Izabela Podgorski (ak5520)

 Professor

540 E. Canfield
6312 Scott Hall
Detroit, MI 48201 

 Alexis Wilson 

 Pharmacology

• 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.

Wilson A, Garmo L, and Podgorski I. “Interplay between fat cells and immune cells in bone: Impact on malignant progression and therapeutic response”, Pharmacology and Therapeutics, 2022; 238:108274

Herroon M.K., Mecca S, Haimbaugh A, Garmo L.C., Rajagurubandara E, Todi SV, Baker TR, and Podgorski I. “Adipocyte-driven unfolded protein response is a shared transcriptomic signature of metastatic prostate carcinoma cells” BBA- Molecular Cell Research, October 2021; 1868(11):119101

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.

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.

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 

540 East Canfield, 6312 Scott Hall
Detroit, MI 48201

Office: 313-577-0514
Lab: 313-577-0941

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.

 Our current work focuses on:

• 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
  
• We also collaborate on the development and characterization of photoactivatable protease inhibitors as potential agents in treatment of primary cancer and metastatic disease.

Current Lab Personnel: 

• Mackenzie Herroon, M.A., Research Assistant
• Shane Mecca, B.S., Research Assistant
• Alexis Wilson, B.S., Cancer Biology PhD Student
• Laimar Garmo, B.S., Pharmacology PhD Student
• Shrila Rajendran, B.S., M2 Medical Student
• David Allen, B.S., M2 Medical Student

Select Publications:

Hazelton J, Kims S, Boerner JL, Podgorski I, Perk, T, Cackowski, F, Aoun, HD and Heath EI. “18F-sodium fluoride positron emission tomography quantitation of bone metastases in African American and non-African American men with metastatic prostate cancer”. Prostate, 2023, May 21.

Wilson A, Garmo L, and Podgorski I. “Interplay between fat cells and immune cells in bone: Impact on malignant progression and therapeutic response”, Pharmacology and Therapeutics, 2022; 238:108274.

Herawi G, Yazdanpanah. O, Podgorski I, Matherly L and Liu W "Lipid Metabolism Reprogramming in Renal Cell Carcinoma" Cancer Metastasis Reviews, 2022 41(1):17-31

Herroon M.K., Mecca S, Haimbaugh A, Garmo L.C., Rajagurubandara E, Todi SV, Baker TR, and Podgorski I. “Adipocyte-driven unfolded protein response is a shared transcriptomic signature of metastatic prostate carcinoma cells” BBA- Molecular Cell Research, October 2021; 1868(11):119101;

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(12): 2508-2521

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 Jan 15;25(2):652-662

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, Jan 2018, 8(1), 40.

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 Aug;16(4):443-457

Chkourko-Gusky, H; Diedrich, D.; MacDougald, O, and Podgorski, I. “Omentum and bone marrow: how adipocyte-rich organs create tumor microenvironments conducive for metastatic progression”, Obesity Reviews; 17(11); 1015-1029; 2016

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; Oncotarget; 7(40): 64854: 64877; 2016

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); 7:84; 2016.

Diedrich, D, Chkourko-Gusky, H, and Podgorski I. Adipose tissue dysfunction and its effects on tumor metabolism. Special issue on adiposopathy in cancer and metabolic diseases: an endocrine approach. Hormone Molecular Biology and Clinical Investigation; 21; 17-41, 2015

 Herroon, MK, Rajagurubandara, E, Hardaway, AL, Powell, K., Turchick, A, Feldmann, D, and Podgorski I. "Bone Marrow Adipocytes Promote Tumor Growth in Bone via FABP4- dependent Mechanisms" Oncotarget, 4(11):2108-2123, 2013

B.S., Chemistry. Saint Mary's College, Orchard Lake, MI, 1995
Ph.D., Biomedical Sciences (Specialization in Health and Environmental Chemistry), Oakland University, Rochester, MI, 2001