Research Interest Statement:
My research focuses on understanding the mechanisms by which cancer myeloma (MM) cells alter the biology of other cells in the tumor/bone marrow microenvironment, in particular osteocytes, with the final goal of identifying targetable factors for the treatment of cancer that grows in bone. My expertise is on osteocyte biology and pathophysiology, with experience in ex vivo and in vitro models to study osteocyte-tumor biology, and characterization of tumor growth and bone remodeling in animal models of MM-induced bone disease using genetic and pharmacologic approaches. Current projects in my laboratory investigate the effects of osteocyte-derived factors (i.e. Sclerostin) and Notch signaling communication in the tumor niche on MM growth, disease relapse, and bone disease. I also maintain an international collaboration with PharmaMar (Spain) to test the effects of Aplidin, a novel anti-tumor drug, on bone cells and MM growth. Moreover, I collaborate in studies examining the role of osteocytes in cancer-induced bone pain and muscle weakness.
“Bone-Targeted Therapies to Improve Bone Health and Prevent Relapse in Multiple Myeloma”
09/01/20 – 05/31/25
NIH/Nat. Cancer Institute – 1R01CA241677
“Manipulating the N-end Rule Protein Degradation Pathway to Build Bone and Decrease Tumor Growth in Multiple Myeloma Bone Disease”
07/01/20 – 02/28/25
Sabol HM, Amorim T, Ashby C, [et al., including Delgado-Calle J]. Notch3 signaling between myeloma cells and osteocytes in the tumor niche promotes tumor growth and bone destruction. Neoplasia (New York, N.Y.). 2022 28:100785. PMID: 35390742.
Delgado-Calle J, McAndrews K, Wu G, [et al.]. The Notch pathway regulates the bone gain induced by PTH anabolic signaling. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2022 36(3):e22196. PMID: 35137455. PMCID: PMC8855690.
Sabol HM, Ferrari AJ, Adhikari M, [et al., including Delgado-Calle J]. Targeting Notch inhibitors to the myeloma bone marrow niche decreases tumor growth and bone destruction without gut toxicity. Cancer research. 2021. PMID: 34348968.
Delgado-Calle J, Bellido T. The Osteocyte as a Signaling Cell. Physiological reviews. 2021. PMID: 34337974.
Adhikari M, Delgado-Calle J. Role of Osteocytes in Cancer Progression in the Bone and the Associated Skeletal Disease. Current osteoporosis reports. 2021. PMID: 33818732.
Sabol HM, Delgado-Calle J. The multifunctional role of Notch signaling in multiple myeloma. Journal of cancer metastasis and treatment. 2021 7. PMID: 34778567. PMCID: PMC8589324.
Chen J, Yuan X, Pilawski I, [et al., including Delgado-Calle J]. Molecular Basis for Craniofacial Phenotypes Caused by Sclerostin Deletion. Journal of dental research. 2020:22034520963584. PMID: 33078679.
Mulcrone PL, Edwards SKE, Petrusca DN, [et al., including Delgado-Calle J]. Osteocyte Vegf-a contributes to myeloma-associated angiogenesis and is regulated by Fgf23. Scientific reports. 2020 10(1):17319. PMID: 33057033. PMCID: PMC7560700.
Miyagawa K, Ohata Y, Delgado-Calle J, [et al.]. Osteoclast-derived IGF1 is required for pagetic lesion formation in vivo. JCI insight. 2020 5(6). PMID: 32078587. PMCID: PMC7213785.
Bellido T, Delgado-Calle J. Ex Vivo Organ Cultures as Models to Study Bone Biology. JBMR plus. 2020 4(3). PMID: 32161838. PMCID: PMC7059827.
Delgado-Calle J, Kurihara N, Atkinson EG, [et al.]. Aplidin (plitidepsin) is a novel anti-myeloma agent with potent anti-resorptive activity mediated by direct effects on osteoclasts. Oncotarget. 2019 10(28):2709-2721. PMID: 31105871. PMCID: PMC6505631.
Fernández AF, Bayón GF, Urdinguio RG, [et al., including Delgado-Calle J]. Corrigendum: H3K4me1 marks DNA regions hypomethylated during aging in human stem and differentiated cells. Genome research. 2019 29(4):710.2. PMID: 30936177. PMCID: PMC6442389.
Atkinson EG, Delgado-Calle J. The Emerging Role of Osteocytes in Cancer in Bone. JBMR plus. 2019 3(3):e10186. PMID: 30918922. PMCID: PMC6419608.
Marino S, Bishop RT, de Ridder D, [et al., including Delgado-Calle J]. 2D and 3D In Vitro Co-Culture for Cancer and Bone Cell Interaction Studies. Methods in molecular biology (Clifton, N.J.). 2019 1914:71-98. PMID: 30729461.
Delgado-Calle J, Hancock B, Likine EF, [et al.]. MMP14 is a novel target of PTH signaling in osteocytes that controls resorption by regulating soluble RANKL production. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2018 32(5):2878-2890. PMID: 29401593. PMCID: PMC5901377.
McDonald MM, Delgado-Calle J. Sclerostin: an Emerging Target for the Treatment of Cancer-Induced Bone Disease. Current osteoporosis reports. 2017 15(6):532-541. PMID: 28956252.
Delgado-Calle J, Anderson J, Cregor MD, [et al.]. Genetic deletion of Sost or pharmacological inhibition of sclerostin prevent multiple myeloma-induced bone disease without affecting tumor growth. Leukemia. 2017 31(12):2686-2694. PMID: 28529307. PMCID: PMC5699973.
Delgado-Calle J, Bellido T. New Insights Into the Local and Systemic Functions of Sclerostin: Regulation of Quiescent Bone Lining Cells and Beige Adipogenesis in Peripheral Fat Depots. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2017 32(5):889-891. PMID: 28370281. PMCID: PMC5489913.
Pérez-Campo FM, May T, Zauers J, [et al., including Delgado-Calle J]. Generation and characterization of two immortalized human osteoblastic cell lines useful for epigenetic studies. Journal of bone and mineral metabolism. 2017 35(2):150-160. PMID: 27038990.
Delgado-Calle J. Osteoclasts Control Lipid Secretion to Regulate Breast Cancer Bone Metastasis. Endocrinology. 2017 158(3):458-460. PMID: 28430916.
Delgado-Calle J, Sato AY, Bellido T. Role and mechanism of action of sclerostin in bone. Bone. 2017 96:29-37. PMID: 27742498. PMCID: PMC5328835.
Delgado-Calle J, Tu X, Pacheco-Costa R, [et al.]. Control of Bone Anabolism in Response to Mechanical Loading and PTH by Distinct Mechanisms Downstream of the PTH Receptor. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2017 32(3):522-535. PMID: 27704638.
Sato AY, Cregor M, Delgado-Calle J, [et al.]. Protection From Glucocorticoid-Induced Osteoporosis by Anti-Catabolic Signaling in the Absence of Sost/Sclerostin. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2016 31(10):1791-1802. PMID: 27163932.
Toraño EG, Bayón GF, Del Real Á, [et al., including Delgado-Calle J]. Age-associated hydroxymethylation in human bone-marrow mesenchymal stem cells. Journal of translational medicine. 2016 14(1):207. PMID: 27393146. PMCID: PMC4938941.
Delgado-Calle J, Anderson J, Cregor MD, [et al.]. Bidirectional Notch Signaling and Osteocyte-Derived Factors in the Bone Marrow Microenvironment Promote Tumor Cell Proliferation and Bone Destruction in Multiple Myeloma. Cancer research. 2016 76(5):1089-100. PMID: 26833121. PMCID: PMC4775415.
Delgado-Calle J, Bellido T. Osteocytes and Skeletal Pathophysiology. Current molecular biology reports. 2015 1(4):157-167. PMID: 26693137. PMCID: PMC4673661.