Protein trafficking and membrane transport in relation to the processes of cell polarity establishment and carcinogenic transformation
The role of protein phosphatases in regulating cellular plasticity and therapeutic resistance in cancer
Epigenetic mechanisms in liver cancer pathogenesis due to chronic infection with the Hepatitis B Virus.
Obesity is associated with an increased risk of and/or mortality from several forms of cancer, including breast and colon cancer. Given that obesity rates in the U.S. are now approaching 40%, the development of mechanism-based interventions for this population could have a significant impact on public health. My research program focuses on investigating the molecular mechanisms linking obesity with increased breast and colon cancer risk and progression, with the goal of developing dietary and pharmaceutical interventions that reduce risk and improve prognoses in the obese patient population.
Role of histone methylation in gene expression and oncogenesis
Cell and developmental biology, membrane trafficking, molecular genetics, cell polarity
Structure and function of large protein complexes; Cryo-electron microscopy.
Chemical Immunology: Cell specific chemical perturbation of immune microenvironments in cancer, neurological and immunological disorders
Our major goal is to understand how the misregulation of chromatin leads to cancer progression. A major focus for the lab is on chromatin targeting subunits of chromatin remodeling complexes, in particular the heterogeneous collection of SWI/SNF chromatin remodeling complexes. We have determined that Polybromo 1 (PBRM1), a chromatin targeting subunit of the PBAF subcomplex, is important for the transcription of stress response genes in renal cancer, and that BRD9, a chromatin targeting subunit of the recently characterized GBAF (or ncBAF) subcomplex, is required for androgen receptor signaling in prostate cancer. Another focus of the lab is on the CBX chromatin targeting subunit of Polycomb repressive complex 1, which is represented by five CBX paralogs in mammals. We have made significant progress in establishing glioblastoma's dependence on CBX8 expression for viability, defining downstream targets of CBX8, and defining the contribution of the chromodomain to CBX8 targeting. Our current goal is to use our recently developed CBX8 inhibitors in combination with biochemical and proteomic approaches to connect paralog-specific biochemical function for CBX8 to a paralog-specific role in glioblastoma.
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.
Environmental and molecular toxicology (developmental toxicology, developmental neurotoxicology, neurotoxicology), Developmental origin of health and disease, Genome and epigenome alterations, Molecular cytogenetics, Neuroendocrine dysfunction, Neurodegenerative diseases, Toxicogenomics, Zebrafish model system
Regulation of gene expression by epigenetic mechanisms has emerged as a fundamental process that controls mammalian development and normal function. Epigenetic mechanism constitutes DNA methylation, post translational modification of histone tails, chromatin conformation and non-coding RNA. The histone tail modifications and DNA methylation are established and maintained by various enzymes which include methyltransferases. The expression and activity of these enzymes particularly the DNA methyltransferases (DNMTs) is subjected to a tight regulation during development and in somatic cells. Research in Gowher lab is largely focused on unravelling mechanism/s that regulate the expression and activity of the mammalian DNA methyltransferases during development and in diseased state. Dr. Gowher has published 37 peer-reviewed publications in the field of epigenetics. Most of her work has focused on questions related to DNA methylation, including the specificity of Dnmts, their distinct functions, and interactions with other epigenetic regulators. All these studies are performed using innovative biochemistry and molecular biology techniques, which include high throughput Bisulphite-sequencing (Bis-SEQ), Chromatin Immunoprecipitation-sequencing (ChIP-SEQ), RNA-SEQ and Mass Spectrometry. The lab is currently funded for four major projects. 1) Regulation of enhancer activity by cross talk of chromatin modifiers and Dmt3A and 3B; 2) Role of chromatin configuration (enhancer-promoter interactions) in regulation of DNMT3A and DNMT3B activity; 3) Mechanism by which Vezf1 regulates gene expression during endothelial differentiation and angiogenesis; 4) co-regulation of DNMT3B transcription and alternative splicing by its upstream enhancer and non-coding RNA.
Macromolecular sequences and the evolution, structure and function of molecules; databases and computational tools for functional genomics
The Hall lab is generally interested in mechanisms cell cycle control that protect genome stability. Our work provides insight into how normal cells maintain genome fidelity during the complex process of cell division and how defects in the regulation of cell division can lead to various forms of genome instability and disease, including cancer.
We study the initiation, progression, and metastasis of vascular sarcomas with a focus on the role of microRNAs.
Systems biology investigation of eukaryotic N-terminal methylation. Metabolomics and chemogenomics analysis of Candida albicans gastrointestinal colonization. Chemogenomics of Candida and Saccharomyces.
Multidrug resistance in human cancer
Biological roles of miRNAs and their use as cancer therapeutics
Epigenetics, Impacts of Chromatin on Gene Expression, DNA Replication & DNA Repair
bio-organic chemistry, bioconjugate chemistry, in vitro evolution, drug discovery
Skeletal muscle and adipose tissue stem cells, regeneration, muscular dystrophy, obesity, type 2 diabetes, aging.
Development of mass spectrometry imaging for mapping lipids, metabolites, proteins in biological samples.
Immunotherapy, A regulatory mechanism of anti-tumor immunity, A resistance mechanism of target therapy and/or immunotherapy, Antibody engineering
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.
Cardiovascular disease is a growing problem worldwide and the leading cause of death in the United States. Phospholipase C (PLC) enzymes, in particular PLCβ and PLCε, are essential for normal cardiovascular function. These proteins generate second messengers that regulate the concentration of intracellular calcium and the activation of protein kinase C (PKC). Dysregulation of calcium levels and PKC activity can result in cardiovascular diseases and heart failure. A new direction of research being explored is to understand how PLCε also functions as a tumor suppressor in certain cancers. We use an innovative combination of X-ray crystallography, electron microscopy, small angle X-ray scattering, and atomic force microscopy to gain structural insights into phospholipase C (PLC) regulation and activation. Structure-based hypotheses are validated through functional assays and cell-based assays, and ultimately whole animal studies. Our studies will aid in the identification and development of novel chemical probes that could be used to study the roles of PLCε in disease and serve as lead compounds for new therapeutics in cardiovascular disease and cancer.
MDM2, p53, cerebellar development and tumorigenesis, mouse models of human disease
Our research addresses cancer health racial disparity, focusing on aggressive triple-negative breast cancer that affects predominantly black women.
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
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.
Our research group is deeply interested in unraveling the molecular mechanisms of cancer and Alzheimer's Disease in cells, animal models and human diseased tissues, with the goal of identifying novel therapeutic targets, which can be targeted independently or in combination to prevent or treat human diseases.
Macromolecular structure and assembly using X-ray crystallography; membrane associated proteins; enzyme structure and function
Proteomics and biological mass spectrometry
The focus of our research is to investigate the basic cellular mechanisms involved in regulating energy and lipid metabolism, including the roles that the enzyme pyruvate carboxylase (PC; in metastasis promotion) and vitamin D (in cancer prevention) play in stages during the development of cancer, including metastases.
We primarily study the molecular basis of GPCR-mediated signal transduction, principally via the techniques of X-ray crystallography and single particle electron microscopy. By determining atomic structures of signaling proteins alone and in complex with their various targets, we can provide important insights into the molecular basis of signal transduction and how diseases result from dysfunctional regulation. The lab is also interested in rational drug design and the development of biotherapeutic enzymes.
Signal transduction in development; mechanisms of robustness, cell fate decisions, and tissue patterning by morphogen gradients
Metastatic breast cancer, cell plasticity, and drug resistance.
1. Structures and functions of DNA G-quadruplex secondary structures. We seek to understand the molecular structures and cellular functions of the biologically relevant DNA G-quadruplexes, including those formed in the promoter regions of human oncogenes such as MYC, BCL-2, and PDGFR-b, as well as in human telomeres. 2. Protein interactions of G-quadruplexes. We work to understand the structures and cellular functions of proteins that interact with DNA G-quadruplexes, and their therapeutic targeting. 3. Targeting G-quadruplexes for anticancer drug development. DNA G-quadruplexes are emerging as a new class of cancer-specific molecular targets. We seek to discover small molecular anticancer drugs that target the DNA G-quadruplexes for oncogene suppression (e.g. MYC). We hope to combine the potency of DNA-interactive anticancer drugs with the selectivity properties of molecular-targeted approaches. 4. Structure-based rational drug design. We use structure-based rational design in combination with structural biology, biophysical, biochemical, and cellular methods for our drug development efforts. 5. Topoisomerases’ and transcription factors’ inhibitors.
Phytohormone ethylene biosynthesis and its signaling pathway in Arabidopsis thaliana
Cancer genetics and genomics, Developmental Biology.
Protein tyrosine phosphatases, cellular signaling mechanism, cancer biology, chemical and structural biology, drug discovery, protein structure and function.
