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.
- Research Professor, Rheumatology (Arthritis), Medicine, Boston University School of Medicine
- University of Wisconsin Madison, PhD
- Michigan State University, BS
- Published on 3/31/2018
St Clair EW, Baer AN, Wei C, Noaiseh G, Parke A, Coca A, Utset TO, Genovese MC, Wallace DJ, McNamara J, Boyle K, Keyes-Elstein L, Browning JL, Franchimont N, Smith K, Guthridge JM, Sanz I, James JA. The Clinical Efficacy and Safety of Baminercept, a Lymphotoxin-ß Receptor Fusion Protein, in Primary Sjögren's Syndrome: Results from a Randomized, Double-Blind, Placebo-Controlled Phase II Trial. Arthritis Rheumatol. 2018 Mar 31. PMID: 29604186.
- Published on 2/2/2017
Grzegorzewska AP, Seta F, Han R, Czajka CA, Makino K, Stawski L, Isenberg JS, Browning JL, Trojanowska M. Dimethyl Fumarate ameliorates pulmonary arterial hypertension and lung fibrosis by targeting multiple pathways. Sci Rep. 2017 Feb 02; 7:41605. PMID: 28150703.
- Published on 10/19/2016
Gardet A, Chou WC, Reynolds TL, Velez DB, Fu K, Czerkowicz JM, Bajko J, Ranger AM, Allaire N, Kerns HM, Ryan S, Legault HM, Dunstan RW, Lafyatis R, Lukashev M, Viney JL, Browning JL, Rabah D. Pristane-Accelerated Autoimmune Disease in (SWR X NZB) F1 Mice Leads to Prominent Tubulointerstitial Inflammation and Human Lupus Nephritis-Like Fibrosis. PLoS One. 2016; 11(10):e0164423. PMID: 27760209.
- Published on 10/10/2016
Chia JJ, Zhu T, Chyou S, Dasoveanu DC, Carballo C, Tian S, Magro CM, Rodeo S, Spiera RF, Ruddle NH, McGraw TE, Browning JL, Lafyatis R, Gordon JK, Lu TT. Dendritic cells maintain dermal adipose-derived stromal cells in skin fibrosis. J Clin Invest. 2016 Nov 01; 126(11):4331-4345. PMID: 27721238.
- Published on 8/23/2016
Nazari B, Rice LM, Stifano G, Barron AM, Wang YM, Korndorf T, Lee J, Bhawan J, Lafyatis R, Browning JL. Altered Dermal Fibroblasts in Systemic Sclerosis Display Podoplanin and CD90. Am J Pathol. 2016 Oct; 186(10):2650-64. PMID: 27565038.
- Published on 4/13/2016
Mejías-Luque R, Zöller J, Anderl F, Loew-Gil E, Vieth M, Adler T, Engler DB, Urban S, Browning JL, Müller A, Gerhard M, Heikenwalder M. Lymphotoxin ß receptor signalling executes Helicobacter pylori-driven gastric inflammation in a T4SS-dependent manner. Gut. 2017 Aug; 66(8):1369-1381. PMID: 27196595.
- Published on 1/4/2016
Seleznik G, Seeger H, Bauer J, Fu K, Czerkowicz J, Papandile A, Poreci U, Rabah D, Ranger A, Cohen CD, Lindenmeyer M, Chen J, Edenhofer I, Anders HJ, Lech M, Wüthrich RP, Ruddle NH, Moeller MJ, Kozakowski N, Regele H, Browning JL, Heikenwalder M, Segerer S. The lymphotoxin ß receptor is a potential therapeutic target in renal inflammation. Kidney Int. 2016 Jan; 89(1):113-26. PMID: 26398497.
- Published on 11/1/2015
Rice LM, Ziemek J, Stratton EA, McLaughlin SR, Padilla CM, Mathes AL, Christmann RB, Stifano G, Browning JL, Whitfield ML, Spiera RF, Gordon JK, Simms RW, Zhang Y, Lafyatis R. A longitudinal biomarker for the extent of skin disease in patients with diffuse cutaneous systemic sclerosis. Arthritis Rheumatol. 2015 Nov; 67(11):3004-15. PMID: 26240058.
- Published on 10/26/2015
Finkin S, Yuan D, Stein I, Taniguchi K, Weber A, Unger K, Browning JL, Goossens N, Nakagawa S, Gunasekaran G, Schwartz ME, Kobayashi M, Kumada H, Berger M, Pappo O, Rajewsky K, Hoshida Y, Karin M, Heikenwalder M, Ben-Neriah Y, Pikarsky E. Ectopic lymphoid structures function as microniches for tumor progenitor cells in hepatocellular carcinoma. Nat Immunol. 2015 Dec; 16(12):1235-44. PMID: 26502405.
- Published on 11/18/2014
Bienkowska J, Allaire N, Thai A, Goyal J, Plavina T, Nirula A, Weaver M, Newman C, Petri M, Beckman E, Browning JL. Lymphotoxin-LIGHT pathway regulates the interferon signature in rheumatoid arthritis. PLoS One. 2014; 9(11):e112545. PMID: 25405351.
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