David W. (Ted) Hackstadt, Ph.D.
Chief, Host-Parasite Interactions Section
Senior Investigator
Host-Parasite Interactions Section
Dr. Hackstadt received his Ph.D. from Washington State University. His postdoctoral work was in the Laboratory of Microbial Structure and Function at the Rocky Mountain Laboratories. Dr. Hackstadt left the Rocky Mountain Laboratories for an associate professorship in the Departments of Pathology and Microbiology at the University of Texas Medical School in Galveston. He returned to the Laboratory of Intracellular Parasites at the Rocky Mountain Laboratories in 1990 where he was appointed chief of the Host-Parasite Interactions Section and awarded tenure in 1995. He serves as an associate editor of the journal Traffic and is on the editorial board of Cellular Microbiology.
Description of Research Program
The Host-Parasite Interactions Section studies the basic molecular and cellular biology of chlamydiae and other obligate intracellular parasites. Chlamydia trachomatis is the etiological agent of several significant diseases of humans, including trachoma, the leading cause of infectious blindness worldwide. It is also the most common cause of sexually transmitted disease in the United States.
Chlamydiae are obligate intracellular bacteria with a biphasic developmental cycle that involves cell types adapted for extracellular survival and intracellular multiplication. This developmental cycle consists of an environmentally stable cell form, termed the elementary body (EB), and a functionally and morphologically distinct vegetative cell type, termed the reticulate body (RB). Chlamydiae undergo their developmental cycle entirely within a parasitophorous vacuole, termed an inclusion, that is isolated from established routes of endocytic vesicle trafficking. Whereas the majority of intracellular parasites are thought to block maturation of the endocytic vesicle to a lysosome, chlamydiae rapidly dissociate themselves from this pathway and establish a functional interaction with an exocytic pathway that delivers sphingolipids and cholesterol from the Golgi apparatus to the plasma membrane. Interaction with this secretory pathway is thought to constitute a novel pathogenic mechanism whereby chlamydiae establish themselves in a site not destined to fuse with lysosomes.
Understanding the initial events in chlamydial differentiation, including the transition in properties of the endocytic vesicle to one which intersects an exocytic pathway, remains a significant challenge in deciphering the pathogenic mechanisms of chlamydiae. A number of scientific approaches are integrated in studies of early differentiation and subversion of host functions. These include global regulation of chlamydial gene expression via histone-like proteins, vesicular trafficking, cytoskeletal interactions, cell signaling, chlamydial modification of the inclusion membrane, and interactions mediated by Type III secreted protein effectors, which control entry and subsequent events.
Research Group Members
Pictured left to right: Mort Peacock, Janet Sager, Travis Jewett, Betsy Kleba, Dave Mead, Lisa Moore, Damon Ellison, Tina Clark, Ted Hackstadt, Jeff Mital, Cheryl Dooley, and Wendy Jamison
Selected Publications
(View list in PubMed.)
Ellison DW, Clark TR, Sturdevant DE, Virtaneva K, Porcella SF, Hackstadt T. Genomic comparison of virulent Rickettsia rickettsii Sheila Smith and avirulent Rickettsia rickettsii Iowa. Infect Immun. 2008 Feb;76(2):542-50.
Carabeo RA, Dooley CA, Grieshaber SS, Hackstadt T. Rac interacts with Abi-1 and WAVE2 to promote an Arp2/3-dependent actin recruitment during chlamydial invasion. Cell Microbiol. 2007 Sep;9(9):2278-88.
Jewett TJ, Fischer ER, Mead DJ, Hackstadt T. Chlamydial TARP is a bacterial nucleator of actin. Proc Natl Acad Sci U S A. 2006 Oct 17;103(42):15599-604.
Grieshaber NA, Grieshaber SS, Fischer ER, Hackstadt T. A small RNA inhibits translation of the histone-like protein Hc1 in Chlamydia trachomatis. Mol Microbiol. 2006 Jan;59(2):541-50.
Dautry-Varsat A, Subtil A, Hackstadt T. Recent insights into the mechanisms of Chlamydia entry. Cell Microbiol. 2005 Dec;7(12):1714-22. Review.
Clifton DR, Fields KA, Grieshaber SS, Dooley CA, Fischer ER, Mead DJ, Carabeo RA, Hackstadt T. A chlamydial type III translocated protein is tyrosine-phosphorylated at the site of entry and associated with recruitment of actin. Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):10166-71.
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