In spite of major therapeutic advances there is an unmet need to gain fundamental insights into the pathogenesis of myeloma (MM) and develop newer approaches to prevent clinical malignancy. Our research program will build on our prior efforts in two areas- understanding the etio-pathogenesis of myeloma and harnessing host response to prevent cancer. In recent studies, we have discovered that chronic activation by lysolipids underlies the etiology of MM in nearly a third of patients. We have also developed new humanized mouse models that span the entire spectrum of malignancy, including precursor states. These advances set the stage for next studies to better understand how lipid-mediated inflammation may drive the development of myeloma and how to prevent it. Understanding these pathways may have implications for mechanisms underlying lipid-mediated inflammation in diverse states including obesity. MM and its precursor states are also an important model to probe basic questions about how to harness the biology of both adaptive and innate immune system to prevent cancer.

Public Health Relevance

Our research program focuses on understanding how the immune cells surrounding tumors can be harnessed to prevent cancers. We have also gained fundamental insights into how lipids and inflammation can drive the development of tumors. These studies take advantage of several new tools including mouse models developed by our group.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Unknown (R35)
Project #
5R35CA197603-02
Application #
9323356
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Howcroft, Thomas K
Project Start
2016-08-01
Project End
2018-02-28
Budget Start
2017-08-01
Budget End
2018-02-28
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Yale University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Nair, Shiny; Sng, Joel; Boddupalli, Chandra Sekhar et al. (2018) Antigen-mediated regulation in monoclonal gammopathies and myeloma. JCI Insight 3:
Garfall, Alfred L; Stadtmauer, Edward A; Hwang, Wei-Ting et al. (2018) Anti-CD19 CAR T cells with high-dose melphalan and autologous stem cell transplantation for refractory multiple myeloma. JCI Insight 3:
Jagannath, Sundar; Laubach, Jacob; Wong, Ellice et al. (2018) Elotuzumab monotherapy in patients with smouldering multiple myeloma: a phase 2 study. Br J Haematol 182:495-503
Weinreb, Neal J; Mistry, Pramod K; Rosenbloom, Barry E et al. (2018) MGUS, lymphoplasmacytic malignancies, and Gaucher disease: the significance of the clinical association. Blood 131:2500-2501
Costa, Federica; Das, Rituparna; Kini Bailur, Jithendra et al. (2018) Checkpoint Inhibition in Myeloma: Opportunities and Challenges. Front Immunol 9:2204
Das, Rituparna; Bar, Noffar; Ferreira, Michelle et al. (2018) Early B cell changes predict autoimmunity following combination immune checkpoint blockade. J Clin Invest 128:715-720
Nair, Shiny; Dhodapkar, Madhav V (2017) Natural Killer T Cells in Cancer Immunotherapy. Front Immunol 8:1178
Stroncek, David F; Butterfield, Lisa H; Cannarile, Michael A et al. (2017) Systematic evaluation of immune regulation and modulation. J Immunother Cancer 5:21
Kini Bailur, Jithendra; Mehta, Sameet; Zhang, Lin et al. (2017) Changes in bone marrow innate lymphoid cell subsets in monoclonal gammopathy: target for IMiD therapy. Blood Adv 1:2343-2347
Dhodapkar, Madhav V; Borrello, Ivan; Cohen, Adam D et al. (2017) Hematologic Malignancies: Plasma Cell Disorders. Am Soc Clin Oncol Educ Book 37:561-568

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