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Gwendalyn J. Randolph

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Gwendalyn J. Randolph
Born
Hart, Texas, U.S.
Alma materTemple University
State University of New York, Stony Brook
Known forDendritic cell differentiation and trafficking, immune cell and lipoprotein trafficking in inflammatory bowel disease and atherosclerosis
AwardsAmerican Heart Association Established Investigator Award, Pioneer Award for High Risk High Reward Initiative Programs NIH Director's Office, NIH MERIT Award, Special Recognition Award in Atherosclerosis American Heart Association
Scientific career
FieldsImmunology, vascular biology
InstitutionsWashington University in St. Louis, Mount Sinai School of Medicine

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 where she is currently co-director of the Immunology Graduate Program. 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. Her work now focuses on the immunological mechanisms driving atherosclerosis and inflammatory bowel disease (IBD) by exploring lymphatic function and lipoprotein trafficking.

Early life and education

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Randolph, born Gwendalyn Wilson, was born in the small farming town of Hart, Texas.[1] She grew up helping her parents on their maize and cotton farm by tending to weeds and helping with harvests.[1] At school at Hart High School, she showed an early passion for design and textiles,[2] winning awards and funding to travel to New York and Los Angeles for her sewing achievements.[1] She accepted a sports scholarship to play basketball at Wayland Baptist University in Plainview, Texas in 1987, and majored in biology.[2]

In 1989, she married Keith Randolph; they moved to the east coast where she continued her studies at Temple University in Philadelphia, Pennsylvania.[2] She graduated with a Bachelors of Science in biological sciences in 1991, .[1] She received her PhD in Immunology and Pathology in 1995 from the State University of New York, Stony Brook.[3] working under the mentorship of Martha B. Furie studying themoocyte migration.[4]

Randolph stayed in New York for postdoctoral training at The Rockefeller University and Weill Medical College of Cornell University in the departments of Cellular Immunology and Pathology.[1] She worked under the mentorship of Bill Muller, vascular biologist, and Ralph Steinman studying dendritic cell maturation and migration.[1]

Dendritic cell maturation and migration

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Randolph's postdoctoral work, in collaboration with Steinman and Muller, investigated the differentiation of dendritic cells and their migration to lymph nodes from the periphery.[5] She developed an in vitro model to assess monocyte differentiation into dendritic cells (DCs) or macrophages.[6] 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.[6] Randolph also showed that monocytes could also differentiate into macrophages if they remained in the sub-endothelial matrix.[6] This work was followed with a validation of these findings in vivo, published one year later in Immunity.[7]

Career and research

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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.[1] In 2000, she joined Mount Sinai School of Medicine where she spent 11 years on the faculty in the Department of Gene and Cell Medicine.[8] At Mt. Sinai, her lab explored monocyte fate and differentiation, and their trafficking out of inflamed tissues through lymphatic vessels.[8] One objective was to determine if macrophages could migrate out of organs, via lymphatics or blood, in healthy or diseased states; the laboratory concluded that they do not.[9][10] 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.[11] Her lab conducted comparisons of mouse and human monocyte subsets, and created a universal classification nomenclature of myeloid cells.[12]

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.[13] 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 and co-director in 2020.[1]

Immunological Genome Project and macrophage diversity

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Randolph's lab has contributed to the Immunological Genome Project, a project whose goal is to explore how gene expression relates to immune system function in mice.[14] 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.[15]

Lymphatic vasculature and cholesterol trafficking

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Randolph's focus changed towards the implications of immune trafficking and lymphatic vasculature in disease processes after moving to Washington University.[16] They showed that lymphatic vessels are critical to the mobilization of cholesterol for excretion and that enhancing lymphatic function might be therapeutic in atherosclerosis.[17] 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.[18]  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.[19] Specifically, they found that Th17 cells drive the collagen mediated changes seen in experimental psoriasis, and that blocking IL17 rescues cholesterol transport and reduces vascular stiffness.[19]

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[16] in collaboration with gastroenterologist, Jean-Frederic Colombel, .[16][1] In order to understand if damage to lymphatic collecting vessels might contribute to human disease, as it has been shown to do in mice, Randolph's lab developed a three-dimensional imaging approach to explore lymphatic vasculature abnormalities in human mesenteric tissue.[20] 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.[20]

Personal life

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Randolph is now married to Hermann Kyrychenko and has two children.[1]

Select publications

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  • L Huang, BH Zinselmeyer, CH Chang, BT Saunders, AF Elvington, O Baba, TJ Broekelmann, L Qi, JS Rueve, MA Swartz, BS Kim, RP Mecham, H Wiig, MJ Thomas, MG Sorci-Thomas, GJ Randolph. 2019. Interleukin 17 drives interstitial entrapment of tissue lipoproteins in experimental psoriasis. Cell Metabolism, 29:475-487. PMC 6365189[21]
  • 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
  • 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[18]
  • Gautier, E.L., Shay, T., Miller, J., Greter, M., Jakubzick, C., Ivanov, S., Helft, J., Chow, A., Elpek, K.G., Gordonov, S., Mazloom, A.R., Ma’ayan, A., Chua, W.J., Hansen, T.H., Turley, S.J., Merad, M., and Randolph, G.J. (2012). Gene expression profiles and transcriptional regulatory pathways underlying murine tissue macrophage identity and diversity. Nature Immunology, 13(11):1118-1128. PMCID: PMC3558276[15]
  • Jakubzick, C., Gautier, E.L., Gibbings, S.L., Sojka, D.K., Schlitzer, A., Johnson, T.E., Ivanov, S., Duan, Q., Bala, S., Condon, T., van Rooijen, N., Grainger, J.R., Belkaid, Y., Ma’ayan, A., Riches, D.W., Yokoyama, W.M., Ginhoux, F., Henson, P.M., and Randolph, G.J. (2013). Minimal differentiation of classical monocytes as they survey steady-state tissues and transport antigen to lymph nodes. Immunity, 39(3):599-610. PMCID: PMC3820017[22]
  • Ingersoll, M.A., Spanbroek, R., Lottaz, C., Gautier, E.L., Frankenberger, M., Hoffmann, R., Lang, R., Haniffa, M., Collin, M., Tacke, F., Habenicht, A.J., Ziegler-Heitbrock, L., and Randolph, G.J. (2010). Comparison of gene expression profiles between human and mouse monocyte subsets.  Blood, 115(3):e10-19. PMCID: PMC2810986
  • Tacke F, Alvarez D, Kaplan TJ, Jakubzick C, Spanbroek R, Llodrá J, Garin A, Liu J, Mack M, van Rooijen N, Lira SA, Habenicht AJ, and Randolph GJ. Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques. J. Clin. Invest. 2007;117(1):185-194. [with commentary]. PMCID: PMC1716202
  • Angeli V, Ginhoux F, Llodrá 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
  • 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[23]
  • 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[24]

References

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  1. ^ a b c d e f g h i j "Washington People: Gwen Randolph". Washington University School of Medicine in St. Louis. 2019-09-17. Retrieved 2020-12-31.
  2. ^ a b c Williams, Neoma; Correspondent, Herald (2017-09-22). "Hart grad Dr. Gwen Wilson is distinguished medical school professor". Plainview Herald. Retrieved 2020-12-31.
  3. ^ "2020 Inflammation Co-Chair". www.navbo.org. Retrieved 2020-12-31.[permanent dead link]
  4. ^ "Mononuclear Phagocytes Egress from an In Vitro Mode 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" (PDF). core.ac.uk/. February 1996. Retrieved December 31, 2020.
  5. ^ Randolph, Gwendalyn J.; Angeli, Veronique; Swartz, Melody A. (August 2005). "Dendritic-cell trafficking to lymph nodes through lymphatic vessels". Nature Reviews Immunology. 5 (8): 617–628. doi:10.1038/nri1670. ISSN 1474-1741. PMID 16056255. S2CID 28795897.
  6. ^ a b c Randolph, Gwendalyn J.; Beaulieu, Sylvie; Lebecque, Serge; Steinman, Ralph M.; Muller, William A. (1998-10-16). "Differentiation of Monocytes into Dendritic Cells in a Model of Transendothelial Trafficking". Science. 282 (5388): 480–483. Bibcode:1998Sci...282..480R. doi:10.1126/science.282.5388.480. ISSN 0036-8075. PMID 9774276.
  7. ^ Randolph, Gwendalyn J.; Inaba, Kayo; Robbiani, Davide F.; Steinman, Ralph M.; Muller, William A. (1999-12-01). "Differentiation of Phagocytic Monocytes into Lymph Node Dendritic Cells In Vivo". Immunity. 11 (6): 753–761. doi:10.1016/S1074-7613(00)80149-1. ISSN 1074-7613. PMID 10626897.
  8. ^ a b "NIH VideoCast - Macrophages and lymphatics: guardians of the tissue microenvironment". videocast.nih.gov. 21 February 2018. Retrieved 2020-12-31.
  9. ^ Potteaux, Stephane; Gautier, Emmanuel L.; Hutchison, Susan B.; van Rooijen, Nico; Rader, Daniel J.; Thomas, Michael J.; Sorci-Thomas, Mary G.; Randolph, Gwendalyn J. (May 2011). "Suppressed monocyte recruitment drives macrophage removal from atherosclerotic plaques of Apoe-/- mice during disease regression". The Journal of Clinical Investigation. 121 (5): 2025–2036. doi:10.1172/JCI43802. ISSN 1558-8238. PMC 3083793. PMID 21505265.
  10. ^ Gautier, Emmanuel L.; Ivanov, Stoyan; Lesnik, Philippe; Randolph, Gwendalyn J. (2013-10-10). "Local apoptosis mediates clearance of macrophages from resolving inflammation in mice". Blood. 122 (15): 2714–2722. doi:10.1182/blood-2013-01-478206. ISSN 1528-0020. PMC 3795463. PMID 23974197.
  11. ^ Qu, Chunfeng; Edwards, Emmerson W.; Tacke, Frank; Angeli, Véronique; Llodrá, Jaime; Sanchez-Schmitz, Guzman; Garin, Alexandre; Haque, Nasreen S.; Peters, Wendy; van Rooijen, Nico; Sanchez-Torres, Carmen (2004-11-15). "Role of CCR8 and Other Chemokine Pathways in the Migration of Monocyte-derived Dendritic Cells to Lymph Nodes". The Journal of Experimental Medicine. 200 (10): 1231–1241. doi:10.1084/jem.20032152. ISSN 0022-1007. PMC 2211916. PMID 15534368.
  12. ^ Ziegler-Heitbrock, Loems; Ancuta, Petronela; Crowe, Suzanne; Dalod, Marc; Grau, Veronika; Hart, Derek N.; Leenen, Pieter J. M.; Liu, Yong-Jun; MacPherson, Gordon; Randolph, Gwendalyn J.; Scherberich, Juergen (2010-10-21). "Nomenclature of monocytes and dendritic cells in blood". Blood. 116 (16): e74–e80. doi:10.1182/blood-2010-02-258558. hdl:11379/41075. ISSN 0006-4971. PMID 20628149. S2CID 1570404.
  13. ^ "Randolph to receive NIH director's Pioneer Award | The Source | Washington University in St. Louis". The Source. 2015-10-06. Retrieved 2020-12-31.
  14. ^ Aguilar, Stephanie Vargas; Aguilar, Oscar; Allan, Rhys; Amir, El Ad David; Angeli, Veronique; Artyomov, Maxim N.; Asinovski, Natasha; Astarita, Jilian; Austen, K. Frank; Bajpai, Geetika; Barrett, Nora (July 2020). "ImmGen at 15". Nature Immunology. 21 (7): 700–703. doi:10.1038/s41590-020-0687-4. ISSN 1529-2916. PMID 32577013. S2CID 219988250.
  15. ^ a b Gautier, Emmanuel L.; Shay, Tal; Miller, Jennifer; Greter, Melanie; Jakubzick, Claudia; Ivanov, Stoyan; Helft, Julie; Chow, Andrew; Elpek, Kutlu G.; Gordonov, Simon; Mazloom, Amin R. (November 2012). "Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages". Nature Immunology. 13 (11): 1118–1128. doi:10.1038/ni.2419. ISSN 1529-2916. PMC 3558276. PMID 23023392.
  16. ^ a b c Health (2015-11-13). "The Journey from Innovator to Pioneer". Kenneth Rainin Foundation. Retrieved 2020-12-31.
  17. ^ Martel, Catherine; Li, Wenjun; Fulp, Brian; Platt, Andrew M.; Gautier, Emmanuel L.; Westerterp, Marit; Bittman, Robert; Tall, Alan R.; Chen, Shu-Hsia; Thomas, Michael J.; Kreisel, Daniel (April 2013). "Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice". The Journal of Clinical Investigation. 123 (4): 1571–1579. doi:10.1172/JCI63685. ISSN 1558-8238. PMC 3613904. PMID 23524964.
  18. ^ a b Kuan, Emma L.; Ivanov, Stoyan; Bridenbaugh, Eric A.; Victora, Gabriel; Wang, Wei; Childs, Ed W.; Platt, Andrew M.; Jakubzick, Claudia V.; Mason, Robert J.; Gashev, Anatoliy A.; Nussenzweig, Michel (2015-06-01). "Collecting lymphatic vessel permeability facilitates adipose tissue inflammation and distribution of antigen to lymph node-homing adipose tissue dendritic cells". Journal of Immunology. 194 (11): 5200–5210. doi:10.4049/jimmunol.1500221. ISSN 1550-6606. PMC 4433841. PMID 25917096.
  19. ^ a b "Link between autoimmune, heart disease explained in mice". Washington University School of Medicine in St. Louis. 2018-11-08. Retrieved 2020-12-31.
  20. ^ a b Randolph, Gwendalyn J.; Bala, Shashi; Rahier, Jean-François; Johnson, Michael W.; Wang, Peter L.; Nalbantoglu, ILKe; Dubuquoy, Laurent; Chau, Amélie; Pariente, Benjamin; Kartheuser, Alex; Zinselmeyer, Bernd H. (December 2016). "Lymphoid Aggregates Remodel Lymphatic Collecting Vessels that Serve Mesenteric Lymph Nodes in Crohn Disease". The American Journal of Pathology. 186 (12): 3066–3073. doi:10.1016/j.ajpath.2016.07.026. ISSN 1525-2191. PMC 5225286. PMID 27746181.
  21. ^ Huang, Li-Hao; Zinselmeyer, Bernd H.; Chang, Chih-Hao; Saunders, Brian T.; Elvington, Andrew; Baba, Osamu; Broekelmann, Thomas J.; Qi, Lina; Rueve, Joseph S.; Swartz, Melody A.; Kim, Brian S. (5 February 2019). "Interleukin-17 Drives Interstitial Entrapment of Tissue Lipoproteins in Experimental Psoriasis". Cell Metabolism. 29 (2): 475–487.e7. doi:10.1016/j.cmet.2018.10.006. ISSN 1932-7420. PMC 6365189. PMID 30415924.
  22. ^ Jakubzick, Claudia; Gautier, Emmanuel L.; Gibbings, Sophie L.; Sojka, Dorothy K.; Schlitzer, Andreas; Johnson, Theodore E.; Ivanov, Stoyan; Duan, Qiaonan; Bala, Shashi; Condon, Tracy; van Rooijen, Nico (2013-09-19). "Minimal differentiation of classical monocytes as they survey steady-state tissues and transport antigen to lymph nodes". Immunity. 39 (3): 599–610. doi:10.1016/j.immuni.2013.08.007. ISSN 1097-4180. PMC 3820017. PMID 24012416.
  23. ^ Randolph, Gwendalyn J.; Sanchez-Schmitz, Guzman; Liebman, Ronald M.; Schäkel, Knut (2002-08-19). "The CD16(+) (FcgammaRIII(+)) subset of human monocytes preferentially becomes migratory dendritic cells in a model tissue setting". The Journal of Experimental Medicine. 196 (4): 517–527. doi:10.1084/jem.20011608. ISSN 0022-1007. PMC 2196052. PMID 12186843.
  24. ^ Randolph, G. J.; Furie, M. B. (1996-02-01). "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". The Journal of Experimental Medicine. 183 (2): 451–462. doi:10.1084/jem.183.2.451. ISSN 0022-1007. PMC 2192453. PMID 8627158.
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