Izabela Podgorski, Ph.D.
540 E. Canfield
6304 Scott Hall
Detroit, MI 48201
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 interests are to identify molecular mechanisms underlying the association between bone marrow adiposity and metastatic prostate and kidney cancers. We are focusing specifically on:
- The role of HIF-1a and hypoxia signaling in tumor cell survival in bone
- Marrow adipocyte lipolysis and adipocyte phenotype and secretome in a context of metastatic disease;
- The link between fatty-acid driven endoplasmic reticulum (ER) stress and chemoresistance; and
- Peroxisome proliferator-activated receptor signaling in metastatic progression and response 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 research interests involve the development and characterization of photoactivatable protease inhibitors as potential agents in treatment of primary cancer and metastatic disease.
Arora K, Herroon M, Al-Afyouni MH, Toupin NP, Rohrabaugh TN Jr, Loftus LM, Podgorski I, Turro C, Kodanko JJ. "Catch and Release Photosensitizers: Combining Dual Action Ruthenium Complexes with Protease Inactivation for Targeting Invasive Cancers. J Am Chem Soc. Oct, 2018 (epub ahead of print).
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.
Huisman M, Kodanko JP, Arora K, Herroon M, Alnaed M, Endicott J, Podgorski I, Kodanko JJ. Affinity-Enhanced Luminescent (Re(I) –and Ru(II)-Based Inhibitors of the Cysteine Protease Cathepsin L Inorg Chem. 2018;57:7881-91.
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; Oncotarget; 2016;;7):64854-77.
Huisman. M White,. JK, Lewalski, W, Podgorski, I, Turro, C, and Kodanko J, "Caging the Uncageable: Using Metal Complex Release for Photochemical Control over Irreversible Inhibition, Chemical Communications 2016;52:12590-93.
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.
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
CB7460 Mechanisms of Neoplasia: Alterations to Cellular Signaling