Izabela Podgorski

Izabela Podgorski

Associate Professor

ipodgors@med.wayne.edu

Izabela Podgorski

Office Address

540 East Canfield, 6304 Scott Hall
Detroit, MI 48201

Office Phone

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

Biography

 

Bone is a primary site of metastasis from prostate cancer (PCa). More than 80% of patients with recurrent PCa suffer from metastatic bone lesions, and there are currently no available treatments that can significantly improve patient outcomes. Obesity and age are significant risk factors for development of bone metastatic lesions. Obese and overweight men with PCa are three times more likely to develop metastatic disease compared to normal weight men with same treatment regimen. The mechanisms behind this association are currently not understood. Both age and obesity greatly increase numbers fat cells (adipocytes) in the bone marrow. Fat cells negatively affect bone metabolism and function, and escalate bone degradation making the bone marrow more supportive of tumor growth.

Our main research interests are to identify molecular mechanisms underlying the association between bone marrow adiposity and metastatic prostate cancer.

Our current work focuses on:

  • Role of HIF-1a and hypoxia signaling in tumor cell survival in bone
  • Marrow adipocyte lipolysis and adipocyte phenotype in a context of metastatic disease
  • Lnk between fatty-acid driven endoplasmic reticulum (ER) stress and chemoresistance
  • Peroxisome proliferator-activated receptor signaling in metastatic progression and response to therapy

Working hypothesis

The increased amount of marrow fat content is a consequence of age, obesity and/or metabolic dysfunction . We propose that bi-directional interactions between marrow fat cells and tumor cells are responsible for activating HIF-1α signaling and driving Warburg phenotype in metastatic prostate cancer cells. Adipocyte-supplied lipids drive ER stress response in tumor cells and render them more aggressive and resistant to therapy

Our studies involve multiple independent mouse models of marrow adiposity, models of intraosseous tumor growth, and novel cell culture approaches combined with pharmacological and genetic manipulation and lipidomic technology. Our ultimate goal is to determine whether targeting tumor metabolism and/or associated pathways would create new treatment options, and provide improvement in outcomes for men with metastatic disease.

Our additional collaborative research projects focus on:

  • Link between metabolic syndrome/inflammation-, insulin resistance- and oxidative stress and health disparities in prostate cancer patients
  • Role of tumor-associated macrophages and related inflammation in radiotherapy resistance in prostate cancer patients
  • Development and characterization of photoactivatable protease inhibitors as potential agents in treatment of bone metastatic disease


       o Current Lab Personnel:

              Mackenzie Heroon, M.A., Research Assistant
              Erandi Rajagurubandara, M.S. - Research Assistant

      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, Oakland University, Rochester, MI, 2001

Publications

 
Selected Recent Publications:
 
  • 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, Oct 2017, 7(1), 13021
  • Diedrich, J, Rajagurubandara, E, Herroon, M, Mahapatra, G, Huttemann, M, and Podgorski, I. BoneMarrow Adipocytes Promote Warburg Phenotype in Metastatic Prostate Tumors through HIF-1a. Oncotarget, 2016, Oct 4; 7(40);  64854-64877
  • 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; 2016 Nov;17(11):1015-1029
  • Herroon, MK, Diedrich, J, and Podgorski, I. “New 3D culture approaches to study bone marrow adipocyte interactions with prostate cancer cells”, Frontiers in Endocrinology, 2016 Jul 6;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 Biol Chem. 2016 Jun 1;397(6):571-82
  • Hardaway AL, Herroon, M.K, Rajagurubandara, E., and Podgorski I. Marrow Adipocyte-derived CXCL1 and CXCL2 Contribute to Bone Osteolysis in Metastatic Prostate Cancer. Clin Exp Met; 32(4):353-68; 2015
  • Hardaway AL, Herroon, M.K, Rajagurubandara, E., and Podgorski I. Bone marrow fat: linking adipocyte-induced inflammation with skeletal metastases. Cancer Metastasis Reviews; 33(2-3): 527-543, 2013
  • 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):2108-23, 2013.
  • Herroon, M.K., Rajagurubandara, E., Rudy, D.L., Chalasani, A., Hardaway, A.L, and Podgorski, I. Macrophage Cathepsin K Promotes Prostate Tumor Progression in Bone. Oncogene, 32(12):1580-1593, 2013.
  • Respondek, T*., Garner, R., Herroon, M.K., Podgorski, I, Turro, C., and Kodanko, J. Light Activation of a Cysteine Protease Inhibitor: Caging of a Peptidomimetic Nitrile by Ru(bpy)2 . Journal of American Chemical Society 133(43): 17164-12167, 2011.

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

Faculty Status

Cell Biology
facebook twitter instagram flickr youtube

Department of Pharmacology