George Dimopoulos

I have studied the molecular biology of the Anopheles / Plasmodium transmission system since 1991. These are exciting times since we now have the experimental capability to functionally analyze almost every single mosquito gene and protein. The group's research focus has evolved over the past years to encompass two unique infection systems, Anopheles - Plasmodium and Aedes - dengue, and  we are specifically interested in understanding how the mosquito's innate immune system and intestinal microflora can compromise transmission of human pathogens. VIDEO PRESENTATION. Contact: gdimopou@jhsph.edu

Bio - research - THE PAPERLESS PROFESSOR

Bio:
I joined the Johns Hopkins School of Public Health, Department of Molecular Microbiology and Immunology, Malaria Research Institute in August 2003 after spending two years as a Senior Lecturer at Imperial College London, Biological Sciences Department and Centre for Molecular Microbiology & Infection. I pursued my first research project on the medicinal herb Dictamnus creticus while studying eco-technology at Mid Sweden University in the eighties. My interest in pursuing a research career was stimulated while working on my B.Sc. diploma thesis research in Prof. Uno Lindberg’s group at Stockholm University in the spring of 1991. My graduate research initiated in the fall of 1991 at the Institute of Molecular Biology and Biotechnology at the University of Crete where I pursued my Ph.D. in Prof. Kitsos Louis group working on Anopheles gambiae molecular population biology and tissue specific gene expression. I spent a significant period of my graduate studies in Dr. Fotis Kafatos lab at Harvard University, Department of Molecular and Cellular Biology where I developed a RADP (Random Amplified Polymorphic DNA) -based cytogenetic map for A. gambiae and identified several sex and tissue specific mosquito genes through differential display mRNA analyses. After a mandatory “brake” in the Greek Army as a microbiology assistant, I joined Dr. Kafatos’ group at the EMBL (European Molecular Biology Laboratory) in Heidelberg as a postdoctoral Marie Curie Fellow in 1996. At EMBL, I focused my research on mosquito immunity and studied the Plasmodium infection responsive patterns of several novel immune genes. As a postdoctoral fellow I also collaborated extensively with Prof. Jules Hoffmann’s group in Strasbourg on the discovery and characterization of mosquito antimicrobial peptides and Prof. Robert Sinden’s group in London on the characterization of novel Plasmodium mutants. Together with colleagues at EMBL I developed the first A. gambiae EST repertoire and spotted cDNA microarrays that have been extensively used for transcriptomic analysis of mosquito infection responses. I was recruited as a Senior Lecturer by Imperial College London in 2001 and that’s where I started my independent research. I decided to join the Johns Hopkins University, Bloomberg School of Public Health, Department of Molecular Microbiology and Immunology in August 2003 because of the establishment of the Malaria Research Institute that provided unique opportunities for malaria research, and also because of the unbearably high cost of living in London.

                             
Current research:
My group’s ongoing and future research program broadly focuses on the innate immune systems and midgut microbiomes of mosquito disease vectors, and comprises several independent but synergistically interacting projects. We are interested in understanding the role and mechanisms of the mosquito’s innate immune system in the defense against human pathogens such as Plasmodium and the Dengue virus. A major focus is concentrated on the mosquito IMD pathway –regulated anti-Plasmodium defense system that is activate in killing malaria parasite in the major malaria vectors A, gambiae, A. stephensi and A. albimanus. We have generated the first genetically modified super-immune mosquitoes that turn on this defense system earlier and stronger, thereby resulting in resistance to parasite infection. We are currently studying the genes and molecules, and dissecting the mechanisms that are implicated in parasite killing using a combination of genetic, proteomic and biochemical analyses. We have characterized several immune genes that are part of by the transgene-activated anti-parasitic immune response and used those to identify novel proteins that that are part of complexes and mechanisms which kill Plasmodium in the mosquito intestine. We are also studying the impact of these transgene –regulated immune responses on mosquito fitness, to fine-tune the immune activation and make sure that the genetically modified resistance trait can be spread in natural malaria-transmitting mosquito populations. Towards this, we are also studying additional factors of the IMD pathway that can be used to create genetically modified super-immune mosquito phenotypes.


Another major interest of my research group is the study of the mosquito midgut microflora and how it can directly and indirectly influence the ability of
the mosquito to transmit human pathogens. We have shown that the intestinal microflora stimulates a basal immune activity that, in turn, is acting against parasite (Plasmodium falciparum) and viral (Dengue virus) pathogens in the mosquito gut. We have also identified bacteria of the natural midgut flora that exert direct anti-pathogen activities, through either the production of reactive oxygen species or secondary metabolites. We are currently assessing the feasibility of using such bacteria, of the mosquito’s intestinal microflora, to develop environmentally friendly and logistically simple malaria and dengue control strategies. Towards this goal, we are using a trans-organismal systems biology approach that involves the elucidation of the tripartite reciprocal interactions that take place between the bacteria, pathogens and mosquito. We are also developing methods by which these pathogen inhibiting bacteria can be exposed to, and introduced into the mosquito. Our research on specific mosquito intestinal bacteria has also led to the discovery of secondary metabolite extracts with highly potent anti-pathogen activity, that may have a potential for the development of therapeutic drugs for humans.


Our research activities spans from the
field to the bench, across several mosquito vector species and pathogens, but is at the same time highly focused on specific biological processes of vector-pathogen-microbiota interactions. Over the past 8 years at the Johns Hopkins University we have contributed with several pioneering discoveries and have maintained a leading position in the development of mosquito vector functional genomics tools, as we designed and produced the first whole-genome glass slide oligonucleotide microarrays for A. gambiae, Aedes aegypti, Culex pipiens and Anopheles stephensi. Our mission is to characterize and understand the molecular mechanisms that are implicated in restricting infections of mosquito vectors with human pathogens, and assess the suitability of these discoveries for the development of novel disease control strategies. Our competitive advantage derives from a unique blend of core competencies in molecular entomology, innate immunity and functional genomics, as well as the access to state-of-the-art research infrastructure. The long-term goal of our research program is to broaden the basic knowledge of this field and provide new weapons for the war against vector-borne diseases.

 

Recent & Current Collaborators: Dr. Roberto Barrera (CDC, Puerto Rico), Dr. Bruce Christensen (University of Wisconsin), Dr. George Christophides (Imperial College London), Dr. Mariano Garcia-Blanco (Duke University), Dr. Marc Muskavitch (Boston College), Dr. Clara Ocampo (CIDEIM, Cali, Colombia), Dr. Pedro Oliviera (Universidade Federal do Rio de Janeiro, Brasil), Dr. Alexander Raikhel (University of California, Riverside), Dr. Claudia Romero (Universidad del Norte, Barranquilla, Colombia), Dr. Mike Strand (University of Georgia), Dr. Marcos Sorgine (Universidade Federal do Rio de Janeiro, Brasil), Dr. Giuliano Gasperi and Dr. Ludvik Gumulski (University of Pavia, Italy), Dr. Juan Pascale (Gorgas Institute, Panama). Dr. Andy Waters (University of Glasgow, UK)

The group and its members have received funding from: National Institutes of Health, National Science Foundation, Ellison Medical Foundation, American Society of Microbiology, A STAR, Johns Hopkins School of Public Health, Lang Family, Bloomberg Family Foundation.

I am also directing the JHMRI Parasitology Core Facility which supports a variety of projects that focus on the parasite’s interactions with the mosquito vector and human host, and other biological processes that are relevant for its capacity to transmit and infect. The Parasitology Core Facility provides Plasmodium falciparum asexual blood- and gametocyte-stage cultures, and both human and rodent Plasmodium sporozoite stages. Specialized services are also provided upon request.

 

In 2008 I completed my MBA with concentration in Management & Leadership to better lead the group in today’s highly competitive environment. As a consequence I also give a graduate course on the “Business of Academic Biomedical Research”.


JHSPH Faculty Page
JHMRI PI Page
Current CV (October 2011)



The Paperless Professor::
My productivity has to a significant extent benefitted from optimizing and streamlining my office work by going paperless. I am in fact close to 100% paperless and do all my work tasks electronically. Johns Hopkins School of Public Health has highlighted my office as the "greenest" at:

                    http://www.jhsph.edu/green/paperless_prof.html

               

T
hose who would like to learn more about this new and effective paperless business- and life-style may find my book "Paperless Joy" useful and interesting, at: