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Prem Ponka, MD, PhD, FCMA
 
Senior Investigator, Lady Davis Institute
Professor, Departments of Physiology and Medicine, McGill University

Dr. Ponka obtained his MD in 1964 and his PhD (in Physiology) in 1969 from Charles University, Prague. From 1968 to 1979 he served as an Assistant Professor in the Department of Pathophysiology at Charles University. From 1979 to 1987 he was an Associate Professor, and since 1987, a full Professor at McGill University. In 1984, he assumed the position of Staff Investigator at the Lady Davis Institute. He spent 1987-88 as a Visiting Professor in the
Laboratoire de Génétique Moléculaire, Faculté Médecine Xavier Bichat at the Université de Paris VII.

Dr. Ponka is a prominent and internationally recognized scientist who, in several mutually overlapping projects, studies how iron balance in the body and cells is regulated and how disregulated iron homeostasis causes numerous diseases. Additionally, he is interested in the regulation of heme biosynthesis and erythropoiesis. Among Dr. Ponka’s most significant achievements is his original concept of tissue-specific heme synthesis regulation in hemoglobin synthesizing cells that is now widely accepted. More recently, his laboratory provided evidence for his novel hypothesis that, in erythroid cells, iron is directly delivered to mitochondria by endosomes in a “kiss and run” paradigm. His research has been continuously supported for more than 30 years, mostly by the CIHR. Dr. Ponka has an outstanding publication record and his papers, most of which have been published in high impact journals, are extensively cited in the world literature. He has also given numerous invited presentations at various international conferences and research institutes.

Dr. Ponka served on the Hematology Study Section at the National Institutes of Health in Bethesda, Maryland, where he is now “on reserve.” He has served on the CIHR Pharmaceutical Sciences Operating Grants Committee, and has been an ad hoc reviewer for numerous national and foreign research granting agencies (e.g., in Australia, the Czech Republic, France, Hong Kong, Israel, Italy, and the United Kingdom). He is a frequent reviewer for a number of international scientific journals. In 1996, Dr. Ponka succeeded in establishing, and for four years chaired, the Scientific Committee on Iron and Heme at the American Society of Hematology. He served as Chair of the First Congress of the International BioIron Society (BioIron 2005), a highly successful event held in Prague. He was a co-organizer of the Fifth Conference of the Canadian Oxidative Stress Consortium in Montréal in 2007. That same year, he received the Award for Excellence in Medical Research from the Jewish General Hospital. In 2008, he was appointed to serve at the Scientific Council, First Faculty of Medicine, Charles University. In 2010, the Jewish General Hospital bestowed the 47th Annual André Aisenstadt Memorial Clinical Day to Dr. Ponka for "bringing international recognition to our Hospital for his research accomplishments in the field of iron metabolism." In February 2014, Dr. Ponka was elected as a Fellow of the Czech Medical Academy, which is a member of The Federation of European Academies of Medicine.


Major Research Activities

The ultimate goal of Dr. Ponka’s research in the biochemistry and molecular biology of intracellular iron and heme metabolism is to enhance our knowledge about iron metabolism and heme synthesis in erythroid cells, and to examine the pathophysiology behind some diseases caused by defective hemoglobin formation. He demonstrated that transferrin-borne iron is utilized in hemoglobin-producing cells with astonishing efficiency and hypothesized that erythroid precursors have special adaptations facilitating the high rate of iron transport from transferrin-endosomes to mitochondria. Recently, his laboratory provided strong support for this hypothesis. Dr. Ponka’s future goals in this area are: (1) to analyze the interaction between mitochondria and endosomes in immature erythroid cells by using flow cytometry, immunofluorescence and electron microscopy; and (2) to analyze the interaction between endosomes and mitochondria at a molecular level.

His laboratory has embarked on a new project involving the investigation of the role of heme oxygenase 1 during erythroid differentiation. The only physiological mechanism of heme degradation is by heme oxygenases (HO1 and HO2) that catalyze the rate-limiting step in the oxidative catabolism of heme. Although the heme-inducible HO isoform, HO1, has been extensively studied in hepatocytes and many other non-erythroid cells, virtually nothing is known about the expression of HO1 in developing red blood cells that synthesize the largest amounts of heme in the organism. Preliminary results from Dr. Ponka’s laboratory suggest that increased levels of HO1 could play a role in some pathophysiological conditions such as thalassemias.

Macrophages are known as fundamental components of the innate immune system. However, in a much less heralded, but equally vital role, macrophages are responsible for recycling hemoglobin iron acquired from the phagocytosis of senescent erythrocytes. Rather unexpectedly, Dr. Ponka’s laboratory has demonstrated that natural resistance-associated macrophage protein 1 (Nramp1) promotes efficient macrophage recycling of iron following erythrophagocytosis, both
in vitro and in vivo. The in vivo study has revealed that the absence of Nramp1 results in a marked retention of iron within macrophages and decreases the availability of recycled iron for erythropoiesis, a scenario similar to that seen in patients with iron overload caused by mutations of the cellular iron exporter ferroportin. More recently, his laboratory demonstrated that divalent metal transporter 1 (DMT1, homolog of Nramp1) also plays an important role in the recycling of hemoglobin iron in macrophages. Since the only physiological mechanism for liberating iron from heme in macrophages is the endoplasmic reticulum enzyme HO1, Dr. Ponka plans to investigate whether HO1 is recruited into phagosomes (that can be expected to harbor both Nramp1 and DMT1) following erythrophagocytosis. He also intends to investigate the effect of inflammatory cytokines on the recycling of hemoglobin iron in macrophages. This research will enhance our understanding of the pathogenesis of anemia of inflammation (the most common type of anemia in developed countries) and may provide basis for new therapies for this condition.

Recent Publications

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 (please see video showing the interaction of endosomes [green] with mitochondria [red] in reticulocytes).
 
Richardson D, Lane D, Becker E, Michael Huang M, Whitnall M, Suryo Rahmanto Y, Sheftel A, Ponka P. Mitochondrial iron trafficking and the integration of iron metabolism between the mitochondrion and cytosol. Proc Natl Acad Sci USA 107:10775-10782, 2010.

Ponka P, Sheftel AD. Erythroid Iron Metabolism. In: Iron Physiology and Pathophysiology in Humans, Nutrition and Health (Anderson GJ, McLaren G, eds.) Chapter 10, Springer Science + Business Media, pp 191-209, 2012.

Garcia-Santos D1, Schranzhofer M, Horvathova M, Jaberi MM, Bogo Chies JA, Sheftel AD, Ponka P. Heme oxygenase 1 is expressed in murine erythroid cells where it controls the level of regulatory heme. Blood. 2014 Apr 3;123(14):2269-77. doi: 10.1182/blood-2013-04-496760. Epub 2014 Feb 7.

Dr. Prem Ponka is an internationally recognized scientist in the fields of iron metabolism, heme synthesis and erythropoiesis.

He documented several unique mechanisms, in particular the role of iron, involved in the regulation of heme synthesis in erythroid cells.

He was the first to identify PIH and SIH as highly efficient intracellular chelators.

He continues with detailed analysis of the interaction between endosomes and mitochondria.

He studies the role of HO1 in erythroid cells and macrophages.

 

Dr. Ponka's Publications Indexed on PubMed

Dr. Ponka at the McGill Department of Physiology

 
 

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