540 E. Canfield
6304 Scott Hall
Detroit, MI 48201
• Tumor-induced lipolysis in adipocytes and its role in tumor progression and chemotherapy response
• Lipid-induced endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in tumor survival and chemoresistance
• Lipid-mediated modulation of metabolic enzymes
• Factors driving tumor-induced bone destruction
• Targeting mitochondrial metabolism in bone marrow macrophages as therapeutic approach in metastatic disease
Bone marrow is a common host of several types of tumors, including secondary cancers of the prostate, breast, thyroid, kidney, lung, and bladder as well as hematological malignancies, such as multiple myelomas and leukemias. A common feature of tumor cells that reside in bone is that their proliferation and survival are critically dependent on the interaction with the bone marrow microenvironment. One important component of bone marrow stroma are the adipocytes, whose numbers are significantly augmented with age or metabolic pathologies. Fat cells negatively affect bone metabolism and function, and escalate bone degradation, making the bone marrow more supportive of tumor growth. Metastatic tumor cells have high avidity for lipids and lipid-mediated cross-talk between marrow adipocytes and tumor cells alters cellular energetics, disrupts redox homeostasis and profoundly affects signaling pathways that allow the cells to gain pro survival advantage and thrive in the metastatic niche.
Our main research objectives are to identify molecular mechanisms underlying the association between bone marrow adiposity and metastatic prostate, breast and kidney cancers and to pinpoint key factors responsible for aggressiveness and chemoresistance. Our studies involve mouse models of lipolysis, PDX models, 3D culture techniques and patient samples in combination with pharmacological and genetic manipulation, RNAseq and proteomic technologies. Our ultimate goal is to provide translational insight into advancing current treatment options for bone-metastatic disease.
We also collaborate on the development and characterization of photoactivatable protease inhibitors as potential agents in treatment of primary cancer and metastatic disease.
Herroon M.K., Diedrich J.D., Rajagurubandara R., Martin C., Maddipati K.R., Kim S., Heath E.I., Granneman J.G., and Podgorski I. ”Prostate tumor cell-derived IL-1β induces an inflammatory phenotype in bone marrow adipocytes and reduces sensitivity to docetaxel via lipolysis-dependent mechanisms”. Molecular Cancer Research. 2019;17:2508-21.
Vaishampayan, U, Podgorski, I , Heilbrun L, Lawhorn-Crews J , Dobson K, Boerner J , Stark K , Smith D, Heath E , Fontana J and Shields A . Biomarkers and Bone Imaging Dynamics associated with Clinical outcomes of Oral Cabozantinib Therapy in Metastatic Castrate Resistant Prostate Cancer. Clinical Cancer Research. 2019;25:652-62
Diedrich, JD, Herroon, MK., Rajagurubandara, E and Podgorski I. The lipid side of bone marrow adipocytes: how tumor cells thrive and survive in bone. Curr Osteoporos Rep. 2018;16:443-57.
Herroon, M., E. Rajagurubandara, J. Diedrich, E.I. Heath, and I. Podgorski, Adipocyte-activated oxidative and ER stress pathways promote tumor survival in bone via upregulation of Heme Oxygenase 1 and Survivin. Sci Rep, 2018;8:40.
Chen G, Zhou, G, Aras, S, He, Z, Lucas, S, Podgorski, I, Sakr, W, Granneman jG, and Wang, J. Loss of ABHD5 promotes aggressiveness of prostate cancer cells. Sci Rep, 2017;7:13021.
Diedrich, J, Rajagurubandara, E, Herroon, M, Mahapatra, G, Huttemann, M, and Podgorski, I. Bone Marrow Adipocytes Promote Warburg Phenotype in Metastatic Prostate Tumors through HIF-1a activation. Oncotarge. 2016;7:64854-77.
Herroon, M, Diedrich J, and Podgorski, I. "New 3D-culture approaches to study interactions of bone marrow adipocytes with metastatic prostate cancer cells.", Frontiers in Endocrinology (Lausanne). 2016;7:84.
PhD (2001) Oakland University, Rochester Hills, Michigan
CB7300 Special Topics F31 Grant Writing Course
CB7460 Mechanisms of Neoplasia: Alterations to Cellular Signaling
CB7700 Recent Developments in Cancer Biology