An increasingly in-depth understanding of the microbiome and identification of susceptibility genes have changed the landscape for researchers seeking to reduce the health burden of inflammatory bowel disease (IBD). Despite these advances, and expanding detail of immunological activities in normal and diseased intestine, fundamental observations related to the course of disease in IBD remain starkly unexplained. For instance, key features of Crohn's disease include transmural inflammation, skip lesions characterized by the separation of inflamed and diseased intestinal segments with normal regions of intestine, and the proverbial creeping fat in which a tell-tale sign of the intensity of IBD is the appearance of fat that no longer stops at its usual boundary along the anti-mesenteric border but instead progressively creeps over and around the intestinal wall. None of these features are explained at a genetic, molecular, or cellular level, and yet surely they relate to the most harrowing complication of Crohn's disease: the formation of fibrostenotic lesions that serve as the principal cause for patients to be admitted to surgery, often emergency surgery to prevent bowel obstruction, and for which a large subgroup of patients experience repeatedly through the course of their disease. The work proposed will bring new approaches, conceptual and technical, to the study of IBD that have potential to transform our understanding of human Crohn's disease as a major form of IBD. The overarching hypothesis is that blood vessel remodeling is at the core of the disease, that it has in part an immunological basis, and that its remodeling goes hand-in-hand with alterations in the lymphatic vasculature that in turn contributes to disease pathogenesis and fibrosis. We will carry out patient-based studies to address this hypothesis.
| Czepielewski, Rafael S; Randolph, Gwendalyn J (2018) Lymph nodes go with the flow. J Exp Med 215:2699-2701 |
| Williams, Jesse W; Martel, Catherine; Potteaux, Stephane et al. (2018) Limited Macrophage Positional Dynamics in Progressing or Regressing Murine Atherosclerotic Plaques-Brief Report. Arterioscler Thromb Vasc Biol 38:1702-1710 |
| Huang, Li-Hao; Zinselmeyer, Bernd H; Chang, Chih-Hao et al. (2018) Interleukin-17 Drives Interstitial Entrapment of Tissue Lipoproteins in Experimental Psoriasis. Cell Metab : |
| Williams, Jesse W; Giannarelli, Chiara; Rahman, Adeeb et al. (2018) Macrophage Biology, Classification, and Phenotype in Cardiovascular Disease: JACC Macrophage in CVD Series (Part 1). J Am Coll Cardiol 72:2166-2180 |
| Williams, Jesse W; Randolph, Gwendalyn J; Zinselmeyer, Bernd H (2017) A Polecat's View of Patrolling Monocytes. Circ Res 120:1699-1701 |
| Williams, Jesse W; Elvington, Andrew; Ivanov, Stoyan et al. (2017) Thermoneutrality but Not UCP1 Deficiency Suppresses Monocyte Mobilization Into Blood. Circ Res 121:662-676 |
| Westerterp, Marit; Gautier, Emmanuel L; Ganda, Anjali et al. (2017) Cholesterol Accumulation in Dendritic Cells Links the Inflammasome to Acquired Immunity. Cell Metab 25:1294-1304.e6 |
| Zhu, Yu; Herndon, John M; Sojka, Dorothy K et al. (2017) Tissue-Resident Macrophages in Pancreatic Ductal Adenocarcinoma Originate from Embryonic Hematopoiesis and Promote Tumor Progression. Immunity 47:323-338.e6 |
| Randolph, Gwendalyn J; Ivanov, Stoyan; Zinselmeyer, Bernd H et al. (2017) The Lymphatic System: Integral Roles in Immunity. Annu Rev Immunol 35:31-52 |
| Cifarelli, Vincenza; Ivanov, Stoyan; Xie, Yan et al. (2017) CD36 deficiency impairs the small intestinal barrier and induces subclinical inflammation in mice. Cell Mol Gastroenterol Hepatol 3:82-98 |
Showing the most recent 10 out of 16 publications
