Philip Leder

Formin1 disruption confers oligodactylism and alters Bmp signaling (2009)

Zhou, Fen, Leder, Philip, Zuniga, Aimée, Dettenhofer, Markus

Proper limb development requires concerted communication between cells within the developing limb bud. Several molecules have been identified which contribute to the formation of a circuitry loop...

Structure and Expression of the Human Immunoglobulin X (2008)

J Vasicek, Philip Leder

Wedetermined theDNA sequence oftwo large regions ofchromosome 22: 33.7 kb containing the Ct, complex; and 5.2 kb 5 ' of the functionally rearranged X gene from the human myeloma, U266. Analysis...

Identifying genes preferentially expressed in undifferentiated embryonic stem cells (2007)

Li, Xiajun, Leder, Philip

Abstract Background The mechanism involved in the maintenance and differentiation of embryonic stem (ES) cells is incompletely understood. Results To address this issue, we have developed a...

{zeta}-/- Thalassemic mice are affected by two modifying loci and display unanticipated somatic recombination leading to inherited variation (2005)

Leder, Aya, McMenamin, Jennifer, Fontaine, Karen, Bishop, Alexander, Leder, Philip

Thalassemia is a disease caused by a variety of mutations affecting both the adult and embryonic α- and β-globin loci. A mouse strain carrying an embryonic ζ-globin gene disrupted by the insertion...

{zeta}-/- Thalassemic Mice are Affected by Two Modifying Loci and Display Unanticipated Somatic Recombination Leading to Inherited Variation (2005)

Leder, Aya, McMenamin, Jennifer, Fontaine, Karen, Bishop, Alexander, Leder, Philip

Thalassemia is a disease caused by a variety of mutations affecting both the adult and embryonic α- and β-globin loci. A mouse strain carrying an embryonic ζ-globin gene disrupted by the insertion...

Mouse Models of the Neu Ligand Interaction with its Receptor in Mammary Gland Tumorigenesis and Development. (1998)

Leder, Philip, Krane, Ian

Recently, a family of stimulatory ligands for the EGF/erbB family of receptor tyrosine kinases has been described. This family includes Neu differentiation factor (NDF), heregulin (HRG),...

Characterization of Two Novel Oncogenic Pathways Collaborating With Loss of p53 or Activated Neu in Mouse Models of Breast Cancer (1998)

Lu, Jiangrong, Leder, Philip

Cancer is a complex multi step disease and progresses through successive accumulation of genetic mutations. Loss of tumor suppressor gene p53 and activation of oncogene Neu/ErbB2 are among the most...

Characterization of Two Novel Oncogenic Pathways Collaborting With Loss of p53 or Activated Neu in Mouse Models of Breast Cancer (1998)

Lu, Jianrong, Leder, Philip

Cancer is a complex multistep disease and progresses through successive accumulation of genetic mutations. Loss of tumor suppressor gene p53 and activation of oncogene Neu/ErB2 are among the most...

Characterization of Two Novel Oncogenic Pathways Collaborating With Loss of P53 or Activated Neu in Mouse Models of Breast Cancer (1998)

Lu, Jianrong, Leder, Philip

Cancer develops through accumulation of multiple genetic mutations. Loss of tumor suppressor gene p53 and activation of oncogene Neu/ErbB2 are among the most frequent genetic alterations in human...

Targeted disruption of the chemokine eotaxin partially reduces antigen-induced tissue eosinophilia. (1997)

Rothenberg, Marc E., MacLean, James A., Pearlman, Eric, Luster, Andrew D., Leder, Philip

The chemokines are a large group of chemotactic cytokines that regulate leukocyte trafficking and have recently been shown to inhibit human immunodeficiency virus entry into cells. Eotaxin is a C-C...

Int-2, an Autocrine and/or Ultra—Short-Range Effector in Transgenic Mammary Tissue Transplants (1992)

Ornitz, David M., Cardiff, Robert D., Kuo, Ann, Leder, Philip

Background: Previous studies have shown associations between over-expresion of int-2 messenger RNA (mRNA) and murine mammary tumors and between amplification of the int-2 genomic locus and human...

In vitro and in vivo analysis of the c-myc RNA polymerase II promoter (1991)

Sussman, Daniel J., Chung, Jay, Leder, Philip

The c-myc promoter has the unusual property of displaying both RNA polymerase II (Pol II) and RNA polymerase III (Pol III) activities. Both Pol II and Pol III utilize the same transcription...

Structure and expression of a human subgroup II immunoglobulin x gene (1986)

Weir, Lawrence, Leder, Philip

We have determined the entire nucleotide sequence of an active immunoglo-bulin Vk gene of the human subgroup II. Comparison of the main coding sequence of this gene to another member of this subgroup...

Structural analysis of both products of a reciprocal translocation between c-myc and immunoglobulin loci in Burkitt lymphoma (1985)

Moulding, Christopher, Rapoport, Aaron, Goldman, Paula, Battey, Jim, Lenoir, Gilbert M., Leder, Philip

The balanced translocations that occur between the c-myc and immunoglobulin loci in Burkitt lymphoma provide an unusual opportunity to analyze both products of a reciprocal recombination....

Localization of human variable and constant region immunoglobulin heavy chain genes on subtelomeric band q32 of chromosome 14 (1982)

McBride, O. Wesley, Battey, James, Hollis, Gregory F., Swan, David C., Siebenlist, Ulrich, Leder, Philip

Analysis of a group of human/rodent somatic cell hybrids with nucleic acid probes prepared from cloned human variable region (VH), junctional (JH), and constant region (Cϵ) heavy chain...

A deletion within the murine Werner syndrome helicase induces sensitivity to inhibitors of topoisomerase and loss of cellular proliferative capacity

Lebel, Michel, Leder, Philip

Werner syndrome (WS) is an autosomal recessive disorder characterized by genomic instability and the premature onset of a number of age-related diseases. The gene responsible for WS encodes a member...

Pleiotropic defects in ataxia-telangiectasia protein-deficient mice

Elson, Ari, Wang, Yaoqi, Daugherty, Cathie J., Morton, Cynthia C., Zhou, Fen, Campos-Torres, Juanita, ...

We have generated a mouse model for ataxia-telangiectasia by using gene targeting to generate mice that do not express the Atm protein. Atm-deficient mice are retarded in growth, do not produce...

Loss of p21 increases sensitivity to ionizing radiation and delays the onset of lymphoma in atm-deficient mice

Wang, Y. Alan, Elson, Ari, Leder, Philip

Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by growth retardation, cerebellar ataxia, oculocutaneous telangiectasias, and a high incidence of lymphomas and leukemias....

A normal β-globin allele as a modifier gene ameliorating the severity of α-thalassemia in mice

Leder, Aya, Wiener, Edith, Lee, Matthew J., Wickramasinghe, Sunitha N., Leder, Philip

Thalassemia is a heritable human anemia caused by a variety of mutations that affect expression of the α- or the β-chain of hemoglobin. The expressivity of the phenotype is likely to be influenced...

A Murine Homologue of the Drosophila brainiac Gene Shows Homology to Glycosyltransferases and Is Required for Preimplantation Development of the Mouse

Vollrath, Benedikt, Fitzgerald, Kevin J., Leder, Philip

The neurogenic gene brainiac was first isolated in Drosophila melanogaster, where it interacts genetically with members of the Notch signaling cascade. We have isolated a murine homologue of the...

Human MCF10A Mammary Epithelial Cells Undergo Apoptosis following Actin Depolymerization That Is Independent of Attachment and Rescued by Bcl-2

Martin, Stuart S., Leder, Philip

Many tumor cells are impaired in adhesion-regulated apoptosis, which contributes to their metastatic potential. However, suppression of this apoptotic pathway in untransformed cells is not mediated...

Isolation of a Murine Homologue of the Drosophila neuralized Gene, a Gene Required for Axonemal Integrity in Spermatozoa and Terminal Maturation of the Mammary Gland

Vollrath, Benedikt, Pudney, Jeffrey, Asa, Sylvia, Leder, Philip, Fitzgerald, Kevin

The Drosophila neuralized gene shows genetic interactions with Notch, Enhancer of split, and other neurogenic genes and is thought to be involved in cell fate specification in the central nervous...

Homeodomain-Interacting Protein Kinase 1 Modulates Daxx Localization, Phosphorylation, and Transcriptional Activity

Ecsedy, Jeffrey A., Michaelson, Jennifer S., Leder, Philip

We describe an interaction between homeodomain-interacting protein kinase 1 (HIPK1) and Daxx, two transcriptional regulators important in transducing growth-regulatory signals. We demonstrate that...

Critical Role for Mouse Hus1 in an S-Phase DNA Damage Cell Cycle Checkpoint

Weiss, Robert S., Leder, Philip, Vaziri, Cyrus

Mouse Hus1 encodes an evolutionarily conserved DNA damage response protein. In this study we examined how targeted deletion of Hus1 affects cell cycle checkpoint responses to genotoxic stress. Unlike...

TRANSLOCATION OF MRNA CODONS, II. PROPERTIES OF AN ANTI-TRANSLOCASE ANTIBODY

Leder, Philip, Skogerson, Lawrence E., Roufa, Donald J.

A purified preparation of translocase, one of several enzymes required for protein biosynthesis, has been used to prepare a specific anti-translocase antibody. This antibody provides an extremely...

TRANSLOCATION OF MRNA CODONS, I. THE PREPARATION AND CHARACTERISTICS OF A HOMOGENEOUS ENZYME

Leder, Philip, Skogerson, Lawrence E., Nau, Marion M.

This report describes a convenient scheme for the further purification of an E. coli enzyme which is required for the translocation step in protein biosynthesis. The homogeneous enzyme translocase...

Inactivation of mouse Hus1 results in genomic instability and impaired responses to genotoxic stress

Weiss, Robert S., Enoch, Tamar, Leder, Philip

The eukaryotic cell cycle is overseen by regulatory mechanisms, termed checkpoints, that respond to DNA damage, mitotic spindle defects, and errors in the ordering of cell cycle events. The DNA...

Loss of Daxx, a promiscuously interacting protein, results in extensive apoptosis in early mouse development

Michaelson, Jennifer S., Bader, Debra, Kuo, Frank, Kozak, Christine, Leder, Philip

The mammalian Daxx gene has been identified in a diverse set of yeast interaction trap experiments. Although a facilitating role for Daxx in Fas-induced apoptosis has been suggested, Daxx’s...

Stage-specific apoptosis, developmental delay, and embryonic lethality in mice homozygous for a targeted disruption in the murine Bloom’s syndrome gene

Chester, Nicholas, Kuo, Frank, Kozak, Christine, O’Hara, Cathie D., Leder, Philip

Bloom’s syndrome is a human autosomal genetic disorder characterized at the cellular level by genome instability and increased sister chomatid exchanges (SCEs). Clinical features of the disease...

An Association Between Globin Messenger RNA and 60S RNA Derived from Friend Leukemia Virus

Ikawa, Yoji, Ross, Jeffrey, Leder, Philip

The association between certain cellular RNAs and purified RNA tumor viruses prompted us to examine the possibility that specific host messenger RNAs might also be incorporated into RNA tumor...

Characterization of the Initial Peptide of Qβ RNA Polymerase and Control of Its Synthesis

Skogerson, Lawrence, Roufa, Donald, Leder, Philip

Bacteriophage Qβ RNA directs the cell-free synthesis of two fMet-containing dipeptides prior to the first round of ribosomal translocation. One of these, fMet-Ala, corresponds to the initial segment...

Globin Messenger-RNA Induction During Erythroid Differentiation of Cultured Leukemia Cells

Ross, Jeffrey, Ikawa, Yoji, Leder, Philip

A cloned line of murine proerythroblastoid cells (T-3-Cl-2), transformed by Friend leukemia virus, undergoes changes associated with erythroid differentiation when treated with dimethylsulfoxide in...

Purification of Biologically Active Globin Messenger RNA by Chromatography on Oligothymidylic acid-Cellulose

Aviv, Haim, Leder, Philip

A convenient technique for the partial purification of large quantities of functional, poly(adenylic acid)-rich mRNA is described. The method depends upon annealing poly(adenylic acid)-rich mRNA to...

In Vitro Synthesis of DNA Complementary to Purified Rabbit Globin mRNA

Ross, Jeffrey, Aviv, Haim, Scolnick, Edward, Leder, Philip

Several properties of the viral RNA-dependent DNA polymerases and of rabbit globin mRNA make it possible to consider synthesis of the globin gene in vitro. These enzymes copy an RNA template using a...

The Organization and Diversity of Immunoglobulin Genes*

Leder, Philip, Honjo, Tasuku, Packman, Seymour, Swan, David, Nau, Marion, Norman, Barbara

We have used purified mouse immunoglobulin light chain mRNA and synthetic DNA which is complementary to it to assess the reiteration frequency of gene sequences corresponding to the κ constant...

Enzymatic Synthesis of Solid Phase-Bound DNA Sequences Corresponding to Specific Mammalian Genes

Venetianer, Pal, Leder, Philip

With oligo(dT)-cellulose as primer, RNA-dependent DNA polymerase catalyzes the synthesis of cellulose-bound DNA that is complementary to mouse globin mRNA. The resulting cellulose-bound or solid...

Direct induction of T lymphocyte-specific gene expression by the mammalian Notch signaling pathway

Reizis, Boris, Leder, Philip

The Notch signaling pathway regulates the commitment and early development of T lymphocytes. We studied Notch-mediated induction of the pre-T cell receptor α (pTa) gene, a T-cell-specific...

A deletion within the murine Werner syndrome helicase induces sensitivity to inhibitors of topoisomerase and loss of cellular proliferative capacity

Lebel, Michel, Leder, Philip

Werner syndrome (WS) is an autosomal recessive disorder characterized by genomic instability and the premature onset of a number of age-related diseases. The gene responsible for WS encodes a member...

Pleiotropic defects in ataxia-telangiectasia protein-deficient mice

Elson, Ari, Wang, Yaoqi, Daugherty, Cathie J., Morton, Cynthia C., Zhou, Fen, Campos-Torres, Juanita, ...

We have generated a mouse model for ataxia-telangiectasia by using gene targeting to generate mice that do not express the Atm protein. Atm-deficient mice are retarded in growth, do not produce...

Loss of p21 increases sensitivity to ionizing radiation and delays the onset of lymphoma in atm-deficient mice

Wang, Y. Alan, Elson, Ari, Leder, Philip

Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by growth retardation, cerebellar ataxia, oculocutaneous telangiectasias, and a high incidence of lymphomas and leukemias....

A normal β-globin allele as a modifier gene ameliorating the severity of α-thalassemia in mice

Leder, Aya, Wiener, Edith, Lee, Matthew J., Wickramasinghe, Sunitha N., Leder, Philip

Thalassemia is a heritable human anemia caused by a variety of mutations that affect expression of the α- or the β-chain of hemoglobin. The expressivity of the phenotype is likely to be influenced...

A Murine Homologue of the Drosophila brainiac Gene Shows Homology to Glycosyltransferases and Is Required for Preimplantation Development of the Mouse

Vollrath, Benedikt, Fitzgerald, Kevin J., Leder, Philip

The neurogenic gene brainiac was first isolated in Drosophila melanogaster, where it interacts genetically with members of the Notch signaling cascade. We have isolated a murine homologue of the...

Human MCF10A Mammary Epithelial Cells Undergo Apoptosis following Actin Depolymerization That Is Independent of Attachment and Rescued by Bcl-2

Martin, Stuart S., Leder, Philip

Many tumor cells are impaired in adhesion-regulated apoptosis, which contributes to their metastatic potential. However, suppression of this apoptotic pathway in untransformed cells is not mediated...

Isolation of a Murine Homologue of the Drosophila neuralized Gene, a Gene Required for Axonemal Integrity in Spermatozoa and Terminal Maturation of the Mammary Gland

Vollrath, Benedikt, Pudney, Jeffrey, Asa, Sylvia, Leder, Philip, Fitzgerald, Kevin

The Drosophila neuralized gene shows genetic interactions with Notch, Enhancer of split, and other neurogenic genes and is thought to be involved in cell fate specification in the central nervous...

Homeodomain-Interacting Protein Kinase 1 Modulates Daxx Localization, Phosphorylation, and Transcriptional Activity

Ecsedy, Jeffrey A., Michaelson, Jennifer S., Leder, Philip

We describe an interaction between homeodomain-interacting protein kinase 1 (HIPK1) and Daxx, two transcriptional regulators important in transducing growth-regulatory signals. We demonstrate that...

Critical Role for Mouse Hus1 in an S-Phase DNA Damage Cell Cycle Checkpoint

Weiss, Robert S., Leder, Philip, Vaziri, Cyrus

Mouse Hus1 encodes an evolutionarily conserved DNA damage response protein. In this study we examined how targeted deletion of Hus1 affects cell cycle checkpoint responses to genotoxic stress. Unlike...

Direct induction of T lymphocyte-specific gene expression by the mammalian Notch signaling pathway

Reizis, Boris, Leder, Philip

The Notch signaling pathway regulates the commitment and early development of T lymphocytes. We studied Notch-mediated induction of the pre-T cell receptor α (pTa) gene, a T-cell-specific...

TRANSLOCATION OF MRNA CODONS, II. PROPERTIES OF AN ANTI-TRANSLOCASE ANTIBODY

Leder, Philip, Skogerson, Lawrence E., Roufa, Donald J.

A purified preparation of translocase, one of several enzymes required for protein biosynthesis, has been used to prepare a specific anti-translocase antibody. This antibody provides an extremely...

TRANSLOCATION OF MRNA CODONS, I. THE PREPARATION AND CHARACTERISTICS OF A HOMOGENEOUS ENZYME

Leder, Philip, Skogerson, Lawrence E., Nau, Marion M.

This report describes a convenient scheme for the further purification of an E. coli enzyme which is required for the translocation step in protein biosynthesis. The homogeneous enzyme translocase...

Inactivation of mouse Hus1 results in genomic instability and impaired responses to genotoxic stress

Weiss, Robert S., Enoch, Tamar, Leder, Philip

The eukaryotic cell cycle is overseen by regulatory mechanisms, termed checkpoints, that respond to DNA damage, mitotic spindle defects, and errors in the ordering of cell cycle events. The DNA...

Loss of Daxx, a promiscuously interacting protein, results in extensive apoptosis in early mouse development

Michaelson, Jennifer S., Bader, Debra, Kuo, Frank, Kozak, Christine, Leder, Philip

The mammalian Daxx gene has been identified in a diverse set of yeast interaction trap experiments. Although a facilitating role for Daxx in Fas-induced apoptosis has been suggested, Daxx’s...

Stage-specific apoptosis, developmental delay, and embryonic lethality in mice homozygous for a targeted disruption in the murine Bloom’s syndrome gene

Chester, Nicholas, Kuo, Frank, Kozak, Christine, O’Hara, Cathie D., Leder, Philip

Bloom’s syndrome is a human autosomal genetic disorder characterized at the cellular level by genome instability and increased sister chomatid exchanges (SCEs). Clinical features of the disease...

An Association Between Globin Messenger RNA and 60S RNA Derived from Friend Leukemia Virus

Ikawa, Yoji, Ross, Jeffrey, Leder, Philip

The association between certain cellular RNAs and purified RNA tumor viruses prompted us to examine the possibility that specific host messenger RNAs might also be incorporated into RNA tumor...

Characterization of the Initial Peptide of Qβ RNA Polymerase and Control of Its Synthesis

Skogerson, Lawrence, Roufa, Donald, Leder, Philip

Bacteriophage Qβ RNA directs the cell-free synthesis of two fMet-containing dipeptides prior to the first round of ribosomal translocation. One of these, fMet-Ala, corresponds to the initial segment...

Globin Messenger-RNA Induction During Erythroid Differentiation of Cultured Leukemia Cells

Ross, Jeffrey, Ikawa, Yoji, Leder, Philip

A cloned line of murine proerythroblastoid cells (T-3-Cl-2), transformed by Friend leukemia virus, undergoes changes associated with erythroid differentiation when treated with dimethylsulfoxide in...

Purification of Biologically Active Globin Messenger RNA by Chromatography on Oligothymidylic acid-Cellulose

Aviv, Haim, Leder, Philip

A convenient technique for the partial purification of large quantities of functional, poly(adenylic acid)-rich mRNA is described. The method depends upon annealing poly(adenylic acid)-rich mRNA to...

In Vitro Synthesis of DNA Complementary to Purified Rabbit Globin mRNA

Ross, Jeffrey, Aviv, Haim, Scolnick, Edward, Leder, Philip

Several properties of the viral RNA-dependent DNA polymerases and of rabbit globin mRNA make it possible to consider synthesis of the globin gene in vitro. These enzymes copy an RNA template using a...

The Organization and Diversity of Immunoglobulin Genes*

Leder, Philip, Honjo, Tasuku, Packman, Seymour, Swan, David, Nau, Marion, Norman, Barbara

We have used purified mouse immunoglobulin light chain mRNA and synthetic DNA which is complementary to it to assess the reiteration frequency of gene sequences corresponding to the κ constant...

Enzymatic Synthesis of Solid Phase-Bound DNA Sequences Corresponding to Specific Mammalian Genes

Venetianer, Pal, Leder, Philip

With oligo(dT)-cellulose as primer, RNA-dependent DNA polymerase catalyzes the synthesis of cellulose-bound DNA that is complementary to mouse globin mRNA. The resulting cellulose-bound or solid...

Mutation of the Murine Bloom's Syndrome Gene Produces Global Genome Destabilization

Chester, Nicholas, Babbe, Holger, Pinkas, Jan, Manning, Charlene, Leder, Philip

Bloom's syndrome (BS) is a genetic disorder characterized cellularly by increases in sister chromatid exchanges (SCEs) and numbers of micronuclei. BS is caused by mutation in the BLM DNA helicase...

The Bloom's Syndrome Helicase Is Critical for Development and Function of the αβ T-Cell Lineage▿ †

Babbe, Holger, Chester, Nicholas, Leder, Philip, Reizis, Boris

Bloom's syndrome is a genetic disorder characterized by increased incidence of cancer and an immunodeficiency of unknown origin. The BLM gene mutated in Bloom's syndrome encodes a DNA helicase...

A genome-wide RNA interference screen identifies putative chromatin regulators essential for E2F repression

Lu, Jianrong, Ruhf, Marie-Laure, Perrimon, Norbert, Leder, Philip

Regulation of chromatin structure is critical in many fundamental cellular processes. Previous studies have suggested that the Rb tumor suppressor may recruit multiple chromatin regulatory proteins...

The Upstream Enhancer Is Necessary and Sufficient for the Expression of the Pre-T Cell Receptor α Gene in Immature T Lymphocytes

Reizis, Boris, Leder, Philip

The expression of the pre-T cell receptor α (pTa) gene occurs exclusively in immature T lymphocytes and is regulated by poorly defined mechanisms. We have analyzed the role of the upstream enhancer...

Expression of the Mouse Pre-T Cell Receptor α Gene Is Controlled by an Upstream Region Containing a Transcriptional Enhancer

Reizis, Boris, Leder, Philip

The pre-T cell receptor α (pTα) protein is a critical component of the pre-T cell receptor complex in early thymocytes. The expression of the pTα gene is one of the earliest markers of the T cell...

Targeted Disruption of the Chemokine Eotaxin Partially Reduces Antigen-induced Tissue Eosinophilia

Rothenberg, Marc E., MacLean, James A., Pearlman, Eric, Luster, Andrew D., Leder, Philip

The chemokines are a large group of chemotactic cytokines that regulate leukocyte trafficking and have recently been shown to inhibit human immunodeficiency virus entry into cells. Eotaxin is a C–C...

An Apoptosis-inducing Isoform of Neu Differentiation Factor (NDF) Identified Using a Novel Screen for Dominant, Apoptosis-inducing Genes

Grimm, Stefan, Leder, Philip

Apoptosis is a genetically programmed series of events that results in cell death. As a consequence, it is difficult to identify dominant genes that play a role in this process using genetic...

Neu Differentiation Factor (NDF), a Dominant Oncogene, Causes Apoptosis In Vitro and In Vivo

Grimm, Stefan, Weinstein, Edward J., Krane, Ian M., Leder, Philip

Neu differentiation factor (NDF, also called neuregulin) is a potent inducer of epithelial cell proliferation and has been shown to induce mammary carcinomas in transgenic mice. Notwithstanding this...

A Network of Conserved Damage Survival Pathways Revealed by a Genomic RNAi Screen

Ravi, Dashnamoorthy, Wiles, Amy M., Bhavani, Selvaraj, Ruan, Jianhua, Leder, Philip, Bishop, Alexander J. R.

Damage initiates a pleiotropic cellular response aimed at cellular survival when appropriate. To identify genes required for damage survival, we used a cell-based RNAi screen against the Drosophila...