium berghei Glutathione S- Transferase Identifies CB-27 as a Novel Antiplasmodial Compound. Front. Pharmacol., 2020 Mar 17;11:246. doi: 10.3389/fphar.2020.00246. eCollection 2020. PMID:32256353.
  7. Mayo-Santana, R, Rabionet, SE, Peña-Carro, L and Serrano, AE. Marvels and Shadows: Science and Education at the University of Puerto Rico School of Tropical Medicine under the Auspices of Columbia University: An Introduction. 2016. P R Health Sci J, 35 (2), 49-52. PMID: 27232864
  8. Urgaonkar, S; Cortese, J; Barker, R; Cromwell, M; Serrano, AE; Wirth, D; Clardy, J; Mazitschek, R. (2010). A Concise Silylamine Approach to 2-Amino-3-hydroxy-indoles with Potent in vivo Antimalaria Activity. Organic Letters. Org Lett. 2010 Aug 18. PMID: 20718474.
  9. Utter C, Serrano AE, Glod JW, Leibowitz MJ. Association of Plasmodium falciparum with Human Endothelial Cells in vitro. Yale J Biol Med.2017 Jun;90(2):183-193. eCollection 2017 Jun. PubMed PMID: 28656007; PubMed Central PMCID: PMC5482297.
  10. Padín-Irizarry V, Colón-Lorenzo EE, Vega-Rodríguez J, Castro Mdel R, González-Méndez R, Ayala-Peña S, Serrano AE. Glutathione-deficient Plasmodium berghei parasites exhibit growth delay and nuclear DNA damage. Free Radic Biol Med. 2016 Jun;95:43-54. doi: 10.1016/j.freeradbiomed.2016.02.032. Epub 2016 Mar 4. PubMed PMID: 26952808; PubMed Central PMCID: PMC4934901.
  11. Mayo-Santana R, Rabionet SE, Peña-Carro L, Serrano AE. Marvels and Shadows: Science and Education at the University of Puerto Rico School of Tropical Medicine under the Auspices of Columbia University: An Introduction. P R Health Sci J. 2016 Jun;35(2):49-52. PubMed PMID: 27232864.
  12. Rijpma SR, van der Velden M, González-Pons M, Annoura T, van Schaijk BC, van Gemert GJ, van den Heuvel JJ, Ramesar J, Chevalley-Maurel S, Ploemen IH, Khan SM, Franetich JF, Mazier D, de Wilt JH, Serrano AE, Russel FG, Janse CJ, Sauerwein RW, Koenderink JB, Franke-Fayard BM. Multidrug ATP-binding cassette transporters are essential for hepatic development of Plasmodium sporozoites. Cell Microbiol. 2016 Mar;18(3):369-83. doi: 10.1111/cmi.12517. Epub 2015 Nov 10. PubMed PMID: 26332724; PubMed Central PMCID: PMC4984424.
  13. Vega-Rodríguez J, Pastrana-Mena R, Crespo-Lladó KN, Ortiz JG, Ferrer-Rodríguez I, Serrano AE. Implications of Glutathione Levels in the Plasmodium berghei Response to Chloroquine and Artemisinin. PLoS One. 2015;10(5):e0128212. doi: 10.1371/journal.pone.0128212. eCollection 2015. PubMed PMID: 26010448; PubMed Central PMCID: PMC4444287.Comer E, Beaudoin JA, Kato N, Fitzgerald ME, Heidebrecht RW, Lee Md 4th, Masi D, Mercier M, Mulrooney C, Muncipinto G, Rowley A, Crespo-Llado K, Serrano AE, Lukens AK, Wiegand RC, Wirth DF, Palmer MA, Foley MA, Munoz B, Scherer CA, Duvall JR, Schreiber SL.Diversity-oriented synthesis-facilitated medicinal chemistry: toward the development of novel antimalarial agents. J Med Chem. 2014 Oct 23;57(20):8496-502. doi: 10.1021/jm500994n. Epub 2014 Oct 13. PubMed PMID: 25211597; PubMed Central PMCID: PMC4207553.
  1. le Roux D, Burger PB, Niemand J, Grobler A, Urbán P, Fernàndez-Busquets X, Barker RH, Serrano AE, I Louw A, Birkholtz LM. Novel S-adenosyl-L-methionine decarboxylase inhibitors as potent antiproliferative agents against intraerythrocytic Plasmodium falciparum parasites.Int J Parasitol Drugs Drug Resist. 2014 Apr;4(1):28-36. doi: 10.1016/j.ijpddr.2013.11.003. eCollection 2014 Apr. PubMed PMID: 24596666; PubMed Central PMCID: PMC3940083.
  2. Dong CK, Urgaonkar S, Cortese JF, Gamo FJ, Garcia-Bustos JF, Lafuente MJ, Patel V, Ross L, Coleman BI, Derbyshire ER, Clish CB, Serrano AE, Cromwell M, Barker RH Jr, Dvorin JD, Duraisingh MT, Wirth DF, Clardy J, Mazitschek R. Identification and validation of tetracyclic benzothiazepines as Plasmodium falciparum cytochrome bc1 inhibitors. Chem Biol. 2011 Dec 23;18(12):1602-10. doi: 10.1016/j.chembiol.2011.09.016. PubMed PMID: 22195562; PubMed Central PMCID: PMC3474356.
  3. Gerena Y, Gonzalez-Pons M, Serrano AE. Cytofluorometric detection of rodent malaria parasites using red-excited fluorescent dyes.Cytometry A. 2011 Nov;79(11):965-72. doi: 10.1002/cyto.a.21119. Epub 2011 Aug 25. PubMed PMID: 22015734; PubMed Central PMCID: PMC3210507.
  4. Barker RH Jr, Urgaonkar S, Mazitschek R, Celatka C, Skerlj R, Cortese JF, Tyndall E, Liu H, Cromwell M, Sidhu AB, Guerrero-Bravo JE, Crespo-Llado KN, Serrano AE, Lin JW, Janse CJ, Khan SM, Duraisingh M, Coleman BI, Angulo-Barturen I, Jiménez-Díaz MB, Magán N, Gomez V, Ferrer S, Martínez MS, Wittlin S, Papastogiannidis P, O’Shea T, Klinger JD, Bree M, Lee E, Levine M, Wiegand RC, Munoz B, Wirth DF, Clardy J, Bathurst I, Sybertz E. Aminoindoles, a novel scaffold with potent activity against Plasmodium falciparum. Antimicrob Agents Chemother. 2011 Jun;55(6):2612-22. doi: 10.1128/AAC.01714-10. Epub 2011 Mar 21. PubMed PMID: 21422215; PubMed Central PMCID: PMC3101419.
  5. Booker ML, Bastos CM, Kramer ML, Barker RH Jr, Skerlj R, Sidhu AB, Deng X, Celatka C, Cortese JF, Guerrero Bravo JE, Crespo Llado KN, Serrano AE, Angulo-Barturen I, Jiménez-Díaz MB, Viera S, Garuti H, Wittlin S, Papastogiannidis P, Lin JW, Janse CJ, Khan SM, Duraisingh M, Coleman B, Goldsmith EJ, Phillips MA, Munoz B, Wirth DF, Klinger JD, Wiegand R, Sybertz E. Novel inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase with anti-malarial activity in the mouse model. J Biol Chem. 2010 Oct 22;285(43):33054-33064. doi: 10.1074/jbc.M110.162081. Epub 2010 Aug 11. PubMed PMID: 20702404; PubMed Central PMCID: PMC2963363.
  6. Urgaonkar S, Cortese JF, Barker RH, Cromwell M, Serrano AE, Wirth DF, Clardy J, Mazitschek R. A concise silylamine approach to 2-amino-3-hydroxy-indoles with potent in vivo antimalaria activity. Org Lett. 2010 Sep 17;12(18):3998-4001. doi: 10.1021/ol101566h. PubMed PMID: 20718474; PubMed Central PMCID: PMC7479540.
  7. Pastrana-Mena R, Dinglasan RR, Franke-Fayard B, Vega-Rodríguez J, Fuentes-Caraballo M, Baerga-Ortiz A, Coppens I, Jacobs-Lorena M, Janse CJ, Serrano AE. Glutathione reductase-null malaria parasites have normal blood stage growth but arrest during development in the mosquito. J Biol Chem. 2010 Aug 27;285(35):27045-27056. doi: 10.1074/jbc.M110.122275. Epub 2010 Jun 23. PubMed PMID: 20573956; PubMed Central PMCID: PMC2930704.
  8. Colón-Lorenzo EE, Serrano AE, Nicholas Jr. HB, Wymore T, Ropelewski AJ, González-Méndez R. The Plasmodium glutathione S-transferase: Bioinformatics Characterization and Classification into the Sigma Class. (2010). In: Fred A, Filipe J, Gamboa H, editors. Proceedings of Bioinformatics 2010, 1st International Conference on Bioinformatics, pp 173-180. Lisbon, Portugal, ISBN: 978-989-674-019-1
  9. Vega-Rodríguez J, Franke-Fayard B, Dinglasan RR, Janse CJ, Pastrana-Mena R, Waters AP, Coppens I, Rodríguez-Orengo JF, Srinivasan P, Jacobs-Lorena M, Serrano AE. The glutathione biosynthetic pathway of Plasmodium is essential for mosquito transmission. PLoS Pathog.2009 Feb;5(2):e1000302. doi: 10.1371/journal.ppat.1000302. Epub 2009 Feb 20. PubMed PMID: 19229315; PubMed Central PMCID: PMC2636896.
  10. González-Pons M, Szeto AC, González-Méndez R, Serrano AE. Identification and bioinformatic characterization of a multidrug resistance associated protein (ABCC) gene in Plasmodium berghei. Malar J. 2009 Jan 2;8:1. doi: 10.1186/1475-2875-8-1. PubMed PMID: 19118502; PubMed Central PMCID: PMC2630995.
  11. Ferrer-Rodríguez I, Pérez-Rosado J, Gervais GW, Peters W, Robinson BL, Serrano AE. Plasmodium yoelii: identification and partial characterization of an MDR1 gene in an artemisinin-resistant line. J Parasitol. 2004 Feb;90(1):152-60. doi: 10.1645/GE-3225. PubMed PMID: 15040683.
  12. Szeto AC, Pérez-Rosado J, Ferrer-Rodríguez I, Vega J, Torruella-Thillet C, Serrano AE. Identification and expression analysis of ABC genes in Plasmodium yoelii and P. berghei. Parasitol Res. 2004 Jan;92(1):1-11. doi: 10.1007/s00436-003-1001-8. Epub 2003 Oct 17. PubMed PMID: 14564508.
  13. Pérez-Rosado J, Gervais GW, Ferrer-Rodríguez I, Peters W, Serrano AE. Plasmodium berghei: analysis of the gamma-glutamylcysteine synthetase gene in drug-resistant lines. Exp Parasitol. 2002 Aug;101(4):175-82. doi: 10.1016/s0014-4894(02)00138-8. PubMed PMID: 12594957.
  14. Carrasquilla G, Banguero M, Sanchez P, Carvajal F, Barker RH Jr, Gervais GW, Algarin E, Serrano AE. Epidemiologic tools for malaria surveillance in an urban setting of low endemicity along the Colombian Pacific coast. Am J Trop Med Hyg. 2000 Jan;62(1):132-7. doi: 10.4269/ajtmh.2000.62.132. PubMed PMID: 10761738.
  15. Ferrer-Rodríguez I, Vázquez GJ, Córdova GJ, Serrano AE. Diagnosis of malaria by polymerase chain reaction. P R Health Sci J. 1999 Jun;18(2):99-103. PubMed PMID: 10461315.
  16. Serrano AE, Robinson BL, Peters W, Trujillo-Nevárez K. Plasmodium berghei and Plasmodium yoelii: molecular karyotypes of drug-resistant lines. Exp Parasitol. 1999 Jan;91(1):93-6. doi: 10.1006/expr.1999.4345. PubMed PMID: 9920047.
  17. Gervais GW, Trujillo K, Robinson BL, Peters W, Serrano AE. Plasmodium berghei: identification of an mdr-like gene associated with drug resistance. Exp Parasitol. 1999 Jan;91(1):86-92. doi: 10.1006/expr.1999.4344. PubMed PMID: 9920046.
  18. Ramajo Martin, V., López Aban, J., A.E. Serrano, A. Oleaga Pérez and A. Muro Alvarez. 1996. A long term study on the prevalence of gastrointestinal, hepatic and pulmonary parasitism in sheep from Salamanca province, Western Spain. Research & Review in Parasitology. 56:173-177.
  19. Ramajo Martin, V., López Aban, J., A.E. Serrano, A. Oleaga Pérez and A. Muro Alvarez. 1995. A long term study on the prevalence of gastrointestinal, hepatic and pulmonary parasitism in adult cattle from Salamanca province, Western Spain. Research & Review in Parasitology. 55:231-234.
  20. Wilson CM, Serrano AE, Wasley A, Bogenschutz MP, Shankar AH, Wirth DF. Amplification of a gene related to mammalian mdr genes in drug-resistant Plasmodium falciparum. 1989 Jun 9;244(4909):1184-6. doi: 10.1126/science.2658061. PubMed PMID: 2658061.
  21. Hillyer GV, Serrano AE. Fractionation of Fasciola hepatica tegument antigens and their application to the serodiagnosis of experimental fascioliasis by the enzyme-linked immunosorbent assay. J Helminthol. 1986 Sep;60(3):173-8. doi: 10.1017/s0022149x00026055. PubMed PMID: 3091677.
  22. Hillyer GV, Serrano AE. The antigens of Paragonimus westermani, Schistosoma mansoni, and Fasciola hepatica adult worms. Evidence for the presence of cross-reactive antigens and for cross-protection to Schistosoma mansoni infection using antigens of Paragonimus westermani. Am J Trop Med Hyg. 1983 Mar;32(2):350-8. doi: 10.4269/ajtmh.1983.32.350. PubMed PMID: 6404188.
  23. Hillyer GV, Serrano AE. Cross protection in infections due to Schistosoma mansoni using tegument antigens of Fasciola hepatica. J Infect Dis. 1982 May;145(5):728-32. doi: 10.1093/infdis/145.2.728. PubMed PMID: 7077096.

Book Chapters

  • Anti-protozoan drugs. A. Muro, A.E. Serrano,and J.L. Pérez de Arellano. Chapter 22, pp. 331-343. In: Guía de Autoformación en Enfermedades Infecciosas”, Madrid, España
  • Anti-helminthic drugs. A. Muro, A.E. Serrano,and J.L. Pérez de Arellano. Chapter 23, pp. 345-353.In: Guía de Autoformación en Enfermedades Infecciosas”, Madrid, España

This book received “El Medico” Award, XIII Edition, Best Medical Book 1st. prize”

  • Vega-Rodríguez J, Franke-Fayard B, Dinglasan RR, Janse CJ, Pastrana-Mena R, Waters AP, Coppens I, Rodríguez-Orengo JF, Jacobs-Lorena M, and Serrano AE. (2009). The glutathione biosynthetic pathway of Plasmodium is essential for mosquito transmission. PLoS Pathog. Feb;5(2):e1000302. Epub 2009 Feb 20 PMID: 19229315. PMCID: PMC2636896.
  • Pastrana-Mena R, Dinglasan RR, Franke-Fayard B, Vega-Rodriguez J, Fuentes-Caraballo M, Baerga-Ortiz A, Coppens I, Jacobs-Lorena M, Janse CJ, Serrano AE. (2010). Glutathione reductase-null malaria parasites have normal blood stage growth but arrest during development in the mosquito. (2010). J Biol Chem. 285: 27045 – 27056 2010, Epub 2010 Jun 23. PMID: 20573956. PMCID: PMC2930704.
  • Vega-Rodríguez J, Pastrana-Mena R, Crespo-Lladó KN, Ortiz JG, Ferrer-Rodríguez I, Serrano AE. Implications of Glutathione Levels in the Plasmodium berghei Response to Chloroquine and Artemisinin. PLoS One. 2015 May 26;10(5):e0128212. doi: 10.1371/journal.pone.0128212. eCollection2015. PMID: 26010448. PMCID: PMC4444287.
  • Padín-Irizarry V, Colón-Lorenzo E, Vega-Rodríguez J, Castro MR, Gonzalez-Méndez, R, Ayala-Peña S, Serrano AE. Glutathione-Deficient Plasmodium berghei Parasites Exhibit Growth Delay and NuclearDNA Damage. 2016. Free Radic Biol Med. 2016 Mar 4;95:43-54. doi: 10.1016/j.freeradbiomed.2016.02.032. PMID: 26952808.
  • Wilson CM, Serrano AE, Wasley A, Bogenschutz MP, Shankar AH, and Wirth DF. Amplification of a gene related to mammalian mdr genes in drug-resistant Plasmodium falciparum. (1989). Science 244:1185- 1186. PMID: 2658061.
  • Gervais G, Trujillo-Nevárez K, Robinson BL, Peters WA, and Serrano AE. Plasmodium berghei: Identification of an mdr-like gene associated with drug resistance. (1999). Exp Parasitol 91: 86-92. PMID: 9920046
  • Gonzalez-Pons M, Szeto AC, Gonzalez-Mendez R, and Serrano AE. (Identification and bioinformatic characterization of a multidrug resistance associated protein (ABCC) gene in Plasmodium berghei. (2009). Malar J. Jan 2;8(1): 1. PMID: 19118502. PMCID: PMC2630995.
  • Rijpma SR, van der Velden M, González-Pons M, Annoura T, van Schaijk BC, van Gemert GJ, van den Heuvel JJ, Ramesar J, Chevalley-Maurel S, Ploemen IH, Khan SM, Franetich JF, Mazier D, de Wilt JH, Serrano AE, Russel FG, Janse CJ, Sauerwein RW, Koenderink JB, Franke-Fayard BM. Multidrug ABC transporters are essential for hepatic development of Plasmodium sporozoites. Cell Microbiol. 2015 Aug 29. doi: 10.1111/cmi.12517. PMID: 26332724. PMCID:
  • Hillyer GV and Serrano, AE.1986. Fractionation of Fasciola hepatica tegument antigens and their application to the serodiagnosis of experimental fascioliasis by the enzyme-linked immunosorbent assay. J Helminth 60:173-178. PMID: 3091677.
  • Hillyer GV and Serrano AE. Cross-protection in infections due to Schistosoma mansoni using tegument antigens of Fasciola hepatica. (1982). J Infec Dis 145: 728-732. PMID: 7077096.
  • Hillyer GV and Serrano AE. The antigens of adult worms. Evidence for the presence of cross-protection to Schistosoma mansoni infection using antigens of Paragonimus westermani. (1983). Am J Trop Med Hyg 32: 350-358. PMID: 6404188.