Rodriguez Lab - Microbiology

Ana Rodriguez, Ph.D.
Associate Professor, Department of Microbiology (Parasitology)

Old Public Health Building, Rm 509B
341 East 25th Street, New York, NY 10010
Office: (212) 263-6757
Fax: (212) 263-8116
Lab: (212) 263 6589
Email: Ana.Rodriguez@nyumc.org

 

 

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 one million deaths per year, mainly among children in third world countries. 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 accumulates precipitates of uric acid that are released upon rupture of the erythrocyte at the end of the replicative cycle. Release of uric acid precipitates in the blood is very inflammatory, mediates the increase of TNF and strongly modulates the production of other cytokines that control the inflammatory response. 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:

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: