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About Malaria

 

Pre- and Post-doctoral Fellows that have been awarded JHMRI Fellowships

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Research conducted by JHMRI fellows covers molecular and structural biology,
vaccine development, chemotherapy and entomology.

Predoctoral fellow, Katy Shaw Saliba, is studying the genetics and molecular mechanisms of Plasmodium falicparum gametocytogenesis, an essential component to malaria transmission.

Predoctoral Fellows                 Postdoctoral Fellows                 Visiting Scientists               


Armistead, Jennifer
Anidi, Ifeanyi

Das, Smita
Ferrer, Patricia

Gisselberg, Jolyn
Hain, Ulli
Jayabalasingham, Bamini
K
ent, Rebekah
Lagasse, Daniel
LeBlanc, Ralph
McLean, Kyle
Noland, Greg
Overstreet, Michael
Pike, Andrew
Pinchoff, Jessie

Radtke, Andrea
Ruben, Adam
Shaw, Katy
Spalding, Maroya
Tse, Eva
 


Bano, Nazneen
Bosch, Gundula

Brant, Gabriel
Cha, Sung-Jae
Chen, Yang
Chowdhury, Debabani
Cockburn, Ian
deFreitas, Renatos
Hughes, Grant
Kanzok, Stefan
Lu, Jeff Zhiqiang

Ma, Jinxia
Matthews, Krista
Mlambo, Godfree
Pavlovic-Djuranovic, Slavica 
Smith, Ryan
Souza-Neto, Jayme
Tripathi, Abhai
Voss, Christiane
Wang, Sibao

Xi, Zhiyong


 

Krairojananan, Panadda
Nyakundi, Ruth
Moreira, Luciano
Hawela, Moonga
Dhar, Ravi
Santosh Anand Sripada

 


PREDOCTORAL and POSTDOCTORAL FELLOWS
Sept 2003

Gregory Noland - Predoctoral
Host Response to Malaria and Helminth Co-Infection: Implications for Natural and Vaccine-Induced Immunity

Aims
1. Evaluate host response to malaria during intestinal helminth co-infection

2. Compare relative malaria transmission potential between trematode-co-infected and malaria-only-infected mice

3. Characterize immunologic basis of interactions between intestinal trematodes and malaria parasites

4. Evaluate protection conferred by two candidate malaria vaccines in helminth-infected mice


Sept 2004

Bamini Jayabalasingham-Predoctoral
Elucidating the Molecular Function of Plasmodium falciparum Sexual Stage-Specific Protein Pfg27

Aims
1. Identify proteins with which Pfg27 interacts during the process of gametocytogenesis

2. Characterize the nature of the interaction between Pfg27 and interacting protein(s)

3. Investigate the possible role of Pfg27 in translational regulation in P. falciparum 

 

Jeff Zhiqiang Lu - Postdoctoral
Structure and Inhibition Studies of Plasmodium falciparum KAS Enzymes

Aims
1. To investigate the mode of action of PfKASIII inhibitors using biochemical techniques

2. To study the activity of PkFASI/II and test thiolactomycin and the PfKASIII inhibitors for activity against this enzyme

3. To structurally characterize the atomic level interactions of novel KAS inhibitors with PfKASIII enzyme

 

Rebekah J. Kent-Predoctoral
Malaria Transmission in Macha, Zambia: Entomological Inoculation Rates of Anopheles arabiensis and Anopheles funestus S.S and Vectorial Capacity of An. arabiensis

Aims
1. Determine the relative importance of An. arabiensis and An. funestus to P. falciparum transmission in Macha by comparison of their entomological inoculation rates

2. Describe the blood feeding behavior of An. arabiensis in Macha

3. Estimate the efficiency of P. falciparum transmission by An. arabiensis 


 

Nazneen Bano-Postdoctoral
Identification of the Host Cellular Pathway/s and Parasite Transporter/s Involved in Host Cholesterol Trafficking to Intrahepatic Plasmodium

Aims
1.  Identification of the host cellular pathways mediating cholesterol delivery from host cell to intrahepatic parasites

2.  Functional analysis of the role Plasmodium ABCG1 transporter homologues in parasite cholesterol homeostasis

 

Adam Ruben-Predoctoral
Thermodynamic Characterization of Plasmepsin Family Inhibitors Adaptable against Multiple Targets

Aims
1.  Continue designing and screening potential inhibitors of Plm II

2.  Continue to determine the Ki of selected inhibitors against secondary targets Plm I and Plm IV

3.  Crystallize Plms in complex with selected inhibitors

4.  Based on the results of  Specific Aims 1-3, identify candidates for erythrocyte assays. Use the results of those assays to relate structural and thermodynamic properties with in vitro function

5.  Identify inhibitors to test in mouse and monkey models


January 2006

Stefan Kanzok-Postdoctoral
Genetic Analysis of Plasmodium falciparum Gametocyte Formation

Aims
1.  Gametocyte reporter strain

2.  Transposon-mediated mutagenesis 

March 2006

Michael Overstreet-Predoctoral
Crosstalk between CD4+ T cells and CD8+ T cells in Immunity to Malaria

Aims
1.  Examine crosstalk between transgenic CD4+ T cells and CD8+ T cells in response to irradiated sporozoites using an adoptive transfer model

2.  Examine CD8+ T cells behavior in response to peptide immunization in presence or absence of CD4+ T cell activation 

 

Debabani Chowdhury-Postdoctoral
Evaluation of B cell Responses against Plasmodium falciparum Transmission-blocking Vaccine Antigen (Pfs25) in Naive and Helminth-infected Mice

Aims
1.  To evaluate the efficacy of Pfs25 DNA vaccine in production of memory B cells and long-lasting plasma cell (LLPC) responses

2.  To characterize the effectiveness of Pfs25 DNA vaccine in generation of memory B cells and LLPC responses, when the host (mice) is pre-infected with the helminth Heligmosomoides polygyrus (Hp)

3.  To determine the formatin of germinal center (GC) in response to Pfs25 DNA vaccine in mice, which are uninfected or pre-infected with Hp

 

Zhiyong Xi-Postdoctoral
The role of Anopheles gambiae MD2-like Genes in Innate Immune Defense Against the Human Malaria Parasite

Aims
1.  Determination of expression patterns upon infection

2.  Determination of defense specificity

3.  Assessing immune pathway regulatory functions of AGMLs

4.  Assessing the interaction of AGMLs with plasmodium

April 2006

Ralph LeBlanc-Predoctoral
"Development of a Malaria Transmission-Blocking Mono-and Multivalent Vaccine (TBV) Based on Pfs230, Pfs48/45 and Pfs25

Aims
1. To determine the immunogenicity of selected antigens by ELISA, IFA and immunoprecipitation (I.P.)

2. To assess functional transmission-blocking activity (TBA) by gamete lysis and membrane feeding assay (MFA)

3. To evaluate combinations of pre- and post-fertilization antigens in a multiple-antigen vaccine

4. To evaluate natural boosting potential of immune responses primed by DNA plasmid vaccine


January 2007

Abhai Tripathi-Postdoctoral
Antigen Presentation Following Infection with Malaria Sporozoites

Aims
1.  Identification of dendritic cell subsets involved in presentation of sporozoite antigens to CD8+ T cells

2.  Examine the role of innate immune system components in the development of CD8+ T cell responses

Sept 2007

Maroya Spalding-Predoctoral
The Role of Lipoate Metabolism in P. falciparum Survival

Aims
1.  Investigate whether lipoate synthesis is essential in the apicoplast through conditional disruption of lipoylation in this organelle and to use lipoate-disrupted parasites to determine the relationship between lipoate synthesis and fatty acid synthesis

2.  To investigate whether lipoate scavenging is essential in the mitochondrion and the cytosol through conditional disruption of lipoylation, and if lipoate scavenging is essential in the cytosol, to identify the lipoylated protein(s) in this subcellular compartment


January 2008

Sung-Jae Cha-Postdoctoral

Aims
1.  Identification and characterization of sporozoite ligands for Kupffer cell invasion

2.  Identification and characterization of putative Kupffer cell receptors

3.  Identification and characterization of human orthologs of Kupffer cell invasion

 


Ian Cockburn-Postdoctoral

Aim
To identify the DCs that present sporozoite antigens to CD8 T cells and how the DC-T cell interactions are influenced by innate responses

November 2008

Gabriel Brandt-Postdoctoral
Plastid DNA Replication in P. falciparum

Aims
1.  Production of apicoplast replication proteins: Express and purify the apicoplast-targeted polyprotein Prex in its full-length form, along with its helicase, primase, helicase-primase and polymerase domains. Express and purify the putative apicoplast single-stranded DNA binding protein

2.  Begin reconstitution of plastid genomic replication in vitro: Examine, using mini-circle models of the replication fork, the ability of the helicase-primase and polymerase domains to replicate DNA. Determine the effect of helicase activity and single-stranded DNA binding proteins on polymerase activity

3.  Undertake structural studies of the apicoplast replication proteins: Purify and concentrate Prex helicase, primase, helicase/primase and polymerase domains. Screen for crystallization conditions using sparse matrix methods and liquid-handling robot. Undertake co-crystallization of polymerase domain with primer and template DNA oligomers


January 2009

Godfree Mlambo-Postdoctoral
Development of an Animal Model for Pre-clinical Evaluation of Plasmodium falciparum Transmission-blocking Vaccine (Pfs48/45) Using Transgenic P. berghei Parasites

Aims
1.  To make transgenic P. berghei parasites expressing the P. falciparum sexual antigen Pfs48/45

2.  To evaluate sera from non-human primates immunized with the Pfs48/45 vaccine

3.  To test whether natural infection with the transgenic parasite boosts antibodies to the antigen Pfs48/45

4.  To understand fertilization receptor functional conservation between P. berghei and P. falciparum

 

Jayme Souza-Neto-Postdoctoral
The Generation and Characterization of Immune Pathway Inducible Plasmodium Resistant Transgenic Mosquitoes

Aims
1.  Generate an inducible Rel2 construct for the generation of transgenic A. stephensi mosquitoes

2.  Characterize the dox-dependent rtTa-driven induction of the Rel2 factor

3.  Characterize the dox-induced Rel2 mediated resistance to Plasmodium infection at the ookinete stage

4.  Assess the impact of dox-mediated Rel2 activation on mosquito longevity and fecundity

 

Gundula Bosch-Postdoctoral
Structural and Functional of Iron-Sulfur Proteins in Isoprenoid Biosynthesis and Utilization in Plasmodium falciparum

Aims
1.  To produce and characterize the IspG, IspH and MiaB enzymes

2.  To reveal the active site architecture and catalytic mechanism of IspG, IspH and MiaB

Sept 2009

Ifeanyi Anidi-Predoctoral
Malaria and Lung Macrophages

Aims
1.  To definite the phenotypic and functional consequences that malaria infection has on the lung-derived macrophages

2.  To determine the role that lung macrophages play in the pathogenesis of pulmonary malaria


January 2010

Daniel Lagasse-Predoctoral
The role of lung macrophages in the control of malaria-induced pulmonary inflammation

Aims
1.  Dynamics of immune cell influx into the lungs upon malaria infection

2.  Selective depletion of lung macrophages

3.  Selective depletion of lung macrophages during P. berghei infection

4.  Adoptive transfer of macrophages into the lungs

 

Katy Shaw-Predoctoral
Genetic Analysis of Plasmodium falciparum Gametocytogenesis

Aims
1.  Transposon-mediated mutagenesis and screening for genes involved in gametocytogenesis

2.  Interesting genes identified by the mutagenesis screen

3.  Hypothesis about the function of Class I genes

 

Eva Tse-Predoctoral
Migration and Residency of Antigen Specific Memory CD8+ T cells in the Liver 

Aims
1.  To characterize the expression pattern of homing and adhesion molecules on antigen specific CD8+ T cells in the liver 

2. To investigate the functional role of selected homing and adhesion molecules of antigen specific CD8+ T cells in the liver

3. To investigate the proliferation, circulation and renewal properties of memory CD8+ T cells establishing residence in the liver Background and Significance: Our laboratory has demonstrated that the priming of antigen specific CD8+ T cells first occurs at skin

July 2010

Grant Hughes-Postdoctoral
Introduction of Wolbachia into Anopheles gambiae and Modulation of Plasmodium Vector Competence

Aims
1. Artificially trans-infect Anopheles gambiae with Wolbachia. Trans-infections will be performed with two strains of Wolbachia (wMelPop and wAlbB), which have been pre-adapted to Anopheles in cell culture

2. Characterize the novel Wolbachia-Anopheles association. Transmission rates, life-shortening and reproductive manipulations on the host will be assessed in the mosquito. Additionally, the distribution of Wolbachia within the mosquito will be characterized. Anopheles gene expression in response to Wolbachia infection will be analyzed in whole mosquitoes by microarrays

3. Determine Wolbachia-Plasmodium interactions. Wolbachia infected mosquitoes will be challenged with Plasmodium and development of the parasite analyzed to determine if Wolbachia interferes with parasite development and transmission


  
January 2011

Jinxia Ma-Postdoctoral
Development of efficient anti-malaria vaccines

Aims
1.  Analysis of susceptibility of parasite-infected hepatocytes to granzyme B

2. Identification of mechanisms of resistance to perforin

 

Jennifer Armistead-Predoctoral
Mechanism of action of a mosquito-based malaria transmission-blocking vaccine

Aims
1.  Characterize the APN1-ookinete molecular interaction

2.  Identify protective epitopes of the NT135APN1 fragment

 

Jolyn Gisselberg-Predoctoral
Iron Sulfur Cluster Synthesis in the Apicoplast of Plasmodium falciparum

Aims
1.  Determine the subcellular location and activity of Suf pathway proteins

2.  Probe the essentiality of the Suf pathway using reverse genetic approaches

 

Sibao Wang-Postdoctoral
Engineering symbiotic bacteria as a delivery system to block Plasmodium transmission by the mosquito

Aims
1.  Select for bacteria that are well adapted to the mosquito midgut and are vertically transmitted

2.  Engineer symbiotic bacteria to secret anti-malarial effector molecules

3.  Test blocking efficiency of effector molecules produced by the engineered bacteria

March 2011

 Slavica Pavlovic-Djuranovic-Postdoctoral
Biological comparison between chimpanzee Plasmodium reichenowi and human Plasmodium falciparum

Aims
1.  Developing in vitro culturing conditions for P. reichenowi in chimpanzee and human erythrocytes

2.  Cultivation of P. reichenowi gametocytes for mosquito infectivity studies

3.  Identify differences between P. falciparum and P. reichenowi using comparative transcriptional analysis

4.  Develop in vitro culturing conditions for P. falciparum isolated from bonobo chimpanzees


January 2012

Adelaide (Ulli) Hain-Predoctoral
Targeting Atg8 and its essential interactions in the malaria parasite

Aims
1.  Characterize Plasmodium Atg8's role in autophagy

2.  Identify novel functions of Atg8 in Plasmodium

3.  Develop specific inhibitors against Atg8 and its crucial interactions

 

Krista Matthews-Postdoctoral

Characterization of Plasmodium falciparum ELO3 in fatty acid elongation and its role in gametocytogenesis

Aims
1.  Determine the role of ELO3 and its protein domains in gametocytogenesis using reverse genetics

2.  Characterize the localization, elongase activity and substrate specificity of ELO3 class="Normal" 

August 2012

Christiane Voss-Postdoctoral

Aims
1.  Determine whether the membranous structures enveloping sporozoite organelles are functional autophagosomes

2.  Provide mechanistic insights into the specificity of the PbAtg8-conjugation system that is activated during sporozoite conversion

September 2012

Smita Das-Predoctoral
Mosquito bionomics and human malaria infection rates in Nchelenge, Zambia

Aims
1.  Identification and bionomics of malaria infected mosquito vector(s) in Nchelenge

2.  Measuring the crude entomological inoculation rate (EIR) of malaria in Nchelenge

3.  Measuring the human infection rate of malaria using rapid diagnostic testing (RDT) in Nchelenge

 

Patricia Ferrer-Predoctoral
 Iron and Exoerythrocytic malaria

Aims
1.  To compare and determine the effect of hepatocyte iron reduction by additional exogenous hepciding, Nramp2 RNAi and/or FBS0701 iron chelator to during in vitro malaria infection using calcein as a reporter

2.  To characterize the timing, dosing and duration of FBS0701 on oocyst production and intermediate stages in anemic and non-anemic mice

 

Kyle McLean-Predoctoral
Dissecting the role of PfMaf1 in the early stages of Plasmodium falciparum gametocytogenesis

Aims

1.  Validation of PfMaf1 as a phospho-regulated repressor of RNA polymerase III

2.  Determiantion of the role of PfMaf1 in teh hierarchical progression of gametocyte development

 

Renato deFreitas-Postdoctoral
Pharmacokinetic Optimization of Plasmepsin Inhibitors

Aims
1.  To identify the inhibitors with the most favorable cellular efficacy for further pharmacokinetic studies, including microsomal stability, permeability, bioavailability and toxicity

2.  To perform toxicity studies in mice and rats and to perform efficacy studies in humanized mice model that can be infected by P. falciparum  

3.  To use animal results to build a QSAR model in order to find a correlation between the structure, pharmacokinetic and efficacy parameters of the inhibitors

4.  Application of the QSAR models to design new compounds with better efficacy in animals and potentially in humans

5.  To generate the appropriate data to begin a Phase 0 study in humans

 

Andrea Radtke-Predoctoral
The induction of protective CD8+ T cells against Plasmodium liver stages

Aims
1.  To determine the role of skin and lymph node resident DCs in the induction of protective CD8+ T cell responses

2.  To characterize the location and kinetics of CD8+ T cell priming in skin-draining lymph nodes

3.  To investigate the innate immune signaling pathways required for inducing protective CD8+ T cell responses


January 2013

Yang Chen-Postdoctoral
IMD-pathway engineered Anopheles mosquito fighting against Plasmodium

Aims
1.  Generate transgenic mosquitoes which could inducibly transcribe dsRNAs targeting Caspar and CAudal mRNAs

2.  Test the anti-Plasmodium effect of the transgenic mosquitoes

3.  Compare the gene expression profile differences between transgenic lines

4. Compare fitness cost between transgenic mosquito lines

 

Andrew Pike-Predoctoral
The effects of transgenesis on various P. falciparum resistant Anopheles stephensi mosquito lines

Aims
1.  To identify the effects of transgenesis on A. stephensi fitness

2.  Global transcriptome characterization of transgenic mosquitoes

 

Jessie Pinchoff-Predoctoral
Malaria prevention strategies and prospects for elimination: Variation in insecticide-treated net (ITN) effectiveness and use in rural Zambia

Aims
1.  Compare individual and household level factors that influence ITN use in Choma and Nchelenge districts

2. Compare the spatial distribution of environmental features influencing ITN use in Choma and Nchelenge districts

3. Determine spatio-temporal trends in ITN use in Macha, Zambia

April 2013

Ryan Smith-Postdoctoral
Characterization of athe mosquito late-phase immune response

Aims
1.  Investigate LL3 expression and cellular distribution in mosuito hemocytes

2. Determine the relationship of LL3 with known mediators of late-phase immunity

3.  Identify cellular/humoral immune components regulated by the expression of LL3



 
VISITING SCIENTISTS
2003

Ravi Dhar, PhD
Dr. Dhar is a scientist with the National Institute of Immunology, New Delhi, India. He spent five months in the laboratory of Nirbhay Kumar, learning advanced molecular techniques for genotype analysis of Plasmodium falciparum in India. With the knowledge he gained during his fellowship, he will study parasite diversity in severe and non-severe infections in Indian patients, apply this information to the study of responses to antimalarial drugs and build bridges for future collaboration with JHMRI investigators.

2006

Moonga Hawela, Msc
Mr. Hawela is a Biomedical Scientist and Acting Chief Parasitologist with the National Malaria Control Centre in Zambia.  He spent three months in the laboratory of Dr. David Sullivan where he mastered the techniques of extraction of parasite DNA, amplification of MSP2 for P. falciparum, trained to use MSP2 primers and received extensive training in performance of electrophoresis and reading of gels.    

2007

Luciano Moreira, PhD
Dr. Moreira is an Associate Researcher with the Malaria Laboratory of Centro de Pesquisas Rene Rachou/FIOCRUZ, Brazil.  He spent 1 month in the laboratory of Dr. Marcelo Jacobs-Lorena learning Plasmodium falciparum culture and mosquito transmission techniques. 

2008

Ruth Nyakundi, Msc
Ms. Nyakundi is an Assistant Research Scientist with the Department of Tropical and Infectious Diseases, Institute of Primate Research in Nairobi, Kenya.  She spent 3 months in the laboratory of Dr. Nirbhay Kumar, to gain expertise in P. falciparum culture and mosquito transmission methods to introduce her and her institution to new technology and new techniques. 

2009

Panadda Krairojananan, MS
Ms. Krairojanan is a PhD candidate and Assistant Chief with the Molecular Biology Section, Department of Entomology for the Armed Forces Research Institute of Medical Sciences in Bangkok, Thailand.  She spent 3 months in the laboratory of Dr. Rhoel Dinglasan studying the molecular mechanisms of Plasmodium-mosquito interactions.  The experiences she gained not only benefited her but her Institution in molecular techniques as much of these techniques were not available at the Mahidol University and AFRIMS.

2011

Santosh Anand Sripada, PhD
Dr. Sripada is a PhD student at the University of Hyderabad, Department of Biotechnology, School of Life Sciences in India. Spent 3 months in the laboratory of Dr. Isabelle Coppens studying the liver stages of Plasmodium understanding the hepatocyte-sporozoite interactions and developing novel therapeutic interventions. 

 

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