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Sherman Weissman |
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| Sterling Professor of Genetics, Director, Molecular Oncology&Development, Boyer Center for Molecular Medicine |
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* B.S. Northwestern University, 1950
* M.S. University of Chicago, 1951
* M.D. Harvard Medical School, 1955
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| Research Interests: | |
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* Globin and Histocompatibility Gene Structure and Function
* Genome wide mapping of gene activity and chromosome structure in man
* Transcription Factors
* Lymphocyte and myeloid Transcription Networks.
* Stem Cells
* Cell Senescence
* Methods for Molecular Genetics
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| Honors: | |
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* Fellow, American Association for the Advancement of Science
* Member, National Academy of Sciences
* Outstanding Investigator Award, NIH
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| Current Research: | | |
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| We have collaborated in a range of studies using genomic tiling arrays to map sites of transcription factor binding, intergenic transcripts, genomic structure variation, sites of early and late DNA replication, and chromatin structure
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| mRNA expression patterns in the hematopoietic/immune
system. We have analyzed patterns of mRNA
expression in purified cell types in the immune and
hematopoietic system, and are characterizing at a genomic level transcription factor binding sites and chromatin structure in these cells.. One area of focus is the differentiation and response
patterns of neutrophils and monocytes to various
stimuli. Similar studies
are planned for dendritic cells and various subsets of
immunocytes.
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| Genome wide mutation or polymorphism detection. We have
developed approaches for efficiently separating DNA
fragments containing internal mismatches from perfectly
matched fragments and are working on methods for
applying this at an entire genome level to rapidly
detect somatic mutations in neoplasias, as well as newly
arising mutations in experimental systems or man. In collaboration with Professor M. Snyder and the Yale Center for Genomics, we are working on approaches to detect at an unprecedented level of sensitivity, speed, and accuracy, deletions and perhaps even inversions across the genome.
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| Protein expression patterns. We have using 2d PAGE and
mass spectrophotometric identification of proteins to
investigate changes in protein patterns in hematopoietic
cells and correlate these with mRNA changes. In
particular we will be investigating the complement of
transcription factors in these cell types and their
modifications, using approaches that can give us
relative information about these on a very broad scale.
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| We are studying two genes in the major
hjistocompatibility complex that may represent
additional roles for the complex in the function of the
immune system. One gene is strongly expressed in
dendritic cells and induces a number of cell types to
from long (cytonemes-like) filopodia, so that it may be
involved in the formation of dendritic cell morphology.
The other gene is ubiquitin analogue with some
differences, and is also selectively expressed in
certain cells of the immune system and may be involved
in regulating cell response to external signaling.
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| We are investigating the role of certain globin gene
upstream sequences and a particular members of the
SWI/SNF family of genes in regulating globin gene
switching and response to enhancers, and are characterizing previously undescribed multi-protein complexes that bind to globin regulatory regions..
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| Studies are continuing on WRN, a helicase that is
mutated in Werner disease, a Mendelian disorder that
mimics premature aging in man. We are interested in the
types of DNA structures that WRN may interact with in
vivo, the proteins that associate with WRN, and the
possibility that the role for WRN in resistance to oxidative damage is responsible for the aging-like phenotype seen in Werner patients.
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| Representative Publications: | | |
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Raghunathan, A., Sivakamasundari, R., Wolenski, J., Poddar, R. Weissman, SM. Functional analysis of B144/LST1: A gene in the tumor necrosis factor cluster that induces formation of long filopodia in eukaryotic cells. Experimental Cell Research 286: 230-244 (2001)
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Kluger, Y., Tuck, D.P., Chang, J., Nakayama, Y., Poddar, R., Kohya, N., Lian, Z.,Ben Nasr, A., Halaban, R., Krause, D., Newburger, P., Weissman, S.M. Lineage specificity of gene expression patterns. Proc Natl Acad Sci USA (2004).
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Kluger, Y. Lian, Z., Zhang, X., Newburger, P., Weissman, S. A panorama of lineage-specific transcription in hematopoiesis. BioEssays (2004)
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Bertone P, Stolc V, Royce TE, Rozowsky JS, Urban AE, Zhu X, Rinn JL, Tongprasit W, Samanta M, Weissman S, Gerstein M, Snyder M. (2004) Global identification of human transcribed sequences with genome tiling arrays.
Science 306:2242-2246.
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| Contact Information: | | |
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