Izabela Podgorski

 

 

 

 

 


Izabela Podgorski, Ph.D.
Associate Professor
540 E. Canfield
6304 Scott Hall
Detroit, MI 48201
313-577-0514
ipodgors@med.wayne.edu

Mentoring: Jonathan Diedrich ( Graduated 07/11/2017)

Research Description:
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 of 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:

  • The involvement of Fatty Acid Binding Protein 4 (FABP4) and the pro-inflammatory cytokine IL-1B in prostate cancer growth and survival in bone
  • The role of obesity-induced tumor metabolic stress in chemoresistance in metastatic prostate cancer

These studies are being conducted using multiple independent mouse models of marrow adiposity, models of intra-osseous tumor growth, and novel cell culture approaches, combined with pharmacological and genetic manipulation and lipidomic technology. Our ultimate goal is to determine whether targeting FABP4/ IL-1B axis and/or associated pathways would create new treatment options, and provide improvement in outcomes for men with metastatic disease.

Our additional collaborative research projects involve:

  • Assessing how metabolic syndrome/inflammation-, insulin resistance- and oxidative stress-related factors differentially influence prostate cancer aggressiveness in African American and European American men
  • Identifying bone- and tumor-specific molecular signatures that drive aggressive behavior of metastatic prostate tumors and determine their responses to treatments using novel chemotherapeutic agents and PET imaging technology in prostate cancer patients and mice
  • Development and characterization of photoactivatable protease (e.g. cathepsin K) inhibitors as potential agents in treatment of bone metastatic disease

Selected Publications:

Respondek T, Sharma R, Herroon MK, Garner RN, Knoll JD, Cueny E, Turro C, Podgorski I, Kodanko JJ. Inhibition of cathepsin activity in a cell-based assay by a light-activated ruthenium compound. ChemMedChem. 2014;9:1306-15.

Sharma R, Knoll JD, Martin PD, Podgorski I, Turro C, Kodanko JJ. Ruthenium tris(2-pyridylmethyl)amine as an effective photocaging group for nitriles. Inorg Chem. 2014;53:3272-4.

Hardaway AL, Herroon, M.K, Rajagurubandara, E., and Podgorski I. "Bone marrow fat: linking adipocyte-induced inflammation with skeletal metastases." Cancer Metastasis Reviews, 2014; epub ahead of print.

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. 2013;4:2108-23.

Hardaway AL, and Podgorski I. IL-1β, RAGE and FABP4: targeting the dynamic trio in   metabolic inflammation and related pathologies. Future Medicinal Chemistry. 2013;5:1089-108.

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. 2013;32:1580-93.

Education and Training:
PhD (2001) Oakland University, Rochester Hills, Michigan

Cancer Biology Courses Taught:
CB7300 Special Topics F31 Grant Writing Course
CB7700 Recent Developments in Cancer Biology (Course Co-Director)