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  • Andrew Feinberg Laboratory

    The Feinberg Laboratory studies the epigenetic basis of normal development and disease, including cancer, aging and neuropsychiatric illness. Early work from our group involved the discovery of altered DNA methylation in cancer as well as common epigenetic (methylation and imprinting) variants in the population that may be responsible for a significant population-attributable risk of cancer.

    Over the last few years, we have pioneered the field of epigenomics (i.e., epigenetics at a genome-scale level), founding the first NIH-supported NIH epigenome center in the country and developing many novel tools for molecular and statistical analysis. Current research examines the mechanisms of epigenetic modification, the epigenetic basis of cancer, the invention of new molecular, statistical, and epidemiological tools for genome-scale epigenetics and the epigenetic basis of neuropsychiatric disease, including schizophrenia and autism.

    Research Areas: autism, cancer, epigenetics, schizophrenia, human development, aging, DNA, genomics, neuropsychiatric disease

    Lab Website

    Principal Investigator

    Andrew Feinberg, M.D., M.P.H.

    Department

    Medicine

  • Beer Lab

    The goal of research in the Beer Lab is to understand how gene regulatory information is encoded in genomic DNA sequence. Our work uses functional genomics DNase-seq, ChIP-seq, RNA-seq, and chromatin state data to computationally identify combinations of transcription factor binding sites that operate to define the activity of cell-type specific enhancers. We are currently focused on improving SVM methodology by including more general sequence features and constraints predicting the impact of SNPs on enhancer activity (delta-SVM) and GWAS association for specific diseases, experimentally assessing the predicted impact of regulatory element mutation in mammalian cells, systematically determining regulatory element logic from ENCODE human and mouse data, and using this sequence based regulatory code to assess common modes of regulatory element evolution and variation.

    Research Areas: computational biology, biomedical engineering, DNA, genomics, RNA

  • Berger Lab

    The Berger Lab's research is focused on understanding how multi-subunit assemblies use ATP for overcoming topological challenges within the chromosome and controlling the flow of genetic information. A long-term goal is to develop mechanistic models that explain in atomic level detail how macromolecular machines transduce chemical energy into force and motion, and to determine how cells exploit and control these complexes and their activities for initiating DNA replication, shaping chromosome superstructure and executing myriad other essential nucleic-acid transactions.

    Our principal approaches include a blend of structural (X-ray crystallography, single-particle EM, SAXS) and solution biochemical methods to define the architecture, function, evolution and regulation of biological complexes. We also have extensive interests in mechanistic enzymology and the study of small-molecule inhibitors of therapeutic potential, the development of chemical approaches to trapping weak protein/p...rotein and protein/nucleic acid interactions, and in using microfluidics and single-molecule approaches for biochemical investigations of protein dynamics. view more

    Research Areas: biochemistry, proteomics, ATP, DNA, genomics

  • Best Laboratory

    The Best Laboratory focus on therapeutic vaccine development for HPV-related diseases by developing a murine model of papilloma analogous to Recurrent Respiratory Papillomatosis (RRP) for testing of DNA vaccine technology. We also work to understand the immunosuppressive tumor microenvironment that facilitates RRP development, and translate this work into novel therapies and clinical practice.

    Research Areas: Recurrent Respiratory Papillomatosis, HPV-related diseases, vaccines, Laryngeal papillomas, otolaryngology, papillomas, DNA vaccine technologies

  • Daniel Weinberger Laboratory

    The Daniel Weinberger Laboratory focuses on the neurobiological mechanisms of genetic risk for developmental brain disorders. We study the genetic regulation of the transcriptome in normal human brain across the human life span and in brains from patients with various psychiatric disorders. We also study the impact of genetic variation on aspects of human brain development and function linked with risk for schizophrenia and related psychiatric disorders. Our lab uses unique molecular and clinical datasets and biological materials from a large sample of families with affected and unaffected offspring and normal volunteers. These datasets include DNA, lymphoblast and fibroblast cell lines, and extensive quantitative phenotypes related to genetic risk for schizophrenia, including detailed cognitive assessments and various neuroimaging assays. In other research, we are working on a human brain transcriptome project that is RNA sequencing over 1,000 human brain samples in various regi...ons and based also on sorting of specific celliular phentypes. We are exploring the molecular processing of the gene and its implications for cognition and aspects of human temperament. view more

    Research Areas: neurobiology, brain, transcriptome, schizophrenia, psychiatric disorders, genomics, developmental disorders, RNA

  • Daria Gaykalova Lab

    The Daria Gakalova Lab defines the functional role of epigenetics in transcriptional regulation of head and neck squamous cell carcinoma (HNSCC) progression. To evaluate the whole-genome distribution of various histone marks, her team is using chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-Seq) for primary tissues, a method recently developed by her lab. The research group of Daria Gaykalova was the first to demonstrate the cancer-specific distribution of H3K4me3 and H3K27ac marks and their role in cancer-related gene expression in HNSCC. The research showed that an aberrant chromatin alteration is a central event in carcinogenesis and that the therapeutic control of chromatin structure can prevent the primary of secondary cancerization. Further preliminary data suggest that the differential enrichment of these disease-specific histone marks and DNA methylation correlate with alternative splicing events (ASE) formation. For this project, Dr. Gaykalova... and her team employed a novel bioinformatical tool for the detection of cancer-specific ASEs. Through thorough functional validation of the individual ASEs, the lab demonstrated that each of them has a unique mechanism of malignant transformation of the cells. Due to high disease specificity, ASEs represent the perfect biomarkers of the neoantigens and have direct application to clinical practice. view more

    Research Areas: Head and neck squamous cell carcinoma, Human papillomavirus, Alternative splicing, epigenetics, Chromatin structure, Cancer genomics, head and neck cancer

  • David Sullivan Lab

    Research in the David Sullivan Lab focuses on malaria, including its diagnosis, treatment, molecular biology as it relates to iron, and pathology as it relates to severe anemia. We test and develop new malaria diagnostics — from real-time polymerase chain reaction (PCR) to novel urine and saliva detection platforms. This includes the adaptation of immuno-PCR (antibody coupled to DNA for PCR detection) to malaria and a lead blood stage drug that contains a quinine derivative used to treat malaria in the 1930s.

    Research Areas: molecular immunology, iron, anemia, malaria, molecular microbiology

    Principal Investigator

    David Sullivan, M.D.

    Department

    Medicine

  • DNA Diagnostic Lab

    Established in 1979, the Johns Hopkins DNA Diagnostic Laboratory is a CLIA and CAP certified; Maryland, New York, and Pennsylvania licensed clinical genetics testing laboratory specializing in rare inherited disorders. Led by renown professor of pediatrics and medical genetics Dr. Garry R. Cutting, the lab offers testing for a range of approximately 50 phenotypes and disorders totaling 3,500 tests annually.

    Research Areas: genetics, genetic sequencing, genetic counseling, rare inherited disorders

    Lab Website

    Principal Investigator

    Garry Cutting, M.D.

    Department

    Pediatrics

  • Erwin Lab

    Schizophrenia, autism and other neurological disorders are caused by a complex interaction between inherited genetic risk and environmental experiences. The overarching goal of the group are to reveal molecular mechanisms of gene by environment interactions related to altered neural development and liability for brain disorders. Our research uses a hybrid of human stem cell models, post-mortem tissue and computational approaches to interrogate the contribution of epigenetic regulation and somatic mosaicism to brain diseases. Our previous work has demonstrated that the human brain exhibits extensive genetic variability between neurons within the same brain, termed "somatic mosaicism" due to mobile DNA elements which mediate large somatic DNA copy number variants. We study environment-responsive mechanisms and consequences for somatic mosaicism and are discovering the landscape of somatic mosaicism in the brain. We also study the epigenetic regulation of cell specification and activity-d...ependent states within the human dorsal lateral prefrontal cortex and striatum. view more

    Research Areas: autism, Cellular and Molecular Neuroscience, stem cells, Developmental Neuroscience, Neurobiology of Disease, Induced Pluripotent Stem Cell Models, Organoids, schizophrenia, genomics, Dystonia, Epigenomics

    Lab Website

    Principal Investigator

    Jennifer Erwin, Ph.D.

    Department

    Neurology

  • Gary S. Hayward Laboratory

    Research in the Gary S. Hayward Laboratory is related to human herpesvirus. Specifically, researchers are seeking to understand how the different classes of herpes viruses take control of transcription, DNA replication, cell cycle and other nuclear processes of their host cells and how they also block or evade apoptotic and immune responses in both the lytic and latent state.

    Research Areas: immunology, herpesvirus, pathogenesis, transcriptional regulation

    Lab Website

    Principal Investigator

    Gary Hayward, Ph.D.

    Department

    Oncology

  • GI Early Detection Biomarkers Lab

    Dr. Meltzer is an internationally renowned leader in the molecular pathobiology of gastrointestinal malignancy and premalignancy. He invented molecular methods to detect loss of heterozygosity in tiny biopsies, triggering an avalanche of research on precancerous lesions. He was the first to comprehensively study coding region microsatellite instability, leading to the identification of several important tumor suppressor genes. He performed several groundbreaking genomic, epigenomic and bioinformatic studies of esophageal and colonic neoplasms, shifting the GI research paradigm toward genome-wide approaches. He directed an ambitious nationwide validation study of DNA methylation-based biomarkers for the prediction of neoplastic progression in Barrett’s esophagus.

    Dr. Meltzer founded and led the Aerodigestive Cancer and Biomarker Interdisciplinary Programs at the University of Maryland, also becoming associate director for core sciences at that school’s Cancer Center. He currently hol...ds an endowed professorship and is the director of GI biomarker research at Johns Hopkins.

    The laboratory group focuses its efforts on the molecular genetics of gastrointestinal cancers and premalignant lesions, as well as on translational research to improve early detection, prognostic evaluation, and treatment of these conditions. Below, some examples of this work are described.
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    Research Areas: gastrointestinal cancer, gastrointestinal

    Principal Investigator

    Stephen Meltzer, M.D.

    Department

    Medicine

  • Greider Lab

    The Greider lab uses biochemistry to study telomerase and cellular and organismal consequences of telomere dysfunction. Telomeres protect chromosome ends from being recognized as DNA damage and chromosomal rearrangements. Conventional replication leads to telomere shortening, but telomere length is maintained by the enzyme telomerase. Telomerase is required for cells that undergo many rounds of divisions, especially tumor cells and some stem cells. The lab has generated telomerase null mice that are viable and show progressive telomere shortening for up to six generations. In the later generations, when telomeres are short, cells die via apoptosis or senescence. Crosses of these telomerase null mice to other tumor prone mice show that tumor formation can be greatly reduced by short telomeres. The lab also is using the telomerase null mice to explore the essential role of telomerase stem cell viability. Telomerase mutations cause autosomal dominant dyskeratosis congenita. People with ...this disease die of bone marrow failure, likely due to stem cell loss. The lab has developed a mouse model to study this disease. Future work in the lab will focus on identifying genes that induce DNA damage in response to short telomeres, identifying how telomeres are processed and how telomere elongation is regulated. view less

    Research Areas: telomerase, biochemistry, stem cells, cell biology, DNA

  • Haig Kazazian Lab

    The Kazazian Lab focuses on the biology of LINE-1 (L1) retrotransposons. Retrotransposons are pieces of genomic DNA that have the ability to duplicate themselves and insert into a new genomic location. Current studies use innovative DNA sequencing to locate all human-specific L1s in any genome. By understanding L1 biology, we hope to better understand the role of these genomes and their behavior in complex human disease, such as cancer and mental disorders. The lab is also examining how to carry out gene therapy of hemophilia A using AAV vectors.

    Research Areas: cell biology, cancer, retrotransposons, DNA, genomics, mental disorders

    Lab Website

    Principal Investigator

    Haig Kazazian, M.D.

    Department

    Pediatrics

  • James Hamilton Lab

    The main research interests of the James Hamilton Lab are the molecular pathogenesis of hepatocellular carcinoma and the development of molecular markers to help diagnose and manage cancer of the liver. In addition, we are investigating biomarkers for early diagnosis, prognosis and response to various treatment modalities. Results of this study will provide a molecular classification of HCC and allow us to identify targets for chemoprevention and treatment. Specifically, we extract genomic DNA and total RNA from liver tissues and use this genetic material for methylation-specific PCR (MSP), cDNA microarray, microRNA microarray and genomic DNA methylation array experiments.

    Research Areas: cancer, molecular genetics, genomics, pathogenesis, liver diseases, hepatocellular carcinoma

    Principal Investigator

    James Hamilton, M.D.

    Department

    Medicine

  • Lee Martin Laboratory

    In the Lee Martin Laboratory, we are testing the hypothesis that selective vulnerability--the phenomenon in which only certain groups of neurons degenerate in adult onset neurological disorders like amyotrophic lateral sclerosis and Alzheimer's disease--is dictated by brain regional connectivity, mitochondrial function and oxidative stress. We believe it is mediated by excitotoxic cell death resulting from abnormalities in excitatory glutamatergic signal transduction pathways, including glutamate transporters and glutamate receptors as well as their downstream intracellular signaling molecules.

    We are also investigating the contribution of neuronal/glial apoptosis and necrosis as cell death pathways in animal (including transgenic mice) models of acute and progressive neurodegeneration. We use a variety of anatomical and molecular neurobiological approaches, including neuronal tract-tracing techniques, immunocytochemistry, immunoblotting, antipeptide antibody production, transmissi...on electron microscopy and DNA analysis to determine the precise regional and cellular vulnerabilities and the synaptic and molecular mechanisms that result in selective neuronal degeneration.
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    Research Areas: ALS, neurodegeneration, selective vulnerability, cell death, Alzheimer's disease

    Lab Website

    Principal Investigator

    Lee Martin, Ph.D.

    Department

    Pathology

  • Mihaela Pertea Lab

    The Mihaela Pertea Lab develops computational tools for RNA sequence analysis, gene finding, splice-site prediction and sequence-motif finding. Previous research projects led to the development of open-source software systems related to finding genes.

    Research Areas: computational biology, DNA, genomics, RNA

    Lab Website

    Principal Investigator

    Mihaela Pertea, M.S., M.S.E., Ph.D.

    Department

    Medicine

  • Richard F. Ambinder Lab

    Epstein-Barr virus and Kaposi's sarcoma herpesvirus are found in association with a variety of cancers. Our laboratory studies are aimed at better defining the role(s) of the virus in the pathogenesis of these diseases and the development of strategies to prevent, diagnose or treat them. We have become particularly interested in the unfolded protein response in activation of latent viral infection. Among the notions that we are exploring is the possibility that activation of virus-encoded enzymes will allow the targeted delivery of radation. In addition, we are investigating a variety of virus-related biomarkers including viral DNA, antibody responses, and cytokine measurements that may be clinically relevant.

    Research Areas: virology, antiviral therapy

  • Salzberg Lab

    Research in the Salzberg Lab focuses on the development of new computational methods for analysis of DNA from the latest sequencing technologies. Over the years, we have developed and applied software to many problems in gene finding, genome assembly, comparative genomics, evolutionary genomics and sequencing technology itself. Our current work emphasizes analysis of DNA and RNA sequenced with next-generation technology.

    Research Areas: computational biology, DNA, genomics, sequencing technology, biostatistics, RNA

  • Stivers Lab

    The Stivers Lab is broadly interested in the biology of the RNA base uracil when it is present in DNA. Our work involves structural and biophysical studies of uracil recognition by DNA repair enzymes, the central role of uracil in adapative and innate immunity, and the function of uracil in antifolate and fluoropyrimidine chemotherapy. We use a wide breadth of structural, chemical, genetic and biophysical approaches that provide a fundamental understanding of molecular function. Our long-range goal is to use this understanding to design novel small molecules that alter biological pathways within a cellular environment. One approach we are developing is the high-throughput synthesis and screening of small molecule libraries directed at important targets in cancer and HIV-1 pathogenesis.

    Research Areas: biophysics, enzymes, cell biology, uracil, cancer, HIV, DNA, RNA

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