David S. Roos
Merriam Professor of Biology,
Depts of Biology, Microbiology, Pathobiology, and Bioengineering
Director, Penn Genomics Institute

Microbiology, Virology and Parasitology Program

Address

304B Lynch Laboratories(Office)
Lynch Laboratories (Lab)
433 South University Ave
Philadelphia PA 19104

Office tel.: 215-898-2118/573-6299
Lab tel.: 215-898-2120 /898-1205
Fax: 215-746-6697
E-mail: droos@sas.upenn.edu

Link(s)

Dr. Roos' Biology faculty page
Dr. Roos' Lab

Education

Harvard University: AB, magna cum laude (Biological Sciences), 1979.

The Rockefeller University: PhD (Virology/Cell Biology), 1984.

Stanford University: Postdoc (Molecular Genetics), 1988.

Research Interests

• Molecular parasitology, host-pathogen interactions.
• Drug targets & resistance mechanisms.
• Evolution of eukaryotic cells & organellar function.
• Genome databases & database mining.
• Comparative genomics, computational biology.
• Toxoplasma gondii, Plasmodium falciparum.

Key words: Molecular parasitology, drug resistance, organellar targeting, eukaryotic evolution, pathogen genomics, database mining, computational biology, Toxoplasma, Plasmodium, malaria.

Search PubMed for articles

Description of Research

Studies in the Roos laboratory employ a variety of modern techniques in cell biology, molecular genetics, biochemistry, and genomics to study protozoan parasites, eukaryotic evolution, and host-pathogen interactions.

Our primary focus is on the phylum Apicomplexa, a group of protozoan parasites that typically replicate within specialized vacuoles inside the cells of infected animals. Plasmodium parasites cause malaria, afflicting hundreds of millions of people each year and killing millions of children, primarily in sub-Saharan Africa. Toxoplasma gondii is even more widespread, chronically infecting ~30% of the US population; this parasite is a leading source of congenital neurological birth defects in humans and farm animals, a prominent opportunistic infection associated with immunosuppressive treatments and diseases (including AIDS), and a waterborne pathogen of some concern from a biodefense standpoint.

By virtue of its evolutionary position, molecular genetic accessibility, and subcellular architecture, T. gondii has proved useful for studying central features of eukaryotic biology, and attributes specific to apicomplexan parasites. The availability of effectively complete genome sequences for several apicomplexan parasite species also opens up new realms to experimental analysis, both at the laboratory bench, and at the computer.

Ongoing projects focus on:

• Genetic analysis of parasite biology -- exploiting the genetic accessibility of T. gondii to study such phenomena as drug resistance mechanisms, parasite differentiation, and immune effector molecules.
  
• Drug targets and biochemical mechanisms of resistance -- focusing on nucleoside metabolic pathways, and elucidating function(s) of the apicoplast, a distinctive organelle acquired by horizontal transfer from an ancestral plant/alga.
  
• Evolution and function of eukaryotic organelles -- including the apicomplexan plastid (see above), secretory pathway organelles, and cytoskeletal mechanisms involved in the assembly of Plasmodium and Toxoplasma cells.
  
• Computational biology -- including the sequencing, analysis, and comparison of (pathogen) genomes, designing and mining of genome databases, and development of computational tools and algorithms for the analysis and integration of genomic-scale datasets.

Recent Publications

Foth BJ et al. Dissecting apicoplast targeting in the malaria parasite Plasmodium falciparum. Science 299:705-8 (2003).

Li L, CJ Stoeckert Jr & DS Roos. OrthoMCL: Identification of ortholog groups for eukaryotic genomes. Genome Res 13:2178-90 (2003).

Ralph SA et al. Metabolic pathway maps and functions of the Plasmodium falciparum apicoplast. Nature Rev Microbiol 2:203-16 (2004).

Harb OS et al. Multiple functionally redundant signals mediate targeting to the apicoplast in the apicomplexan parasite Toxoplasma gondii. Eukaryotic Cell 3:663-74 (2004).

Chaudhary K et al. Purine salvage pathways in the apicomplexan parasite Toxoplasma gondii. J Biol Chem 279:31221-7 (2004).

McKee AS et al. Functional inactivation of immature dendritic cells by the intracellular parasite Toxoplasma gondii. J Immunol 173:2632-40 (2004).

Dzierszinski, F, M Nishi, L Ouko & DS Roos. Dynamics of T. gondii differentiation. Eukaryotic Cell 3:992-1003 (2004).

Hu, K, DS Roos, SO Angel & JM Murray. Variability and heritability of cell division pathways in Toxoplasma gondii. J Cell Sci 117:5697-5705 (2004).

Lab

Rotation Projects

• Comparative genomics of apicomplexan parasites and eukaryotic evolution.
• Mutant screens to identify pathogen genes affecting immune signalling.
• Characterization of a potential regulator of bradyzoite differentiation.
• Protein processing and organellar targeting in Toxoplasma gondii and Plasmodium falciparum.

Lab personnel:

Post-docs:

Daniel Beiting (PhD, Cornell).  Host-pathogen relationship in Apicomplexa.

Anat Caspi (PhD, UC Berkeley ). The population genetics of apicomplexan parasites (Plasmodium and Toxoplasma)

Paul Davis (PhD, Washington University School of Medicine).  Host-pathogen interactions and molecular virulence.

Omar Harb (PhD, Univ Kentucky). Exploring organellar targeting signals and the cell biology of parasite replication, in both Toxoplasma and Plasmodium.

Viviana Pszenny (PhD, University of Buenos Aires).  Identification  of genes involved in bradyzoite differentiation and parasite virulence.

Dhanasekaran Shanmugam (PhD, Indian Inst Science, Bangalore). Biochemistry of the apicoplast and mitochondrion; identification and validation of drug targets.

Students:

Amit Bahl (Genomics & Computational Biology). Design and construction of T. gondii microarrays; expression profiling throughout the parasite life cycle.

Feng Chen (Chemistry). Computational methods for the identification and automated annotation of orthologs in eukaryotic taxa.

Zhongqiang Chen (Genomics & Computational Biology). Integrated computational and experimental definition of organellar targeting signals.

Beth Gregg (MVP). Toxoplasma gondii—Intestinal Mucosa Interactions and antigen presentation.

Natalie Miller (DVM/PhD rotation student). In vivo imaging of Toxoplasma infection.

Lucia Peixoto (Biology). Biology and Pathogenesis of Apicomplexa Parasites through Phylogenomic approach.

Greg Peterfreund (MD/PhD rotation student). 

Laurel Redding (VMD/PhD rotation student).

Tomoyo Saito (visiting student, from Tokyo University). Biochemistry and subcellular localization of pyruvate kinase in Toxoplasma gondii.

Staff:

Brian Brunk, Sr. Manager, Apicomplexan Genome Database

Tamika Seals, Lab Manager & Research Specialist: Tissue Culture.

Bindu Gajria. Project Manager, the Plasmodium Genome Database.

Mariann Winkelman, Coordinator and Assistant to Dr. Roos