MAY 27 - 28, 2008

The Bloom's Sydrome Foundation was a partial sponsor of a workshop entitled Molecular and Clinical Mechanisms in Bloom's Syndrome and Related Disorders held at the University of Chicago Gleacher Center on May 27 - 28, 2008. The workshop was organized by Nathan Ellis (University of Chicago), Vilhem A. Bohr (National Institute of Aging, NIH), and Curtis C. Harris (National Cancer Institute). The workshop was attended by approximately 50 Scientists and Medical Researchers from all across the world.

Please click here for a summary of the scientific workshop.

Alongside this scientific workshop there was also a more personal conference, organized by Sheryl Grossman and her Bloom's Connect organization. This conference brought together families and individuals with BS for discussions, amongst themselves and with professionals, about living and coping with Bloom's Syndrome and its side effects.


CURRENT SCIENTIFIC GRANT RESEARCH INCLUDES:

Maureen Sanz, Ph.D., Professor at Weill Medical College of Cornell University, was awarded a grant (commencing October, 2006) to maintain and expand the Bloom's Syndrome Registry. Dr. Sanz has described the work as follows: "The Registry, instituted 47 years ago, is a program of clinical investigation in a genetical context. It follows the clinical courses of the vast majority of persons diagnosed Bloom's syndrome worldwide, which to date is approximately 250 persons. Information obtained pertains not only to the normal control of growth -- unusually small size at all stages of development is the major and the constant clinical feature of Bloom's syndrome -- but also to the etiology of two major human health problems, each of which is a very common complication of Bloom's syndrome, namely cancer and diabetes. Clinical and genetic information pertaining to each registered person is accumulated, as well as experimental laboratory data generated in through the study of biological material from persons with the syndrome; periodically the information is summarized and reported in the standard scientific and medical literature. Biological specimens collected from affected persons and their close relatives include blood and other tissues, both normal and neoplastic, and whenever possible, tissue culture cell lines are established and cryopreserved. Both the data and the specimens stored in the Registry are made freely available to other investigational groups.

The Registry is a research resource rather than either clinical investigation or basic laboratory research in the usual sense. The Foundation's support will help maintain, and now expand, this central repository of knowledge about rare Bloom's syndrome. Some of the information that has been and will be acquired by the program is of general clinical value, while some is of fundamental biological significance. Often the information proves to be of immediate medical use to registered persons and their families.

Ian Hickson, Ph.D., Professor & Deputy Director, CR-UK Oxford Cancer Centre, Weatherall Institute of Molecular Medicine, University of Oxford & Nathan Ellis, Ph.D. Associate Professor of Medicine at the University of Chicago have been awarded a joint grant (commencing February 2007) Towards a Pharmacological Cure of Bloom's Syndrome. The Doctors describe their endeavor as follows: "Bloom's syndrome cells are characterized by excessive genetic recombination, a process that leads to exchanges between chromosomes that can have harmful effects. We hypothesize that this characteristic of Bloom's syndrome cells is the predominant causative factor in the cancer predisposition in Bloom's syndrome. The goal of the on-going work supported by the Bloom's Syndrome Foundation is to identify factors in Bloom's syndrome cells that could be targeted with drugs to effect a reduction in the level of recombination. The gene mutated in Bloom's syndrome, BLM, is highly conserved from bacteria to humans. Because of this conservation, one of the specific aims of the work is to analyze a model organism, baker's yeast, which is easy to manipulate genetically. We will use a yeast strain that lacks that lack BLM-like activity; this strain has elevated recombination and is sensitive to agents that cause DNA damage. We will then the identify genes that when altered genetically reduce the DNA-damage sensitivity of this strain. In addition, using the novel human cell genetic methods made possible by the development of systems biology technologies, we will perform genetic screens of Bloom's syndrome cells for genes that, when inhibited, will reduce the excessive recombination of the human cells. By combining these two approaches to the identification of genes involved in the regulation of genetic recombination, we will target the genes that we find in our genetic screen to identify pharmacologic agents that will act similarly to reduce recombination in the cells of a person with Bloom's syndrome. We envisage that by bringing into check the excessive recombination in Bloom's syndrome we will decrease the risk of cancer development, which is the major and most important, life-threatening complication in this disorder."

Ralph Scully, M.D., PhD., Assistant Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center has been awarded a grant by the Bloom's Syndrome Foundation (commencing January 2007) to study the role of the Bloom's Syndrome gene in repair of DNA breaks that arise during cell division a process called "sister chromatid recombination" (SCR). There are strong indications that this process is not properly regulated in individuals with Bloom's Syndrome. Dr. Scully believes that a defect in the regulation of sister chromatid recombination may explain the majority of abnormalities in Bloom's Syndrome including the high cancer risk. He will use novel methods, developed in his lab, to define how sister chromatid recombination goes wrong in cells lacking BLM. He is using fluorescent biomarkers to measure SCR directly, generating a remarkably fast and accurate readout in living cells. With funding from the Milo Gladstein Foundation, he will develop rapid, quantitative and specific measures of Bloom's Syndrome gene (BLM) activity. He will use this rapid test to screen for chemicals and genes that modify BLM activity. In Dr. Scully's words: "If we could correct the DNA repair imbalance in Bloom's Syndrome cells, this might help us to discover new drug treatments for Bloom's patients. We hope that these new therapies might improve the health and quality of life of individuals with Blooms' Syndrome and reduce their risks of developing cancer."

Yilun Liu, Ph.D., Department of Therapeutic Radiology, Yale University School of Medicine has been awarded a grant (commencing February, 2007). Dr. Liu stated "Human RecQ family helicases are important for cancer prevention. Even though there are five RecQ proteins in humans, these proteins are not redundant. Mutations in three RecQ proteins result in different clinical diseases. In particular, individuals lacking BLM, one member of the five RecQ helicases in human, develop Bloom's Syndrome and have a high risk of developing cancer of all types. Cells derived from Bloom's Syndrome patients show many alterations in their DNA, and this phenotype was thought to be the primary cause for cancer development in Bloom's Syndrome patients. However, recent studies indicated that cells lacking another RecQ helicase, RECQ5, show similar phenotype, yet mice lacking RECQ5 grow normally. This raises the question whether these DNA alterations contribute to the increase in cancer rate. Alternatively, are these changes in DNA in fact different in the cells lacking BLM and RECQ5, and that only those in cells without BLM are fatal? We will carry out biochemical and genomic analyses to compare BLM and RECQ5 to understand whether the DNA alterations observed in cells without BLM play a role in cancer development in Bloom's Syndrome patients."

Rick Fishel Ph.D. & Joanna L. Groden Ph.D., Professors of Molecular Virology, Immunology and Medical Genetics at The Ohio State University Comprehensive Cancer Center were awarded a 5 year grant (commencing In January 2006). This is our most significant investment to date and is a major program. Dr.'s Fischel and Groden and their staff have created a lab officially called THE MILO GLADSTEIN BLOOM'S SYNDROME LABOROTORY. Individuals with Bloom's syndrome "have an extra-ordinarily high risk of developing cancer(s) at early ages", and therefore the Doctors are proposing to discover targeted Chemo-preventives and therapeutics. This first requires a "detailed understanding of the genetic and biophysical links between the BLM protein (and its absence in BS individuals), the associated cancers, and the cancer process", which the Dr.'s are undertaking. The establishment of our lab "provides a focus and a mission to identify genetic and chemical suppressors of BS, and to make discoveries that will lead to a novel therapeutic options for affected individuals."

Dr. Wiliam Hollomon Ph.D., Professor of Microbilogy and Immunology at Weill Medical College of Cornell University is currently in his second year of his research grant. This will fund Dr. Hollomon from July 2006 thru June 2007. He is studying "Genetic & Biochemical Approaches to BLM Mechanism and Bloom's Syndrome Therapy". Dr. Hollomon has said "key to gaining more insight to the mechanism of BLM action and to therapies for afflicted individuals is knowledge about BLM's molecular role in the cell and about BLM's interacting partners. He proposes "to address the issues using four different lines of attack relying on both human cultured cells and the Ustilago maydis fungal system as models for experimentation. The experimental design consists of a mix of strategies ranging from aggressive to more conservative in terms of approaches". He believes "that such a rationale will maximize possibility of success in gaining new insight into BLM mechanism and for making progress toward a therapy." His aims include: (1) Identifying a Bloom's syndrome drug, (2) Identifying antagonists of BLM, (3) developing a gene therapy, and (4) the investigation of BLM and Rad51

Dr. Constantine A. Stratkis, MD and Director of the Pediatric Endocrinology Program at the NIH was awarded a One year grant by the Milo Gladstein for Bloom's Syndrome Foundation commencing in June 2005. He studied the "Bloom's syndrome protein (BLM) in cells and tissues from patients with another genetic disease, Carney complex (CNC) believing that there is a good chance that the CNC gene, PRKARIA directly or indirectly interacts with BLM."


THE BLOOM'S SYNDROME FOUNDATION continues to receive and evaluate scientific proposals and desires to fund significantly more research relating to Bloom's Syndrome, and a possible therapy and cure.

Investigators who would like to contribute towards this goal are invited to submit a letter of intent. After appropriate consultation, a decision will be reached whether the applicant will be invited to submit a formal NIH style research application.

This letter of intent should contain the following information:

- Name, address and academic affiliation of the potential applicant
- Two page NIH style Bio-bibliography form
- A brief outline of the investigation to be initiated (not to exceed 2 pages).
- An outline of current resources and support

The letter-of-intent should be addressed to Richard Gladstein via email to info@bloomssyndrome.org.

The foundation's founding Board members will evaluate proposals:

James L. German, III, M.D.
Professor, Department of Pediatrics
Weill Medical College of Cornell University
New York, NY

Eberhard Passarge, M.D.
Emeritus Director, Department of Human Genetics,
University of Essen School of Medicine
University of Essen
Essen, Germany

David L. Rimoin, M.D., PhD.
Director, Medical Genetics Institute
Stephen Spielberg Chair
Cedars-Sinai Medical Center
Professor of Pediatrics, Medicine and Human Genetics
David Geffen School of Medicine at UCLA
Los Angeles, CA