UMASS MEDICAL SCHOOL RESEARCHERS HONORED FOR DISCOVERY OF GENES CONTROLLING BONE DEVELOPMENT AND CANCER 
American Society for Bone and Mineral Research presents two scientists with the William F. Neuman Award 

September 21, 2006 

WORCESTER, Mass. — For the past 26 years, the American Society for Bone and Mineral Research (ASBMR), the world’s largest society of basic scientists, clinicians and nurse practitioners researching skeletal biology and pathology, has annually recognized a researcher for his or her significant contributions to the field of bone and mineral research with the bestowal of the William F. Neuman Award. This year, for the first time, the prestigious award is shared by two professors, both of whom are from the University of Massachusetts Medical School: Gary S. Stein, PhD, the Gerald L. Haidak, MD, and Zelda S. Haidak Professor of Cell Biology, professor and chair of cell biology and deputy director of the University of Massachusetts Cancer Center, and his colleague Jane B. Lian, PhD, professor of cell biology. 

“We are absolutely thrilled to receive this award,” said Dr. Lian, a resident of Westborough, Mass. “It is extremely rewarding for our UMass research group and collaborators to be recognized for years of dedication to understand bone biology and skeletal disease.” 

The Neuman Award is named for the world-renowned scientist, whose work on bone-seeking isotopes as part of the Manhattan Project was influential and followed by several major works, including the formation of bone cells and the concept of bone membrane.    The award acknowledges Dr. Stein and Lian’s 20 years of collaborative work and contributions to the discovery of genes that control skeletal development as well as the metastasis of tumors to bone. 

Stein and Lian first joined forces in 1985 on a National Institutes of Health grant, while employed by separate institutions. They continued to work together on additional grants, and by the late 1980s, both Stein and Lian had accepted faculty positions at UMMS. During their early collaborations, Stein and Lian developed a technique to isolate the DNA and RNA of bone. This approach led to defining a series of stages during bone cell differentiation, each containing a distinct marker for gene expression. In working with UMMS clinicians, Stein and Lian used the technique to study the bone of patients suffering from skeletal diseases. This method enabled researchers and clinicians to understand the diseases’ abilities to alter gene expression, which is important in monitoring the effectiveness of treatment and in understanding the preferred modality of treatment, according to Stein. 

Following this success, Stein and Lian cloned the osteocalcin gene. The gene, which was identified by Lian, is a marker for mature bone-forming cells known as osteoblasts. Stein and Lian used a cloned osteocalcin gene and histone gene, which represents the growth stage of a bone cell, to extract regulatory factors detailing the osteoblasts’ stages of maturation. This led them to discover an entire series of proteins essential for regulating the osteoblasts’ course of growth for bone formation. 

Currently Stein and Lian’s work is focused on “intranuclear-trafficking,” the directing of a regulatory protein to its correct microenvironment within a cell nucleus, which will allow the protein to engage in its proper function. This new process has allowed Stein and Lian to study the regulation of genes in bone cells within the nucleus’ structure during the development of skeletal diseases. “This process has a profound influence on the interaction of a tumor that metastasizes to bone and the impact on bone,” said Stein. 

Stein and Lian have learned that when Runx1, a hematopoietic tissue specific transcription factor, carries a mutation that prevents it from traveling to the correct microenvironment, leukemia cells develop. In observing the bone tissue specific transcription factor, Runx2, which they discovered, Stein and Lian learned that it is not only needed to produce bone, but also must be organized in the nucleus with other regulatory factors. “Without this master regulatory gene, the skeleton would be composed of cartilage,” said Lian. They have also found when the expression of Runx2 is reduced or inhabited in metastatic cancer cells, and the cancer cells are placed in bone, the tumor cells no longer cause osteolytic disease. 

Stein and Lian’s research is not only biologically significant, but it is clinically relevant as well. Stein cited osteoporosis and breast and prostate cancer tumors metastasizing to bone as the two bone diseases that have greatly impacted public health. “Osteoporosis and bone metastasis are very important right now. They both cause great pain and suffering, and there is a tremendous economic impact,” said Stein, who resides in Shrewsbury, Mass. “Consequently, trying to understand how bone is formed and altered as well as the way tumors interact with bones are extremely important from a clinical standpoint.”

By developing a culture system and isolating bone cells at different stages, Stein and Lian laid the groundwork for clinicians to treat metabolic bone disorders with hormones and growth factors and to observe the various effects of these treatments. This information provides a better understanding for designing treatments for a patient. “For example, some hormones needed for bone formation cannot be given continuously; rather, intermittent therapy is required to activate the bone cells,” said Lian. 

Stein and Lian received the Neuman Award at the ASBMR’s 28th Annual Meeting held in Philadelphia. In addition to recognizing Stein and Lian’s research, the award also acknowledges the mentorship they have provided to post-doctoral fellows, clinical investigators and graduate students. “From day one, this has been a collaborative effort, and outstanding scientists and researchers from the institution’s basic science and clinical departments as well as the graduate students and post-docs working in ours labs have enabled us to cover areas that had not been previously explored. The University’s support of this kind of collaboration really allowed our work to move forward,” said Stein.

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About UMMS 

The University of Massachusetts Medical School is one of the fastest growing medical schools in the country, attracting more than $174 million in research funding annually.   A perennial top finisher in the annual U.S.News & World Report ranking of primary care medical schools, UMMS comprises a medical school, graduate school of nursing, graduate school of biomedical sciences and an active research enterprise, and is a leader in health sciences education, research and public service. 

Contact: Nicole Soucy, 508-856-2000, ummsnews@umassmed.edu