Jeffrey L. Browning, Ph.D.
Research Professor Microbiology
72 East Concord Street; E-5
BS Michigan State University
PhD University of Wisconsin
My interests focus on understanding how the immune system interacts with stromal elements to form the specialized structures that orchestrate immunological encounters in lymphoid organs. On a different plane, the barriers to effective quantitation of disease are formidable in some autoimmune diseases especially those with considerable unmet need such as lupus and scleroderma. I am interested in bringing new views onto the human immune system to improve clinical studies.
Mesenchymal cell differentiation pathways are intimately interwoven with pathological processes e.g. compromised vascular integrity, aberrant tissue remodeling and fibrosis and tumor-stromal interactions. In lymphoid organs, the lymphotoxin pathway, a TNF family member, is one mechanism by which both innate and adaptive lymphoid cells communicate with their stromal microenvironments. The maintenance of a differentiated follicular dendritic cell network to scaffold the B cell follicle is a well-studied example of this communication. More recently, it is becoming clearer that another network, the fibroblastoid reticular cell network, is a differentiated form of mural cells, e.g. pericytes or vascular smooth muscle cells. The precise role of the lymphotoxin pathway in controlling this structure is an area of investigation. As lymph nodes can undergo massive expansion in response to danger following by involution, they form an intriguing model of physiological tissue remodeling. One-approach we are taking addresses whether the control of these cells in lymphoid tissue provides lessons that are applicable to non-lymphoid disease settings such as scleroderma skin and lung.
The ability to assess drug function in complex immunological diseases can be seriously limited by the quality of the metrics used to quantitate disease. One focus is on a potential new blood test for salivary gland function in Sjogren’s disease. Additionally, there is interest in understanding the origin of the blood RNA interferon signature commonly observed in autoimmune diseases and how this signature may provide insight into the ongoing pathology in lupus, Sjogren’s and scleroderma. The overarching goal is to understand how readily measureable blood parameters such as chemokine levels or various RNA signatures can report on the activity in lymph nodes and the spleen and hence inform on whether the immune system is flaring or smoldering.
- Browning, JL, N Allaire, A Ngam-ek, E Notidi, J Hunt, S Perrin, and RA Fava. 2005. Lymphotoxin-beta Receptor Signaling is Required for the Homeostatic Control of HEV Differentiation and Function. Immunity 23:539-550. PMID: 16286021
- Browning, JL. 2006. B cells Move to Centre Stage: Novel Opportunities for Autoimmune Disease Treatment. Nat. Rev. Drug Discov. 5:564-576. PMID: 16816838
- Lukashev, M, D LePage, C Wilson, V Bailly, E Garber, A Lukashin, A Ngam-ek, W Zeng, N Allaire, S Perrin, X Xu, K Szeliga, K Wortham, R Kelly, C Bottiglio, J Ding, L Griffith, G Heaney, E Silverio, W Yang, A Gill, M Jarpe, S Fawell, M Reff, A Carmillo, X Wang, K Miatkowski, J Amatucci, H Prentice, W Meier, S Violette, F Mackay, D Yang, R Hoffman and JL Browning. 2006. Targeting the Lymphotoxin-Beta Receptor with Agonist Antibodies as a Potential Cancer Therapy. Cancer Res. 66:9617-9624. PMID: 17018619
- Browning, JL. 2008. Inhibition of the Lymphotoxin Pathway as a Therapy for Autoimmune Disease. Immunol. Rev. 223:202-220. PMID: 18613838
- Michaelson, JS, SJ Demarest, B Miller, A Amatucci, WB Snyder, X Wu, F Huang, S Phan, S Gao, A Doern, GK Farrington, S Lugovskoy, I Joseph, V Bailly, X Wang, E Garber, JL Browning, and SM Glaser. 2009. Anti-tumor Activity of Stability-engineered IgG-like Bispecific Antibodies Targeting TRAIL-R2 and LTβR. Monoclonal Antibodies 1:128-141. PMID: 20061822
- Haybaeck, J, N Zeller MJ Wolf, A Weber, U Wagner, MO Kurrer, J Bremer, G Iezzi, R Graf, PA Clavien, R Thimme, H Blum, SA Nedospasov, K Zatloukal, M Ramzan, S Ciesek, T Pietschmann, PN Marche, M Karin, M Kopf, JL Browning, A Aguzzi, and M Heikenwalder. 2009. A Lymphotoxin-driven Pathway to Hepatocellular Carcinoma. Cancer Cell 16:295-308. PMID: 19800575
- Fava, RA, SM Kennedy, SG Wood, AI Bolstad, J Bienkowska, P Papandile, JA Kelly, CP Mavragani, M Gatumu, K Skarstein, DL Hitchmoth and JL Browning. 2011. Lymphotoxin-beta Receptor Blockade Reduces CXCL13 in Lacrimal Glands and Improves Tear Secretion and Corneal Integrity in the NOD Model of Sjögren’s Syndrome. Arthritis Res. Ther. 13:R182. PMID: 22044682
- McCarthy, DD, J Kujawa, C Wilson, A Papandile, U Poreci, L Ward, M Lawson, AJ Macpherson, K McCoy, Y Pei, B Julian, J Novak, A Ranger, JL Gommerman and JL Browning. 2011. Mice Over-expressing BAFF Develop a Commensal Flora-Dependent, IgA-Associated Nephropathy. J. Clin. Invest. 121:3991-4002. PMID: 21881212
- Browning, JL. 2012. Lymphotoxin and the Amazing Technicolor Circus of Intestinal Homeostasis. Mucosal Immunol. 5:228-231. PMID: 22318496
- Krautler, NJ, V Kana, J Kranich, Y Tian, D Perera, D Lemm, P Schwarz, A Armulik, JL Browning, M Tallquist, T Buch, JB Oliveira-Martins, C Zhu, M Hermann, U Wagner, R Brink, M Heikenwalder, and A Aguzzi. 2012. Follicular Dendritic cells Emerge from Ubiquitous Perivascular Precyrsirs. Cell 150:194-206. PMID: 22770220
- Edwards, KR, J Goyal, T Plavina, J Kujawa, S Goelz, A Ranger, D Diego Cadavid, and JL Browning. 2013. Feasibility of the Use of Combinatorial Chemokine Arrays to Study Blood and CSF in MS. PLoS (accepted)
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