News

Lindy McClelland, a Genetics Ph.D. student, has been awarded an NIH F31 grant award. This award will provide three years of support toward stipend, tuition, health fees and lab supplies. Project Title: Tis11 Mediated mRNA degradation regulates intestinal stem cell quiescence

Salivary gland cells are viable encapsulated within hydrogels: A dissociated cell prep prepared from whole submandibular gland was seeded into PEG hydrogels and incubated in serum-free media.

Biomedical Genetics assistant professor, Catherine Ovitt, Ph.D. and Danielle Benoit, Ph.D., assistant professor of Biomedical Engineering and Chemical Engineering, have been awarded a four year grant from the National Institutes of Health (NIH), for the project, entitled Hydrogel encapsulation of salivary gland cells promotes cell survival, proliferation, and assembly.

This project deals with potential utility of adult stem or progenitor cells for repair of radiation-damaged salivary glands. While the potential is high, it is currently only a theoretical solution for patients suffering from xerostomia. There remain several critical obstacles that must be resolved before cell-based therapy for dysfunctional salivary glands can be moved into the clinical arena. These include the identification of appropriate donor cells, the technology for promoting implantation, and direct functional assays to assess the outcomes.

The goal is to determine if the use of hydrogels can promote in vivo differentiation of transplanted progenitor cells. The successful completion of this project will establish a foundation for subsequent translational research to progress the technology into clinical applications.

For more information please visit the Ovitt Lab and the Benoit Lab.

University of Rochester Medical Center scientists discovered new genetic evidence linking cholesterol and cancer, raising the possibility that cholesterol medications could be useful in the future for cancer prevention or to augment existing cancer treatment.

The data, published in the online journal Cell Reports, support several recent population-based studies that suggest individuals who take cholesterol-lowering drugs may have a reduced risk of cancer, and, conversely that individuals with the highest levels of cholesterol seem to have an elevated risk of cancer.

The cancer-cholesterol question has been debated since the early 20^th century, and along with it doctors and scientists have observed various trends and associations. However, until now genetic evidence directly linking cholesterol and malignancy has been lacking, said senior author Hartmut (Hucky) Land, Ph.D., Robert and Dorothy Markin Professor and chair of the Department of Biomedical Genetics and Professor in the department of Biochemistry & Biophysics, and director of research and co-director of the James P. Wilmot Cancer Center at URMC.

University of Rochester Medical Center scientists believe they are the first to identify genes that underlie the growth of primitive leukemia stem cells; and then to use the new genetic signature to identify currently available drugs that selectively target the rogue cells.

Nicole Scott, a Genetics Ph.D. student in Dr. Mark Noble's lab, has been awarded an NIH F31 grant award. This award will provide three years of support toward stipend, tuition, health fees and lab supplies. Project Title: Effect of early psychosine accumulation in Krabbe disease on CNS progenitor cells

Melanoma is devastating on many fronts: rates are rising dramatically among young people, it is deadly if not caught early, and from a biological standpoint, the disease tends to adapt to even the most modern therapies, known as VEGF inhibitors. University of Rochester researchers, however, made an important discovery about proteins that underlie and stimulate the disease, opening the door for a more targeted treatment in the future.

A mother's iron deficiency early in pregnancy may have a profound and long-lasting effect on the brain development of the child, even if the lack of iron is not enough to cause severe anemia, according to a University of Rochester Medical Center study published in the scientific journal PLoS One.

The results are important because obstetricians might not notice or treat mild or moderate iron deficiency, and therefore the study authors believe their research underscores the need for monitoring a pregnant woman's iron status beyond anemia.

What convinced us to conduct the present study were our preliminary data suggesting that cells involved in building the embryonic brain during the first trimester were most sensitive to low iron levels, said Margot Mayer-Proschel, Ph.D., the lead researcher and an associate professor of Biomedical Genetics at URMC.

A mother's iron deficiency early in pregnancy may have a profound and long-lasting effect on the brain development of the child, even if the lack of iron is not enough to cause severe anemia, according to a University of Rochester Medical Center study published in the scientific journal PLoS One.

What convinced us to conduct the present study were our preliminary data suggesting that cells involved in building the embryonic brain during the first trimester were most sensitive to low iron levels, said Margot Mayer-Proschel, Ph.D., the lead researcher and an associate professor of Biomedical Genetics at URMC.

Co-author Anne Luebke, Ph.D., an associate professor of Biomedical Engineering and Neurobiology & Anatomy at UR, suggested and directed the use of ABR testing, which can detect the speed of information moving from the ear to the brain.

For the first time, scientists discovered that a specific type of human cell, generated from stem cells and transplanted into spinal cord injured rats, provide tremendous benefit, not only repairing damage to the nervous system but helping the animals regain locomotor function as well.

The study, published today in the journal PLoS ONE, focuses on human astrocytes – the major support cells in the central nervous system – and indicates that transplantation of these cells represents a potential new avenue for the treatment of spinal cord injuries and other central nervous system disorders.

We’ve shown in previous research that the right types of rat astrocytes are beneficial, but this study brings it up to the human level, which is a huge step, said Chris Proschel, Ph.D., lead study author and assistant professor of Genetics at the University of Rochester Medical Center. What’s really striking is the robustness of the effect. Scientists have claimed repair of spinal cord injuries in rats before, but the benefits have been variable and rarely as strong as what we’ve seen with our transplants.

To create the different types of astrocytes used in the experiment, researchers isolated human glial precursor cells, first identified by Margot Mayer-Proschel, Ph.D., associate professor of Genetics at the University of Rochester Medical Center, and exposed these precursor cells to two different signaling molecules used to instruct different astrocytic cell fate – BMP (bone morphogenetic protein) or CNTF (ciliary neurotrophic factor).

Researchers from the Departments of Biology and Biomedical Genetics have identified a genetic switch that controls oxidative stress in stem cells and governs stem-cell function.

The Sally Edelman-Harry Gardner Cancer Research Foundation, a Hilton-based grassroots organization dedicated to finding cures for cancer, has awarded $50,000 grant to a pair of scientists working to better understand the mechanisms of pancreatic cancer.

Hartmut Hucky Land, Ph.D., chair of Biomedical Genetics and scientific director of Wilmot Cancer Center, and Aram Hezel, M.D., assistant professor of Medicine and gastrointestinal oncologist, received the funding to study a new potential target in pancreatic cancer that Land recently identified. Hezel will build upon Land's laboratory findings to determine whether the new target is effective in treating the disease.

Each year, about 43,000 Americans are diagnosed with pancreatic cancer, a deadly disease with few warning signs or symptoms until it has spread to other organs. Survival rates are poor. Pancreatic cancer has received significant attention in recent years after actor Patrick Swayze succumbed to the disease.

Any advances that we can make to improve the treatment of pancreatic cancer are a major step forward, says Richard I. Fisher, M.D., director of the Wilmot Cancer Center. It's wonderful to see this Foundation continue to partner with us to find cures.

Dirk Bohmann, Ph.D., an accomplished molecular biologist and geneticist, today received the 2010 Davey Memorial Award for outstanding cancer research.

Two large federal grants received this summer will allow researchers at the James P. Wilmot Cancer Center to continue their work into stem cells that give rise to cancer.

University of Rochester Medical Center scientists discovered a defect in cellular pathways that provides a new explanation for the earliest stages of abnormal skull development in newborns, known as craniosynostosis.

The University of Rochester Medical Center has received a $3.3 million grant from the Empire State Stem Cell Board for the construction of a new facility that will enable scientists to produce human stem cells suitable for testing new therapies.

Today, the department of Biomedical Genetics 22^nd Annual Genetics Day was highlighted by the 8^th Annual Fred Sherman Lecture. Dr. Fred Sherman, Professor Emeritus of Biochemistry & Biophysics has been honored for his contributions to Genetics and Yeast Genetics for the past nine years with a lecture named after him. The NIH has funded Fred for a remarkable 45 years, during which time he has published over 280 papers, with more on the way.

In 1970, Fred initiated the famous yeast course at Cold Spring Harbor, which has trained scores of today’s leading investigators. He served as an instructor in this course for 17 years. Fred’s many landmark contributions to several fields of molecular biology were recognized by his election to the National Academy of Sciences in 1985.

Genetics Day is an annual event, including a poster session and plenary lectures, that brings together the University genetics community defined in its broadest sense. This year, Dr. Stuart L. Schreiber, Director of Chemical Biology at and Founding Member of the Broad Institute of Harvard and MIT, gave the Sherman Lecture entitled, Relating the genetic features of cancers to drug efficacies using small-molecule probes.

Scientists trying to understand how cancer cells invade healthy tissue have used the fruit fly’s metamorphosis from maggot to flying insect as a guide to identify a key molecular signal that may be involved in both processes.

Scientists at the James P. Wilmot Cancer Center who investigate lymphoma and leukemia were among the top presenters at the American Society of Hematology 51st Annual Meeting, Dec. 5-8, 2009, in New Orleans.

A University of Rochester Medical Center researcher sorts out the controversy and promise around a dangerous subtype of cancer cells, known as cancer stem cells.

Scientists have identified a protein in the brain that plays a key role in the function of mitochondria – the part of the cell that supplies energy, supports cellular activity, and potentially wards off threats from disease. The discovery, which was reported today in the Journal of Cell Biology, may shed new light on how the brain recovers from stroke.

Ten scientists from the University of Rochester Medical Center (URMC) have been awarded more than $6.8 million by the Empire State Stem Cell Board. The grants are for a wide range of research programs in the fields of neurological disorders, cancer, musculoskeletal diseases, the blood system, and efforts to understand the fundamental mechanics of stem cell biology.

A system of opposing genetic forces determines why mammals develop a single row of teeth, while sharks sport several, according to a study published February 26, 2009 in the journal Science. When completely understood, the genetic program described in the study may help guide efforts to re-grow missing teeth and prevent cleft palate, one of the most common birth defects.

The promise of cancer stem cell research has reached a critical point and the University of Rochester Medical Center is establishing itself as a leader in the field by creating a Cancer Stem Cell Research Program. The Medical Center's top scientists are collaborating to discover cures for cancer by closely examining the master cells of this deadly disease. This program is one of only three formal programs in the United States. The two others are at Harvard and Stanford universities. This is a new avenue for scientists to pursue in an effort to find the underlying causes of cancer.

Oncologists have long treated cancer by attacking the tumors, but in many cases without getting at the root of the disease - the cancer stem cells - which tend to be drug resistant and a potential cause of relapse, said Craig Jordan, Ph.D., director of Translational Research for Hematologic Malignancies at the James P. Wilmot Cancer Center and associate professor of Medicine and Biomedical Genetics.

Jordan and colleagues, Monica Guzman, Ph.D., and Mark Noble, Ph.D., authored a primer on cancer stem cells in the Sept. 21 issue of The New England Journal of Medicine, outlining the data available today and challenges that are ahead for scientists and oncologists.

University of Rochester Medical Center scientists discovered a gene mutation that impairs the placenta and also is influential in cancer development, according to a study published online December 16, 2008, in the journal PLoS (Public Library of Science) Biology.

Many scientists like to discuss how each form of cancer is a distinct disease with its own causes and its own treatments. But researcher Hartmut Hucky Land, Ph.D., takes the opposite approach: He is hunting for the most basic rules that all cancers share to make good cells go bad.

His unique, far-reaching effort to understand the disease at its roots poses a huge challenge that is matched only by the potential payoff - findings that could lead to new treatments for not just one but many forms of cancer.

The project has taken a big step forward with a $2.7 million grant from the National Cancer Institute to unravel the gene networks at the heart of colon cancer. The funding will support work for the next five years in the laboratory of Land, who is scientific director of the James P. Wilmot Cancer Center at the University of Rochester Medical Center.

A new approach to finding genes important in the onset of cancer is described in Nature. The findings could help to identify new targets for tumor therapy.

Several genes, or oncogenes, cooperate with each other to transform normal cells into cancer cells. Hartmut Land and colleagues have now identified a list of other genes - termed cooperation response genes (CRGs) - that are regulated downstream of these oncogenes. By interfering with each CRG individually, the team were able to show that 14 out of 24 of them had a critical role in tumor formation. Restoring expression of these genes to the levels observed in normal cells prevented the formation of tumors. What's more, genetic perturbations of CRGs with relatively smaller effects when examined on their own show evidence of being essential when analyzed in combination.

The findings represent an important step in the search for the chink in the armor in human cancer - the elusive gene that cancer cells simply cannot live without.

Pinpointing new targets for cancer treatments is as difficult as finding a needle in a haystack, yet a University of Rochester team has discovered an entire novel class of genes they believe will lead to a greater understanding of cancer cell function and the next generation of effective and less harmful therapies for patients.

Changing dendritic spines on a neuron - evidence of brain rewiring

New findings about a protein called the nogo receptor are offering fresh ways to think about keeping the brain sharp. Scientists have found that reducing the nogo receptor in the brain results in stronger brain signaling in mice, effectively boosting signal strength between the synapses, the connections between nerve cells in the brain. The ability to enhance such connections is central to the brain's ability to rewire, a process that happens constantly as we learn and remember. The findings are in the March 12 issue of the Journal of Neuroscience.

The work ties together several research threads that touch upon the health benefits of exercise. While those benefits are broadly recognized, how the gains accrue at a molecular level has been largely unknown. The new research gives scientists a way to produce changes in the brain that mirror those brought about by exercise, by reducing the effect of the nogo receptor.

The find comes as a surprise, because for much of the last decade, the nogo receptor has been a prime target of researchers trying to coax nerves in the spinal cord to grow again. They named the protein after its ability to stop neurons from growing. Its action in the brain has not been a hot topic of study.

A green glow from a fruit fly is giving researchers the green light when they are on the right path in their quest to develop compounds that help prevent cancer.

Hartmut Hucky Land, Ph.D., professor and chair of the Department of Biomedical Genetics, will give a talk titled Construction and Deconstruction of Cancer Cells, as part of a lecture series highlighting biological and biomedical research at the University of Rochester.

Land will lead a discussion at 4 p.m. on Friday, Oct. 12, in the Adolph Auditorium (1-7619). The talk is the latest installment of the Second Fridays Science Social for faculty, staff and students at the University, although the public is welcome to attend. The lectures are free.

Cancer-causing genes can work in more powerful and sneaky ways than has been realized. Scientists have shown that a gene named JAK that is closely related to a common cancer-causing gene in people tips the scales toward cancer in an unexpected manner. JAK disrupts the activity of an organism’s DNA on a broad scale, thwarting a critical molecular event very early on in an embryo’s development.

University of Rochester scientists, while investigating the two most frequent types of mutations in cancer, discovered a possible new route to treatment that would take advantage of the mutations instead of trying to repair them. The research is reported online this week in the journal Nature Structural & Molecular Biology.

In experiments with rodent and human cells, co-authors Mingxuan Xia, Ph.D., and Hartmut Land, Ph.D., explored how the Rho family of proteins, which are involved in cell movement, and thus in the progression from benign to malignant cancer, are controlled by two well-known cancer genes, p53 and Ras. By closing in on this deadly collaboration, researchers showed for the first time why some molecules such as Rho are targeted by cancer genes - and how they might lead to a promising way to intervene against cancer.

We have very little understanding of how Ras and p53 or any other potent gene mutations cooperate to cause malignant tumors, said Land, who is professor and chair of the Department of Biomedical Genetics and scientific director of the James P. Wilmot Cancer Center at the University of Rochester. But we have suspected for a long time that the way to develop rational searches for new drug targets is to first understand how these oncogenes cooperate. And in this study we’ve shown for the first time that this idea might work.

As far as Mark Noble is concerned, the next medical revolution arrived more than 30 years ago. That’s when the Rochester professor of biomedical genetics and scientists like him at academic medical centers across the country first began to grasp the potential of stem cells.

In Noble’s lab and in the labs of scientists across the Medical Center, Rochester scientists have been exploring that potential for several years, helping lead research projects focused on new cancer treatments, the role nutrition plays in early development, and in understanding how to repair damage to the brain and nervous system.

Chris Proschel, Mark Noble, and Margot Mayer-Proschel have worked together as a team since 1990. They played key roles in identifying—and are considered to be among the best in the world at handling—the four known progenitor cells for the various cells found in the central nervous system.

Researchers believe they have identified a new way, using an advance in stem-cell technology, to promote recovery after spinal cord injury of rats, according to a study published in today’s Journal of Biology. Scientists from the New York State Center of Research Excellence in Spinal Cord Injury showed that rats receiving a transplant of a certain type of immature support cell from the central nervous system (generated from stem cells) had more than 60 percent of their sensory nerve fibers regenerate. Just as importantly, the study showed that more than two-thirds of the nerve fibers grew all the way through the injury sites eight days later, a result that is much more promising than previous research. The rats that received the cell transplants also walked normally in two weeks.

These studies provide a way to make cells do what we want them to do, instead of simply putting stem cells into the damaged area and hoping the injury will cause the stem cells to turn into the most useful cell types, explains Mark Noble, Ph.D., co-author of the paper, professor of Genetics at the University of Rochester, and a pioneer in the field of stem cell research. It really changes the way we think about this problem.

The breakthrough is based on many years of stem cell biology research led by Margot Mayer-Proschel, Ph.D., associate professor of Genetics at the University of Rochester. In the laboratory, Mayer-Proschel and colleagues took embryonic glial stem cells and induced them to change into a specific type of support cell called an astrocyte, which is known to be highly supportive of nerve fiber growth. These astrocytes, called glial precursor-derived astrocytes or GDAs, were then transplanted into the injured spinal cords of adult rats. Healing and recovery of the GDA rats was compared to other injured rats that received either no treatment at all or treatment with undifferentiated stem cells.

Many drivers feel the urge to floor the accelerator on a crisp sunny day when the highway ahead seems to stretch straight to eternity. But only the most foolish would cut the brake line while pushing the pedal to the metal. Yet one of the body's most potent cancer-causing genes does precisely that inside a cell, scientists at the University of Rochester Medical Center have found. The result of the unfettered molecular joy ride is, oftentimes, cancer. Details of the research are in the October issue of the Journal of the European Molecular Biology Organization (EMBO).

Scientists have long recognized that the protein produced by a gene known as myc spurs a cell to grow. Just like pushing the accelerator makes a car move forward, producing more myc makes a cell grow and divide. Too much myc spells an invitation to cancer, where cells grow uncontrollably and invade other tissues.

Now scientists have found that myc is even more powerful than they anticipated: The gene also has a role in disabling the molecular signals, the brakes, that cells rely on to slow growth. When myc is out of control, not only is the accelerator floored but the brakes are out. It's no wonder that the gene plays a role in many human cancers, including those in the lung, colon, breast, bladder, and brain.

Myc is central to our cells' ability to grow, divide, and even die when they should, says Hartmut Land, Ph.D., director of the University's Center for Cancer Biology and lead investigator of the EMBO study. Basically, myc is like the starter of an engine; it's responsible for making the whole cell go. It's a very potent gene, but one that's been slow to yield its secrets. Myc has been a conundrum.