Honor Recognizes Nation's Most Promising Biomedical Scientists
Dr. Shahin Rafii Is One of Nation's Few Clinician-Researchers Selected
NEW YORK (March 22, 2005) — Dr. Shahin Rafii of Weill Cornell Medical College — an internationally known cancer and vascular biologist and stem-cell authority — has been named by the Howard Hughes Medical Institute (HHMI) as one of 43 new HHMI investigators, an honor bestowed on only the nation's most promising and gifted biomedical scientists.
Dr. Rafii is one of the few clinician-researchers named this year.
"I am very pleased to announce that our own Dr. Shahin Rafii is the first physician-scientist in Weill Cornell history to be named an HHMI investigator at the Medical College," says Dr. Antonio M. Gotto, Jr., Dean of Weill Cornell Medical College. "As both clinician and researcher, Dr. Rafii has the unique ability to conduct translational research — to transform groundbreaking research from bench to bedside efficiently and successfully. His innovative work on stem cells and angiogenesis promises to make lasting impact on the treatment of cancer and vascular diseases."
The Arthur Belfer Professor of Genetic Medicine and Director of The Ansary Stem Cell Institute at Weill Cornell Medical College, Dr. Rafii pioneered the concept that tumors and regenerating or damaged organs rely on circulating stem cells to build new blood vessels. He has shown that interaction between blood vessel cells and organ-specific stem cells contributes to the generation of functional vascularized organs, including bone marrow, heart, and muscle tissues. This work has paved the way for stem-cell therapy for the treatment of vascular insufficiencies, such as heart attack, or targeting tumor vasculature in cancer treatment.
In this regard, Dr. Rafii's most recent research, just published in this month's issue of Circulation, demonstrates that a specific type of human fetal stem cell can develop into functional vascularized muscle tissue — a finding that could be the long-awaited breakthrough in using stem cells to repair damaged hearts. [See related article: Human Stem Cells Can Develop Into Functional Vascularized Muscle Tissue, Weill Cornell Team Finds.]
Additionally, Dr. Rafii's discovery that normal or tumor stem cells are dependent on interactions with vascular micro-environments for survival, has led to novel approaches for treating hematological malignancies and monitoring responses to anti-angiogenic therapies. He has also identified specific mobilizing factors called "chemokines," which, through rapid recruitment of stem cells, restore blood production much faster than those growth factors currently in clinical use.
This discovery may have a tremendous impact for the treatment of blood and vascular disorders, as well as for preventing toxic side effects associated with chemotherapy, radiation, and bone marrow transplantation. Dr. Rafii's group is currently designing gene and cell therapy models to exploit the potential of stem cell-active chemokines for therapeutic restoration of blood production.
Dr. David P. Hajjar — Rhodes Professor and Dean of the Weill Graduate School of Medical Sciences, and Vice Provost and Executive Vice Dean of the Medical College — states in his nomination letter: "Shahin Rafii's work on the role of the bone marrow in angiogenesis and vasculogenesis has put this institution, represented, in part, by The Ansary Stem Cell Institute, at the vanguard of stem-cell research."
"I am truly honored to join the HHMI, which will give me the scientific freedom to further understanding of stem cell biology, as well as the means to develop and test innovative approaches to treat cancer and vascular disorders," says Dr. Rafii. "In addition, this award will bolster our collaborations with other scientists at Weill Cornell and elsewhere to explore new frontiers of investigation that are otherwise difficult to secure through the conventional avenues of funding. I hope this award will advance our efforts to harness and exploit the therapeutic potential of human fetal and embryonic stem cells for treatment of human malignancies, vascular diseases, and genetic disorders in the very near future."
"HHMI investigators are on the rapidly rising slope of their careers and have made surprising discoveries in a short period of time," says Dr. Thomas Cech, Nobel laureate and president of HHMI. "We have every reason to believe that they will use their creativity to extend the boundaries of scientific knowledge for many years to come."
Dr. Rafii and the other 42 men and women selected must now be formally appointed, a process that will take up to six months. The general competition for new investigators, the first since 2000, represents a continued expansion of the Institute's biomedical research mission.
The HHMI investigators are drawn from 31 institutions nationwide, representing traditional biomedical research disciplines, as well as engineering, physics, chemistry, and computer science.
Through its flagship investigator program, HHMI currently employs 298 of the nation's most innovative scientists, who lead Hughes laboratories at 64 institutions. These scientists are widely recognized for their creativity and productivity: More than 100 are members of the National Academy of Sciences and 10 have been honored with the Nobel Prize.
Once selected, investigators continue to be based at their host institutions, but become HHMI employees and derive their entire salaries and benefits from the Institute. The collaboration agreement also provides for payment to the host institution for a researcher's laboratory space. Investigators retain their faculty positions and continue to participate in teaching and other professional activities at their university or research institute. Their research groups, which typically include 10 to 25 students, postdoctoral associates, and technicians, some of whom are HHMI employees, are supported by HHMI field staff throughout the country.
About Dr. Shahin Rafii
Dr. Shahin Rafii is motivated by his cancer patients to explore innovative therapeutic frontiers. The work in his lab suggests entirely new approaches to treating myeloma, leukemia, and lymphoma — and may soon enable higher, more effective doses of chemotherapy that do not induce severe toxicity. He has also paved the way for stem-cell therapy for vascular insufficiencies, such as stroke and heart attack and targeting tumor vasculature.
Dr. Rafii introduced the concept that both tumors and regenerating organs are dependent on stem cells recruited from the bone marrow to help build new blood vessels. By deciphering the molecular pathways that orchestrate recruitment, differentiation, and patterning of these vessels, he hopes to exploit those pathways for multiple clinical applications.
Both tumor cells and injured tissue — such as that at the site of a heart attack, stroke, or organ transplant — recruit stem cells hibernating in the bone marrow as the source of their new blood vessels. In collaboration with Dr. David Lyden of Weill Cornell, he has shown that by the time the stem cells arrive within certain tumors, they have begun to differentiate into two types of cells: a specialized white blood cell and the maturing endothelial progenitor cell, which work together to create the lining of the new vessels that fuel the growth of tumors or new or regenerating tissue. Similarly, in collaboration with Weill Cornell's Dr. Ronald Crystal, Dr. Barbara Hempstead and Dr. Jay Edelberg, he demonstrated that molecular and cellular interaction between vascular and organ-specific stem cells is essential for the generation of functional vascularized organs, including bone marrow, heart and muscle tissues.
Dr. Rafii has also found that specific types of mobilizing factors, known as "chemokines," "wake up" the stem cells in bone marrow and move them to vascular micro-environments, where new blood vessels are formed, dramatically speeding up restoration of the blood cells destroyed by chemotherapy or radiation. In collaboration with Dr. Ronald Crystal of Weill Cornell, Dr. Rafii has taken advantage of gene therapy approaches to induce robust production of chemokines in circulation to restore blood production after high doses of chemotherapy and radiation. Conversely, he has shown that interfering with the migration of stem cells from the bone marrow can halt tumor growth. He and colleagues have harnessed the selective homing mechanism of stem cells to deliver toxic payloads to the "tumor vascular niches" by arming the stem cells with cancer-killing agents.
Stem-cell active chemokines, identified by Dr. Rafii, increase the supply of stem cells that rush into the circulation to repair or regenerate tissue. Dr. Rafii has shown that the number of circulating stem cells represent reliable predictive markers to assess the degree of active neo-angiogenic processes and the capacity of the mobilized stem cells to repair damaged tissue. By the same token, the quantification of the number of circulating pro-angiogenic stem cells could be exploited to assess the level of tumor activity and response to chemotherapy and radiation. This innovative approach to non-invasively evaluate active angiogenic processes has become standard practice in many institutions to determine the body's ability to revascularize damaged tissue or assess the capacity of anti-angiogenic agents to block tumor neo-angiogenesis and growth.
Accumulating evidence suggests that a new class of experimental cancer drugs targeting the molecules needed for blood vessel growth, or angiogenesis, would only be useful in halting solid tumors by depriving them of oxygen and nutrients. But Dr. Rafii — in collaboration with Dr. Eric Feldman, Dr. Gail Roboz, Dr. John Leonard and Dr. Ruben Niesvizky of Weill Cornell — has found that tumor-activated angiogenic endothelial cells are also crucial in promoting the growth of hematological malignancies — including myelomas, leukemias, and lymphomas — as they release growth factors that fuel proliferation and invasion. Now, clinical trials are underway to test anti-angiogenic agents to treat hematological malignancies.
Shahin Rafii received his B.A. in chemistry from Cornell University and his M.D. from Albert Einstein College of Medicine. He has been funded by multiple grants from NIH's Heart, Lung, and Blood Institute, and is an active member of the Tumor Microenvironment Study Section at the National Cancer Institute. He is an elected member of the American Society of Clinical Investigation, an American Cancer Society Scholar, and a Translational Researcher of the Leukemia and Lymphoma Society.
About HHMI
The Howard Hughes Medical Institute is dedicated to discovering and disseminating new knowledge in the basic life sciences. HHMI grounds its research programs on the conviction that scientists of exceptional talent and imagination will make fundamental contributions of lasting scientific value and benefit to mankind when given the resources, time, and freedom to pursue challenging questions. The Institute prizes intellectual daring and seeks to preserve the autonomy of its scientists as they pursue their research.
A nonprofit medical research organization, HHMI was established in 1953 by the aviator-industrialist. The Institute, headquartered in Chevy Chase, Maryland, is one of the largest philanthropies in the world with an endowment of $12.8 billion at the close of its 2004 fiscal year. HHMI spent $573 million in support of biomedical research and $80 million for support of a variety of science education and other grants programs in fiscal 2004.
The largest privately funded education initiative of its kind in the United States, HHMI's grants program is enhancing science education for students at all levels, from the earliest grades through advanced training. HHMI investigators have made many important research advances — from the discovery of genes related to cystic fibrosis, obesity, high blood pressure, colon cancer and other diseases, to new insights about memory, vision and olfaction.
About Weill Cornell Medical College
The Joan and Sanford I. Weill Medical College of Cornell University in New York City is committed to excellence in research, teaching, patient care, and the advancement of the art and science of medicine. Affiliated with the NewYork-Presbyterian Hospital, the Medical College offers an innovative curriculum that integrates the teaching of basic and clinical sciences, problem-based learning, office-based preceptorships, and primary care and doctoring courses.
Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research in such areas as genetics and gene therapy, neuroscience, vascular and structural biology, AIDS, cancer, and psychiatry — and continue to delve deeper into the molecular basis of disease in an effort to unlock the mysteries behind the human body and the malfunctions that result in serious medical disorders. Weill Cornell Medical College is the birthplace of many medical advances — from the development of the Pap test for cervical cancer to the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., and most recently, the world's first clinical trial for gene therapy for Parkinson's disease. Weill Cornell's Physician Organization includes 650 clinical faculty who provide the highest quality of care to patients.
In 2001, Cornell University established the Weill Cornell Medical College in Qatar, becoming the first American university to establish a medical school location outside the United States. Weill Cornell Medical College-Qatar will confer Cornell University's M.D. degree to its first graduating class in 2008.
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