Pathobiology | Investigators/Teams
Guojun Bu, Ph.D., Unit Leader
Our laboratory is interested in studying biogenesis, intracellular trafficking and biological functions of members of the low-density lipoprotein (LDL) receptor family. Our studies have been focused primarily on a large endocytic receptor, the LDL receptor-related protein (LRP), which binds over 30 ligands. We are particularly interested in how LRP plays a role in the pathogenesis of Alzheimer's disease. We are also studying another large member of the family, called LRP1B, which was discovered as a putative tumor suppressor and exhibits the slowest endocytosis rate.
F. Sessions Cole, M.D.
Our laboratory hopes to elucidate the genetic basis of lung disease in newborns. Our studies focus on analysis of polymorphisms in a critical lung protein, surfactant protein B, in causing respiratory difficulty in both term and preterm newborns.
Allan Doctor, M.D.
Our research program is focused upon the novel role of erythrocyte based signaling in matching regional blood flow to metabolic need. The RBC transport portfolio is newly appreciated to include 3 gases (O2, CO2, NO), and RBCs appear to serve as vascular control elements by exerting O2 - responsive control over the bioavailability of vasoactive effectors in plasma. My lab explores the biochemical and molecular events critical to this process.
Thomas Ferkol, M.D.
The respiratory epithelium is the first line of defense in the lung, and it is constantly exposed to innumerable inhaled pathogens, aeroallergens and other noxious agents. Innate host defenses have evolved to prevent acute pulmonary injury, relying on complex interactions that occur between effector cells present in the respiratory tract. Research in our laboratory has focused on developing cell and animal models to study pulmonary inflammation characteristic of cystic fibrosis, and developing novel therapies to better treat the pulmonary manifestations of this disorder.
Anthony R. French, M.D., Ph.D.
Our laboratory is focused on elucidating the in vivo responses of natural killer (NK) cells during viral infections as well as on characterizing the evasion of these responses by large DNA viruses such as murine cytomegalovirus (MCMV), HSV-1, and vaccinia. We are particularly interested in understanding the factors driving and controlling NK cell proliferation and expansion during viral infection as well as the subsequent homeostasis of NK cells following resolution of the infection.
Aaron Hamvas, M.D.
David B. Haslam, M.D.
Our laboratory is investigating how bacterial toxins damage human cells. In particular, we are investigating the mechanisms by which some toxins transit the endoplasmic reticulum (ER) on their way to the host cell cytoplasm. Most of our studies are focused on shiga toxin, the agent responsible for hemolytic-uremic syndrome in children. In these studies, we identified a novel ER-localized chaperone, and are investigating its role both in toxin trafficking and normal cell biology. We are also studying the biology of Clostridium difficile toxins.
Keith A. Hruska, M.D.
Our laboratory studies mechanisms of chronic kidney disease progression and its complications. We have discovered that the critical renal morphogen, bone morphogenetic protein (BMP)-7, is expressed in the adult kidney and reduced by renal injuries. Moreover, BMP-7 exhibits therapeutic potential against renal fibrogenesis and diabetic nephropathy. Other members of the bone morphogenetic protein family differentially affect lineage allocation of mesenchymal stem cells. Our studies in basic bone cell biology are focused on the role of these proteins in lineage commitment of mesenchymal stem cells and novel mechanisms of osteoclast cytoskeletal regulation.
David A. Hunstad, M.D.
We utilize tissue culture systems and the murine cystitis model to study questions in bacterial pathogenesis. First, we are investigating how Gram-negative bacteria, in particular uropathogenic Escherichia coli, modulate host immune responses during infection. Second, we are studying the functions of the conserved periplasmic chaperone SurA in virulence, aiming to target this protein with anti-infective strategies. In addition, we are leveraging recent knowledge about uropathogenesis to develop nanoparticle-based targeted therapies for urinary tract infection. Finally, we participate in collaborative, translational studies of community-acquired Staphylococcus aureus infections in children.
Alan L. Schwartz, Ph.D., M.D.
Our laboratory focuses on the cellular and molecular biology of intracellular protein targeting and degradation. Specifically, we have defined two areas of concentration that are closely integrated. First, we study the molecular mechanisms of protein processing and degradation within the endosomal/lysosomal pathway and in the cytoplasm. Second, we continue to evaluate the cell and molecular biology of receptor-mediated endocytosis and its regulation.
Phillip I. Tarr, M.D., Unit Leader
Our laboratory is focused on several projects related to the human intestinal microbiota. First, we maintain a surveillance network in the Pacific Northwest, where we identify children who are infected with Escherichia coli O157:H7, and study the progression of their illness into the hemolytic uremic syndrome (HUS), or to spontaneous resolution. Second, we are determining the etiology of unexplained diarrhea in urban and rural populations in the Pacific Northwest in a unique case-control study. Third, we are attempting to determine the risk factors for acquisition of reportable enteric infections in urban and rural populations in the Pacific Northwest. Fourth, we are attempting to determine the evolutionary basis for acquisition of virulence loci by diarrheagenic E. coli O157:H7 and other Shiga toxin-producing pathogens. Finally, we are beginning to explore microbial precipitants of inflammatory bowel disease and necrotizing enterocolitis.