|Jewish General Hospital|
Lady Davis Institute
3755 Cote Ste. Catherine Road
(514) 340-8260 ext 5289
prem [dot] ponka [at] mcgill [dot] ca
Research Area: Physiology of Blood
Iron (Fe) is an essential nutrient required for oxygen transfer, energy production, and cell growth. While it is necessary for life, it is highly toxic in excess, and Fe balance in the body must be strictly regulated. Current research focuses on:
1) The biochemistry and molecular biology of intracellular Fe metabolism, primarily in immature erythroid cells.
2) The development of new Fe chelating agents for the treatment of Fe overload and possibly for the management of pathological conditions caused by oxidative stress. We have identified pyridoxal isonicotinoyl hydrazone (PIH) as an Fe chelating agent and are developing novel and more effective PIH analogs.
3) Defining the role of nitric oxide (NO) in cellular Fe metabolism. NO was recently found to affect an astonishing range of physiological processes, and we have discovered that NO influences the metabolism of Fe in cells.
Education: M.D. Ph.D., Charles University (Prague)
Sheftel AD, Kim SF, Ponka P
Non-heme induction of heme oxygenase-1 does not alter cellular iron metabolism. J Biol Chem 282: 10480-10486, 2007.
Sheftel ad, Zhang A-S, Brown C, Shirihai OS, Ponka P
Direct interorganellar transfer of iron from endosome to mitochondrion. Blood 110: 125-132, 2007.
Kim S, Wing S, Ponka P. S-nitrosylation of IRP2 regulates its stability via the ubiquitin-proteasome pathway. Mol Cell Biol 24:330-337, 2004.
Zhang, A-S, Sheftel A, Ponka P.
Intracellular kinetics of iron in reticulocytes: evidence for endosome involvement in iron targeting to mitochondria. Blood, Jan 1 2005; 105(1):368-75.
Nie G, Sheftel AD, Kim SF, Ponka P. Overexpression of mitochondrial ferritin causes cytosolic iron starvation and changes cellular iron homeostasis. This article was accompanied by Editorial Commentary by Chitambar CR: Cellular iron metabolism; Mitochondria in the spotlight. Blood 105, 1844-1845, 2005.
Nie G, Chen G, Sheftel A, Pantopoulos K, Ponka P.
Effects of mitochondrial ferritin expression on tumor iron metabolism and on tumor growth in nude mice xenografts. Blood 108: 2428-2434, 2006. This article was accomplished by Editorial Commentary by Richardson DR, Lovejoy DR. Iron mining to inhibit tumor growth. Blood 108: 2140, 2006.
Whitnall M, Howard J, Ponka P, Richardson D..
A class of iron chelators with a wide spectrum of potent antitumor activity that oversomes resistance to chemotherapeutics. PNAS 2006; 103; 14901-14906