URMC Research

A decades-old tradition of research excellence at the University of Rochester Medical Center continued in 2008 as pioneering work changed the nature of treatment for yet another major disease, while strategic investments laid the groundwork for future breakthroughs.

Our scientists led the study that resulted in this year’s approval of a new drug for the treatment of Huntington’s disease, a fatal, inherited neuromuscular disorder that strikes 30,000 Americans. Called tetrabenazine, the drug reduces the involuntary movements of patients with the disease by about 25 percent. Like the vaccine for cervical cancer to which URMC researchers also contributed, the new treatment for Huntington’s resulted from work that went forward within a rare, ingrained culture of collaboration, an interdisciplinary environment in which science thrives.

Collaboration Gets Results

best places to work bannerThe value of Rochester’s collaborative culture was recognized this year as the University of Rochester earned a top-ten ranking for “Best Places to Work” for life scientists by The Scientist magazine, bolstered by high scores in collegiality and professionalism as well as mentoring.

URMC has worked for many years to foster an environment where the typical researcher not only leads his or her own grant-funded study, but also works closely with colleagues as a co-investigator on a number of other research projects. While multiple viewpoints certainly encourage out-of-the-box thinking, our collaborative culture also increases the likelihood that our scientists will be fully funded through grants.

This helps explain why the Medical Center’s research funding (excluding contracts) from the National Institutes of Health (NIH) has remained researcherrelatively stable despite the decline in NIH funding to medical schools. In 2008, URMC’s total NIH funding declined just 2 percent, from $151.9 million in Fiscal Year 2007 to $148.8 million in Fiscal Year 2008. Among our peers, NIH funding is down as much as 6 percent in comparison. Further, the Empire State Stem Cell Board announced in December that Medical Center scientists will receive $6.8 million in new stem cell research funding, offsetting the decline in federal funding. Our researchers continue to compete for funds very effectively, winning as many new investigator-initiated Research Project (RO1) grants in FY08 as they did in FY07 despite challenging circumstances.

Continuing to leverage our flair for teamwork will be crucial to continuing our research growth. One new tool in that effort is a database known as the “e-CV” or “electronic CV” system. Not only does the system record data on researchers’ productivity, but it helps engender collaboration by mapping out areas where scientists’ interests overlap. As we grow and continue to attract more researchers, e-CV will help scientists identify potential collaborators within the institution instantly, with the click of a mouse.

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Strategic Vision

URMC’s 2007-2012 Strategic Plan takes advantage of this collaborative environment by establishing nine high-priority signature programs where URMC is furthering its reputation for innovation and excellence through strategic investment in people and facilities.

These programs include five Integrated Disease Programs (IDPs) that bring scientists together daily with physicians to find cures, as well as four Innovative Science Programs (ISPs), areas of emerging scientific discovery. Of note, three of the four ISPs represent cross-campus collaborations. Already, the Medical Center is investing in recruits and technology to further its scientific portfolios in:

  • stem cell and regenerative medicine
  • biomedical imaging and biomarkers
  • nanomedicine
  • genomics and systems biology

research labAmong the most exciting strategic plan recruits in 2008 was the husband-and-wife team of Troy Randall, Ph.D., and Frances Lund, Ph.D. The immunologists relocated to URMC from the Trudeau Institute, bringing with them about a dozen scientists – and a multi-million-dollar research portfolio that fits squarely within the Immunology and Infectious disease IDP and relates to other priority areas such as orthopaedics, cancer, and stem cells. In total, URMC recruited 47 basic science and clinical faculty members this year, more than replacing those lost to retirement or recruited to other medical centers.

In addition to new recruits, the strategic plan calls for key investments in research facilities, the most prominent example being the Clinical and Translational Science Building (CTSB). As the hub for all translational activity, the CTSB will fundamentally re-engineer the way research is conducted at the Medical Center, speeding basic research discoveries into improved care. Aided by $50 million in construction funding from New York State, the CTSB will enable the University and its partner institutions to build research networks among more than 600 scientists, physicians, nurses, statisticians and support staff. It will be deliberately located in tandem to the School of Nursing, essential partners in translational science efforts.

While CTSB is not yet built, the work of translating basic research discoveries into developments to benefit patients continues at a rapid pace. The number of clinical trials under way at the Medical Center rose to more than 700 this year, bringing more early-stage treatment options to our patients. A team within the Department of Orthopaedics, for instance, began a trial testing the ability of an existing osteoporosis drug, teriparatide, to heal fractures in aging patients that would never heal otherwise. In early results, 93 percent of patients showed significant healing and pain control. Meanwhile, cardiac specialists took part in the PEERLESS-HF clinical trial in which an elastic device was wrapped around the hearts of cardiac failure patients to prevent their hearts from expanding further and to stop them from losing the ability to pump blood.

Next to the CTSB, there is no better example of URMC’s commitment to translation than the new James P. Wilmot Cancer Center. The four-story, 164,000-square-foot Cancer Center consolidates all outpatient cancer care and translational research programs into a single location by co-locating researchers along with physicians caring for patients. Dedicated in May of 2008, the Center is now expanding research and treatment programs in lung, breast, prostate and colon cancers as well as lymphomas and leukemias. The Wilmot Cancer Center also boasts one of just three formal cancer stem cell research programs in the country.

The added space at the Cancer Center is needed to house a growing research portfolio. In 2008, the Medical Center saw a 62 percent increase in National Cancer Institute funding, fueled in part by the School of Medicine and Dentistry’s receipt of an $11.5 million NCI grant for lymphoma research and clinical trials. The Medical Center is one of just four lymphoma Specialized Programs of Research Excellence (SPORE) centers in the nation. Wilmot’s growing research funding better positions it to recapture NCI center designation, awarded to organizations proven to be major sources of new knowledge on treatment of cancer.

In 2008, we also completed the addition of 22,000 square feet of laboratory space for the University of Rochester Eye Institute, bringing to fruition a $5.5 million project funded largely by NIH. The new space is devoted to understanding and treating conditions such as macular degeneration, dry eye, and recovery of vision after stroke. Central to much of the work is a unique technology developed by researchers at the Eye Institute that allows doctors to see the back of the eye in unprecedented detail.

Researchers working in all areas benefit from an increasingly important set of resources known as core facilities. These are highly sophisticated processes or equipment, such as a functional genomics center, flow cytometry, and confocal microscopy, which serve scientists throughout the institution. Last year we invested $4 million in new technology to improve these shared resources.

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Key Discoveries

In 2008, scientific inquiry resulted in new approaches to treatment, not coincidentally, in the Medical Center’s signature programs:

  • cancer
  • heart disease
  • infectious disease
  • musculoskeletal disease
  • neurological disorders

researcherWork this year at the James P. Wilmot Cancer Center underscores the importance of collaboration at Rochester. Its researchers collaborated with a team of biostatisticians from the Department of Biostatistics and Computational Biology on a landmark study on a new class of genes with potential to yield next-generation chemotherapies. Published in the journal Nature, the study led by Hartmut Land, Ph.D., featured the discovery of approximately 100 genes that work downstream of known cancer-causing mutations, providing a host of new opportunities for interventional treatments.

Another team worked to explain how a commonly used chemotherapy drug, 5-fluorouracil (5-FU), causes “chemo brain,” the loss of mental clarity that many cancer patients experience. Study leader Mark Noble, Ph.D., brought together a team of oncologists and stem cell biologists in cooperation with the University of Rochester Stem Cell and Regenerative Medicine Institute to clarify how the drug causes key stem cells in the brain to die off, an effect that continues long after treatment ends.

Within the Aab Cardiovascular Research Institute, researchers found the first direct proof that a key protein drives the clogging of arteries in two ways, and that lowering levels of it opens them up. The work establishes cyclophilin A as an exciting target in the design of drugs against atherosclerosis, the number-one cause of heart attacks and strokes, according to study leader Bradford C. Berk, M.D., Ph.D. A second research team led, not by a cardiologist but instead by Paul S. Brookes, Ph.D., in the Department of Pharmacology and Physiology, discovered the mechanism by which briefly cutting off, then restoring, blood flow to arteries prior to a heart attack lessens the damage. In the near term, the work may help to prevent damage caused as U.S. heart surgeons temporarily stop blood flow 450,000 times each year to perform coronary artery bypass graft surgeries.

Researchers in the Department of Microbiology and Immunology announced that a drug once looked at for cancer also attacks the human immunodeficiency virus (HIV) in a new and powerful way. Past research has established that HIV has “learned” to hide out in certain human cells where it is safe from the body’s counterattack, as the cells come to serve as viral reservoirs. Rochester scientists have shown how the virus makes chemical changes that keep its chosen reservoirs alive long past their normal lifespan, and they’ve identified an existing drug that could reverse this deadly longevity.

A team of researchers within the Center for Musculoskeletal Research found that donated, freeze-dried tendon grafts loaded with gene therapy offer effective repair of injured tendons. This new graft technique may provide the first effective framework around which flexor tendon tissue can reorganize as it heals. Hani Awad, Ph.D., served as liaison in this effort between orthopaedic researchers and bioengineers seeking to design materials that can replace diseased or damaged human tissue.

Of course, striking research findings were made in additional areas by scientists throughout the Medical Center. Researchers from the Center for Oral Biology were part of a multi-institutional team that first catalogued the salivary proteome, the complete set of proteins in human saliva. Thanks to such work, patients may soon spit in a cup, instead of bracing for a needle prick, when being tested for cancer and other major illnesses.

In addition to the work on Huntington’s disease, Medical Center neurologists led by Steven Goldman, M.D., Ph.D., this year used human stem cells to dramatically improve the condition of mice with a neurological condition similar to a set of diseases that are fatal in human children. With a one-time injection of stem cells just after birth, scientists were able to repair defective wiring throughout the central nervous system of mutant “shiverer mice,” so called because of the way they shake. The work marks an important step toward stem-cell-based treatments for children with related syndromes.
Berislav Zlokovic, M.D., Ph.D., led a study in Neurosurgery this year, the results of which help to explain a major risk factor for Alzheimer’s disease. Researchers found that those patients born with the wrong type of a protein called ApoE4 cannot efficiently rid themselves of the toxic protein amyloid-beta that damages the brain in these patients.

In addition, a landmark 2008 paper published in the journal Cell by Lynne E. Maquat, Ph.D., provided important new detail about how human cells protect themselves against constant genetic mistakes that contribute to most diseases. After many years of work, her team has achieved an in-depth understanding of the natural process that finds genetic flaws, and hopes to create new approaches to the treatment of many genetic syndromes.

Researchers at the School of Nursing reached across disciplines as well, joining with social service providers to earn a $6.5 million grant for efforts aimed at advancing the health and safety of at-risk mothers and reducing rates of maltreatment for their children. The grant from the National Institute on Drug Abuse – the largest research award in the School’s history – will support research to examine the long-term effects of home visits by nurses to more than 600 low-income mothers and their children.

At the Eastman Institute for Oral Health, researchers discovered that pain, more than a symptom of osteoarthritis, is an inherent and damaging part of the disease itself. Scientists found that signals of pain that originate in arthritic joints, along with related biochemical events in the spine, worsen arthritis, and that interfering with the signals may represent a new way to treat arthritis.

And at Golisano Children’s Hospital, doctors learned that the flu vaccine is very beneficial for children, even in years when the vaccine is a poor match for the flu viruses that are actually circulating that year. The work was conducted by pediatricians through the New Vaccine Surveillance Network, a group that tracks the effectiveness of vaccines, including some developed at URMC. The work reminds us that URMC discoveries like those described here aren’t simply one-time occurrences; rather, each discovery offers the hope of improving the lives of people within our own community and around the world.

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