International Fellowship Awards Summary

Dr. Soheil Meshinchi, M.D., Ph. D.

Dr. Soheil Meshinchi is the recipient of the second José Carreras International Fellowship to be awarded in 2000. His project is titled Biologic and Clinical Significance of Flt3 Internal Tandem Duplication in Pediatric Acute Myeloid Leukemia. His study is part of the Children's Cancer Group (CCG), an affiliation of institutions using common protocols to treat cancers in children with the aim to collect data from participating groups, analyze results and design new therapies based on these data. The CCG will provide specimens of blood and marrow from AML patients for determination of the prevalence of Flt3. These findings can then be correlated with clinical information to determine the significance of this gene in the outcome of the disease. The work may provide significant insight into the biology of AML and may provide a marker for determining patients with a poor prognosis. Such patients would then be candidates for more aggressive therapy and innovative treatment options.

Claudia S. Huettner, Ph.D.

The Carreras International Fellowship for 2000 is awarded to Claudia S. Huettner, Ph.D. Her project is entitled Conditional transgenic models of BCR/ABL leukemia. Her work will be conducted at the Beth Israel/Deaconess Medical Center/Harvard Institutes of Medicine in Boston, Massachusetts. Chronic myeloid leukemia is known to be the result of a BCR/ABL fusion gene. Dr. Huettner's work will focus on a conditional transgenic model of BCR/ABL using tetracycline either to induce or reverse leukemia. With this model it will be possible to characterize the role of the BCR/ABL oncogene and determine which hematopoietic cells express the oncogene. Dr. Huettner will also test several new classes of potentially valuable therapeutic agents in treating myeloid leukemias.

Francesco Galimi, M.D., Ph. D.

Francesco Galimi, M.D., Ph. D. received the 1999 International Fellowship from the José Carreras International Leukemia Foundation. His project is entitled The Role of Telomere Maintenance in Human Hematopoietic Stem Cells: A Gene Transfer Approach. The research is designed to study a model to investigate the role of telomere dynamics in the regulation of stem cell growth, self-renewal and life span. Telomeres are terminal sequences on chromosomes that undergo shortening at every cell division, thus playing a role in the life span of the stem cell. The practical application of these studies will be important in future cell transplantation studies involving attempts to manipulate stem cell growth. Galimi works at the Salk Institute for Biological Studies in La Jolla, California. "My professional aim," he says, "is to give a contribution in filling the current gap between theoretical and practical medicine, by working at the transfer of basic science to the hemato-oncological clinical area."

Koichi Akashi, M.D.

Koichi Akashi, M.D. was awarded the 1998 Carreras fellowship. Identification of a Human Common Lymphoid Progenitor is the title of his project. He is identifying certain cells that are instrumental in the body’s ability to fight infection, and ways to isolate and transplant them into people with immune problems. Dr. Akashi began his research at Stanford University School of Medicine and transferred to Boston's Dana Farber Cancer Center in March, 2000.

Matthew L. Fero, M.D.

Matthew L. Fero, M.D. received the 1997 Carreras International Fellowship for his study titled Tumor Suppression by CDK Inhibitors. His lab work centered on cell cycles, with emphasis on the causal relationship between p27 protein levels and proliferation (or inhibition) of cell cycles. Fero’s study of p27 mutations continues at the Fred Hutchinson Cancer Research Center in Seattle. He is passionate about furthering "understanding of the pathogenesis of acute leukemia and the control of proliferation in normal hematopoietic stem cells through... novel approaches," and is excited about "progress with the human genome project" as it applies to his research.

In appreciation of the support he received from the Foundation for his research, Fero says, "The support and recognition provided by the Carreras foundation comes at a pivotal time in the careers of young scientists."

Martin Sattler, Ph. D.

Martin Sattler, Ph. D., is the 1996 recipient of the Friends of José Carreras International Leukemia Foundation three year fellowship award. Sattler’s winning project was selected from among 23 applications from researchers in 10 countries. The project was titled The Role of Activation of STAT Proteins by BCR/ABL in the Pathogenesis of Chronic Myeloid Leukemia (CML). In more simplified terms, Sattler investigated the factors that influence the transformation of the BCR/ABL oncogene, the gene that undergoes abnormal changes, causing the CML form of leukemia to occur. Since CML is a common form of leukemia that is fatal unless the patient undergoes a bone marrow transplant, research into its cause helps to understand its treatment and prevention.

Sattler was born and educated in Germany, receiving his doctorate in 1992 from the University of Hanover. He came to the U.S. in 1993 as a research fellow at the Dana-Farber Cancer Institute in Boston. He is the author or co-author of 23 publications in major medical journals.

Isidro Sánchez-García, M.D.

Isidro Sánchez-García was awarded the 1995 José Carreras International Leukemia fellowship for his work conducted at the Instituto de Microbiologia Bioquimica in Salamanca, Spain. His project dealing with genetic engineering was entitled Gene Therapy for the Treatment of Philadelphia Positive Leukemia. The basic premise of the investigation was to generate a retrovirus to interact specifically with the abnormal gene which is responsible for chronic myeloid leukemia and some forms of acute lymphoblastic leukemia. These specific antitumor agents could be introduced into an affected model. Only the malignant cells bearing the abnormal tumor maker are killed, sparing the normal marrow cells. The next step in Sánchez-García's work will be to utilize these techniques to apply to the eradication of these leukemic cells in patients.

Bruce Clurman, M.D., Ph. D.

Bruce Clurman, M.D., Ph. D. was granted the Carreras International Fellowship in 1994 for his project titled Targeted Disruption of "Essential" Genes in Lymphoma Cells. As unforeseen tangents worth exploring developed in the first few months of his fellowship, his project diverged markedly from the original concept. With the scientific board's consent, the Carreras grant allowed Clurman to take his investigation in an unexpected direction.

Clurman investigated the regulation of a group of proteins that are critical determinants of cell division and are frequently mutated in cancer cells. His studies focused mainly on two key growth regulators in normal cells, cyclin E and p27kipl. The interactions of these regulators initiate a pathway leading to the elimination of p27, a negative growth regulator, from the cell. This investigation led to new insights into the regulation of these proteins, and set the stage for the next generation of experiments which address the abnormal regulation of these proteins in cancer cells. The ultimate goal of these studies is to determine if these and related proteins constitute novel therapeutic targets for the development of cancer treatment strategies.

Although his Carreras fellowship is complete, Clurman continues his investigation of cell cycles at the Fred Hutchinson Cancer Research Center in Seattle. He was recognized by the William Keck Foundation as a 1999 Distinguished Young Scholar with a $1 million grant to continue his work.

"The Carreras fellowship [was] truly invaluable in allowing me to initiate and succeed in these experiments," Clurman notes. "It provided support for virtually all aspects of this work and gave me the freedom to follow these experiments wherever they led! It was also a key factor in allowing me to successfully compete for additional support which will allow me to transition from postdoctoral work to independent investigator."

Robert S. Negrin, M.D.

Robert S. Negrin, M.D., was awarded the 1993 Friends of José Carreras International Leukemia Foundation fellowship for his study Biology of Cytokine Induced Killer-Cells. The assistant professor at Stanford University has studied the development of natural killer-cells, those special lymphocytes that display an inherent ability to attack cancer cells. He has used growth hormones, produced by recombinant technology, to enhance the killing capacity of these cells in tissue cultures. The eventual practical aspects of these approaches will be to use specific killer cells to act against human leukemia.

Based on some of the preliminary findings generated during his Carreras fellowship, Dr. Negrin is now investigating a population of specific cells (expanded CD8 + T cells) to treat patients who have relapsed following an autologous transplant for leukemia. His laboratory work will focus on further characterizing these cells and utilizing them for a graft-versus-leukemia effect.

Negrin says of his fellowship experience, "This award was an extremely important source of support for me during this very challenging transition from fellowship to faculty status. It enabled me to expand my research directions and allowed me to obtain the necessary preliminary studies to successfully compete for funds from national agencies. In addition, it was a thrill to be associated with Mr. Carreras, whose generosity and commitment were a source of inspiration."

Alessandra Cesano, Ph. D.

Alessandra Cesano, a Ph. D. working at the Wistar Institute in Philadelphia, was the second Carreras Foundation award recipient. She completed her three-year fellowship in 1995. Cesano established methods for treating leukemic cells with a killer cell that could eliminate abnormal cells without damaging normal ones. This effect was even more pronounced when one or more interleukins (one of the many more recently identified cell regulators) were combined with the killer cell. Potential clinical applications are being investigated, including using this method to purge marrow of leukemic cells, making it possible to use the patient’s own marrow for treatment (autologous marrow transplantation).

"The three year award I received from the foundation was instrumental to my career as a scientist at the Wistar Institute and allowed me to further my research on adoptive immunotherapy of cancer and develop its potential in future clinical application," Cesano says.

She was born in Italy and received her medical education from the University of Turin. She came to the U.S. in 1989 as a post doctoral fellow at Wistar Institute in Philadelphia and now has a permanent resident visa. Since 1998, Cesano has been working with the pharmaceutical company SmithKline Beecham "trying to facilitate the long and often frustrating process of bringing what is a bench discovery to the patient bedside in a reasonable timeframe."

Catherine Verfaillie, M.D.

Friends of José Carreras International Leukemia Foundation’s first fellowship winner was Dr. Catherine Verfaillie, who finished her fellowship in 1994. She completed a number of laboratory projects during the three year fellowship, involving isolation of primitive stem cells and separation of normal from leukemic cells in patients with chronic myeloid leukemia. These studies have an important clinical application for patients with this type of leukemia. By separating malignant cells from healthy cells, marrow can be "cleansed" and made suitable for use in transplantation.

Verfaillie, now an associate professor of medicine at the University of Minnesota, is the author of numerous scientific publications. She is a frequently invited speaker at national and international medical symposia and has received several grants from the National Institutes of Health. She is also regarded as a valuable teacher and member of the marrow transplant team. The three year support provided by the Carreras Foundation enabled her to embark on her highly-productive career.