Gwendalyn J Randolph, Ph.D.

Emil R. Unanue Professor
Pathology and Immunology
Immunobiology
Internal Medicine

Immunology Program
Molecular Microbiology and Microbial Pathogenesis Program

Research Abstract:

By focusing on the trafficking of molecules and cells out of tissues, my research laboratory integrates immunology and vascular biology with the study of disease mechanisms linked to inflammation. In parallel to the study of disease mechanisms, we carry out basic science essential to the interpretation of observations in the disease context. Early in my career, I worked on the fate of monocytes as they differentiated to macrophages or dendritic cells, with a particular interest in the development of their ability to traffic out of inflammatory tissues via lymphatic vessels to lymph nodes, as we considered the role of such trafficking in the ability of an inflammatory state to resolve. Over time, in interacting with scientists bringing diverse expertise to atherosclerosis, where I worked on monocyte trafficking for several years, my laboratory developed an interest in the trafficking of not just cells but also of molecules, particularly lipoproteins out of tissues, since the inability of lipoproteins to reach key sites or to become trapped can affect the course of inflammation. We developed approaches to examine trafficking of lipoproteins through tissue interstitial spaces, asking (as we had done for immune cells) how reliant on functional lymphatics was a lipoprotein's ability to leave tissues appropriately to promote key processes like reverse cholesterol transport. In recent years, we realized that the tri-partite expertise we developed (immune cell trafficking, lipoprotein trafficking, lymphatic vessel biology) could be put to work on new questions in disease states less well understood than atherosclerosis. One such question is whether lymphatics that carry lipid nutrients, immune cells, and other cargo away from the gut become dysfunctional in inflammatory diseases like Crohn's disease. We have thus transitioned our research to understanding the trafficking of cellular and molecular cargo out of the intestine to downstream tissues and organs like lymph nodes and liver. The lymphatic vasculature draining the intestine traverses the mesenteric adipose tissue within the peritoneal cavity. We also specialize in the immune cell (especially macrophage) microenvironment of the peritoneal cavity and the impact of its physiology on neighboring organs and intraperitoneal perturbations like inflammation and peritoneal tumor metastasis.

Selected Publications:

N Zhang, SH Kim, A Gainullina, EC Erlich, EJ Onufer, J Kim, RS Czepielewski, BA Helmink, JR Dominguez, BT Saunders, J Ding, JW Williams, JX Jiang, BH Segal, BH Zinselmeyer, *^GJ Randolph, *KW Kim. 2021. LYVE1hi macrophages reside in mesothelium and promote omentum-independent ovarian tumor growth in the peritoneum. J. Exp. Med., 218(12):e20210924. doi: 10.1084/jem.20210924. PMCID: 8575007

Rafael S. Czepielewski, Emma C. Erlich, Emily J. Onufer, Shannon Young, Brian T. Saunders, Yong-Hyun Han, Mary Wohltmann, Peter L. Wang, Ki-Wook Kim, Shashi Kumar, Chyi-Song Hsieh, Joshua P. Scallan, Ying Yang, Bernd H. Zinselmeyer, Michael J. Davis, Gwendalyn J. Randolph. 2021. Ileitis-associated mesenteric tertiary lymphoid organs arise at lymphatic valves and impede lymph flow in response to tumor necrosis factor, Immunity, 54(12):2795-2811. doi: 10.1016/j.immuni.2021.10.003. PMCID: 8678349

YH Han, EJ Onufer, RW Sprung, WS Davidson, RS Czepielewski, M Wohltmann, MG Sorci-Thomas, BW Warner, GJ Randolph. 2021. Enterically derived high-density lipoprotein restrains liver injury through the portal vein, Science, 373, 410; DOI: 10.1126/science.abe6729

O Baba, A Elvington, D Sultan, GS Heo, X Zhang, H Luehmann, L Detering, M Szpakowska, A Chevigne, Y Liu, GJ Randolph. 2021. CXCR4 on atherosclerotic plaque endothelium predicts the magnitude of monocyte recruitment and is readily targeted by PET tracers. Arterio Thromb Vasc Biol 41(2):822-836. doi: 10.1161/ATVBAHA.120.315053. [editorial comment, same issue]

JW Williams, K Zaitsev, KW Kim S Ivanov, BT Saunders, PR Schrank, K Kim, A Elvington, SH Kim, C Tucker, M Wohltmann, BT Fife, S Epelman, M Artyomov, KJ Lavine, BH Zinselmeyer, JH Choi, GJ. Randolph. Limited proliferation capacity of aorta intima resident macrophages requires monocyte recruitment for atherosclerotic plaque progression, Nature Immunology, 21:1194-1204. doi. 10.1038/s41590-020-0768-4

PL Wang, AKY Yim, K Kim, D Avey, RS Czepielewski, M Colonna, *J Milbrandt, *GJ Randolph.. 2020. Peripheral nerve resident macrophages share tissue-specific programming and features of activated microglia. Nature Communications, 11(1):2552. doi: 10.1038/s41467-020-16355-w (* joint corresponding authors)

Zhang N, Czepielewski RS, Jarjour NN, Erlich EC, Esaulova E, Saunders BT, Grover SP, Cleuren AC, Broze GJ, Edelson BT, Mackman N, Zinselmeyer BH, Randolph GJ. (2019). Expression of factor V by resident peritoneal macrophages boosts host defense in the peritoneal cavity. J. Exp. Med, 216: 1291-6. [cover feature] PMCID 6547866

Angeli V, Ginhoux F, LlodrĂ¡ J, Quemeneur L, Frenette PS, Skobe M, Jessberger R, Merad M, and Randolph GJ. B cell driven lymphangiogenesis in inflamed lymph nodes enhances dendritic cell mobilization. Immunity 2006;24(2):203-215. [cover feature and commentary]. PMID: 16473832





Last Updated: 1/17/2022 12:58:48 PM

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