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Pilot Grant Program
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AWARDED: 2002 l 2003 l 2004 l 2005 | 2006 | 2007 | 2008 | 2009
Pharmacokinetic drug Interaction between quinine and lopinavir/ritonavir in healthy volunteers
Myaing Nyunt
1/1/2009-12/31/2009
Mechanisms of Cholesterol Uptake by Plasmodium Liver Forms
Isabelle Coppens
3/1/2009-2/28/2011
Plasmodium oocyst Capsule Proteome and Function in the Mosquito Vector
Marcelo Jacobs-Lorena
3/1/2009-2/28/2011
Alterations of the MHC class I Processing and Presentation Pathway at the Liver Stage of Malaria Infection
Elena Levitskaya
3/1/2009-2/28/2011
Changing Malaria Transmission Dynamics in Southern Zambia and Prospects of Elimination
William Moss
3/1/2009-2/28/2011
Impact of Population Movement and Foraging Behavior of Anopheles Arabiensis
Douglas Norris
3/1/2009-2/28/2011
DNA Topoisomerase VI in Malaria Parasites
Theresa Shapiro
3/1/2009-2/28/2011
Mapping Malaria Epidemiology in Bangladesh
(in cooperation with ICDDR, B)
David Sullivan
4/1/2009-3/31/2012
Development of a PET Imaging Based Mouse Model of Malaria
Steve Cho
4/15/2009-4/14/2011
Using Drosophila to Develop Transmission-Compromised Mosquito Hosts for Malaria
Deborah Andrews
9/1/2009-8/31/2010
Characterization of Plasmodial Proteases Essential for Parasite Survival
Jurgen Bosch
9/1/2009-8/31/2011
Revisting Primaquine Efficacy, Toxicity and Transmission Blocking Activity
Rhoel Dinglasan
9/1/21009-8/31/2011
Identification and Functional Characterization of Aquaporin Genes in An. Gambiae
Jason Rasgon
9/1/2009-8/31/2011
TOP
2008 AWARDS
Characterization of novel non-coding regulatory RNAs in Plasmodium falciparum
Karen Beemon
3/1/2008-2/28/2010
Impact of Microbial Exposure on Mosquito Immunity & Antiplasmodium Defense
George Dimopoulos
3/1/2008-2/28/2010
Structure-based Optimization of Novel Antimalarials
Ernesto Freire
3/1/2008-2/28/2010
Mechanisms of Antigenic variation in P. falciparum
Nirbhay Kumar
3/1/2008-2/28/2010
Biodegradable Microparticles for Oral Delivery of a Malaria Transmission-Blocking Vaccine
Hai-Quan Mao
3/1/2008-2/28/2010
Plasmodium Falciparum evidence in Human Saliva & Urine Samples
Sungano Mharakurwa
3/1/2008-2/28/2010
The Role of Biotin in Malaria Survival
Sean Prigge
9/1/2008-8/31/2010
Malaria in the Lung
Alan Scott
9/1/2008-8/31/2010
Characterization of Liver-Resident Memory CD8+ T cells against Plasmodium
Fidel Zavala
3/1/2008-2/28/2010
Study of the Molecular Events During the Malaria Sporozoite Transformation into the Liver Stage
Isabelle Coppens
3/1/07-2/28/09
Characterization of the Anopheles SRPN6 Defense Pathway Against Plasmodium
Marcelo Jacobs-Lorena
3/1/07-2/28/09
Live Adenovirus Vaccine Against Malaria
Gary Ketner
3/1/07-2/28/08
Improved Molecular Techniques for Malaria Vector Identification in the Amazon
Margaret Kosek
9/01/07-8/31/09
Optimization of Malaria Transmission-Blocking Vaccines by in vivo Electroporation
Nirbhay Kumar
3/1/07-2/28/09
The Role of Platelet Factor 4 in the Pathogenesis of Cerebral Malaria
Craig Morrell
9/1/07-8/31/09
Understanding Vectoral Components of Malaria Transmission at Macha
Douglas Norris
5/1/07-7/31/09
A viral biocontrol agent for Anopheles gambiae
Jason Rasgon
9/1/07-8/31/09
Local Landscape determinants of Anopheles arabienes Developmental Habitats and Dispersal Behavior
Clive Shiff
5/1/07-4/30/09
Role of chemokines in cerebral malaria pathogenisis at the blood brain barrier
Monique Stins
9/01/07-8/31/09
Kinetics of Urine and Saliva Malaria Markers and Hepcidin at Macha
David Sullivan
5/1/07-4/30/09
Investigating the Roles of Intramembrane Proteolysis in Plasmodium
Sin Urban
7/1/07-6/30/09
Using A. aegypti Transposons for Genetic Manipulation of Malarial Mosquitoes
Nancy Craig
3/1/06 – 2/28/08
Pathogenesis of Pulmonary Malaria
Alan Scott
3/1/06 – 2/28/08
Inhibitors of Methionine Aminopeptidases as Novel Anti-Malarial Agents
Jun Liu
3/1/06 – 2/28/08
A Novel Cell Free System for Identification of Physiological Epitope(s) of P. falciparum Liver Stage Antigen-1
Scheheraza Sadegh-Nasseri3/1/06-2/28/07
Pharmacokinetics of SP in the Treatment of Malaria in Pregnancy
Theresa Shapiro / David Sullivan / Myaing Nyunt
9/1/06-8/31/07
Targeting Isoprenoid Biosynthesis in Plasmodium falciparum
Caren L. Meyers
9/1/06-8/31/08
Mosquito midgut and Plasmodium Oocyst Proteome-A search for Novel Malaria Transmission Blocking Targets
Akhilesh Pandey
9/1/06-8/31/08
Investigating Small Molecule Inhibition and Hemozoin Response of MIF in Malaria
Michael McDevitt
9/1/06-8/31/08
Antimicrobial and anti-Plasmodium Immune Defense in Anopheles arabiensis
George Dimopoulos
9/1/06-8/31/07
Development of a Densovirus Expression System for Control of Anopheles gambiae
Jason Rasgon
9/1/06-2/28/07
Nicotinic Acid and var Gene Silencing in P. falciparum
Brendan Cormack
3/1/05–2/28/06
Objective: To characterize an ORF with low but highly significant homology to SIR2, the yeast gene encoding an NAD+-dependent histone deacetylase.
Molecular Genotyping of Plasmodium vivax in the Peruvian Amazon
Robert Gilman
3/1/05–2/28/07
Objective: To establish critical parameters of complexity of P. vivax populations circulating locally in a village; to establish incidence and prevalence of symptomatic and asymptomatic P. vivax infection; to establish whether newly introduced genotypes are associated with the development of symptomatic malaria; and to establish whether circulating P. vivax clones have been acquired locally within villages or introduced from outside.
Acquisition of Natural Immunity to P. falciparum Transmission-Blocking Vaccine Antigens
Nirbhay Kumar
3/1/05–2/28/07
Objective: To determine the percentage of subjects who demonstrate measurable antibody responses to recombinant Pfs230 and Pfs48/45 proteins; to determine functional malaria transmission-blocking activity of sera by membrane feeding assay; and to examine parasite genotypes by PCR to determine presence of sub-patent gametocytaemia by RT-PCR.
Novel Approaches for Detection of Low Frequency Malaria Specific T Cells
Martin Oelke
3/1/05–2/28/07
Objective: To establish and optimize combined methods of aAPC and RT-PCR for activation and detection of T cell responses, using a well established CMV-specific CTL system.
Dynamics of P. falciparum Population Diversity and Host Response in Pemban Children: Implications for Immunity and Pathology
David Sullivan
3/1/05–2/28/07
Objective: To analyze P. falciparum microsatellite data from blood samples and to characterize additional host protein alterations with the SELDI-MS system in case control pairs.
Live Adenovirus Vaccine against Malaria
Gary Ketner
9/1/05–8/31/06
Objective: The long-term objective of this project is a viable orally-administered recombinant adenovirus vaccine against malaria. The pilot studies proposed here will involve construction of recombinants that express the candidate P. falciparum vaccine antigens circumsporozoite protein (CSP) and liver stage antigen 3 (LSA-3), characterization of recombinants in tissue culture, and partial immunological characterization in mice.
Targeting the Ketoacyl-ACP Synthase Enzymes of P. falciparum
Sean Prigge
9/1/05–8/31/07
Objective: To determine the mode of action of KASIII using biochemical and structural approaches. To study the activity and inhibition of KASII using biochemical assays and a genetic complementation system and to validate KASIII and KASII as drug targets in P. falciparum using genetic approaches and metabolite analysis.
Developing a Dendritic-Cell Targeted Malaria Vaccine
Richard Markham
9/1/05–8/31/06
Objective: To evaluate in vitro the responses elicited by three candidate DNA vaccines in BALB/c mice and to evaluate the protective efficacy of these candidate vaccines in a murine malaria challenge model.
Matrix Metalloproteinases in Cerebral Malaria
Katherine Conant
9/1/05–8/31/07
Objective: To determine whether IRBCs and haemozoin, a product of malarial infected RBCs, stimulate MMP release from human brain microvascular endothelial cells (HBMECs) or leukocytes. To determine whether IRBCs and haemozoin stimulate MMP release via activation of specific adhesion molecules and/or toll-like receptors and to determine whether MMPs play a role in the CNS pathology observed in murine malaria.
Aquaporins and the Pathogenesis of Malaria
Peter Agre
3/1/04–2/28/06
Objective: To determine the role of the Plasmodium aquaporins (AQPs) in the survival and proliferation of P. falciparum and P. berghei, to examine the effects of AQP1 and AQP3 deficiency in human red blood cells, and to examine the effects of P. falciparum infection on the distribution of aquaporins in red blood cells.
Identification of Host Cell-Derived Nutrients Required for Plasmodium Development within Hepatocytes
Isabelle Coppens
3/1/04–2/28/06
Objective: To analyze the fine ultrastructure of different liver stages of Plasmodium, to elucidate the source of cholesterol for parasite intracellular membranes; to investigate the molecular mechanisms of cholesterol transfer from the host hepatocyte to the parasite; and to identify the nature of exogenous nutrients accessible to the Plasmodium vacuole.
Modification of Plasmodium RNA Polymerase II
Jeffry Corden
3/1/04–2/28/06
Objective: To determine whether the CTD of RNA polymerase II is proteolytically removed during the intraerythrocytic growth cycle and identify potential novel CTD-related polypeptides.
Transcriptomic and Immune Responsive Diversity in Anopheles Gambiae
George Dimopoulos
3/1/04–2/28/06
Objective: To assess global transcriptomic variations between different field strain/population Anopheles gambiae nd lab strain A. gambiae and assess divergence of immune response regulation between different field strain/population A. gambiae and lab strain A. gambiae.
Optimization of plasmepsin inhibitors as new antimalarials
Ernesto Freire
10/01/04-9/30/06
Study of Cytoadherence of P. falciparum Infected Erythrocytes (IC) in Microvasculature using Microfluidics
Andre Levchenko
9/1/04-8/31/06
Objective: To characterize intercellular transfer of CD36 and other proteins of potential importance to cytoadherence from platelet and peripheral blood mononuclear cells to endothelial cells.
Characterization of Enzymes of the SUMO Modification Pathway in Plasmodium falciparum
Michael Matunis
9/1/04–8/31/06
Objective: To identify and isolate cDNAs coding for P. falciparum SUMO and SUMO, to express P. falciparum SUMO and SUMO and the development of in vitro SUMO conjugating and deconjugating assays using expressed P. falciparum proteins.
Drug-resistant plasmodium falciparum Fitness in Macha
Sungano Mharakurwa
10/01/04-9/31/06
Vectorial Components of Malaria Transmission at Macha, Zambia
Douglas Norris
3/1/04–2/28/06
Objective: To characterize the temporal and spatial structure of malaria vector populations and to associate vector mosquitoes from specific breeding sites to the human habitations.
Kent RJ, Norris DE. Identification of mammalian blood meals in
mosquitoes by a multiplexed polymerase chain reaction targeting
cytochrome b. Am J Trop Med Hyg 73:336-342, 2005. Article
Kent RJ, West AJ, Norris DE. Molecular differentiation of colonized
human malaria vectors by 28S ribosomal DNA polymorphisms.
Am J Trop Med Hyg 71:514-517, 2004. Abstract
A Comprehensive Analysis of the Anopheles gambiae Proteome
Akhilesh Pandey
9/1/04–8/31/06
Objective: To generate a completely annotated A. gambiae genome and proteome to facilitate studies of malaria parasite development and to define novel targets for preventing malaria transmission.
Search for microRNA Genes in Plasmodium falciparum
Fernando Pineda
3/1/04–2/28/05
Objective: To discover candidate miRNA genes in the P. falciparum genome via computational means and to validate candidate miRNA genes in the laboratory.
Development of an in vitro System for Wolbachia Culture, Genetic Adaptation, and Transfection in Anopheles gambiae
Jason Rasgon
9/1/04–8/31/06
Objective: To create a Wolbachia strain that is adapted to and able to infect Anopheles gambiae cells to examine phenotypic changes in Wolbachia and to begin development of protocols to transfer Wolbachia infection into Anopheles mosquitoes.
An in vitro Perfusion System to Study Antimalarial Drug Action
Theresa Shapiro
9/1/04–8/31/06
Objective: To determine the ideal pattern of antimalarial drug concentrations over time for established antimalarials and to explore concentration time requirements for antimalarial drugs in combinations.
Human Brain Endothelial Cell Model to Study Cerebral Malaria
Monique Stins
9/1/04–8/31/06
Objective: To analyze the mechanisms of blood-brain-barrier permeability changes induced by infected erythrocytes and to characterize transcriptional changes by using microarrays for both parasite and host-brain endothelium upon adhesion.
Methods of Malaria Detection by Lasor Desorption Mass Spectrometry
David Sullivan
2/15/04-2/14/06
Immunoglobulin "Knock-In" Mice to Study B-Cell Responses against Malaria Sporozoites
Fidel Zavala
9/1/04–8/31/06
Objective: To generate transgenic "knock-in" mice harboring B cells that express a B cell receptor and produce antibodies specific for the repeat domain of the CS protein of P. yoelii and to study in vivo the response-kinetics of malaria specific B cells activated after immunization with P. yoelii sporozoites.
Structural and Functional Analysis of Peritrophic Matrix Proteins from the Mosquito Anopheles gambiae
Martin Devenport / Marcelo Jacobs-Lorena
9/1/03–8/31/05
Objective: The peritrophic matrix (PM) is a protective layer secreted by the mosquito midgut. The PM completely surrounds the ingested blood and any parasites present in the blood. The major aims of this project are, first, to use a proteomic approach to identify PM protein components and, second, to characterize the corresponding genes by localizing them on the PM and investigating how they interact to form an organized structure.
Structural Basis of DNA Recognition by Novel Anti-Malaria Compounds
Clara Kielkopf
9/1/03–8/31/05
Objective: A unique class of synthetic DNA ligands has been found to be selectively toxic to Plasmodium falciparum in cell culture and mouse models. It is hypothesized that the antimalarial activity results from targeting the unusual AT-rich genome of the parasite. To understand how these novel molecules recognize AT-rich sequences, we are determining the co-crystal structures in collaboration with the groups of Peter B. Dervan (Caltech) and Richard Tanaka (GeneSoft). Structural information will facilitate future design of second-generation compounds with improved sequence selectivity and antimalarial activity.
Malaria and Tuberculosis Co-Infection
Yukari Manabe
9/1/03–8/31/05
Objective: To evaluate the effect of acute malaria infection on latent TB infection (LTBI), to evaluate host immune response to acute malaria infection in active pulmonary tuberculosis, and to establish the effect of malaria-induced Th2 response to acute tuberculosis infection and tuberculosis immunopathogenesis.
The Johns Hopkins Clinical Compound Screening Initiative
Jun Liu / David Sullivan
1/1/03–12/31/05
Objective: To assist researchers in rapid screening for inhibitors of the malaria parasite, we will assemble a library of all 3,000 FDA-approved drugs for use against the disease. This will preclude the industry investment in research and development.
Characterization of Enzymes of the SUMO Modification Pathway in Plasmodium falciparum
Michael Matunis
9/1/03–8/31/04
Objective: To identify molecules that selectively inhibit the Plasmodium falciparum SUMO conjugating and deconjugating enzymes. The ultimate goal is to identify inhibitors that could be used to block parasite replication in humans.
Polyparasitism and Malaria: Interactions between Malaria and Childhood Infections in Zambia
William Moss
9/1/03–8/31/04
Objective: To determine the prevalence of infection with Schistosoma mansoni, Ascaris lumbricoides, Trichuris trichuria, and hookworm in children residing within the catchment area of Macha Mission Hospital. Once the prevalence of these coinfections is determined, we plan to characterize the bi-directional interactions between Plasmodium falciparum infection and selected parasitic coinfections on the clinical features and parasite densities in coinfected children.
Lipoic Acid Metabolism in Plasmodium falciparum
Sean Prigge
9/1/03–8/31/05
Objective: Lipoic acid is an essential molecule required for proper cellular function. Lipoic acid is made and used in the malaria parasite differently than it is in humans. Our goal is to understand the metabolism of lipoic acid in the parasite in an effort to selectively target this process with therapeutics.
An in vitro Perfusion System to Study Antimalarial Drug Action
Theresa Shapiro
9/1/03–8/31/04
Objective: For most in vitro experiments with antimalarial drugs, concentrations are kept constant over time. This is distinctly unlike the actual situation in humans, in which drug concentrations in the blood fluctuate over time, reflecting the rates of absorption, distribution and elimination. To determine the most rational dosing strategies for clinical use, a novel in vitro perfusion system will be used to mimic the natural pharmacokinetics of antimalarial drugs in humans. Studies will include classical as well as experimental agents.
Development of the Human Brain Endothelial Cell Model for Cerebral Malaria
Monique Stins/ David Sullivan
9/1/03–8/31/04
Objectives: To develop a blood-brain-barrier model based on human capillary cells to understand how the malaria parasite interacts with the blood-brain barrier in a manner that may result in brain dysfunction.
HIV and Malaria Co-Infection During Pregnancy and Effects on Mother-to-Child Transmission of HIV in Rakai, Uganda
Heena Brahmbhatt / Ronald Gray / David Sullivan
11/1/02–7/31/04
Objective: To investigate how malaria infection during pregnancy affects mother-to-child transmission of HIV. The research may suggest that HIV-positive women need to take antimalarials more often during pregnancy. Publication
Adult CD4 T Cell Gene Expression after Malaria Infection
Donald Burke
11/15/02–11/14/03
Objective: To use microarray ("gene chip") technology to examine the effect of acute malaria infection on gene activation patterns in blood lymphocytes of patients acutely infected with malaria in Cameroon, West Africa. We hypothesize that acute malaria alters the genes activated in immune function cells.
Sindbis Virus Vectors in Mosquitoes
Marie Hardwick
5/1/02–6/30/04
Objective: To engineer Sindbis virus to activate the cellular death program in mosquito cells and in mosquitoes. To accomplish this goal, we have taken a "death" gene from flies and put it into Sindbis virus. This virus now kills mosquitoes in the laboratory, and we hope to develop a method of targeting mosquitoes that transmit malaria.
Plasmodium falciparum Gametocyte Proteome and High Throughput Analysis
Nirbhay Kumar
11/1/02–10/31/04
Objective: To identify novel targets for the development of transmission-blocking drugs and vaccines. Since the gametocyte stage of the parasite's life cycle is absolutely essential to continued malaria transmission, this project will focus on functional genomic approaches to understanding the immunobiology of gametocytes of P. falciparum.
Transcriptional analysis of DNA Damage Response and Repair Pathways in Plasmodium falciparum
Nirbhay Kumar
12/1/02–11/30/03
Objective: To identify novel antimalarial drug targets is the long-term goal of this study. We have recently identified a key molecule in the parasite that is likely to play a pivotal role in repairing DNA damage induced by a variety of physiological and pathological insults. For the first time, this study will begin to characterize in detail these mechanisms in the parasite by using microarray-based transcriptional analysis of gene expression patterns within the parasite.
Proteomic Analysis of Anopheles gambiae Salivary Glands
Akhilesh Pandey / Nirbhay Kumar
11/15/02–11/14/04
Objective: To identify and provide a comprehensive catalog of the cellular proteins expressed in female mosquito salivary glands, leading to better understanding of A. gambiae biology and, potentially, the identification of mechanisms relevant to malaria transmission.
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