- Bucknell University
- University of Pennsylvania
- Washington University
Awards & Honors
- Gina Finzi Memorial Student Fellowship Award, Lupus Foundation of America (1994)
- Dr. Monica H.M. Shander Fellowship Award, The Wistar Institute (1997–98)
- Saul Winegrad Award for Outstanding Dissertation, University of Pennsylvania (1999)
- Junior Faculty Travel Award, American Association of Immunologists (2010)
- Laboratory Travel Award, American Association of Immunologists (2014 and 2017)
Rheumatoid arthritis (RA) is an autoimmune disease that affects approximately 1.3 million individuals in the United States. Of those, about 75 percent are women.
RA is a chronic (i.e., long-term) disease that causes pain, stiffness, swelling, and limited motion and function of many joints. While the cause of RA is unknown, new research is helping to shed light on what makes the immune system attack the body and create the joint inflammation that plagues patients with RA. We know that immune cells (T and B cells) play critical roles in the disease’s progression.
RA eventually leads to debilitating destruction of cartilage and bone, and unfortunately there is no cure. Treatments to manage symptoms have improved greatly over the years. However, they are ineffective at controlling disease progression, as they rely on the reduction of inflammation by focusing only on the end stage of the disease.
Focus on RA triggers
Dr. Laura Mandik-Nayak is taking a different approach by targeting the early stage of RA. Her lab focuses on the triggering mechanisms by which the immune system becomes activated to induce inflammation in the joints.
Recently, Dr. Mandik-Nayak identified a pathway that triggers the activation of autoreactive T and B cells during the development of arthritis. This pathway involves an enzyme implicated in immune regulation, IDO (indoleamine 2,3-dioxygenase). IDO activity is elevated in arthritis patients. Dr. Mandik-Nayak’s recent data demonstrate that inhibiting IDO activity interferes with immune cell activation and arthritis development, suggesting that the IDO pathway is an important mediator of the disease process.
Her group examined both IDO1 and IDO2 in relation to autoimmune arthritis development. Their work reveals that IDO2, but not IDO1, is an important component of developing arthritis symptoms. They found that IDO2 drives the autoreactive T and B cell response leading to arthritis. The enzyme appears to specifically affect the production of autoantibodies, but does not seem to play a role in mediating antibody responses in general.
Dr. Mandik-Nayak is investigating if using an IDO inhibitor could lead to a therapeutic agent for RA. Her work may lead to a new approach and to novel medicines for the prevention and treatment of RA and possibly other autoimmune diseases.
About her lab
Since starting the first immunological laboratory at LIMR in 2006, Dr. Mandik-Nayak has focused on mediators that drive the inflammatory autoimmune response in mouse models of RA, systemic lupus erythematosus, and rheumatoid heart disease, with an emphasis not only on the immunoregulatory enzymes of IDO, but also the small GTPase RhoB.
- Lauren Merlo, PhD, Research Assistant Professor
- Weidan Peng, PhD, Research Assistant Professor
- James Montgomery, BA, Biomedical Research Assistant
- IDO1 Signaling Through GCN2 in a Subpopulation of Gr-1+ Cells Shifts the IFNγ/IL6 Balance to Promote Neovascularization. Dey S, Mondal A, DuHadaway JB, Sutanto-Ward E, Laury-Kleintop LD, Thomas S, Prendergast GC, Mandik-Nayak L, Muller AJ. Cancer Immunol Res. 2021 May;9(5):514-528.
- Differential Roles of IDO1 and IDO2 in T and B Cell Inflammatory Immune Responses. Merlo L, DuHadaway J, Montgomery J, Peng WD, Prendergast G, Muller A, Mandik-Nayak L. Front Immunol. 2020. doi.org/10.3389/fimmu.2020.01861.
- B-Cell-Targeted 3DNA Nanotherapy Against Indoleamine 2,3-Dioxygenase 2 (IDO2) Ameliorates Autoimmune Arthritis in a Preclinical Model. Merlo LMF, Bowers J, Stefanoni T, Getts R, Mandik-Nayak L. 2020;13: doi.org/10.1177/2632010X20951812.
- Peptide vaccination directed against IDO1-expressing immune cells elicits CD8+ and CD4+ T-cell-mediated antitumor immunity and enhanced anti-PD1 responses. Dey S, Sutanto-Ward E, Kopp KL, DuHadaway J, Mondal A, Ghaban D, Lecoq I, Zocca MB, Merlo LMF, Mandik-Nayak L, Andersen MH, Pedersen AW, Muller AJ. J Immunother Cancer. 2020 Jul;8(2):e000605.
- Host IDO2 gene status influences tumor progression and radiotherapy response in KRAS-driven sporadic pancreatic cancers. Nevler A, Muller AJ, Sutanto-Ward E, DuHadaway JB, Nagatomo K, ... Mandik-Nayak L, Winter JM, Yeo CJ, Prendergast GC, Brody JR. Clin Cancer Res. 2018 Sep 28. doi: 10.1158/1078-0432.CCR-18-0814.
- RhoB blockade selectively inhibits autoantibody production in autoimmune models of rheumatoid arthritis and lupus. Mandik-Nayak L, DuHadaway JB, Mulgrew J, Pigott E, Manley K, Sedano S, Prendergast GC, Laury-Kleintop LD. Dis Model Mech. 2017 Sep 7.
- Therapeutic antibody targeting of indoleamine-2,3-dioxygenase (IDO2) inhibits autoimmune arthritis. Merlo LM, Grabler S, DuHadaway JB, Pigott E, Manley K, Prendergast GC, Laury-Kleintop LD, Mandik-Nayak L. Clin Immunol. 2017 Feb 20;179:8-16.
- IDO2: A Pathogenic Mediator of Inflammatory Autoimmunity. Merlo LM, Mandik-Nayak. L.Clin Med Insights Pathol. 2016 Nov 21;9(Suppl 1):21-28.
- IDO2 Modulates T Cell-Dependent Autoimmune Responses through a B Cell-Intrinsic Mechanism. Merlo LM, DuHadaway JB, Grabler S, Prendergast GC, Muller AJ, Mandik-Nayak L. J Immunol. 2016 Jun 1;196(11):4487-97.
- IDO2 in Immunomodulation and Autoimmune Disease. Prendergast GC, Metz R, Muller AJ, Merlo LM, Mandik-Nayak L. Front Immunol. 2014 Nov 20;5:585.
- 1-Methyl-tryptophan synergizes with methotrexate to alleviate arthritis in a mouse model of arthritis. Pigott E, DuHadaway JB, Muller AJ, Gilmour S, Prendergast GC, Mandik-Nayak L. Autoimmunity. 2014 Sep;47(6):409-18.
- IDO2 is critical for IDO1-mediated T-cell regulation and exerts a non-redundant function in inflammation. Metz R, Smith C, DuHadaway JB, Chandler P, Baban B, Merlo LM, Pigott E, Keough MP, Rust S, Mellor AL, Mandik-Nayak L, Muller AJ, Prendergast GC. Int Immunol. 2014 Jul;26(7):357-67.
- IDO2 is a critical mediator of autoantibody production and inflammatory pathogenesis in a mouse model of autoimmune arthritis. Merlo LM, Pigott E, DuHadaway JB, Grabler S, Metz R, Prendergast GC, Mandik-Nayak L. J Immunol. 2014 Mar 1;192(5):2082-90.
- Addition of indoleamine 2,3-dioxygenase inhibitor to B cell-depletion therapy blocks autoreactive B cell activation and recurrence of arthritis in K/BxN mice. Pigott, E, Mandik-Nayak, L Arthritis Rheum. 2012 64:2169-2178.