International BioIron Society

Memorial News

In Memory of Professor Thomas H. Bothwell

It is with great sadness that I must inform you of the death of Prof Tom Bothwell on Saturday 12th November 2016. He was 90 years old. I hardly need remind you of his seminal contribution to our understanding of internal iron exchange and iron nutrition. The funeral will be on Wednesday 16th November in Cape Town.

I have attached an article which I wrote on the occasion of his 80th birthday on his contribution to iron metabolism plus a list of his publications. The article appeared in Bulletin of the Adler Museum of Medicine. 2006;32(1):18-21. The Adler Museum of Medicine is situated in the Medical Library of the University of the Witwatersrand, Johannesburg.

Prof A Patrick MacPhail MBBCh PhD FCP FRCP
Professor Emeritus
Clinical HIV Research Unit
Department of Medicine
University of the Witwatersrand
South Africa

In Memory of Robert W. Grady, PhD

The passing away of Dr Robert W Grady was a painful blow to his many friends and associates who had the privilege of maintaining close personal and working relations with him over the years.

I first met Bob at the Arden House meeting on Proteins of Iron Metabolism organized by Phil Eisen, Elmer Brown, Bob Crichton and Jack Fieding in April 1977. At that time Bob already had a record of pioneering the development of new iron chelators with Anthony Cerami exploring not only their ability to remove excess iron from the body but also to examine their effect on the immune system and their potential antimicrobial use. Because I have specialized in exploring the mechanism of interaction of iron chelators with distinct iron pools in vivo, we immediately identified common grounds for collaboration to study potentially useful new iron chelators including dihydrobenzoic acid, rhodotorulic acid, EHPG and HDED. By 1978 we have published our paper on the alternative pathways of in vivo iron chelation. Subsequently, our active collaboration has spanned over the next 20 years and our friendship up to the last days.

Bob was a leader in iron research. Following his initial very productive years with Anthony Cerami at Rockefeller University, he joined the Division of Pediatric Hematology/Oncology at New York Presbyterian Hospital, where he established a unit specializing in long term metabolic iron balance studies to provide accurate and very reliable data on the effect of iron chelators on transfusional iron overload in thalassemia major and other clinical conditions. To our knowledge this metabolic unit is the only existing one able to provide critical information to establish rational iron chelating programs for many thousands of patients treated for transfusional iron overload. The most important message from these studies was the finding that combined use of iron chelators such as deferoxamine and deferiprone, or deferoxamine and deferasirox results not only in an additive but in many cases a synergistic effect on iron excretion and, in all cases a negative long term iron balance. The proposed mechanism of the synergistic effect of iron chelators is iron shuttle whereby the first chelator enters the intracellular compartment and delivers the chelated iron to a more powerful extracellular chelator.

Bob was a wonderful human being and a scholar in the true sense of the word. He took great care in establishing reliable and accurate methodology. This allowed him confidence in his findings and conclusions even if these conflicted with current dogmas. He was uncompromising in defending his views. On the other hand, he was modest, friendly, and always prepared to help both with advice and the provision of research tools and materials . His devotion and love to his family was legendary. In recent years our contact was mainly by exchanging news on iron chelation therapy at the yearly ASH meetings. Others had ideas and opinions but Bob knew the facts. His findings and predictions had a major effect on global chelation policies and his wisdom, experience, honesty, and warm humanity will be greatly missed.

Chaim Hershko MD
Professor Emeritus, Department of Medicine
Shaare Zedek Medical Center
and Hebrew University Hadassah Medical School
Jerusalem, Israel

I and many members of my laboratory will sorely miss Robert. Robert was an inspiration to us all. I still remember my first day of work when I approached him and started asking questions about iron overload and thalassemia. He was always available with a smile on his face, even when he had to answer my naïve questions or explain to me an unfamiliar concept. I was always running to him when I had to start a new experiment or get some feedback about a new grant. As the lab acquired new members who were interested on iron metabolism, I saw the same pattern: young people running to Dr. Grady and discuss their results or asking for advice. He would have done anything to help.

With Robert we published some seminal papers on iron metabolism and hepcidin in beta-thalassemia. I remember when I ran by him the idea to overexpress hepcidin in thalassemia. He was not convinced at the beginning, but our conversation led him to support my idea and help me tremendously to frame the experiments using the right controls and reagents. This was one of the many papers co-authored by Robert. He not only performed many of the iron analyses that he loved to do in his laboratory, but also provided a tremendous intellectual feedback on every aspect of the studies.

As our friendship progressed, I started discussing with Robert many different subjects, from family events to political news. He always had a suggestion or an opinion. Although we sometimes had different views, he always listened carefully and gracefully, providing his opinion on the subject we were discussing. Eventually Robert also met my wife and my other family members. When Robert’s wife passed away, we adopted two wonderful cats she bred. He would be happy to know that one of the two is still with us and she constantly reminds us how graciously Dr. Grady lived his life and interacted with his colleagues and friends.

Stefano Rivella, Ph.D.
Kwame Ohene-Frempong Chair on Sickle Cell Anemia
Professor of Pediatrics
Children’s Hospital of Philadelphia (CHoP)
University of Pennsylvania

In Memory of Kenneth D. Bloch, MD

Kenneth D. Bloch, MD, a cardiologist in the Department of Medicine and member of the BioIron Society, died on September 13 at the age of 58.

Professor Bloch was born in New York City on May 17, 1956, and raised in Brookline, Massachusetts, USA. After receiving his undergraduate and medical degrees from Brown University in 1978 and 1981, he began his career as a medical resident at the Massachusetts General Hospital. A cardiology fellowship and a position on the division staff in 1990 followed. Two years later, he became an investigator in the Cardiovascular Research Center. In 2007 Kenneth D. Bloch received the Harvard Medical School (HMS) William T. G. Morton Professorship.

For Professor Bloch, medicine was more than just a way to make a living. His idea of a sabbatical was to spend six months, seven days per week in his own lab. It was there he spent his happiest hours, studying three cell signaling molecules important to regulating the cardiovascular system: atrial natriuretic peptide (ANP), nitric oxide (NO), and the bone morphogenetic proteins (BMPs). With deep respect we would like to acknowledge his achievements within the iron research field: Professor Bloch generated the small molecule BMP inhibitor Dorsomorphin (LDN.193189) to inhibit the hepatic hormone hepcidin- the main systemic iron regulator in the body. LDN-193189 prevented development of the second most common form of anemia, the anemia of inflammation, in a murine model. In addition, LDN-193189 was effective in treatment of anemia of inflammation in mice. Professor Bloch characterized the BMP receptors that are inhibited by LDN-193189 and gained essential insights into the role of BMP receptors in iron homeostasis: Alk2 is responsible for basal hepcidin regulation, while Alk3, the most prominent receptor, is essential to maintain baseline hepcidin levels.

The International BioIron Society remembers his achievements and his personality. He was a passionate scientist, who was called by his friends the pied piper of scientists, always with a flock of young students and physician/scientists to whom he devoted hours, patiently guiding and counseling each day.

IBIS thanks Dr Andrea Steinbicker (Universitätsklinikum Münster) for contributing this tribute to Professor Bloch.

In Memory of Professor Renzo Galanello
Written by Dr. Michael Spino

On May 13, 2013, at 1:00 a.m., Dr. Renzo Galanello lost his battle with cancer, diagnosed only seven months earlier. The members of the International BioIron Society express their most heart-felt condolences to his family and friends. We grieve the loss of Renzo with his wife, Maria-Antonietta, his daughter, Giulia, and his sons Giacomo and Giovanni.

Dr. Galanello was the professor of pediatrics at the University of Cagliari and appointed as the director of the 2nd Pediatric Clinic, department of biomedical sciences and biotechnologies at the University of Cagliari, Ospedale Regionale per le Microcitemie, succeeding the renowned Professor Antonio Cao. Prof. Galanello was an accomplished scientist, a caring physician and a humble and sincere man. His integrity was known to all.

Read the rest of Dr. Michael Spino's touching obituary to Prof. Renzo Galanello here...

In Memory of Dr. Jerome L. Sullivan, III

Dr. Jerome L. Sullivan, III, the pathologist who first theorized of a link between heart disease and iron levels in the blood, died Friday, May 3, 2013, of complications from diabetes. He was 68 and is survived by his wife, five children and two grandchildren.

Dr. Sullivan, a physician, scientist and professor; was recognized around the world as the father of the "iron hypothesis," which states that people with elevated levels of iron in their blood face a greater risk of heart attacks.

Read the rest of the article by Jason Garcia, Orlando Sentinel, here...

In Memory of Dr. Giuliana (Giuli) Zanninelli

With great sorrow we announce the death of Dr. Giuliana (Giuli) Zanninelli, who passed away on February 2, 2011, after a long and courageous struggle against a malignant disease. She was only 50 years old when she left a husband, Itzik, two daughters, Ylenia 14 years and Liza 12 years, a mother and two sisters and numerous friends and colleagues worldwide. Giuli was known in the iron research community for her flair for clinical research on iron overload disorders and chelation, but above all for her radiant, warm, generous and captivating personality.

Giuli earned a medical degree in Rome, trained in Internal Medicine and Gastroenterology. While working in John Gollan's laboratory in Harvard Medical School she made her first steps in iron metabolism and toxicity, together with Pierre Brissot, whom she followed to Rennes for PhD studies, part of which she completed in Jerusalem with Ioav Cabantchik. Wherever she worked she left the footprints of kindness, enthusiasm for medical research and a zest for life that, although it came to an early end, it will not be forgotten by all those who had the privilege to know her.

Pierre Brissot, Rennes
Ioav Cabantchik, Jerusalem

In Memory of Dick van der Helm, an internationally recognized siderophore researcher and a crystallographer.

Professor Dick van der Helm, one of the pioneers of the structural siderophore field, passed away on April 28, 2010, aged 77. Dick was born on March 16, 1933 in Velsen, the Netherlands and after completing his regular primary and secondary school education he enrolled at the University of Amsterdam. He obtained the Dutch equivalents of the Bachelors and Masters degrees in 1952 and 1956, respectively. He then worked abroad at Indiana University for a number of years but he briefly returned to his alma mater to obtain his Doctoral degree in crystallography in 1960. Of particular importance during his further crystallography training were the postdoctoral years from 1959-1962 which he spent working with Lindo Patterson at the Institute for Cancer Research in Philadelphia. During this time important computer programs for the analysis of crystallographic data were developed that have since been used extensively by numerous scientists worldwide. Dick has worked for most of his career (from 1962-2002) at the University of Oklahoma in Norman, where he was a highly valued member of the Chemistry department. He rapidly rose through the ranks and he was appointed as a George Lynn Cross Research Professor in 1977; this is the highest research honor that a faculty member can receive from the University of Oklahoma, and it reflects Dicks’ national and international recognition over a number of years. Dick has also been a recipient of an NIH Career development award from 1969 to 1974 and the Oklahoma Scientist award in 1980.

Shortly after moving to Norman, Oklahoma, Dick became fascinated by the structures of siderophores and related iron-chelating compounds. His research group has purified and structurally characterized many different siderophores and through this work they have helped to firmly establish the chemical features and the preferred coordination chemistry that characterize a potent naturally occurring iron chelator that can be used to fulfill the need for the essential element iron of micro organisms such as bacteria or fungi. Glancing over Dick’s publication record from the 60’s, 70’s and the early 80’s reads like a ‘Who’s Who of the ferric-siderophore world’ as we currently know it: ferrichrome, ferrioxamine, pseudobactin, anguibactin, agrobactin, just to name a few. This work helped to firmly establish the important biological role of siderophores and it brought him in contact with many microbiologists and other scientists that were studying bacterial and fungal iron uptake pathways. During these years Dick also spent a sabbatical leave at the University of Groningen in the Netherlands, to further hone his skills as a single crystal crystallographer. Moreover, in the early parts of his career Dick also played an important role in various committees of the American Crystallographic Association and in 1978 he organized and hosted their national meeting in Norman. Dick’s research on siderophores extended well into the 90’s and also included some related studies on potentially clinically useful iron chelators.

In 1984 Dick and his family spent a sabbatical year in Tuebingen, Germany, where he worked together with Guenther Winkelmann. During this extended visit he also interacted with many other European researchers, most notably the other members of the Tuebingen “IronMen”: Volkmar Braun and Klaus Hantke. It was after this experience that Dick decided to start working towards solving the structures of the proteins that are involved in siderophore uptake in bacteria. Although Dick and his group already reported on the purification and initial crystallization of the FepA outer membrane siderophore-receptor in 1989, it took an additional 10 years before the protein crystals diffracted well enough and the first structures for these dedicated outer membrane transporters could be reported. By this time Dick had decided to team-up with the Deisenhofer group in Dallas and this fruitful collaboration resulted in the high-resolution structures of the bacterial enterobactin transporter FepA and the iron-citrate carrier FecA from E. coli. These two early membrane protein structures should be considered as excellent achievements and they are still highly cited contributions. This seminal work triggered a flurry of activity and currently almost 50 different outer membrane transporter structures have been deposited in the protein database. Around the same time crystal structures for periplasmic siderophore-binding proteins also became available as well as several unexpected structures of siderophores bound to the human lipocalin protein, which is now called ‘siderocalin’. The latter serendipitous discovery has opened up a whole new area in siderophore biology. Dick was clearly delighted by these developments and the renewed and widening interests in the role of siderophores. With help from Ranjan Chakroborty, he spent the last few years of his career studying various mutants of the bacterial outer membrane siderophore transport proteins, trying to further understand their mechanism of action. As one of the long-serving members of the Editorial Board of the BioMetals journal Dick remained actively in involved in science until very recently, and he took great pride in keeping on top of the current scientific literature in this area.

Dick is survived by his wife, Louise, and by all 6 of his children and his 9 grandchildren. We wish them well in this difficult time. Dick will also be greatly missed by many colleagues of the BioIron Society. Not only did we loose a friend, but also his research work has had a major impact on the field and he has been a source of inspiration to many of us.

Hans J. Vogel

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