Rodriguez Lab - Microbiology

Ana Rodriguez, PhD
Associate Professor, Department of Microbiology (Parasitology)
Alexandria Center for Life Science – West Tower
430 East 29th Street, AW 3rd Floor
Office Rm. 308, Lab Rm. 524
New York, NY 10016
Office: (646) 501-6997
Lab: (646) 501-6996

 

 

 

KEY INTERESTS:

Malaria, Plasmodium, Chagas Disease, Trypanosoma cruzi

BIOGRAPHIC DETAILS:

Graduate Education:

1993 Ph.D. Immunovirology, Universidad Autonoma de Madrid, Spain

Postdoctoral Training:

1993-97 Dr. Norma Andrews, Yale University School of Medicine
1997-99 Immunology, Dr. Sebastian Amigorena, Institut Curie, Paris, France

Academic Appointments:

1999: Instructor, New York University School of Medicine, Department of Medical Parasitology
2000: Assistant Professor, New York University School of Medicine
Department of Medical Parasitology
2010: Associate Professor, New York University School of Medicine
Department of Microbiology, Division of Medical Parasitology

Major Responsibilities:

Director Parasitology Division
Director Insectary Core Facility
Director Anti-infectives Screening Core Facility

Major Honors:

 

1997 Marie Curie Fellow, European Community
2000 Liver Scholar Award,American Liver Foundation
2006 Career Scientist Award, The Irma Hirschl Trust
2006 Pathogenesis of Infectious Disease Award, Burroughs Wellcome Fund

RESEARCH INTERESTS:

Our lab studies two different parasites, Plasmodium, which causes Malaria and Trypanosoma cruzi, which causes Chagas disease.

Malaria is a devastating disease that causes more than 400,000 deaths per year, mainly among African children. Despite many efforts to control the disease with anti-malarial drugs and insecticides to eliminate mosquito vectors, the appearance of resistant populations of parasites and mosquitoes respectively have impaired the efficacy of these approaches. There is an urgent need for new strategies to control malaria, but there is a lack of detailed knowledge of the basic biological processes of Plasmodium, that would allow faster development of anti-malaria drugs and vaccines.

A main interest of our laboratory is the study of malaria-induced inflammatory pathology. We have found that Plasmodium synergizes with oxidative stress to activate the inflammasome and the production of cytokines. This novel pathway that regulates anti-malaria inflammatory response opens the possibility of new exciting approaches to control disease pathology and death.

We also study cerebral malaria, a complication of severe malaria that frequently leads to coma and death. During cerebral malaria, erythrocytes infected with Plasmodium falciparum bind to endothelial cells in the brain blocking normal circulation. We have observed that infected erythrocytes induce the rupture of inter-endothelial cell junctions and detachment of endothelial cells. Our work is focused on the inhibition of this process, with the aim to find inhibitors that would preserve the integrity of the endothelium during cerebral malaria and would allow the development of a specific treatment against cerebral malaria.

We also collaborate with a Pharmaceutical company, GlaxoSmithKline to develop effective drugs against Chagas Disease. In collaboration with GSK, we have performed a high through put screening of 2 million compounds for intracellular Trypanosoma cruzi, to find compounds with anti-trypanosomal activities. Selected compounds are being tested for efficacy in mice.


Human brain microvascular endothelial cells after incubation with RBC (control), or different ratios of P. falciparum infected RBC (iRBC) for 18 h. Actin (red), ZO-1 (green), nuclei (blue)
 

PUBLICATIONS:

Anti-Self Phosphatidylserine Antibodies Recognize Uninfected Erythrocytes Promoting Malarial Anemia.
Fernandez-Arias C, Rivera-Correa J, Gallego-Delgado J, Rudlaff R, Fernandez C, Roussel C, Götz A, Gonzalez S, Mohanty A, Mohanty S, Wassmer S, Buffet P, Ndour PA, Rodriguez A.
Cell Host Microbe. 2016 Feb 10;19(2):194-203. doi: 10.1016/j.chom.2016.01.009.
PMID: 26867178

Angiotensin receptors and β-catenin regulate brain endothelial integrity in malaria.
Gallego-Delgado J, Basu-Roy U, Ty M, Alique M, Fernandez-Arias C, Movila A, Gomes P, Weinstock A, Xu W, Edagha I, Wassmer SC, Walther T, Ruiz-Ortega M, Rodriguez A.
J Clin Invest. 2016 Oct 3;126(10):4016-4029. doi: 10.1172/JCI87306. Epub 2016 Sep 19.
PMID: 27643439

Comment in:
Breaking down brain barrier breaches in cerebral malaria.
Petersen JE, Lavstsen T, Craig A.
J Clin Invest. 2016 Oct 3;126(10):3725-3727. doi: 10.1172/JCI90188. Epub 2016 Sep 19.
PMID: 27643435

Comment in:
Common Blood-Pressure Drug May Work on Malaria, Too
The New York Times Health Section, September 19, 2016.

The High Blood Pressure-Malaria Protection Hypothesis.
Gallego-Delgado J, Walther T, Rodriguez A.
Circ Res. 2016 Oct 28;119(10):1071-1075. Epub 2016 Sep 22.
PMID: 27660286

Comment in:
Angiotensin II-Linked Hypothesis to Understand the Advantage of the Coevolution of Hypertension and Malaria: "Sympathy for the Devil".
Volpe M, Battistoni A, Mancia G.
Circ Res. 2016 Oct 28;119(10):1046-1048. No abstract available.
PMID: 27789579

Plasmodium DNA-mediated TLR9 activation of T-bet+ B cells contributes to autoimmune anaemia during malaria.
Rivera-Correa J, Guthmiller JJ, Vijay R, Fernandez-Arias C, Pardo-Ruge MA, Gonzalez S, Butler NS, Rodriguez A.
Nat Commun. 2017 Nov 3;8(1):1282. doi: 10.1038/s41467-017-01476-6.
PMID: 29101363

Atypical activation of dendritic cells by Plasmodium falciparum.
Götz A, Tang MS, Ty MC, Arama C, Ongoiba A, Doumtabe D, Traore B, Crompton PD, Loke P, Rodriguez A.
Proc Natl Acad Sci U S A. 2017 Dec 5;114(49):E10568-E10577. doi: 10.1073/pnas.1708383114. Epub 2017 Nov 21.
PMID: 29162686

Automated high-content assay for compounds selectively toxic to Trypanosoma cruzi in a myoblastic cell line.
Alonso-Padilla J, Cotillo J, Presa JL, Cantizani J, Peña I, Bardera AI, Martín JJ, and Rodriguez A. (2015).
PLoS Neglected Tropical Diseases. 9(1):e0003493.
PMID: 25615687

New Compound Sets Identified from High Throughput Phenotypic Screening against Three Kinetoplastid Parasites: An Open Resource.
Peña I, Manzano MP, Cantizani J, Kessler A, Alonso-Padilla J, Bardera AI, Alvarez E, Colmenarejo G, Cotillo I, Roquero I, de Dios-Anton F, Barroso V, Rodriguez A, Gray DW, Navarro M, Kumar V, Sherstnev A, Drewry D, Brown JR, Fiandor JM & Martin JJ. (2015).
Scientific Reports 5:8771.
PMID: 25740547

Malaria inhibits surface expression of complement receptor-1 in monocyte/macrophages causing decreased immunecomplex internalization.
Fernandez-Arias C, Lopez JP, Hernandez-Perez JN, Bautista-Ojeda MD, Branch O and Rodriguez A.
The Journal of Immunology. 2013 190(7):3363-72.
PMID: 23440418

Plasmodium falciparum-derived uric acid precipitates induce maturation of dendritic cells.
van de Hoef DL, Coppens I, Holowka T, Ben Mamoun C, Branch O, Rodriguez A.
PLoS ONE. 2013 8(2):e55584.
PMID: 23405174

Activity in vivo of anti-Trypanosoma cruzi compounds selected from a high throughput screening.
Andriani, G, Chessler, AC, Courtemanche, G, Burleigh, BA, and Rodriguez A.  
PLoS Neglected Tropical Diseases 2011 5(8):e1298.
PMID: 21912715

Uric Acid is a Mediator of the Plasmodium falciparum-induced Inflammatory Response.
Orengo JM, Leliwa-Sytek A, Evans JE, Evans B, van de Hoef D, Nyako M, Day K and Rodriguez A.
PLoS ONE. 2009  4(4): e5194.
PMID: 19381275

Identification of Three Classes of Heteroaromatic Compounds with Activity against Intracellular Trypanosoma Cruzi by Chemical Library Screening.
Bettiol E, Samanovic M, Murkin AS, Raper J, Buckner F and Rodriguez A. (2009).
PLoS Neglected Tropical Diseases 3(2): e384.
PMID:19238193

Plasmodium infection and endotoxic shock induce the expansion of regulatory dendritic cells.
Wong, KA and A. Rodriguez. (2008).
Journal of Immunology. 180(2):716-26.
PMID:18178809

Adenylyl cyclase a and cAMP signaling mediate Plasmodium sporozoite apical regulated exocytosis and hepatocyte infection.
Ono T, Cabrita-Santos L, Leitao R, Bettiol E, Purcell LA, Diaz-Pulido O, Andrews LB, Tadakuma T, Bhanot P, Mota MM and Rodriguez A. (2008).
PLoS Pathogens.4(2):e1000008.
PMID:18389080

Plasmodium-induced inflammation by uric acid.
Orengo JM, Evans JE, Bettiol E, Leliwa-Sytek A, Day K and Rodriguez A. (2008).
PLoS Pathogens. 4(3):e1000013.
PMID:18369465

Transcriptome profile of dendritic cells during malaria: cAMP regulation of IL-6.
Carapau D, Kruhofer M, Chatalbash A, Orengo JM, Mota MM and A Rodriguez. (2007).
Cellular Microbiology. 9(7):1738-52.
PMID:17324158

Apoptotic Plasmodium infected hepatocytes provide antigens to liver dendritic cells.
P. Leiriao, M.M. Mota, and A. Rodriguez. (2005).
The Journal of Infectious Diseases 191, 1576-81.
PMID:15838783

Malaria blood-stage suppression of liver-stage immunity by dendritic cells.
C. Ocaña-Morgner, Maria M. Mota, and A. Rodriguez. (2003).
Journal of Experimental Medicine. 197, 143-151.
PMID:12538654

Migration through host cells activates Plasmodium sporozoites for infection.
M. M. Mota, J.C.R. Hafalla, and A. Rodriguez. (2002).
Nature Medicine 8, 1318-1322.
PMID:12379848

Migration of Plasmodium sporozoites through cells before infection.
M. M. Mota, G. Pradel, U. Frevert, J. Vanderberg, J. Hafalla, R. Nussenzweig, V. Nussenzweig and A. Rodríguez. (2001).
Science 291, 141-144.
PMID:15527491

LAB MEMBERS:

Julio Gallego-Delgado, Postdoctoral Fellow (2010-present)
Maureen Ty, Graduate Student (2012-present)
Anne Goetz, Postdoctoral Fellow (2013-present)
Juan Rivera-Correa, Graduate Student (2014-present)
Scott Tanghe, Technician (2014-present)

PROFESSIONAL LINKS: