Research Interest

My research focuses on understanding the mechanisms by which myeloma cancer cells alter the biology of other cells in the tumor niche with the final goal of identifying targetable factors for the treatment of multiple myeloma. Current projects in my laboratory investigate the effects of Wnt and Notch signaling between myeloma cells and bone cells on tumor growth, cancer cell dormancy, and bone destruction. Moreover, I collaborate in studies examining the role of bone cells in cancer-induced bone pain and muscle weakness, and the deleterious effects that glucocorticoids have in the skeleton. Other projects in my laboratory investigate the crosstalk between bone and adipose tissues that regulates body fat and whole-body metabolism.

 

Publications

  1. Delgado-Calle J, Anderson J, Cregor M, Condon K, Kuhstoss S, Plotkin LI, Bellido T, and Roodman GD. Genetic deletion of Sost or pharmacological inhibition of Sclerostin prevent multiple myeloma-induced bone disease without affecting tumor growth. Leukemia, 2017; 1(12):2686-2694. PM: 28529307
  2. Delgado-Calle J, Anderson J, Cregor M, Carlesso N, Mohammad KS, Plotkin LI, Roodman GD, and Bellido T. Bidirectional Notch signaling activated by interactions between multiple myeloma cells and osteocytes drives tumor cell proliferation and osteoclast recruitment. Cancer Research 2016; 2016; 76(5):1089-100. PM: 26833121
  3. Delgado-Calle J*, Kurihara N, Atkinson EG, Nelson J, Miyagawa K, Galmarini CM, Roodman GD, Bellido T. 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. PM: 31105871 *corresponding author.
  4. Delgado-Calle J*, Tu X*, Condon K, Maycas Cepeda M, Zhang H, Carlesso N, Taketo MM, Burr D, Plotkin LI and Bellido T. Osteocytes mediate the anabolic actions of canonical Wnt/β-catenin signaling in bone. Proc Natl Acad Sci USA. 2015; 112(5): E478-86. PM: 25605937 *contributed equally
  5. Delgado-Calle J*, Tu X*, Pacheco-Costa R, McAndrews K, Edwards R, Pellegrini GG, Kuhlenschmidt K, Olivos N, Robling A, Peacock M, Plotkin LI and Bellido T. Osteocytes control bone anabolism in response to mechanical loading and PTH by distinct mechanisms downstream of the PTH receptor. J Bone Miner Res. 2017; 32(3):522-535. PM: 27704638 *contributed equally

 

Projects

NIH-NCI 1R37CA209882

Title: “Bone-Targeted Therapies to Improve Bone Health and Prevent Relapse in Multiple Myeloma”.

The objective of this study is to investigate the anti-myeloma efficacy and safety profile of a novel bone-targeted Notch inhibitor alone or in combination with bone anabolic agents.

 

American Cancer Association-Indiana University Simon Cancer Center

Title: “Role of Notch signaling in mieloma cell dormancy”

The aim of this study is to investigate the effects of Notch signaling inhibition targeted to the tumor microenvirnmnet on myeloma cell dormancy.

 

PharmaMar S.A.

Title: “Characterization of Aplidin® (plitidepsin) effects on multiple myeloma (MM)-induced bone disease.”

The goal of this proposal is to investigate the effects of Aplidin on osteocytes and multiple myeloma cells using in vitro, ex vivo and in vivo approaches.

 

NIH-NCI 1R01CA209882

Title: “Musculoskeletal effects of osteocyte-tumor cell interactions in myeloma”.

The objective of this study is to investigate the role of osteocytes and their derived factor to the onset and progression of multiple myeloma-induced bone disease.

 

NIH-NCI R01CA241677

Title: “Manipulating the N-end Rule Protein Degredation Pathway to Build Bone and Decrease Tumor Growth in Multiple Myeloma Bone Disease.”

In this collaboration with Dr. Roodman’s laboratory, we will investigate the mechanisms responsible for XRK’s, a p62 inhibitor, effects in MM as a means to build bone, decrease tumor growth and develop new mechanism-based therapeutic agents for MM.

 

Funding

As principal investigator (PI) or Project Leader

 

  • NIH (PI Delgado-Calle)                                    07/06/2022-07/05/2029      2 calendar

NCI 1R37CA209882                                              $250,000 annual direct costs

 

  • American Cancer Association (PI Delgado-Calle) 08/01/2019-07/30/2020 0 calendar

IRG-IUSCC Pilot funding                                                   $40,000 annual direct costs

 

  • PharmaMar S.A. (PI Bellido, co-PI Delgado-Calle) 10/01/2018-06/31/2020 0.0 calendar

$107,000 annual direct costs

 

As a collaborator

NIH (MPI Bellido/Roodman, co-I Delgado-Calle)   03/15/2017-03/14/2022  7.0 calendar

NCI 1R01CA209882-01A1                                                $256,504 annual direct costs

 

NIH (PI Roodman, co-I Delgado-Calle)                   3/4/2020-2/28/2025        1.2 calendar

NCI R01CA241677                                                             $250,000 annual direct costs

 

Pending

 

  • NIH, Role: (PI Roodman, co-I Delgado-Calle) 4 calendar

NIAMS R01                                                                             $390,983 annual direct costs

“Osteoclast-Osteocyte Interaction’s in Paget’s Disease”

Scored 2/18/20: 19 percentile.

 

Completed research support

 

  • 05/01/2019-04/31/2020. Agency: Marian University, USA. Role: PI. This grant provided funds to support the thesis research work of three master students.

 

  • 03/01/2019-02/28/2020. Agency: CTSI Use of cores program, USA, “Role of osteocytes in the regulation of body energy balance”. Role: PI. This grant provided funds to study the role of osteocytes in energy metabolism.

 

  • 06/01/2016-12/31/2019. Agency: ASH Scholar Award, American Society of Hematology, USA, “Targeting Notch in multiple myeloma”. Role: PI. The objective of this study is to investigate the efficacy of genetic and pharmacologic inhibition of Notch receptor 3 signaling in MM and its associated bone disease.

 

  • 05/01/2018-12/31/2019. Agency: Herman B Wells Center for Pediatric Research, USA, “Actions of Sclerostin in pancreatic beta-cell function.” Role: PI. The aim of this application is to investigate the effects of bone-derived Sclerostin on the regulation of glucose metabolism through direct actions on pancreatic cells.

 

  • 05/01/2018-04/31/2019. Agency: Marian University Master Program MU-COM, USA. Role: PI. This grant provides funds to support the thesis research work of two master students.

 

  • 05/01/2018-12/31/2018. Agency: Marian University Faculty Development Award, USA, “Inhibition of Notch receptor 3 in multiple myeloma“. Role: PI, co-PI Julia Hum. The aim of this application is to investigate the effects inhibiting Notch receptor 3 on multiple myeloma bone disease.

 

  • 01/01/2017-12/31/2018. Agency: International Myeloma Foundation, Brian D. Novis Jr Award, USA, “Bone/bone marrow-targeted inhibition of Notch signaling in combination with glucocorticoid therapy as a novel approach to treat multiple myeloma”. Role: The aim of this application is to investigate the efficacy of pharmacologic inhibition of Notch signaling in MM growth, muscle weakness and bone disease.

 

  • 01/01/2013-01/31/2017. Agency: Instituto de Salud Carlos III (ISC III), PI12/615, Spain, “DNA methylation: role as a pathogenic factor and as a biomarker in bone metabolism disorders”. Role: co-I (PI: Riancho). The goal of this proposal is to determine whether changes in DNA methylation can be used as biomarkers to predict or diagnose bone metabolism disorders.

 

  • 1/13-15-1/13/2016. Agency: NCI Near Miss, IU Melvin and Bren Simon Cancer Center, USA, “Musculoskeletal Effects of Cancer in Bone”. Role: postdoctoral fellow. The goal of this proposal is to determine the mechanisms responsible for the increased tumor growth, bone destruction, muscle dysfunction, and debilitating bone pain that result from interactions between osteocytes and tumor cells, when cancer metastasizes to bone.

 

  • 1/1/2014-12/31/2015. Agency: International bone and Mineral Research Society (IBMS), USA, “Role of osteocytes in multiple myeloma bone disease.” Role: PI. This proposal explored the role of Sclerostin produced by osteocytes in the inhibition of bone formation associated with multiple myeloma bone disease.

 

Trainees

2019-present            Hayley Sabol: master student. Project: Characterization of the bone effects of Aplidin. Training provided: histomorphometry, microCT, RNA isolation, quantitative PCR, cell culture. Master thesis: Role of Notch receptor 3 signaling in multiple myeloma disease. 

2019-2020                Megan Sweet: undergraduate student. Project: role of Sclerostin in the crosstalk between bone and distant organs. Training provided: histomorphometry, microCT, RNA isolation, quantitative PCR, cell culture.

2019-2020                Tania Amorim: postdoctoral fellow. Project: Role of osteocytes in multiple myeloma bone disease. Training provided: histomorphometry, microCT, RNA isolation, quantitative PCR, cell culture.

2018-2019                Ashely Daniel: master student. Project: Role of Sclerostin in the regulation of body composition. Training provided: histomorphometry, microCT, RNA isolation, quantitative PCR, cell culture, viability assays. Master thesis: Bone derived Sclerostin regulates whole-body adipose tissue via paracrine and endocrine actions on adipocyte precursors. 

2018-2019                Adam Ferrari: master student. Project: Role of osteocytes in multiple myeloma bone disease. Training provided: histomorphometry, microCT, RNA isolation, quantitative PCR, cell culture, viability assays. Master thesis: Inhibition of Notch Signaling in the Myeloma-bone Marrow Niche Simultaneously Decreases Tumor Growth and Prevents Bone Loss without Inducing Gut Toxicity.

2018-2019                James Bell: undergraduate student. Project: Inhibition of Notch signaling in multiple myeloma. Training provided: cell culture, RNA isolation, quantitative PCR, tissue harvest.

2017-2019                Jessica Nelson: research technician. Project: Effects of Aplidin on bone cells. Training provided: RNA isolation, quantitative PCR, cell culture, genotyping, PCR, BMD analysis, viability assays.

2017-2018                Emily Atkinson: graduate student (co-mentor with Drs. Bellido and Roodman). Project: Role of osteocytes in multiple myeloma bone disease. Training provided: RNA isolation, quantitative PCR, cell culture, viability assays.

2017                           Mathew Olson: 3rd year medical student at Marian University. Training provided: RNA isolation, quantitative PCR.

2017                           Gerald Wu: summer student. Project: role of Notch signaling on the skeletal actions of PTH. Training provided: DNA/RNA isolation, PCR, quantitative PCR, cDNA conversion, genotyping, and dynamic and static histomorphometry.

2016                           Victor Dominguez: summer student. Project: role of Sclerostin in MM-induced bone disease. Training provided: RNA isolation, quantitative PCR, and dynamic and static histomorphometry.

2016                           Elive Likine: summer student. Project: role of MMP14 in PTH signaling. Training provided: western blot, RNA isolation, quantitative PCR, and dynamic and static histomorphometry.

2015-2016                Dr. Aiji Yajima: postdoctoral fellow. Project: role of MMP14 in PTH signaling. Training provided: dynamic histomorphometry, PCR, statistics, Microsoft package, and Sigma Plot.

2015                           Benjamin Hancock: summer student. Project: role of MMP14 in PTH signaling. Training provided: Dynamic and static histomorphemtry, RNA isolation, gene expression by qPCR, protein expression by ELISA, and cell culture (in vitro and ex vivo models).

2014                           Monica Feustel: summer student. Project: role of MMP14 in PTH signaling. Training provided: dynamic histomorphometry, cell culture, RNA isolation.

 

Lab Personnel

Hayley Sabol (graduate student)

TBD (postdoctoral fellow; position open)

TBD (research technician; position open)