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  • Lee Martin Laboratory

    Lab Website
    Principal Investigator:
    Lee Martin, Ph.D.
    Pathology

    In the Lee Martin Laboratory, we are testing the hypothesis that selective vulnerability--the p...henomenon 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, transmission 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
  • Molecular Oncology Laboratory

    Principal Investigator:
    Valsamo Anagnostou, M.D., Ph.D.
    Oncology

    Our Molecular Oncology lab seeks to understand the genomic wiring of response and resistance to... immunotherapy through integrative genomic, transcriptomic, single-cell and liquid biopsy analyses of tumor and immune evolution. Through comprehensive exome-wide sequence and genome-wide structural genomic analyses we have discovered that tumor cells evade immune surveillance by elimination of immunogenic mutations and associated neoantigens through chromosomal deletions. Additionally, we have developed non-invasive molecular platforms that incorporate ultra-sensitive measurements of circulating cell-free tumor DNA (ctDNA) to assess clonal dynamics during immunotherapy. These approaches have revealed distinct dynamic ctDNA and T cell repertoire patterns of clinical response and resistance that are superior to radiographic response assessments. Our work has provided the foundation for a molecular response-adaptive clinical trial, where therapeutic decisions are made not based on imaging but based on molecular responses derived from liquid biopsies. Overall, our group focuses on studying the temporal and spatial order of the metastatic and immune cascade under the selective pressure of immune checkpoint blockade with the ultimate goal to translate this knowledge into “next-generation” clinical trials and change the way oncologists select patients for immunotherapy. view more

    Research Areas: integrative mutli-omic analyses, Cancer genomics, liquid biopsies, tumor evolution, lung cancer, immunogenomic biomarkers
  • Richard F. Ambinder Lab

    Lab Website

    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. view more

    Research Areas: virology, antiviral therapy
  • Salzberg Lab

    Lab Website

    Research in the Salzberg Lab focuses on the development of new computational methods for analys...is 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. view more

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

    Lab Website

    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. view more

    Research Areas: biophysics, enzymes, cell biology, uracil, cancer, HIV, DNA, RNA
  • The Arking Lab

    Principal Investigator:
    Dan Arking, Ph.D.
    Medicine

    The Arking Lab studies the genomics of complex human disease, with the primary goal of identify...ing and characterizing genetics variants that modify risk for human disease. The group has pioneered the use of genome-wide association studies (GWAS), which allow for an unbiased screen of virtually all common genetic variants in the genome. The lab is currently developing improved GWAS methodology, as well as exploring the integration of additional genome level data (RNA expression, DNA methylation, protein expression) to improve the power to identify specific genetic influences of disease.

    The Arking Lab is actively involved in researching:
    • autism, a childhood neuropsychiatric disorder
    • cardiovascular genomics, with a focus on electrophysiology and sudden cardiac death (SCD)
    • electrophysiology is the study of the flow of ions in biological tissues

    Dan E. Arking, PhD, is an associate professor at the McKusick-Nathans Institute of Genetic Medicine and Department of Medicine, Division of Cardiology, Johns Hopkins University.
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    Research Areas: autism, genetics, aging, cardiovascular diseases, sudden cardiac death
  • The Laboratory for Precision Immunology

    Lab Website
    Principal Investigator:
    H. Larman, Ph.D.
    Pathology

    We are devoted to developing and deploying cutting edge technologies that can be used to define... human immune responses. Much of our work leverages ‘next generation’ DNA sequencing, which enables massively parallel molecular measurements. Examples of our technologies include:
    - bacteriophage display of synthetic peptidome libraries for comprehensive, quantitative profiling of antibodies;
    - display of ORFeome libraries for antigen discovery, protein-protein interaction studies, and drug target identification;
    - ultrasensitive, multiplex RNA quantification techniques to monitor gene expression and detect microbes;
    - pooled genetic screening to elucidate immune cell function and identify new therapeutic targets.

    The Larman Laboratory uses these and other approaches to identify opportunities for monitoring and manipulating immune responses.
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    Research Areas: immunology, precision immunology
  • Vestibular NeuroEngineering Lab

    Lab Website

    Research in the Vestibular NeuroEngineering Lab (VNEL) focuses on restoring inner ear function ...through “bionic” electrical stimulation, inner ear gene therapy, and enhancing the central nervous system’s ability to learn ways to use sensory input from a damaged inner ear. VNEL research involves basic and applied neurophysiology, biomedical engineering, clinical investigation and population-based epidemiologic studies. We employ techniques including single-unit electrophysiologic recording; histologic examination; 3-D video-oculography and magnetic scleral search coil measurements of eye movements; microCT; micro MRI; and finite element analysis. Our research subjects include computer models, circuits, animals and humans. For more information about VNEL, click here.
    VNEL is currently recruiting subjects for two first-in-human clinical trials:
    1) The MVI Multichannel Vestibular Implant Trial involves implantation of a “bionic” inner ear stimulator intended to partially restore sensation of head movement. Without that sensation, the brain’s image- and posture-stabilizing reflexes fail, so affected individuals suffer difficulty with blurry vision, unsteady walking, chronic dizziness, mental fogginess and a high risk of falling. Based on designs developed and tested successfully in animals over the past the past 15 years at VNEL, the system used in this trial is very similar to a cochlear implant (in fact, future versions could include cochlear electrodes for use in patients who also have hearing loss). Instead of a microphone and cochlear electrodes, it uses gyroscopes to sense head movement, and its electrodes are implanted in the vestibular labyrinth. For more information on the MVI trial, click here.
    2) The CGF166 Inner Ear Gene Therapy Trial involves inner ear injection of a genetically engineered DNA sequence intended to restore hearing and balance sensation by creating new sensory cells (called “hair cells”). Performed at VNEL with the support of Novartis and through a collaboration with the University of Kansas and Columbia University, this is the world’s first trial of inner ear gene therapy in human subjects. Individuals with severe or profound hearing loss in both ears are invited to participate. For more information on the CGF166 trial, click here.
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    Research Areas: neuroengineering, audiology, multichannel vestibular prosthesis, balance disorders, balance, vestibular, prosthetics, cochlea, vestibular implant
  • Victor Velculescu Lab

    Lab Website

    The lab currently focuses on identifying genetic alterations in cancer affecting sensitivity an...d resistance to targeted therapies, and connecting such changes to key clinical characteristics and novel therapeutic approaches. We have recently developed methods that allow noninvasive characterization of cancer, including the PARE method that provided the first whole genome analysis of tumor DNA in the circulation of cancer patients. These analyses provide a window into real-time genomic analyses of cancer patients and provide new avenues for personalized diagnostic and therapeutic intervention. view more

    Research Areas: cancer, genomics, immunotherapy
  • William G. Nelson Laboratory

    Lab Website
    Principal Investigator:
    William Nelson, M.D., Ph.D.
    Oncology

    Normal and neoplastic cells respond to genome integrity threats in a variety of different ways.... Furthermore, the nature of these responses are critical both for cancer pathogenesis and for cancer treatment. DNA damaging agents activate several signal transduction pathways in damaged cells which trigger cell fate decisions such as proliferation, genomic repair, differentiation, and cell death. For normal cells, failure of a DNA damaging agent (i.e., a carcinogen) to activate processes culminating in DNA repair or in cell death might promote neoplastic transformation. For cancer cells, failure of a DNA damaging agent (i.e., an antineoplastic drug) to promote differentiation or cell death might undermine cancer treatment.

    Our laboratory has discovered the most common known somatic genome alteration in human prostatic carcinoma cells. The DNA lesion, hypermethylation of deoxycytidine nucleotides in the promoter of a carcinogen-defense enzyme gene, appears to result in inactivation of the gene and a resultant increased vulnerability of prostatic cells to carcinogens.
    Studies underway in the laboratory have been directed at characterizing the genomic abnormality further, and at developing methods to restore expression of epigenetically silenced genes and/or to augment expression of other carcinogen-defense enzymes in prostate cells as prostate cancer prevention strategies.

    Another major interest pursued in the laboratory is the role of chronic or recurrent inflammation as a cause of prostate cancer. Genetic studies of familial prostate cancer have identified defects in genes regulating host inflammatory responses to infections.
    A newly described prostate lesion, proliferative inflammatory atrophy (PIA), appears to be an early prostate cancer precursor. Current experimental approaches feature induction of chronic prostate inflammation in laboratory mice and rats, and monitoring the consequences on the development of PIA and prostate cancer.
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    Research Areas: cellular biology, cancer, epigenetics, DNA
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