Gary Stein

Gary Stein, graduate of the University of Vermont is returning home as co-Director of the Vermont Cancer Center and Chair of the Department of Biochemistry. Following graduate training at UVM in physiology and biology and post-graduate training in pathology, Gary joined the faculty at the University Of Florida College Of Medicine where he became Vice-Chair of the Department of Biochemistry. In 1987 he joined the faculty at the University of Massachusetts Medical School where he has served as the Haidak Distinguished Professor of Cell Biology, Co-Director of the UMass Memorial Health Care Cancer Center of Excellence, Chair of the Department of Cell Biology and Founding director of the UMass Human Stem Cell Bank & Registry.

In Gary’s words, “it is with commitment and enthusiasm that I am partnering with an outstanding clinical investigator, Claire Verschraegen, to provide leadership for the Vermont Cancer Center with strong support from the College of Medicine, the University and Fletcher Allen Health Care”. Equally important, as Chair of the Department of Biochemistry, I have the opportunity to develop new dimensions to an outstanding program with long-standing contributions to biomedical research and education”.

He emphasized “the importance of partnerships between scientists and physician investigators as well as regional collaborations to maximize capabilities for effectiveness in basic, translational and clinical investigation as well as for optimal patient care and infrastructure for research and clinical trials”. Here he provided assurance of his “priority to enhance collaborative academic and clinical initiatives that incorporate faculty and support staff expertise and experience as well as shared resources of UVM, Dartmouth, UMass and JAX Labs.”

Gary will be coming to UVM with his long-standing partners Janet Stein, Jane Lian and Andre van Wijnen and key members of their research team. Together, they have laid a foundation in the bone field for addressing gene regulatory mechanisms (genetic and epigenetic) that are opportune during development of the osteoblast phenotype by developing techniques for RNA isolation from bone and characterizing the promoters of cell growth in bone specific genes as blueprints for responsiveness to physiological regulatory signals. The sequential stages and developmental transitions of osteoblast maturation have proved to be a paradigm used by many investigators for characterizing skeletal cell growth and differentiation as well as bone metabolic diseases (e.g., osteoporosis and osteoporosis) and cancer (osteosarcoma). The laboratory has developed a novel approach to targeting gene therapy to bone using tissue specific promoters and characterized microRNA-mediated control that facilitates osteoblast proliferation and differentiation.

The Stein/Lian/van Wijnen research group has been at the forefront in defining the relevance of subnuclear organization. He provided a new dimension to understanding transcriptional control by identifying the first subnuclear trafficking signal in hematopoietic and bone-specific AML/Cbfa regulatory factors. This signal, a unique 31 amino acid targeting sequence which can function autonomously and independent of a nuclear import signal, directs AML/Cbfa regulatory proteins to nuclear matrix-associated subnuclear domains that support transcription. The laboratory has shown that the t8;21 chromosomal translocation in AML leukemia disrupts the AML locus and results in aberrant intranuclear trafficking of AML transcription factors that compromise fidelity of hematopoietic-specific gene expression. They further linked intranuclear trafficking of transcription factors with control of tissue-specific gene expression by in vivo genetic approaches. The Stein/Lian/van Wijnen laboratory has demonstrated that replacement of the gene encoding the bone-specific AML/Cbfa transcription factor with a gene containing a mutated intranuclear trafficking signal results in the phenotype that occurs when the gene is ablated. These results are key contributions to understanding involvement of nuclear architecture in mechanisms that facilitate the dynamic assembly and activity of transcription complexes for the spatial and temporal control of gene expression.

Current research initiatives of the Stein/Lian/van Wijnen research team focus on genetic and epigenetic control of cell growth and phenotypic genes that regulate proliferation and cell function with emphasis on breast cancer, prostate cancer and leukemia. Their recent discovery of a novel dimension to epigenetic control, transcription factor retention at target gene loci of mitotic chromosomes (published in Nature and reviewed by Stein and colleagues in Nature Reviews Cancer, Nature Reviews Genetics, Journal of Biological Chemistry and Molecular and Cellular Biology), has tremendous potential for expanding understanding of transformation and tumor progression as well as providing “druggable targets”.

Gary Stein has organized and chaired numerous international research conferences and serves on advisory panels for United States and foreign government science policy and granting agencies, scientific advisory boards for biotechnology, pharmaceutical and health care organizations and editorial boards of more than 20 journals. He has been committed to providing mentorship to more than 120 graduate students, postdoctoral students and physician/scientists, developing research and science education programs in his institution as well as with universities in Europe, Asia, the Middle East and South America.

Gary Stein directs a research program of basic scientists and physician/investigators who are dedicated to discovering aberrant regulatory mechanisms in cancer cells and developing new dimensions to cancer diagnosis and therapy. Their research program is sponsored by the National Cancer Institute, pharmaceutical companies and by research foundations.