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Balagopal Lab - Viral Hepatitis and Translational Virology
The Balagopal Lab has adapted high-resolution tools to study viruses in situ. Specifically, we were the first to quantify hepatitis C virus (HCV) infection in single hepatocytes by developing single-cell laser capture microdissection (scLCM) and integrating this tool with highly sensitive quantitative real-time PCR. We reported that HCV infects a minority of hepatocytes that are found in geospatial clusters. More recently, we (PIs Balagopal and Thio) integrated scLCM with droplet digital PCR (ddPCR) to reveal the first observations of hepatitis B virus (HBV) infection at single cell resolution in the liver. We found that HBV infects nearly all hepatocytes prior to antiviral therapy. However, during antiviral therapy, HBV infection is diminished while viral transcription is markedly attenuated.
Our lab has also focused on HIV-1 infection and immune activation for over a decade. Most recently, we have studied type 1 interferon responses to HIV-1 using RNA sequencing (RNAseq). Using th...is technology, we identified novel interferon-stimulated genes (ISGs) that are associated with HIV-1 restriction in vivo. view more
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.
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
Work in the Green Lab is centered on the ribosome. The overall fidelity of protein synthesis appears to be limited by the action of the ribosome, which is the two-subunit macromolecular machine responsible for decoding and translating messenger RNAs (mRNAs) into protein in all organisms. Our work is divided into four general project areas. The longest-standing research area concerns the interactions of eubacterial ribosomes and release factors. The goal is to understand the mechanism of action of release factors on the ribosome. A second research area involves biochemical and structure/function studies of the miRNA pathway, particularly the mechanism of action of the Argonaute proteins and their interacting factors. A third area of work in the lab is centered around regulation of eukaryotic translation, specifically in understanding the mechanism behind various mRNA quality control pathways and the interactions of proteins therein, as well as with the ribosome. The newest area of rese...arch in the lab extends our strengths in ribosome biochemistry to characterize the translation status of the cell using the ribosome profiling. We are using this technique to better understand the role of several factors involved in eukaryotic and prokaryotic translation fidelity. view more
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.
Jay Baraban Laboratory
The Jay Baraban Laboratory studies key aspects of neuronal plasticity induced by environmental stimuli, including drugs. The ability of the microRNA system to regulate protein translation in the vicinity of synapses indicates it is well positioned to play a central role in regulating synaptic plasticity. Accordingly, we are studying how this system regulates synaptic function. In particular, we have identified the translin/trax RNAse complex as a key regulator of microRNA processing and are using genetically engineered mice that lack this complex to understand its role in neuronal function. For example, these mice display defects in responsiveness to cocaine and in certain forms of synaptic plasticity. We use a combination of behavioral and molecular approaches to conduct studies aimed at understanding how the microRNA system regulates these processes.
Jeffry Corden Laboratory
Jeffry Corden's lab is using genetic and biochemical approaches to investigate the functional role of the C-terminal domain (CTD) in the biogenesis of mRNA. We use both yeast and mammalian systems to conduct research.
A major effort in the lab is directed at studies of proteins that bind the CTD. Using the yeast two-hybrid approach, we've identified a family of proteins that interact with the CTD. These proteins are similar to the serine/arginine-rich proteins involved in pre-mRNA splicing. A current focus of the laboratory is to determine how these proteins function in mRNA biogenesis and how CTD phosphorylation regulates this function. Other research in our lab investigates the mechanism by which RNA sequences in the nascent transcript trigger Pol II termination.
Ken Witwer Laboratory
The Ken Witwer Laboratory investigates extracellular vesicles and RNA in the context of HIV infection and inflammatory disease. We are also actively assessing the effects of diet on extracellular RNA as a potential therapeutic approach.
Molecular and Comparative Pathobiology
The Lamichhane Lab strives to understand the fundamental mechanisms used by Mycobacterium tuberculosis to survive, grow and cause disease. Although our lab uses genetic and biochemical approaches to study this organism, we pursue questions irrespective of the expertise required to answer those questions. We work to identify the essential components of the peptidoglycan layer and how the physiology of this layer is maintained. We also explore what non-coding RNAs exist in M. tuberculosis and investigate what their relevance is to the physiology and virulence of this pathogen.
Liliana Florea Lab
Research in the Liliana Florea Lab applies computational techniques toward modeling and problem solving in biology and genetic medicine. We work to develop computational methods for analyzing large-scale sequencing data to help characterize molecular mechanisms of diseases. The specific application areas of our research include genome analysis and comparison, cDNA-to-genome alignment, gene and alternative splicing annotation, RNA editing, microbial comparative genomics, miRNA genomics and computational vaccine design. Our most recent studies seek to achieve accurate and efficient RNA-seq correction and explore the role of HCV viral miRNA in hepatocellular carcinoma.
The Loyal Goff Laboratory seeks to answer a fundamental biological question: How is the genome properly interpreted to coordinate the diversity of cell types observed during neuronal development? We are focused on the acquisition of specific cellular identities in neuronal development and identifying the molecular determinants responsible for proper brain development. Using novel experimental approaches for the enrichment and purification of specific neuronal cell types and recent technological advances in single-cell RNA sequencing, we can discover and explore the cellular factors that contribute to neuronal cell fate decisions during mammalian brain development.
Michael Caterina Lab
The Caterina lab is focused on dissecting mechanisms underlying acute and chronic pain sensation. We use a wide range of approaches, including mouse genetics, imaging, electrophysiology, behavior, cell culture, biochemistry and neuroanatomy to tease apart the molecular and cellular contributors to pathological pain sensation. A few of the current projects in the lab focus on defining the roles of specific subpopulations of neuronal and non-neuronal cells to pain sensation, defining the role of RNA binding proteins in the development and maintenance of neuropathic pain, and understanding how rare skin diseases known as palmoplantar keratodermas lead to severe pain in the hands and feet.
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.
Ryuya Fukunaga Lab
The Fukunaga Lab uses multidisciplinary approaches to understand the cell biology, biogenesis and function of small silencing RNAs from the atomic to the organismal level.
The lab studies how small silencing RNAs, including microRNAs (miRNAs), small interfering RNAs (siRNAs) and piwi-interacting RNAs (piRNAs), are produced and how they function. Mutations in the small RNA genes or in the genes involved in the RNA pathways cause many diseases, including cancers. We use a combination of biochemistry, biophysics, fly genetics, cell culture, X-ray crystallography and next-generation sequencing to answer fundamental biological questions and also potentially lead to therapeutic applications to human diseases.
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.
Sean Taverna Laboratory
The Taverna Laboratory studies histone marks, such as lysine methylation and acetylation, and how they contribute to an epigenetic/histone code that dictates chromatin-templated functions like transcriptional activation and gene silencing. Our lab uses biochemistry and cell biology in a variety of model organisms to explore connections between gene regulation and proteins that write and read histone marks, many of which have clear links to human diseases like leukemia and other cancers. We also investigate links between small RNAs and histone marks involved in gene silencing.
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.
The Arking Lab
The Arking Lab studies the genomics of complex human disease, with the primary goal of identifying 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, D...ivision of Cardiology, Johns Hopkins University. view more
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.
The nervous system has extremely complex RNA processing regulation. Dysfunction of RNA metabolism has emerged to play crucial roles in multiple neurological diseases. Mutations and pathologies of several RNA-binding proteins are found to be associated with neurodegeneration in both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). An alternative RNA-mediated toxicity arises from microsatellite repeat instability in the human genome. The expanded repeat-containing RNAs could potentially induce neuron toxicity by disrupting protein and RNA homeostasis through various mechanisms.
The Sun Lab is interested in deciphering the RNA processing pathways altered by the ALS-causative mutants to uncover the mechanisms of toxicity and molecular basis of cell type-selective vulnerability. Another major focus of the group is to identify small molecule and genetic inhibitors of neuron toxic factors using various high-throughput screening platforms. Finally, we are also highly i...nterested in developing novel CRISPR technique-based therapeutic strategies. We seek to translate the mechanistic findings at molecular level to therapeutic target development to advance treatment options against neurodegenerative diseases. view more