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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.