Izabela Podgorski

Izabela Podgorski

Professor of Pharmacology; Co-leader of Prostate Cancer Research Team

ipodgors@med.wayne.edu

Izabela Podgorski

Office Address

540 East Canfield, 6312 Scott Hall
Detroit, MI 48201

Office Phone

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

Biography

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.


       o Current Lab Personnel:
 

  • Mackenzie Herroon, M.A., Research Assistant
  • Shane Mecca, B.S., Research Assistant
  • Charlea Mossner, B.S., Cancer Biology Masters Student
  • Laimar Garmo, B.S., Pharmacology PhD Student
  • Alexis Wilson, B.S., Cancer Biology PhD Student


      o Former Doctoral Students:

            Aimalie Hardaway, Ph.D (2015), Postdoctoral Fellow at Cleveland Clinic
            Jonathan Diedrich, Ph.D (2017); Postdoctoral Fellow at St. Jude Research Hospital

Education

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

Publications

Selected Recent Publications:

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 Dec;17(12):2508-2521.

Toupin NP, Arora K*, Shrestha P, Fischer L, Rajagurubandara E, Podgorski, I, Winter AH< and Kodanko J. “BODIPY-caged photoactovated inhibitors of cathepsin B flip the light switch on cancer cell apoptosis. ACS Chem Biol, 2019 14(12), 2833-2840

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

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.

Arora K, Herroon M, Al-Afyouni MH, Toupin NP, Rohrabaugh TN Jr, Loftus LM, Podgorski Ic, Turro Cc, Kodanko JJc “Catch and Release Photosensitizers: Combining Dual-Action Ruthenium Complexes with Protease Inactivation for Targeting Invasive Cancers.”. JACS, 2018 Oct 31;140(43):14367-14380

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; Oncotarget; 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.

Herroon, MK, Sharma, R, Rajagurubandara, E., Turro, C, Kodanko, J, and Podgorski, I Photoactivated Inhibition of Cathepsin K in a 3D Tumor Model. Biological Chemistry; 397(6):571-582; 2016.

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

Hardaway AL, Herroon, M.K, Rajagurubandara, E., and Podgorski I. Bone marrow fat: linking adipocyte-induced inflammation with skeletal metastases. Cancer Metastasis Reviews; January 33(2-3): 527-543, 2013; 2014;

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
 

Please go to PubMed for complete list of publications from Podgorski laboratory

Faculty Status

Cell Biology

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