Gwendalyn J. Randolph

Gwendalyn J. Randolph is an American immunologist, the Emil R. Unanue Distinguished Professor in the Department of Immunology and Pathology at Washington University School of Medicine. During her postdoctoral work, Randolph characterized monocyte differentiation to dendritic cells and macrophages and made advances in our understanding of dendritic cell trafficking and the fate of monocytes recruited to sites of inflammation. Her lab has contributed to the Immunological Genome Project by characterizing macrophage gene expression and her laboratory has particularly contributed to our understanding of macrophages in the peritoneal cavity of mice and humans. Her work has also focused on the immunological mechanisms driving atherosclerosis and inflammatory bowel disease (IBD) by exploring lymphatic function and lipoprotein trafficking.

Early life and education Randolph, born Gwendalyn Wilson, was born in the small farming town of Hart, Texas. She grew up helping her parents on their maize and cotton farm by tending to weeds and helping with harvests. winning awards and funding to travel to New York and Los Angeles for her sewing achievements. working under the mentorship of Martha B. Furie studying themoocyte migration.

Randolph stayed in New York for postdoctoral training at The Rockefeller University and Weill Cornell Medicine in the departments of Cellular Immunology and Pathology. She developed an in vitro model to assess monocyte differentiation into dendritic cells (DCs) or macrophages. They found that exposure of monocytes to endothelial cells was critical to DC differentiation and that exposure to phagocytic particles caused cells that had previously reverse-transmigrated to fully displayed a DC-like phenotype in terms of intracellular and extracellular markers as well as a highly ramified phenotype.

Career and research In 1998, Randolph became an instructor in the Department of Pathology at Weill Cornell as well as an Adjunct Faculty at The Rockefeller University's Department of Cellular Physiology and Immunology. At Mt. Sinai, her lab explored monocyte fate and differentiation, and their trafficking out of inflamed tissues through lymphatic vessels. Her lab was among the early labs to identify blood monocytes in mice developing a universal method for doing so using expression of CD115, supplanting the far less selective CD11b used to identify myeloid cells more generally. Her lab conducted comparisons of mouse and human monocyte subsets, and created a universal classification nomenclature of myeloid cells.

Randolph moved her lab to Washington University in St. Louis in 2011, studying the role of cholesterol trafficking in diseases such as atherosclerosis and more recently, Crohn's Disease. From 2015 to 2017, she was the Chief of the Division of Immunobiology at Washington University. She is currently the Emil R. Unanue Distinguished Professor in the Department of Pathology and Immunology at Washington University. In 2017, she became the Immunology Graduate Program Director at the School of Medicine, stepping down in 2023. She spearheaded early work on mouse macrophage gene expression, and her paper published as a part of the Immgen Project is the most highly cited paper of the project.

Lymphatic vasculature and cholesterol trafficking Randolph's focus changed towards the implications of immune trafficking and lymphatic vasculature in disease processes after moving to Washington University. They showed that lymphatic vessels are critical to the mobilization of cholesterol for excretion and that enhancing lymphatic function might be therapeutic in atherosclerosis. Her lab then showed that collecting lymphatic vessels (CLVs) are involved in the immune response by acting as a site for macrophages and dendritic cells to uptake antigens. The results emphasized that CLVs are important in the coordination of immune responses surrounding adipose depots. In 2018, her team found that skin-driven immune responses can cause systemic changes that affect the ability of cholesterol to be taken in by tissues thus promoting plaque build-up in arteries around the heart.

In 2015, Randolph was awarded the National Institutes of Health Director's 2015 Pioneer Award to pursue high risk-high reward research to study the role of lymphatics and cellular transport in inflammatory bowel disease This novel approach has allowed them to identify novel tertiary lymphoid organs along the collecting lymphatic vessels that are likely involved in aberrant delivery of lymph to lymph nodes.

Kuan EL, Ivanov S, Bridenbaugh EA, Victora G, Wang W, Childs EW, Platt AM, Jakubzick CV, Mason RJ, Gashev AA, Nussenzweig M, Swartz MA, Dustin ML, Zaweija DC, Randolph GJ. 2015. Collecting lymphatic vessel permeability facilitates adipose tissue inflammation and distribution of antigen to lymph node-homing adipose tissue dendritic cells. J. Immunol., Jun 1;194(11):5200-10. PMCID: PMC4433841

[with commentary].

Randolph, G.J., Sanchez-Schmitz, G., Liebman, R.M., and Schäkel, K. (2002). The CD16+ (FcgRIII+) subset of human monocytes preferentially becomes migratory dendritic cells in a model tissue setting. Journal of Experimental Medicine, 196(4):517-527. PMCID: PMC2196052 Randolph, G.J. and Furie, M.B. (1996). Mononuclear phagocytes egress from an in vitro model of the vascular wall by migrating across endothelium in the basal to apical direction: role of intercellular adhesion molecule 1 and the CD11/CD18 integrins. Journal of Experimental Medicine, 183(2):451-462. PMCID: PMC2192453