New funding paradigms reshape research

Despite a tougher climate for NIH dollars, school gets its largest grant ever as part of Roadmap initiative.

Flat funding and a new research paradigm have turned federal funding of medical research on its head. After the recent doubling of the budget of the National Institutes of Health (NIH), funding has leveled off, resulting in a net decrease thanks to inflation. And the NIH is shifting the remaining dollars away from lone investigators to multidisciplinary teams of scientists.

Both trends are being felt at the School of Medicine. In October the school received its largest NIH research grant ever, a $57.3-million Clinical and Translational Science Award (CTSA), a new grant designed to encourage interdisciplinary research and the rapid movement of laboratory findings into human studies.

The award, one of 12 made around the country, will “transform how clinical and translational research is conducted,” said NIH Director Elias A. Zerhouni, M.D.

The CTSA fits in with the NIH Roadmap for Medical Research, which calls for reshaping clinical research to accelerate medical discovery. It also fits in with the medical school’s own planning, said Dean Robert J. Alpern, M.D., Ensign Professor of Medicine.

“A strategic planning initiative we launched in 2004 identified clinical research as a top priority and established the Yale Center for Clinical Investigation (YCCI), a focal point for translational research,” Alpern said. “The YCCI’s structure, which builds on Yale’s strengths in education, basic science and community-based research, is virtually identical to the vision put forth by the NIH in this new program.”

“With the CTSA grant we will be able to train many more clinical investigators, known as YCCI Scholars, who will be well-equipped to assemble the expert interdisciplinary teams they need to do top-quality translational research,” said Robert S. Sherwin, M.D., YCCI director and principal investigator on the CTSA grant.

Meanwhile, scientists at Yale and other universities are finding grants harder to acquire. Over the last two years, said Carolyn W. Slayman, Ph.D., deputy dean for academic and scientific affairs, Yale’s success rate has fallen, in line with national trends, but it is still above the national average.

“Some labs might have to cut back on the number of people in the lab, making it more difficult to complete projects,” said Lynn Cooley, Ph.D., professor of genetics and cell biology and director of the Combined Program in the Biological and Biomedical Sciences. “Students and postdocs in training contribute enormously to research excellence in their labs. Both valuable research and the pipeline of new research talent are threatened by these budget cuts.”

Slayman said the medical school’s Grants and Contracts Office, working with the development staff and with the Office of Cooperative Research, is providing information on alternative funding, including nonfederal granting agencies, foundations and corporations. She said these efforts have met with some success—direct grant dollars to Yale researchers increased by 5.9 percent last year.

“We are working closely with department chairs and program directors to provide as much help as possible to faculty members who run into difficulty with grant support,” Slayman said.

—Pem McNerney and John Curtis

University hopes to build on success in campaign for “Yale Tomorrow”

Nearly a decade after the close of its last major fund-raising campaign, Yale has begun a five-year drive to raise $3 billion, a major portion of which will be directed toward science and medicine.

At the public launch of the “Yale Tomorrow” campaign on September 30, President Richard C. Levin announced that donors have already committed $1.3 billion in gifts and pledges during its quiet phase, which began in mid-2004.

The public campaign kicked off with a day of presentations by noted faculty and alumni—including medical school professors Irwin M. Braverman, M.D. ’55; HS ’59, FW ’62; Christopher K. Breuer, M.D.; Carolyn M. Mazure, Ph.D.; Milissa A. McKee, M.D.; R. Lawrence Moss, M.D.; W. Mark Saltzman, Ph.D.; Bennett A. Shaywitz, M.D.; Sally E. Shaywitz, M.D.; and Tian Xu, Ph.D.—followed by a multimedia program narrated by actor Sam Waterston, a 1962 Yale College alumnus, and a gala dinner in University Commons.

The campaign is organized around four major priority areas: “Yale College,” “The Arts,” “The Sciences” and “The World.” In the sciences Yale will seek support for programs focused on translating basic science insights into clinically relevant work. Among the priorities are programs in neural degeneration and repair, stem cell biology, translational immunology, functional genomics and clinical investigation. The ultimate goal is to find new and better methods of diagnosing and treating illness, said medical school Dean Robert J. Alpern, M.D., Ensign Professor of Medicine.

According to Inge Reichenbach, Yale’s vice president for development, the campaign has set specific goals for the medical school, including the establishment of new endowed professorships, financial aid for students, new buildings for research and clinical care, technology resources, educational innovation and support for the cancer hospital addition to Yale-New Haven Hospital.

The drive comes at a time when the university is enjoying record growth in its endowment, which grew from $5.8 billion in 1997, at the conclusion of the university’s “… and for Yale” campaign, to $18 billion for the fiscal year ending June 30. During that same nine-year period, the medical school’s endowment has risen from $446.6 million to $1.5 billion. The university has an operating budget of $1.67 billion for 2006-2007, of which $676 million is expected to come from the endowment.

But the size of the endowment, second only to Harvard’s $29 billion nest egg, does not mean the university has all the resources it needs to grow in new directions, according to campaign leaders. “To expand Yale beyond its current scale and scope, to build the Yale of tomorrow, we will need new financial resources,” said President Levin. “Above all, we need to complete the transformation of Yale from a local to a regional to a national to an international university.”

Yale’s wealth is an issue that fundraising staff must address directly with potential donors, said Jancy Houck, M.A., who became the university’s associate vice president for development and director of medical development and alumni affairs on September 18. Income from the current endowment was committed to specific items at the time of the original gift decades or more ago, she said. “It takes new resources to do new things,” said Houck.

The same is true with grant dollars that come from the federal government, foundations and corporations, she added. For example, the $57.3-million Clinical and Translational Science Award (CTSA) that the medical school received in October (see related story), the largest grant ever received by the school, also presents an opportunity to engage donors in conversations about the medical school’s future.

“This support from the National Institutes of Health doesn’t take away from our need for philanthropy, because grants are very, very specific. You have to use the funding in the exact manner outlined in the proposal,” said Houck. “The philanthropy that we would be looking for would be for items that are not included in a big grant, where people could really leverage their gift, knowing that there is a certain amount of activity that is going to take place already.”

—Michael Fitzsousa

Years after gas attack, the horror lingers in an Iranian town, EPH alumna finds

After every bombing, people in Sardasht, a small town at the foot of Iran’s Zagros Mountains, ran outside to help the injured. On June 28, 1987, they rushed into a world that smelled of garlic. The air burned like acid. Bodies were covered with blisters. Children were crying, beyond comfort. When the blindness came, the villagers had no reason to expect that it would be temporary. For many, it was not.

The physical effects of chemical weapons like the mustard gas that fell on this Iranian town during the 1980-1988 war between Iran and Iraq are well-documented: burns, respiratory problems and temporary or permanent blindness. A new Yale study now sheds light on the psychiatric effects. Farnoosh Hashemian, M.P.H. ’05, a research associate in the Department of Epidemiology and Public Health (EPH), has documented severe and long-term mental health problems in Sardasht residents who survived a chemical attack. Her data were so compelling that the Iranian government made a psychologist, a scarce resource in the country, available to the 4,000 chemical-attack survivors in Sardasht.

Hashemian’s team published their findings in the August 2 issue of JAMA: The Journal of the American Medical Association. They collected data in three Kurdish towns in rural Iran: one was bombed 10 times; another was bombed 75 times; and a third, Sardasht, was bombed 60 times and also was attacked with chemical weapons. Hashemian did not anticipate the magnitude of distress she found in Sardasht—59 percent of those exposed to chemical weapons had experienced post-traumatic stress disorder, and 33 percent were still suffering from the disorder. She found that 65 percent had major anxiety symptoms and 41 percent had severe depressive symptoms.

Growing up in Tehran during the war, Hashemian knew that Saddam Hussein had gassed civilians and Iranian troops. “Will he gas Tehran?” the adults whispered. Believing a chemical attack on the Iranian capital was imminent, her family fled the city, eventually settling in Canada.

Three years ago Hashemian returned to Iran as an EPH student on a Downs International Health Student Travel Fellowship. Although the program usually sends students to countries unfamiliar to them, Hashemian convinced the review committee that rural Kurdish areas would constitute a new culture for a woman raised in fast-paced Tehran. Her parents in Canada were a harder sell. The border region in northern Iran is known for smugglers and land mines. “They were very worried, but now they are proud of me,” she said.

Hashemian collected data along with Farahnaz Falahati, M.D., a physician with the Janbazan Medical and Engineering Research Center, the Iranian equivalent of the Veterans Administration. The women stayed in spartan quarters with no showers or kitchen. But Hashemian said their main challenge was hearing the dreadful and grim stories.

Survivors reported nightmares, inability to work and relationships broken under the weight of stress. They believed another attack would come at any moment. Their fear was heightened during Hashemian’s visit because the United States had just invaded Iraq. Many villagers expected that Saddam would gas them again in retaliation for the U.S. attack. Despite their fearfulness, they invited the researchers into their small houses, offered them special meals and willingly told their stories.

“They felt that they had been forgotten,” Hashemian explained, and she agrees. The international community was silent during and after the attacks, she said.

Hashemian would like to see her work used by international organizations seeking to eradicate chemical weapons. By documenting the suffering of civilians—who account for most war casualties—Hashemian said, public health professionals can raise discussions of war and peace above the realm of politics. “War is a serious public health issue.”

—Colleen Shaddox

Stem cell program gets under way at Yale with arrival of cell biologist

One of the nation’s leading stem cell biologists arrived at Yale last summer to lead a new program that will explore the unique properties and therapeutic potential of these cells. Haifan Lin, Ph.D., and Associate Director Diane S. Krause, M.D., Ph.D., an associate professor of laboratory medicine and pathology and an expert on bone marrow stem cells, will lead the new Yale Stem Cell Program (YSCP). They will oversee a group of a half-dozen scientists and an administrative and technical staff devoted to research on human embryonic and adult stem cells, as well as stem cells in the mouse, fruit fly and roundworm.

The new center comes as the State of Connecticut has allocated $20 million for the Connecticut Stem Cell Research Grants Program, making it one of three states to fund this research. The YSCP has applied for funding from the state program and its applications were still under review this fall.

Stem cells, which can differentiate into many of the myriad cell types that form the body’s tissues and organs, have been much in the news as a potentially powerful treatment for diabetes, Parkinson’s disease, heart disease, spinal cord injury and other serious illnesses. The program will provide a scientific hub for more than 30 faculty members across the medical school and university who work on stem cell-related topics. Over the next few years, the YSCP will recruit four additional faculty members.

Three core research facilities are now being put in place: a human embryonic stem cell culture laboratory directed by Lin and Krause; a cell sorting center directed by Mark J. Shlomchik, M.D., Ph.D., professor of laboratory medicine and immunobiology; and a confocal microscopy laboratory directed by Michael H. Nathanson, M.D., Ph.D., professor of medicine and cell biology. The YSCP will eventually occupy one floor of the Amistad Building on the southern edge of the medical school campus, which is now under construction and slated for occupancy next year.

Lin comes to Yale from Duke University, where he was co-founder and co-director of the Stem Cell Research Program. He received his undergraduate degree from Fudan University in Shanghai, China, and his Ph.D. from Cornell University in 1990. He completed his postdoctoral training at the Carnegie Institution of Washington before joining the Department of Cell Biology at Duke University Medical Center in 1994.

Through his discovery of stem cells in the ovary of the fruit fly and his establishment of these cells as a research tool, Lin obtained direct evidence for the century-old hypothesis of asymmetric division as the means by which stem cells can both self-renew and produce daughter cells with the ability to differentiate into many distinct cell types. Lin has also discovered key genes that regulate stem cell division.

“Haifan Lin is a pre-eminent scientist whose research on the most basic mechanisms of stem cell biology has had a tremendous impact on the field,” said Dean Robert J. Alpern, M.D., Ensign Professor of Medicine. “He has the broad perspective needed to lead this exciting new effort at Yale.”

—Peter Farley

et cetera

Yale licenses AIDS drug

Yale University concluded in June a license agreement granting Oncolys BioPharma of Tokyo exclusive rights to develop a new compound to treat HIV. Yale has also applied for a patent for the compound, Ed4T. Preclinical studies have already begun, and Oncolys BioPharma hopes to begin Phase I/II clinical trials in 2008.

Ed4T is a thymidine analogue that blocks reverse transcriptase, an essential enzyme for viral replication. The compound was discovered and developed jointly by researchers in Japan and Yung-Chi Cheng, Ph.D., the Henry Bronson Professor of Pharmacology at Yale.

Pharmacological studies have shown that Ed4T has more potent anti-HIV activity than existing nucleoside-analogue reverse transcriptase inhibitors (NRTIs) and is active against viruses that are resistant to the existing NRTI and non-NRTI drugs. Further, Ed4T does not affect DNA synthesis in mitochondria, a toxic side effect of some nucleotide analogues. These findings suggested that Ed4T might offer unique therapeutic advantages over existing anti-HIV drugs

—John Curtis

New MR system at Yale

Yale will receive a $2 million High-End Instrumentation (HEI) grant from the National Center for Research Resources (NCRR) to buy a 7-Tesla human magnetic resonance (MR) system that will facilitate ultra-high resolution studies of diabetes, epilepsy, psychiatric disease and learning disorders. The NCRR makes one-time awards to support the purchase of sophisticated instruments costing more than $750,000 to advance biomedical research and increase knowledge of the underlying causes of human disease. Douglas L. Rothman, Ph.D., professor of diagnostic radiology and biomedical engineering, will oversee the MR system, a shared resource for several investigators funded by the National Institutes of Health. Yale has recruited two new faculty members to develop new methods of biochemical image-guided neurosurgery using the system.

—J.C.


			Originally published in Yale Medicine, Winter 2007. Copyright © 2007 Yale University School of Medicine. All rights reserved.