Jorge Galán, PhD, DVM

Microbial pathogens have evolved unique ways to interact with their hosts. In many instances the terms of this interaction reflect the co-evolutionary balance that the host and pathogen must reach in order to secure
their survival. It is therefore not surprising that bacterial pathogens have evolved a large array of virulence
factors well suited to interfere with or stimulate a variety of host-cell responses in order to invade, survive and replicate within their hosts. The identification and characterization of these virulence factors is proving to be a fruitful area of research in more ways than expected.

The understanding of how pathogens interact with their hosts is not only providing the basis for the development of novel therapeutic approaches but also a number of very sophisticated tools for probing basic aspects of cellular physiology and immunology. Our laboratory studies the pathogenesis of two intestinal pathogens, Salmonella enterica and Campylobacter jejuni. Combined, these two pathogens account for the vast majority of cases of infectious diarrhea world-wide leading to an estimated 2,000,000 deads. We are interested in characterizing the bacterial determinants involved in these interactions as well as the cell biology and immunobiology of this process.

We take a multidisciplinary approach in our studies involving bacterial genetics, biochemistry, cell biology, immunology as well as structural biology. As a result, we are beginning to define not only the molecular details of the host pathogen interactions but also the atomic interphase between these pathogens and the host. Our laboratory has also an interest in vaccine development that stems from our discovery of a specialized organelle in Salmonella enterica (the “type III secretion system”) that mediates the transfer of bacterial proteins into host cells. We have harnessed this system for the delivery of heterologous proteins as a means to delivery antigens to the Class I and Class II antigen presenting pathways by avirulent strains of Salmonella.

Specific areas of interest include:

• The study of type III protein secretion machines, specialized bacterial organelles whose function is to delivery bacterial proteins into eukaryotic host cells. We are interested in understanding the mechanism of action of this multi-protein machine, as well as to understand the activities of the effector proteins delivered by this machine. We carried out these studies in Salmonella enterica but it is expected that knowledge gained from these studies may help understand the pathogenesis of many other bacteria since this system is conserved and widespread among several important pathogens.
• The harnessing of the protein-delivery capability of the type III secretion machine for the development of therapeutic approaches, including vaccines.
• The development of strategies that target the activities of type III secretion systems with the ultimate goal of developing new therapeutics to combat diseases caused by pathogens that encode these protein-delivery machines.
• The study the mechanism of pathogenesis of Salmonella typhi, which causes typhoid fever in humans, a life-threatening disease that causes more than 200,000 deaths world-wide. We focus our efforts on the study of "typhoid toxin", a toxin exclusively produced by Salmonella typhi that we recently identified and it is central for the pathogenesis of typhoid fever.
• The study of the mechanisms by which Campylobacter jejuni is able to colonize the gut and the role of the intestinal microbiota in both, facilitating and preventing colonization.
• The investigation of the in vivo metabolism of C. jejuni. We are specifically interested in identifying its carbon sources and respiration substrates during infection and the contribution of the intestinal microbiota in providing those nutrients.