The autoimmune condition rheumatoid arthritis (RA) afflicts over 1 million American adults, causing chronic joint inflammation, pain and destruction. Although several therapies exist, a deeper knowledge of this disease is required to improve the lives of patients living with this chronic illness. HSS, one of the world’s leading hospitals for rheumatology (#3 in the U.S., U.S. News and World Reports), provides an outstanding environment to study RA. With ~2,000 RA patients treated and followed by HSS physicians (includes ~40 rheumatologists), there is ample opportunity to study this disease from the clinical to the molecular level.
Together with outstanding collaborators and the application of cutting-edge molecular technologies, we have advanced the knowledge of cell types and molecular patterns found in the joints of RA patients, at a resolution not possible until now. The Donlin lab has also in particular provided insights into pathologic mechanisms of macrophages in RA joint tissue, including how medications redirect these cells towards phenotypes that may resolve inflammation or continue to drive disease. Using ex vivo patient tissue assays and focusing on complex cellular crossregulatory systems, we have also identified promising therapeutic targets that will be important to test in emerging therapeutic strategies.
Together with outstanding collaborators and the application of cutting-edge molecular technologies, we have advanced the knowledge of cell types and molecular patterns found in the joints of RA patients, at a resolution not possible until now. The Donlin lab has also in particular provided insights into pathologic mechanisms of macrophages in RA joint tissue, including how medications redirect these cells towards phenotypes that may resolve inflammation or continue to drive disease. Using ex vivo patient tissue assays and focusing on complex cellular crossregulatory systems, we have also identified promising therapeutic targets that will be important to test in emerging therapeutic strategies.
Related Publications
HBEGF+ macrophages identified in rheumatoid arthritis promote joint tissue invasiveness and are reshaped differentially by medications
Science Translational Medicine
David Kuo, Jennifer Ding, Ian Cohn, Fan Zhang, Kevin Wei, Deepak Rao, Cristina Rozo, Upneet K Sokhi, Accelerating Medicines Partnership RA/SLE Network, Edward F. DiCarlo, Michael B. Brenner, Vivian P. Bykerk, Susan M. Goodman, Soumya Raychaudhuri, Gunnar Rätsch, Lionel B. Ivashkiv, Laura T. Donlin.
Science Translational Medicine
David Kuo, Jennifer Ding, Ian Cohn, Fan Zhang, Kevin Wei, Deepak Rao, Cristina Rozo, Upneet K Sokhi, Accelerating Medicines Partnership RA/SLE Network, Edward F. DiCarlo, Michael B. Brenner, Vivian P. Bykerk, Susan M. Goodman, Soumya Raychaudhuri, Gunnar Rätsch, Lionel B. Ivashkiv, Laura T. Donlin.
Single-cell RNA-seq of rheumatoid arthritis synovial tissue using low-cost microfluidic instrumentation.
Nature Communications
William Stephenson, Laura T. Donlin, Andrew Butler, Cristina Rozo, Bernadette Bracken, Ali Rashidfarrokhi, Susan M. Goodman, Lionel B. Ivashkiv, Vivian P. Bykerk, Dana E. Orange, Robert B. Darnell, Harold P. Swerdlow & Rahul Satija.
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Nature Communications
William Stephenson, Laura T. Donlin, Andrew Butler, Cristina Rozo, Bernadette Bracken, Ali Rashidfarrokhi, Susan M. Goodman, Lionel B. Ivashkiv, Vivian P. Bykerk, Dana E. Orange, Robert B. Darnell, Harold P. Swerdlow & Rahul Satija.
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Flares in Patients with Rheumatoid Arthritis after Total Hip and Total Knee Arthroplasty: Rates, Characteristics, and Risk Factors. - The Journal of Rheumatology
Susan M. Goodman, Vivian P. Bykerk, Edward DiCarlo, Ryan W. Cummings, Laura T. Donlin, Dana E. Orange, Annie Hoang, Serene Mirza, Michael McNamara, Kayte Andersen, Susan J. Bartlett, Jackie Szymonifka and Mark P. Figgie
Susan M. Goodman, Vivian P. Bykerk, Edward DiCarlo, Ryan W. Cummings, Laura T. Donlin, Dana E. Orange, Annie Hoang, Serene Mirza, Michael McNamara, Kayte Andersen, Susan J. Bartlett, Jackie Szymonifka and Mark P. Figgie
Identification of Three Rheumatoid Arthritis Disease Subtypes by Machine Learning Integration of Synovial Histologic Features and RNA Sequencing Data. -Arthritis and Rheumatology
Dana E. Orange, Phaedra Agius, Edward F. DiCarlo, Nicolas Robine, Heather Geiger, Jackie Szymonifka, Michael McNamara, Ryan Cummings, Kathleen M. Andersen, Serene Mirza, Mark Figgie, Lionel B. Ivashkiv, …, Laura T. Donlin.
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Dana E. Orange, Phaedra Agius, Edward F. DiCarlo, Nicolas Robine, Heather Geiger, Jackie Szymonifka, Michael McNamara, Ryan Cummings, Kathleen M. Andersen, Serene Mirza, Mark Figgie, Lionel B. Ivashkiv, …, Laura T. Donlin.
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Functionally distinct disease-associated fibroblast subsets in rheumatoid arthritis.
Nature Communications
Fumitaka Mizoguchi, Kamil Slowikowski, Kevin Wei, Jennifer L. Marshall, Deepak A. Rao, Sook Kyung Chang, Hung N. Nguyen, Erika H. Noss, Jason D. Turner, Brandon E. Earp, Philip E. Blazar, John Wright, Barry P. Simmons, Laura T. Donlin, …, Michael B. Brenner
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Nature Communications
Fumitaka Mizoguchi, Kamil Slowikowski, Kevin Wei, Jennifer L. Marshall, Deepak A. Rao, Sook Kyung Chang, Hung N. Nguyen, Erika H. Noss, Jason D. Turner, Brandon E. Earp, Philip E. Blazar, John Wright, Barry P. Simmons, Laura T. Donlin, …, Michael B. Brenner
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Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis.
Nature
Deepak A. Rao, Michael F. Gurish, Jennifer L. Marshall, Kamil Slowikowski, Chamith Y. Fonseka, Yanyan Liu, Laura T. Donlin, Lauren A. Henderson, Kevin Wei, Fumitaka Mizoguchi, Nikola C. Teslovich, Michael E. Weinblatt, …, Michael B. Brenner.
Nature
Deepak A. Rao, Michael F. Gurish, Jennifer L. Marshall, Kamil Slowikowski, Chamith Y. Fonseka, Yanyan Liu, Laura T. Donlin, Lauren A. Henderson, Kevin Wei, Fumitaka Mizoguchi, Nikola C. Teslovich, Michael E. Weinblatt, …, Michael B. Brenner.
Mixed Effects Association of Single Cells Identifies an Expanded Th1-Skewed Cytotoxic Effector CD4+ T Cell Subset in Rheumatoid Arthritis
Science Translational Medicine
Chamith Y. Fonseka, Deepak A. Rao, Nikola C. Teslovich, Susan K. Hannes, Kamil Slowikowski, Michael F. Gurish, Laura T. Donlin, Michael E. Weinblatt, Elena M. Massarotti, Jonathan S. Coblyn, Simon M. Helfgott, Derrick J. Todd, Vivian P. Bykerk, Elizabeth W. Karlson, Soumya Raychaudhuri.
Science Translational Medicine
Chamith Y. Fonseka, Deepak A. Rao, Nikola C. Teslovich, Susan K. Hannes, Kamil Slowikowski, Michael F. Gurish, Laura T. Donlin, Michael E. Weinblatt, Elena M. Massarotti, Jonathan S. Coblyn, Simon M. Helfgott, Derrick J. Todd, Vivian P. Bykerk, Elizabeth W. Karlson, Soumya Raychaudhuri.
Modulation of TNF-induced macrophage polarization by synovial fibroblasts.
The Journal of Immunology
Laura T. Donlin, Arundathi Jayatilleke, Eugenia G. Giannopoulou, George D. Kalliolias and Lionel B. Ivashkiv.
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The Journal of Immunology
Laura T. Donlin, Arundathi Jayatilleke, Eugenia G. Giannopoulou, George D. Kalliolias and Lionel B. Ivashkiv.
| Data Set |
Accelerating Medicines Partnership
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The Accelerating Medicines Partnership (AMP) is a public-private partnership between the National Institutes of Health (NIH), the U.S. Food and Drug Administration (FDA), 12 biopharmaceutical and life science companies and 13 non-profit organizations to transform the current model for developing new diagnostics and treatments by jointly identifying and validating promising biological targets for therapeutics. The ultimate goal is to increase the number of new diagnostics and therapies for patients and reduce the time and cost of developing them.
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Defining Inflammatory Cell States in Rheumatoid Arthritis Joint Synovial Tissues by Integrating Single-cell Transcriptomics and Mass Cytometry
Nature Immunology
Fan Zhang, Kevin Wei, Kamil Slowikowski, Chamith Y. Fonseka, Deepak A. Rao, Stephen Kelly, Susan M Goodman, Darren Tabechian, Laura B. Hughes, Karen Salomon-Escoto, Gerald F. M. Watts, William Apruzzese …, Laura T. Donlin, Jennifer H. Anolik, Michael B. Brenner, Soumya Raychaudhuri.
| Data Set |
Nature Immunology
Fan Zhang, Kevin Wei, Kamil Slowikowski, Chamith Y. Fonseka, Deepak A. Rao, Stephen Kelly, Susan M Goodman, Darren Tabechian, Laura B. Hughes, Karen Salomon-Escoto, Gerald F. M. Watts, William Apruzzese …, Laura T. Donlin, Jennifer H. Anolik, Michael B. Brenner, Soumya Raychaudhuri.
| Data Set |
Methods for high-dimensional analysis of cells dissociated from cryopreserved synovial tissue
Journal of Arthritis Research and Therapy
Laura T. Donlin, Deepak A. Rao, Kevin Wei, Kamil Slowikowski, Mandy J. McGeachy, Jason D. Turner, Nida Meednu, Fumitaka Mizoguchi, Maria Gutierrez-Arcelus, David J. Lieb, …, Jennifer H. Anolik
| In the Press | Massive NIH–industry project opens portals to target validation
Journal of Arthritis Research and Therapy
Laura T. Donlin, Deepak A. Rao, Kevin Wei, Kamil Slowikowski, Mandy J. McGeachy, Jason D. Turner, Nida Meednu, Fumitaka Mizoguchi, Maria Gutierrez-Arcelus, David J. Lieb, …, Jennifer H. Anolik
| In the Press | Massive NIH–industry project opens portals to target validation