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James Arthur Lederer, PhD
Associate Research Associate, Brigham and Women's Hospital
Associate Professor of Surgery, Harvard Medical School

Brigham and Women's Hospital
Department of Surgery
75 Francis Street
Boston, MA 02115

Research Location: Thorn Research Building

Email: jlederer@partners.org
Research Email: jlederer@rics.bwh.harvard.edu

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Research Narrative:

My research program addresses how traumatic injuries activate, modulate, and influence the immune system and immunity. We develop immunotherapies to protect critically-injured people from developing infections and complications from trauma. We are also developing immune targeted medical countermeasures to help protect individuals that may be exposed to radiation or radiation combined traumatic injuries following accidental or intentional radionuclear events.  Due to the complex nature of trauma immunology, we use systems immunology approaches like CyTOF mass cytometry to study the cells and mediators of the injury, radiation, and infection response. Overall, advances made by this research has contributed to the concept that traumatic injuries alter immune homeostasis, which has provided us and others with insights for developing novel interventional therapies that could be used to reduce the morbidity and mortality associated with trauma. My research group also houses and runs the Harvard Medical Area CyTOF Antibody Resource and Core.  This resource has provided many research groups with CyTOF-ready antibodies and CyTOF technical help to include staining protocols and data analysis. We are actively involved in several collaborative and consortium funded projects that use CyTOF mass cytometry for single-cell phenotyping of complex disease processes like tumor-site and blood immune responses in cancer and immune system phenotyping in autoimmune diseases – rheumatoid arthritis and lupus – as part of the Accelerating Medicines Partnership


Education:
PhD

Publications (Pulled from Harvard Catalyst Profiles):

1. Lee PY, Nelson-Maney N, Huang Y, Levescot A, Wang Q, Wei K, Cunin P, Li Y, Lederer JA, Zhuang H, Han S, Kim EY, Reeves WH, Nigrovic PA. High-dimensional analysis reveals a pathogenic role of inflammatory monocytes in experimental diffuse alveolar hemorrhage. JCI Insight. 2019 Aug 08; 4(15).

2. Seshadri A, Brat GA, Yorkgitis BK, Giangola M, Keegan J, Nguyen JP, Li W, Nakahori Y, Wada T, Hauser C, Salim A, Askari R, Lederer JA. Altered monocyte and NK cell phenotypes correlate with posttrauma infection. J Trauma Acute Care Surg. 2019 Aug; 87(2):337-341.

3. Arazi A, Rao DA, Berthier CC, Davidson A, Liu Y, Hoover PJ, Chicoine A, Eisenhaure TM, Jonsson AH, Li S, Lieb DJ, Zhang F, Slowikowski K, Browne EP, Noma A, Sutherby D, Steelman S, Smilek DE, Tosta P, Apruzzese W, Massarotti E, Dall'Era M, Park M, Kamen DL, Furie RA, Payan-Schober F, Pendergraft WF, McInnis EA, Buyon JP, Petri MA, Putterman C, Kalunian KC, Woodle ES, Lederer JA, Hildeman DA, Nusbaum C, Raychaudhuri S, Kretzler M, Anolik JH, Brenner MB, Wofsy D, Hacohen N, Diamond B. The immune cell landscape in kidneys of patients with lupus nephritis. Nat Immunol. 2019 07; 20(7):902-914.

4. Zhang F, Wei K, Slowikowski K, Fonseka CY, Rao DA, Kelly S, Goodman SM, Tabechian D, Hughes LB, Salomon-Escoto K, Watts GFM, Jonsson AH, Rangel-Moreno J, Meednu N, Rozo C, Apruzzese W, Eisenhaure TM, Lieb DJ, Boyle DL, Mandelin AM, Boyce BF, DiCarlo E, Gravallese EM, Gregersen PK, Moreland L, Firestein GS, Hacohen N, Nusbaum C, Lederer JA, Perlman H, Pitzalis C, Filer A, Holers VM, Bykerk VP, Donlin LT, Anolik JH, Brenner MB, Raychaudhuri S. Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry. Nat Immunol. 2019 07; 20(7):928-942.

5. Fonseka CY, Rao DA, Teslovich NC, Korsunsky I, Hannes SK, Slowikowski K, Gurish MF, Donlin LT, Lederer JA, Weinblatt ME, Massarotti EM, Coblyn JS, Helfgott SM, Todd DJ, Bykerk VP, Karlson EW, Ermann J, Lee YC, Brenner MB, Raychaudhuri S. Mixed-effects association of single cells identifies an expanded effector CD4+ T cell subset in rheumatoid arthritis. Sci Transl Med. 2018 Oct 17; 10(463).

6. Ledderose C, Liu K, Kondo Y, Slubowski CJ, Dertnig T, Denicoló S, Arbab M, Hubner J, Konrad K, Fakhari M, Lederer JA, Robson SC, Visner GA, Junger WG. Purinergic P2X4 receptors and mitochondrial ATP production regulate T cell migration. J Clin Invest. 2018 Aug 01; 128(8):3583-3594.

7. Donlin LT, Rao DA, Wei K, Slowikowski K, McGeachy MJ, Turner JD, Meednu N, Mizoguchi F, Gutierrez-Arcelus M, Lieb DJ, Keegan J, Muskat K, Hillman J, Rozo C, Ricker E, Eisenhaure TM, Li S, Browne EP, Chicoine A, Sutherby D, Noma A, Nusbaum C, Kelly S, Pernis AB, Ivashkiv LB, Goodman SM, Robinson WH, Utz PJ, Lederer JA, Gravallese EM, Boyce BF, Hacohen N, Pitzalis C, Gregersen PK, Firestein GS, Raychaudhuri S, Moreland LW, Holers VM, Bykerk VP, Filer A, Boyle DL, Brenner MB, Anolik JH. Methods for high-dimensonal analysis of cells dissociated from cyropreserved synovial tissue. Arthritis Res Ther. 2018 07 11; 20(1):139.

8. Baron RM, Kwon MY, Castano AP, Ghanta S, Riascos-Bernal DF, Lopez-Guzman S, Macias AA, Ith B, Schissel SL, Lederer JA, Reeves R, Yet SF, Layne MD, Liu X, Perrella MA. Frontline Science: Targeted expression of a dominant-negative high mobility group A1 transgene improves outcome in sepsis. J Leukoc Biol. 2018 10; 104(4):677-689.

9. Mizoguchi F, Slowikowski K, Wei K, Marshall JL, Rao DA, Chang SK, Nguyen HN, Noss EH, Turner JD, Earp BE, Blazar PE, Wright J, Simmons BP, Donlin LT, Kalliolias GD, Goodman SM, Bykerk VP, Ivashkiv LB, Lederer JA, Hacohen N, Nigrovic PA, Filer A, Buckley CD, Raychaudhuri S, Brenner MB. Functionally distinct disease-associated fibroblast subsets in rheumatoid arthritis. Nat Commun. 2018 02 23; 9(1):789.

10. Seshadri A, Brat GA, Yorkgitis BK, Keegan J, Dolan J, Salim A, Askari R, Lederer JA. Phenotyping the Immune Response to Trauma: A Multiparametric Systems Immunology Approach. Crit Care Med. 2017 Sep; 45(9):1523-1530.