Global Heath Research Faculty
Mosquito vectors of Dengue and West Nile viruses
My research interests center on understanding mechanisms of phenotypic evolution in natural populations. I am particularly interested in investigating how interactions between ecological forces and genetic mechanisms lead to evolutionary change. My approach to these broad questions is necessarily integrative, and utilizes field ecology, quantitative and population genetics, and molecular biology. I have chosen to focus on container-breeding mosquitoes as a model because these mosquitoes represent highly tractable experimental systems.
Modeling of the spread and distribution of infectious disease
We research and develop quantitative tools such as network theory to predict the spread and distribution of infectious diseases in human and livestock populations. We are particularly interested in the impact of specific population structures on the consequences of disease spread, the design of effective and practical intervention strategies, the evolution that results from the interaction between host populations and pathogens, and the effect of this interaction on the epidemiology of the disease. Some of the systems we study are influenza in humans, and foot-and-mouth disease in livestock.
Pathogenesis of Staphylococcus aureus
Low G+C Gram-positive bacteria, including Staphylococcus aureus, are metabolically versatile and can interact with hosts in diverse ways. They can reside in and on our bodies in a commensal state or can cause life-threatening infections. Genetic switches, controlled in part by transcription factors that bind key intracellular metabolites, govern the reconfiguration of physiology that mediates the shift between commensal and pathogenic lifestyles. Despite observations that the expression of virulence genes often correlates with the exhaustion of available nutrients, there is limited knowledge about how the signaling of nutrient status and the resulting physiological responses are coordinated.
We are studying the integrated regulation of metabolism and pathogenesis in S. aureus, an important hospital- and community-acquired infectious disease agent responsible for significant morbidity and mortality. We are currently examining in depth the role of the global regulatory protein CodY in altering the activities of multiple metabolic pathways when faced with changing levels of nutrient depletion, and how this response is coupled to the production of virulence factors. A deeper understanding of cellular mechanisms underlying bacterial disease will reveal new ways to prevent the switch from harmless to harmful lifestyles that lead to potentially life-threatening infections.
Cell Biology and Behavior of the Parasite Giardia lambda
Giardia lamblia is one of the most prevalent intestinal protozoan pathogens worldwide. In the U.S., infections are most common among campers and children in daycare centers. After ingestion of the infective cyst stage by the host, the parasite differentiates in the lumen of the small intestine and its presence often results in severe gastrointestinal symptoms, including diarrhea, vomiting and weight loss. In addition to its medical importance, Giardia is also a representative of one of the earliest diverging eukaryotic lineages. Our laboratory focuses on two main questions: transcriptional regulation and cytoskeleton control of swimming and attachment behavior.
Filamentation in Candida albicans
Research in my laboratory is focused on elucidating the mechanisms that yeast cells use to sense external conditions – such as nutrient abundance and host status – and how they alter gene expression in response to these conditions. We are investigating how filamentation is controlled at the genetic level in C. albicans with a focus on the homeodomain-containing transcription factor Grf10. The ability of this fungus to form hyphae and pseudohyphae is linked to virulence.
Protein Trafficking and Ion Homeostasis
The Rosenwald laboratory investigates a number of different aspects of life at the microbial level, including membrane traffic, cell wall biosynthesis, and ion homeostasis in Saccharomyces cerevisiae (Baker’s yeast) and its close but pathogenic relative Candida glabrata. We use approaches that combine classical techniques of biochemistry, cell biology, and genetics, but more recently have also included bioinformatics and genomics in our arsenal of tools.
Immune responses to Giardia lamblia
My research all centers on the protozoan parasite Giardia lamblia. Giardia replicates in the small intestines of many species of mammals and is a major cause of human diarrheal disease throughout the world. In the U.S. Giardia infections are mainly found in campers and hikers who forgot to treat their water as well as in daycare and nursing home situations. My research area focuses on the host’s immune response to the parasite. While both humans and mice produce a strong antibody response during infections with Giardia, we have recently shown that antibodies are not required to control acute infections with this parasite. Instead, CD4+ T cells and the cytokine interleukin-6 (IL-6) are absolutely required. We are interested in determining which cells produce IL-6 during Giardia infections and in determining which cells the IL-6 acts upon and how this leads to resolution of the infection.