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Brief Biography

Michael Green received his MD and PhD degrees from Washington University School of Medicine in 1981. He carried out postdoctoral work at Harvard University, where he joined as a faculty member in 1984. In 1990, he joined the Program in Molecular Medicine at the University of Massachusetts Medical School (UMMS), and in 1999 became the Director of the Program of Gene Function and Expression (PGFE). In 2014, PGFE merged with the Department of Cancer Biology, and Dr. Green was appointed as Chair of the new Department of Molecular, Cell and Cancer Biology (MCCB). In addition to his role as Chair of MCCB, he is also Vice Provost of Strategic Research Initiatives, Director of the Cancer Center, and Co-Director of The Li Weibo Institute for Rare Diseases Research.

Dr. Green has made pioneering contributions to our understanding of the mechanisms that regulate gene expression in eukaryotes and how alterations in gene expression contribute to cancer and other human diseases. He is an elected member of the National Academy of Sciences, the National Academy of Medicine, the American Academy of Arts and Sciences, and the European Molecular Biology Organization.

Discovery of Therapeutically Targetable Pathways in Cancer and Other Diseases

Identification of New Factors and Regulatory Pathways that Promote or Prevent Cancer

My laboratory has used transcription-based approaches, functional screens (such as genome-wide loss-of-function RNAi- and CRISPR-based screens) and genomic methods to identify new genes and regulatory pathways that contribute to cancer. These studies are intended to enhance our understanding of the molecular basis of cancer and reveal potential new targets for therapeutic intervention. These approaches have enabled us to discover new oncogenes, such as the H2A ubiquitin ligase TRIM37 (Bhatnagar et al. 2014), tumor suppressor genes, such as the CREB coactivator CRTC2 (Fang et al. 2015) and repressors of FGFR signaling (Lin et al. 2014), and metastasis suppressor genes, such as GAS1 (Gobeil et al. 2008) and the histone H3K9 demethylase KDM3A (Pedanou et al. 2016). We have also identified two therapeutically targetable mechanisms that render chronic myeloid leukemia (CML) stem cells resistant to the drug imatinib mesylate (also known as Gleevec), the first-line treatment for CML (Ma et al. 2014; Ma et al. 2019). We are currently conducting functional screens to identify new factors involved in various aspects of cancer biology including transformation, cancer stem cell formation and maintenance, regulation of the epithelial-to-mesenchymal transition, and cancer drug resistance.

Alterations in pre-mRNA splicing lead to numerous diseases, including cancer. We have a long-standing interest in regulation of gene expression at the level of RNA processing, in particular pre-mRNA splicing. The essential splicing factor U2AF, which initiates spliceosome assembly by binding to the intronic polypyrimidine tract/3’ splice site, was originally discovered in our laboratory. Subsequent cancer genome sequencing studies revealed driver mutations in the U2AF 35 kDa subunit (U2AF35). We have shown that oncogenic U2AF35 mutants promote transformation through mis-regulation of both spicing and mRNA 3’ end formation (Park et al. 2016). We are continuing to investigate the role of aberrant RNA processing in cancer as well as other diseases.

Modulating Gene Expression as a Therapeutic Approach

Factors that drive cancer progression are often not druggable and thus their therapeutic inhibition is challenging. We are taking a novel approach to identify inhibitors of these “undruggable” cancer-promoting factors. First, we have developed and carried out reporter-based CRISPR screening strategies to identify factors and pathways required for expression of a cancer-promoting gene. Based upon this information, we then identify biological or small molecule inhibitors of these factors and pathways, which abrogate expression of the cancer-promoting gene and suppress tumor growth. We have used this approach to identify inhibitors of expression of oncogenes and other genes that affect tumor development such as suppressors of anti-tumor immunity. This approach can also be used to identify antagonists of proteins that cause diseases other than cancer, such as neurodegenerative diseases.

Cancer and other diseases can also arise due to the inappropriate transcriptional inactivation of specific genes. My lab has developed and successfully used functional genomic and proteomic approaches to identify factors and pathways involved in epigenetic silencing of tumor suppressor genes. Biological or small molecule inhibitors of these factors and pathways can reactivate expression of the tumor suppressor gene, which is a therapeutic approach that can be used to treat cancer. For example, we have delineated two independent oncoprotein-directed pathways that lead to widespread DNA hypermethylation and epigenetic silencing (known as the CpG island methylator phenotype; CIMP) in colorectal cancers, and shown that genetic or pharmacological inhibition of the pathways can reactivate expression of the silenced genes (Serra et al. 2014; Fang et al. 2014). The epigenetic silencing pathways we have identified are directly linked to cellular transformation, have enhanced our understanding of how normal cells become cancerous, and have revealed new therapeutic targets.

We are taking a similar approach to identify small molecule inhibitors that will reactivate genes whose aberrant epigenetic silencing causes rare monogenic disorders such as Fragile X Syndrome and Friedreich ataxia. We also work on X-linked dominant disorders, such as Rett Syndrome and CDKL5 Deficiency, which are caused by heterozygous mutations in the X-linked genes MECP2 and CDKL5, respectively, and for which reactivation of the wild-type gene on the inactive X chromosome (Xi) is a potential therapeutic approach. For example, we have identified a number of cellular factors that are required for silencing of the Xi (Bhatnagar et al. 2014). Small molecule inhibitors of these factors can reactivate expression of the wild-type Xi-linked MECP2 gene in cultured cells and cerebral cortical neurons of adult living mice (Bhatnagar et al. 2014; Przanowski et al., 2018).

Development of New Gene Therapy Approaches

We have previously identified IGFBP7 (insulin-like growth factor binding protein 7) as a secreted tumor suppressor protein and shown in mouse models that systemic administration of recombinant IGFBP7 can suppress tumor growth of human melanoma and colorectal cancer xenografts expressing oncogenic BRAF or RAS (Wajapeyee et al. 2008, 2009). More recently, in collaboration with Dr. Guangping Gao (Director, UMMS Gene Therapy Center) we have shown that IGFBP7 can also be effectively delivered into mice using an adeno-associated virus (AAV) vector. Intramuscular injection of an AAV9-IGFBP7 vector results in the expression and secretion of IGFBP7 and markedly reduces growth of human melanoma and colorectal cancer xenografts. We have confirmed the generality of this approach using another secreted tumor suppressor protein. Our results indicate that AAV9 delivery of secreted tumor suppressors is a new and promising anti-cancer treatment.

In collaboration with Guangping Gao and Miguel Sena-Esteves (UMMS Gene Therapy Center), we are developing a novel AAV-based gene therapy approach for Rett Syndrome. Several lines of evidence indicate that MECP2 expression levels must be tightly regulated to maintain normal neuronal function and development. We are therefore developing self-regulating AAV vectors that can express MECP2 within a narrow range of levels compatible with normal development and neuronal function.


One or more keywords matched the following items that are connected to Green, Michael

Item TypeName
Academic Article A novel, mitogen-activated nuclear kinase is related to a Drosophila developmental regulator.
Academic Article Intramolecular inhibition of activating transcription factor-2 function by its DNA-binding domain.
Academic Article HIV Rev uses a conserved cellular protein export pathway for the nucleocytoplasmic transport of viral RNAs.
Academic Article Yeast TAF(II)90 is required for cell-cycle progression through G2/M but not for general transcription activation.
Academic Article Localization of HIV-1 RNA in mammalian nuclei.
Academic Article Yeast TAF(II)145 required for transcription of G1/S cyclin genes and regulated by the cellular growth state.
Academic Article Yeast TAF(II)145 functions as a core promoter selectivity factor, not a general coactivator.
Academic Article Transcription activation in cells lacking TAFIIS.
Academic Article Controlling gene expression in living cells through small molecule-RNA interactions.
Academic Article Broad, but not universal, transcriptional requirement for yTAFII17, a histone H3-like TAFII present in TFIID and SAGA.
Academic Article Analysis of selective gene activation in yeast by differential display.
Academic Article The hepatitis B pX protein promotes dimerization and DNA binding of cellular basic region/leucine zipper proteins by targeting the conserved basic region.
Academic Article Enhancement of TBP binding by activators and general transcription factors.
Academic Article Distinct classes of yeast promoters revealed by differential TAF recruitment.
Academic Article A non-canonical base pair within the human immunodeficiency virus rev-responsive element is involved in both rev and small molecule recognition.
Academic Article Sequence-specific interaction between HIV-1 matrix protein and viral genomic RNA revealed by in vitro genetic selection.
Academic Article Promoter-specific activation defects by a novel yeast TBP mutant compromised for TFIIB interaction.
Academic Article U2AF65 recruits a novel human DEAD box protein required for the U2 snRNP-branchpoint interaction.
Academic Article Identification of a human protein that recognizes the 3' splice site during the second step of pre-mRNA splicing.
Academic Article Inhibition of apoptosis by ATFx: a novel role for a member of the ATF/CREB family of mammalian bZIP transcription factors.
Academic Article Selective recruitment of TAFs by yeast upstream activating sequences. Implications for eukaryotic promoter structure.
Academic Article The role of ATF/CREB family members in cell growth, survival and apoptosis.
Academic Article Transcriptional program of apoptosis induction following interleukin 2 deprivation: identification of RC3, a calcium/calmodulin binding protein, as a novel proapoptotic factor.
Academic Article Interaction of Gal4p with components of transcription machinery in vivo.
Academic Article Arginine-serine-rich domains bound at splicing enhancers contact the branchpoint to promote prespliceosome assembly.
Academic Article U2AF homology motifs: protein recognition in the RRM world.
Academic Article Crystal structure of UAP56, a DExD/H-box protein involved in pre-mRNA splicing and mRNA export.
Academic Article A pathway of sequential arginine-serine-rich domain-splicing signal interactions during mammalian spliceosome assembly.
Academic Article A human nuclear-localized chaperone that regulates dimerization, DNA binding, and transcriptional activity of bZIP proteins.
Academic Article HIV-1 Tat stimulates transcription complex assembly through recruitment of TBP in the absence of TAFs.
Academic Article A novel nuclear export activity in HIV-1 matrix protein required for viral replication.
Academic Article Functional recognition of the 3' splice site AG by the splicing factor U2AF35.
Academic Article TBP-associated factors (TAFIIs): multiple, selective transcriptional mediators in common complexes.
Academic Article Cell motility is controlled by SF2/ASF through alternative splicing of the Ron protooncogene.
Academic Article Fluorescence resonance energy transfer as a method for dissecting in vivo mechanisms of transcriptional activation.
Academic Article Structural basis for polypyrimidine tract recognition by the essential pre-mRNA splicing factor U2AF65.
Academic Article p53-mediated inhibition of angiogenesis through up-regulation of a collagen prolyl hydroxylase.
Academic Article Accumulation of substrates of the anaphase-promoting complex (APC) during human cytomegalovirus infection is associated with the phosphorylation of Cdh1 and the dissociation and relocalization of APC subunits.
Academic Article An elaborate pathway required for Ras-mediated epigenetic silencing.
Academic Article Initiation of zebrafish haematopoiesis by the TATA-box-binding protein-related factor Trf3.
Academic Article Oncogenic BRAF induces senescence and apoptosis through pathways mediated by the secreted protein IGFBP7.
Academic Article SAGA is an essential in vivo target of the yeast acidic activator Gal4p.
Academic Article Induction of apoptosis by a secreted lipocalin that is transcriptionally regulated by IL-3 deprivation.
Academic Article Solution conformation and thermodynamic characteristics of RNA binding by the splicing factor U2AF65.
Academic Article Targeting a TAF to make muscle.
Academic Article F-box protein FBXO31 mediates cyclin D1 degradation to induce G1 arrest after DNA damage.
Academic Article Identification of a protein, G0S2, that lacks Bcl-2 homology domains and interacts with and antagonizes Bcl-2.
Academic Article Epigenetic silencing of the RASSF1A tumor suppressor gene through HOXB3-mediated induction of DNMT3B expression.
Academic Article A genome-wide RNA interference screen reveals an essential CREB3L2-ATF5-MCL1 survival pathway in malignant glioma with therapeutic implications.
Academic Article The U2AF35-related protein Urp contacts the 3' splice site to promote U12-type intron splicing and the second step of U2-type intron splicing.
Academic Article Analysis of Gal4-directed transcription activation using Tra1 mutants selectively defective for interaction with Gal4.
Academic Article Characterization of enhancer function from genome-wide analyses.
Academic Article Differential requirement of SAGA components for recruitment of TATA-box-binding protein to promoters in vivo.
Academic Article Structure of phosphorylated SF1 bound to U2AF65 in an essential splicing factor complex.
Academic Article Systematic analysis of essential yeast TAFs in genome-wide transcription and preinitiation complex assembly.
Academic Article TRF3, a TATA-box-binding protein-related factor, is vertebrate-specific and widely expressed.
Academic Article Sequential recognition of the pre-mRNA branch point by U2AF65 and a novel spliceosome-associated 28-kDa protein.
Academic Article Distinct binding specificities and functions of higher eukaryotic polypyrimidine tract-binding proteins.
Academic Article Delineating minimal protein domains and promoter elements for transcriptional activation by lentivirus Tat proteins.
Academic Article Yeast TAFIIS in a multisubunit complex required for activated transcription.
Academic Article Activator-induced conformational change in general transcription factor TFIIB.
Academic Article The RNA polymerase I transcription factor, upstream binding factor, interacts directly with the TATA box-binding protein.
Academic Article Nucleosome disruption and enhancement of activator binding by a human SW1/SNF complex.
Academic Article A single polypyrimidine tract binding protein (PTB) binding site mediates splicing inhibition at mouse IgM exons M1 and M2.
Academic Article The viral protein Apoptin associates with the anaphase-promoting complex to induce G2/M arrest and apoptosis in the absence of p53.
Academic Article The anaphase promoting complex: a critical target for viral proteins and anti-cancer drugs.
Academic Article RS domains contact splicing signals and promote splicing by a common mechanism in yeast through humans.
Academic Article Apoptin nucleocytoplasmic shuttling is required for cell type-specific localization, apoptosis, and recruitment of the anaphase-promoting complex/cyclosome to PML bodies.
Academic Article Inhibition of tumor angiogenesis by p53: a new role for the guardian of the genome.
Academic Article RS domain-splicing signal interactions in splicing of U12-type and U2-type introns.
Academic Article Distinct activities of the DExD/H-box splicing factor hUAP56 facilitate stepwise assembly of the spliceosome.
Academic Article Selective interaction between Trf3 and Taf3 required for early development and hematopoiesis.
Academic Article Maternal Rnf12/RLIM is required for imprinted X-chromosome inactivation in mice.
Academic Article Non-canonical TAF complexes regulate active promoters in human embryonic stem cells.
Academic Article A synthetic interaction screen identifies factors selectively required for proliferation and TERT transcription in p53-deficient human cancer cells.
Academic Article GABP transcription factor is required for development of chronic myelogenous leukemia via its control of PRKD2.
Academic Article U2AF65 adapts to diverse pre-mRNA splice sites through conformational selection of specific and promiscuous RNA recognition motifs.
Academic Article hnRNP A1 contacts exon 5 to promote exon 6 inclusion of apoptotic Fas gene.
Academic Article MEN1 is a melanoma tumor suppressor that preserves genomic integrity by stimulating transcription of genes that promote homologous recombination-directed DNA repair.
Academic Article Genome wide association analysis of a founder population identified TAF3 as a gene for MCHC in humans.
Academic Article A human nucleoporin-like protein that specifically interacts with HIV Rev.
Academic Article Recognition of bZIP proteins by the human T-cell leukaemia virus transactivator Tax.
Concept Protein Binding
Concept Protein Subunits
Concept Protein Folding
Concept Protein Processing, Post-Translational
Concept Ubiquitin-Protein Ligases
Concept Tumor Suppressor Protein p53
Concept Retinoblastoma Protein
Concept Survival of Motor Neuron 2 Protein
Concept Mitogen-Activated Protein Kinase Kinases
Concept Oncogene Protein p21(ras)
Concept Protein Kinase Inhibitors
Concept Herpes Simplex Virus Protein Vmw65
Concept Protein Biosynthesis
Concept Methyl-CpG-Binding Protein 2
Concept Cyclic AMP-Dependent Protein Kinases
Concept Protein Kinases
Concept bcl-2-Associated X Protein
Concept Protein Precursors
Concept Protein Interaction Domains and Motifs
Concept Protein-Serine-Threonine Kinases
Concept Protein Synthesis Inhibitors
Concept GA-Binding Protein Transcription Factor
Concept Protein Kinase C
Concept MyoD Protein
Concept bcl-Associated Death Protein
Concept CREB-Binding Protein
Concept TATA-Box Binding Protein
Concept Protein Structure, Secondary
Concept BRCA1 Protein
Concept Protein Structure, Tertiary
Concept Cyclic AMP Response Element-Binding Protein
Concept Ubiquitin-Protein Ligase Complexes
Concept Protein Multimerization
Concept Receptor Protein-Tyrosine Kinases
Concept Myeloid-Lymphoid Leukemia Protein
Concept Protein Stability
Concept Protein Structure, Quaternary
Concept Fas Ligand Protein
Concept Polypyrimidine Tract-Binding Protein
Concept bcl-X Protein
Concept Protein Sorting Signals
Concept TATA-Binding Protein Associated Factors
Concept TATA Box Binding Protein-Like Proteins
Concept Protein Isoforms
Concept Protein Conformation
Concept CDC28 Protein Kinase, S cerevisiae
Academic Article Oncogenic RAS directs silencing of tumor suppressor genes through ordered recruitment of transcriptional repressors.
Academic Article Resistance to vemurafenib resulting from a novel mutation in the BRAFV600E kinase domain.
Academic Article SC35 promotes splicing of the C5-V6-C6 isoform of CD44 pre-mRNA.
Academic Article A 2-nt RNA enhancer on exon 11 promotes exon 11 inclusion of the Ron proto-oncogene.
Academic Article Polypyrimidine tract binding protein inhibits IgM pre-mRNA splicing by diverting U2 snRNA base-pairing away from the branch point.
Academic Article PSF contacts exon 7 of SMN2 pre-mRNA to promote exon 7 inclusion.
Academic Article Synergistic tumor suppression by combined inhibition of telomerase and CDKN1A.
Academic Article A large-scale RNAi-based mouse tumorigenesis screen identifies new lung cancer tumor suppressors that repress FGFR signaling.
Academic Article PEA15 regulates the DNA damage-induced cell cycle checkpoint and oncogene-directed transformation.
Academic Article Cancer-relevant splicing factor CAPERa engages the essential splicing factor SF3b155 in a specific ternary complex.
Academic Article Genetic and pharmacological reactivation of the mammalian inactive X chromosome.
Academic Article A therapeutically targetable mechanism of BCR-ABL-independent imatinib resistance in chronic myeloid leukemia.
Academic Article The BRAF oncoprotein functions through the transcriptional repressor MAFG to mediate the CpG Island Methylator phenotype.
Academic Article SRSF2 promotes splicing and transcription of exon 11 included isoform in Ron proto-oncogene.
Academic Article Global Promotion of Alternative Internal Exon Usage by mRNA 3' End Formation Factors.
Academic Article F-box protein FBXO31 directs degradation of MDM2 to facilitate p53-mediated growth arrest following genotoxic stress.
Academic Article An extended U2AF(65)-RNA-binding domain recognizes the 3' splice site signal.
Academic Article A role for Tau protein in maintaining ribosomal DNA stability and cytidine deaminase-deficient cell survival.
Academic Article Crebbp loss cooperates with Bcl2 overexpression to promote lymphoma in mice.
Academic Article Loss of KLHL6 promotes diffuse large B-cell lymphoma growth and survival by stabilizing the mRNA decay factor roquin2.

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