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NIH awards four grants over $1M to Upstate researchers in 2014

NIH awards four grants over $1M to Upstate researchers in 2014

“Biomedical research performed at Upstate spans studies on molecules to model organisms and human populations,” said David Amberg. Ph.D, Upstate’s interim vice president for research. “Grants from the NIH help our researchers to continue important explorations into both diseases that affect our local community, like diabetes or cancer, and global health challenges, like dengue.”

Zhu’s Group

The $1.62 million NIH grant awarded to Zhu is a five-year investigator initiated Research Project Grant. The study seeks to understand how a complex brain is generated from neural stem cells and how brain tumor develops using the fruit fly as a model organism. The team will investigate the role of a protein called Buttonhead in generating brain complexity and brain tumor formation. This research will also help understand the development of human brains as well as pathogenesis of various developmental neurological diseases and brain tumor formation. This project will take about five years to finish. Zhu is working alongside two postdoctoral fellows and one graduate student on this project.

Turner’s Group

The approximately $1.5 million award granted to Turner is a four-year competitive renewal of an NIH grant that was first awarded to him in 1991, when he joined the Cell and Developmental Department at Upstate. The grant will support his ongoing investigations into unraveling the fundamental molecular mechanisms underpinning dynamic cell behaviors, such as cell adhesion and migration. The outcomes of his studies may have far-reaching medical relevance, as cell adhesion and migration are essential for normal organism development, tissue remodeling, immune surveillance and wound repair. Their disregulation contributes to the progression of many diseases including cardiovascular disease, neurodegenerative disorders, tissue fibrosis and tumor progression and metastasis. In the current funding period, Turner and his team, which includes Assistant Professor Nick Deakin, Ph.D., and graduate students Greg Goreczny, Anushree Gulvady and Andrew Jacob, will use 2D and 3D matrix in vitro model systems to explore a new role for the cell adhesion adapter protein, paxillin in the regulation of directed cell migration by coordinating microtubule acetylation through the enzyme HDAC6. Since both paxillin and HDAC6 are disregulated in several human cancers, including breast cancer, the group will use both normal and cancer cells in their analyses, with plans to extend their findings into mouse models of cancer progression in the near future.

Damron’s Group

Damron’s team was awarded a $1.7 million grant to explore the changes radiation has on the biomechanics and biochemistry of bone that makes it more prone to fracture in patients that have cancer. The team will also be examining novel ways to try to minimize these damaging effects on the bone. Post-radiation fractures after radiotherapy are prevalent in specific anatomic locations, such as the pelvis following urologic or gynecologic cancer treatment, and may lead to devastating complications including amputation in extremity sites, such as the femur after treatment for soft-tissue sarcoma.  Lack of progress in developing strategies for prevention or treatment is limited by poor understanding of underlying pathophysiology.  While altered histologic and structural properties of irradiated bone have been described, CT and DXA clinical scans are often normal and fail to predict fracture risk. Preliminary animal model work suggests irradiated bone behaves in an embrittled fashion and that it is the compositional parameters that cause this brittleness. Given the current lack of understanding of post-radiation fractures and the availability of potentially translatable therapies, there is a high potential for this study to impact clinical practices.

Pruyne’s Group

Pruyne’s team received a $1.8 million grant to fund a research project exploring how a highly conserved family of proteins called formins help muscle formation. Muscle function depends on small contractile units within muscle cells called sarcomeres. Defects in proteins that make up the sarcomeres result in debilitating myopathies (diseases) of voluntary and heart muscle, and discovering how sarcomeres assemble is key to treating such myopathies. Formins are a group of proteins that work inside cells to stimulate the assembly of filaments composed of the protein actin. Interestingly, actin filaments are a major part of muscle sarcomeres, and earlier work from the Pruyne group showed formins are needed for normal muscle growth in a simple animal model system. The work funded by this new award will help discover the details of how formins assist in sarcomere assembly and muscle development.

Caption: Research by Christopher Turner, Ph.D, and his team has led to greater scientific insight into the mechanism that allows cancerous cells to move away from the primary tumor and colonize or metastasize to one or more distant sites elsewhere in the body--a critical step in tumor progression.

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