We are synthetic organic and medicinal chemists with three predominant interests: (1) Exploring physicochemical and biophysical perturbations imparted by fluorinated functional groups and applying these groups towards drug design; (2) Providing medicinal chemistry support for pharmacological experts, particularly towards treating pain, mood and anxiety disorders, aging, and inflammation; (3) Developing innovative synthetic organic reactions for accessing therapeutically relevant drug-like compounds.
Bacteriophage, bioreporters in bioelectronics, metabolic engineering, recombinant bacterial strains, microbial ecology
Our research is focused on the synthesis of complex glycoproteins, natural products, and oligosaccharides of importance in immunology and oncology. Ideally, in direct collaboration with biologists and clinicians, this will lead to the identification of lead structures as pharmacological tools and potential therapeutics.
The crossing of the intestinal epithelial cell barrier is a crucial initial step for Listeria monocytogenes (Lm) pathogenesis. We reported that Lm can induce epithelial barrier dysfunction allowing bacterial paracellular translocation. This is largely attributed to the interaction of Listeria adhesion protein (LAP; 94 kDa), an alcohol acetaldehyde dehydrogenase enzyme with host cell receptor, Hsp60. The LAP-Hsp60 interaction activates canonical NF-κB signaling, facilitating myosin light-chain kinase (MLCK)-mediated opening of the epithelial barrier via the cellular junctional protein redistribution of claudin-1, occludin, and E-cadherin. Next, bioengineered Lactobacillus probiotics (BLP) strains expressing the LAP from a non-pathogenic Listeria (L. innocua) and Lm robustly colonized the intestine and protected mice from lethal Lm infection (92% survival). The BLP competitively excluded Lm by occupying the epithelial Hsp60 receptor and ameliorated the Lm-induced intestinal barrier dysfunction by limiting the loss of mucus-producing goblet cells, restricting epithelial apoptotic and proliferative cells, and blocking the NF-κB and MLCK-mediated redistribution of the epithelial junctional proteins. Additionally, the BLP increased intestinal immunomodulatory functions by recruiting FOXP3+T cells, CD11c+ dendritic cells and natural killer cells. Engineering a probiotic strain with an adhesion protein provides a novel strategy to prevent enteric pathogen colonization and infection.
Development of small molecules, peptides and peptidomimetics for drug discovery, bionanotechnology, and cellular delivery of therapeutic agents
Chemical Immunology: Cell specific chemical perturbation of immune microenvironments in cancer, neurological and immunological disorders
The research in my lab is geared towards understanding the host-pathogen interaction during migration of zoonotic ascarid larvae of the genera, Toxocara and Baylisascaris within the mammalian host. We use a combination of traditional parasitology, molecular biology and "-omics" related tools for identification and characterization of these parasite proteins. Our goal is to lay down a path to develop efficient diagnostics, identify potential vaccine candidates and drug targets to mitigate the effects of these neglected soil-transmitted nematodes.
Biomaterials, Musculoskeletal Regenerative Engineering, Micro/Nano-technology, Stem Cell Technology, Translational Biomedical Research
Innate immunity using fish, human cells and mice.
Insect Microbial Ecology, Insect-Symbiont Interactions, Metagenomics, Applied Evolutionary Entomology, Vector Biology
Our laboratory develops strategies that can leverage the immune system to simultaneously repair bone and control inflammation or cell viability. The overall therapy goals are to treat tumors and repair bone in tumor models or covid19 related inflammatory models, and treat and repair cartilage/bone in arthritis models.
Use of chemistry as a tool to elucidate biological mechanisms
Mechanism of the transfer to and expression of the Agrobacterium tumefaciens Ti-plasmid in plant cells
Structural basis for RNA function
Systems biology investigation of eukaryotic N-terminal methylation. Metabolomics and chemogenomics analysis of Candida albicans gastrointestinal colonization. Chemogenomics of Candida and Saccharomyces.
Molecular biology of arthropod vectors of disease, with an emphasis on vector-pathogen interactions, characterization of arthropod G protein-coupled receptors, and insecticide discovery.
Intestines harbor trillions of microbes that have evolved in the milieu of a diverse diet-derived small molecules. Gut microbiome (the collection of genetic materials harbored by the gut microbes) contains thousands of distinct genes with an enormous capacity to catalyze chemical reactions. Their functions, however, remains largely unknown. Jeong and Lee lab has been investigating the gut microbiota as (1) a drug-metabolizing organ and (2) a modulator of host response to drugs. Based on the expertise of Dr Jeong (a pharmacologist) and Dr Lee (a microbiologist), we identify and characterize the microbial factors involved in drug metabolism as well as host-microbe interaction that leads to altered drug efficacy and toxicity.
method developments and applications of cryo-EM
veterinary pathology, molecular pathology, immunopathology, mouse models of human disease, inflammatory bowel disease, microbiome, colon cancer, dengue virus
Our lab focuses on acquiring and utilizing high throughput sequencing data (e.g. RNA-seq, ChIP-seq, ATAC-seq) to develop new computational models and biological assays to study genome regulation and human diseases, in particular immune related disorders and cancer. We are now working on the discovery and modeling of the regulatory circuitry of the non-coding genome which is essential for maintaining normal cellular physiology.
Epigenetics, Impacts of Chromatin on Gene Expression, DNA Replication & DNA Repair
We are focused on the preclinical assessment of druggability characteristics that aid in the drug discovery hit to lead translation. Our current projects are focused on antiviral and cyanide countermeasure preclinical assessment. We are also determining the in vitro permeation of neurotoxicants across a novel, triculture blood brain barrier model that we developed.
The Konradt lab studies infections and the subsequent host immune response in two separate, yet overlapping compartments: the vascular system and the placenta.
Skeletal muscle and adipose tissue stem cells, regeneration, muscular dystrophy, obesity, type 2 diabetes, aging.
Viral gene expression; virus-host interactions; pathogenesis; virus receptors and virus assembly
Systems biology of host-pathogen interactions; dengue virus; malaria parasites; protein-protein interactions
Immunotherapy, A regulatory mechanism of anti-tumor immunity, A resistance mechanism of target therapy and/or immunotherapy, Antibody engineering
Diagnostic pathology, molecular pathology, and immunohistopathology of infectious, toxic, and neoplastic diseases
Dietary controls on the gut microbiome, host-microbe and microbe-microbe metabolic exchange, gut inflammation and enteropathogenesis
We develop targeted drugs for many different diseases including cancer, pulmonary fibrosis, rheumatoid arthritis, sickle cell disease, malaria, Crohn's disease, type 1 diabetes, many viral infections, organ transplant rejection, and depression. Our experimental methods include everything from characterization of disease mechanisms to design, synthesis, in vitro testing and in vivo validation of new drugs to treat these diseases.
Type IV protein secretion of Legionella pneumophila; intracellular multiplication and trafficking of bacterial pathogens
Cancer immunotherapy, immunoengineering, natural killer cells, nanomedicine, cell and gene engineering, immunotherapy of solid tumors
Cells function by carefully orchestrating communication between proteins, often via post-translational modifications (PTMs). Dr. Mattoo’s team studies PTMs carried out by the evolutionarily conserved Fic (filamentation induced by cAMP) enzyme family. Predominant amongst these PTMs is AMPylation/adenylylation, which entails breakdown of ATP to add an AMP to the target protein. Dr. Mattoo’s group has discovered roles for AMPylation in microbial pathogenesis, mammalian stress response, and neurodegeneration (Parkinson’s Disease). By manipulating AMPylation, her team aims to intercept detrimental signals to promote cellular health.
Molecular Genetics of Plant Immunity - with emphasis on host defense response to necrotrophic fungi
Gene-to-Lead Drug Discovery
Protein assemblies, viruses, cryo-temperature fluorescence, cryo-electron tomography.
Structural biology, membrane proteins, protein folding, protein transport across membrane, protein import and trafficking, infectious diseases, pathogenic bacteria, multi-drug resistant bacteria, Gram-negative bacterial pathogens
Immune mechanisms of inflammatory diseases; T cell differentiation and function
In the Parkinson lab, we focus on the discovery of novel antibiotic and anticancer natural products from cryptic biosynthetic gene clusters found in soil dwelling
bacteria.
Computational chemistry and biological NMR
Microbial pathogenesis; host-parasite interactions; molecular detection and differentiation of microbial pathogens; recombinant and DNA vaccines
Entry of retroviruses and other enveloped viruses into cells; mechanism of enzymatic phosphoryl transfer
The Scarpelli Lab utilizes electromagnetic radiation as a diagnostic and therapeutic tool in medical applications. The lab’s near-term research aims to understand the biological effects of radiation and in particular the effects of cancer radiotherapy on the immune system. To facilitate this, the lab is developing medical imaging (MRI and PET) techniques to measure different aspects of the immune system, including quantification of macrophages and activated T cells.
Ecology of infectious disease in freshwater organisms (amphibians and zooplankton). We study how changes to the environment alter disease risk in individuals, populations, and communities.
1) Cyclic dinucleotide signaling in bacteria and immune cells. 2) Bacterial quorum sensing. 3) Inhibitors of protein kinases (examples are: FLT3, ABL1, ROCK1/2, LRRK2, RET, CDKs). 4) Novel antibacterial and anti-biofilm agents.
The main focus of the lab is mechanisms by which lipid-enveloped viruses (coronaviruses, filoviruses and paramyxoviruses) replicate via assembly and budding in human cells to form new virus particles.
The proteasome is a multiprotein, multicatalytic site complex that acts as the main pathway for protein degradation in cells. The Trader Lab research program focuses on the development of chemical strategies to control and harness proteasome-mediated protein degradation. Unlike traditional work in this field that has focused on the discovery of proteasome inhibitors, our program seeks to identify and apply compounds that enable us to stimulate, rescue and direct protein degradation.
Dr. Verma’s goal is to engineer human microbiomes for improving health. He aims to achieve this objective by understanding the principles of designing and assembling desired communities of microorganisms.
Organic synthesis, nanostructured materials science, self-assembly principles to produce exotic materials with physical or biomimetic function
Controlled drug delivery, bio-nanotechnology
Salmonella typhimurium Type III secretion; actin cytoskeleton rearrangements and bacteria-host interactions
