JEFFERY DESTEFANO, Professor, Cell Biology and Molecular Genetics
Honors: Editor, ISRN Virology.
 

Research interests: HIV and Picornavirus replication, Aptamer development and biotechnology.

 

Dr. DeStefano’s research focuses on studying the roles of HIV-reverse transcriptase (RT) and poliovirus RNA-dependent RNA polymerase (RdRp) in the processes of viral recombination and replication for the respective viruses.  Current work includes projects to construct nucleic acid aptamers inhibitors to HIV and SARS-2 that are made from “xeno nucleic acids” which nucleic acids made from non-canonical nucleotides that are better able to resist degradation and less likely to trigger innate immune responses. Dr. DeStefano’s lab was the first to demonstrate that poliovirus protein 3AB is a nucleic acid chaperone with activities similar to HIV NC. They are currently using Next Generation Sequencing (NGS) to understand how HIV RT drives the generation of genetic diversity in HIV. By studying unique aspects of retrovirus and picornavirus life cycles, Dr. DeStefano’s group hopes to contribute to new therapies that exploit these unique functions.

 

 

JONATHAN DINMAN, Professor and Head, Department of Cell Biology and Molecular Biology
Honors: Member, NIH Biochemistry, Biophysics, and Chemistry ZRG1 F04 study section;  Founding Editor and Founding Editor and Editor-in-Chief, Virus, Adaptation and Treatment;  Editorial Board, Nucleic Acids Research; Editor-in-Chief, International Journal of Biomedical Science 

 

Research interests: Mechanisms of translational reading frame maintenance using viral programmed ribosomal frameshift signals.

 

The Dinman lab has capitalized on the ability of viruses to reprogram cellular ribosomes to probe the mechanisms governing translational fidelity. In the past 18 years, Dr. Dinman has developed a highly varied toolbox, enabling the group to address a wide array of questions. Programmed Ribosomal Frameshifting (PRF), in particular provides a unique window into the molecular machinery that normally controls reading-frame maintenance. They have found that altering the efficiency of frameshifting changes the balance of viral structural to enzymatic proteins, which in turn interferes with virus particle assembly and viral propagation. Thus, PRF represents an important target for potential antiviral therapies. The development of a yeast and mammalian cell based assay systems have also provided Dr. Dinman with a unique set of tools to probe the mechanisms governing translational fidelity. They use genetic, biochemical and molecular methods to characterize the trans-acting factors, and the physical and biochemical parameters that ultimately determine the frequency with which ribosomes shift reading frame. These tools have enabled Dr. Dinman to lend his expertise in ribosome biochemistry in collaboration with Dr. Simon’s study of the tRNA-like element of TCV. Dr. Dinman’s expertise in translational recoding was used to characterize the frameshift signal in the SARS virus and the termination readthrough signal of Pancreatic necrosis virus. In combination with the high resolution structural understanding of ribosomes, their approaches are leading to new insights into ribosome structure/function relationships and are using this information to identify targets for antiviral agents. Currently, Dr. Dinman’s laboratory is focused on four projects: (1) Programmed -1 ribosomal frameshifting (-1 PRF) alphaviruses, specifically Venezuelan, Eastern and Western Equine viruses; (2) using translational recoding mechanisms to probe the relationships between structure and function of the ribosome; (3) identification and characterization of -1 PRF signals in cellular mRNAs; and (4) characterizing the interactions between -1 frameshift signals (both viral and cellular) and miRNAs.

 

 

JAMES CULVER, Professor, Department of Plant Science and Landscape Archetecture, IBBR
Honors: CAREER Award Recipient, National Science Foundation; Editorial board, Virology
 

Research interests: Tobacco mosaic virus/host interactions; how viruses cause disease and induce resistance responses.

 

Research in Dr. Culver’s laboratory is multidisciplinary with efforts directed at understanding virus biology and its role in disease as well as studies aimed at engineering viruses and other biological components for application in nano-based systems and devices.  Current virus biology studies are directed at understanding the structure-function relationships between interacting virus and host components and the role these interactions play in virus movement and disease development.  Nanotechnology studies are focused on developing viruses as bio-templates for the display and patterning of functional materials onto device surfaces.  Dr. Culver’s laboratory has developed virus-based nanomaterials that function as battery electrodes, light harvesting surfaces and sensors.  The overall goal in Dr. Culver’s laboratory is to utilize discoveries in basic virus research to develop new approaches for their control and use.

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MARGARET A. SCULL, Assistant Professor, Cell Biology and Molecular Genetics

Honors: Parker B. Francis Fellow

 

Research interests: airway biology; respiratory virus-host interactions; antiviral response in the airway; spatiotemporal dynamics of infection; tissue engineering and primary cell systems.

 

 The Scull lab combines transcriptomics, viral genetics, and in vitro primary cell model systems to understand innate defense against respiratory viruses. Our work focuses on the airway epithelium – the primary target for infection by respiratory viruses and also our first line of defense at the interface between the external environment and underlying tissues. We have previously shown that innate defense mechanisms in the airway epithelium limit infection by clinically relevant human respiratory viruses. Still, a comprehensive analysis of the airway epithelial antiviral response in primary human cells is lacking, and the specific contribution of individual populations of cells to this response remains unknown. Current work in the lab takes advantage of unbiased RNAseq technology to first define, then compare and contrast host gene signatures in the airway following infection with influenza virus, parainfluenza virus, rhinovirus, or coronavirus. Our in vitro model of human ciliated airway epithelium also provides unique opportunities to tackle questions regarding the heterogeneity of the host response during infection across different cell types and between infected and uninfected cells. Additional efforts in the Scull lab are geared toward developing tools, including virus and cell-based reporters, to visualize and dissect the dynamics of infection and the host response at the single-cell level. Our overall goal is to reveal novel mechanisms of critical host-pathogen interactions, understand the roles of specific cell populations during pathogenic insult, and translate these findings to understand why infections are often worse in individuals with pre-existing lung disease.

 

 

LAI-XI WANG, Professor, Department of Chemistry and Biochemistry

Honors:  Recipient, Melville L. Wolfrom Award in Carbohydrate Chemistry, American Chemical Society; Member, Faculty of 1000; Editorial Board, Carbohydrate Research; 2015, Chair-elect, American Chemical Society Division of Carbohydrate Chemistry; 2015, Vice Chair of the Carbohydrate Gordon Research Conference (GRC); 2014, Elected AAAS Fellow.

 

Research interests: Design, synthesis, and immunological evaluation of carbohydrate-based HIV vaccines

 

The Wang Lab is working at the interface of chemistry, biology, and immunology with a focus on the structures and functions of glycans and glycoproteins. Glycosylation is one of the most ubiquitous posttranslational modifications of proteins in eukaryotes. The covalent attachment of glycans adds a new level of structural and functional diversity of proteins and expands the biological information of an otherwise concise human genome. Students and postdoctoral researchers in the Wang group explore tools and concepts from various fields including synthetic organic chemistry, molecular biology, structural biology and immunology to understand the functional roles of glycans and glycoproteins in biological systems (host-pathogen interactions, symbiosis, and other important biological recognition processes). The group is also interested in translating the knowledge gained from functional and mechanistic studies into the design and development of more efficient therapeutic agents and vaccines against cancer and infectious diseases.  The HIV vaccine project in the Wang lab is focused on detailed structural characterization and glycan specificity of the neutralizing epitopes of broadly neutralizing antibodies targeting the V1V2 and V3 regions of HIV-1 gp120. The identified glycopeptide-specific neutralizing epitopes are then used as templates for the design of HIV-1 vaccines for raising broadly neutralizing antibodies.