We seek to understand the molecular mechanisms of macromolecular assemblies that organize, express, and preserve the cell’s genetic information. We are particularly interested in developing kinetically accurate, atomic-resolution depictions of the dynamic assemblies that control DNA replication, gene regulation, and chromosome superstructure, and in exploiting this knowledge for chemotherapeutic development.
The Casero laboratory is interested in inflammation/infection-associated carcinogenesis and identifying molecular targets to be exploited in chemoprevention strategies. Spermine oxidase (SMOX) is one such target that is highly induced in several inflammatory conditions. SMOX produces DNA-damaging H2O2 and is linked to carcinogenesis. Studies are ongoing to target SMOX for chemoprevention.
My research focuses on the keratin filament cytoskeleton in epithelial cells with an emphasis on skin tissue. He is working to gain a better understanding of keratin genes at a mechanistic and molecular level. His laboratory discovered several novel functions for keratin proteins, including a role in regulating protein synthesis and epithelial cell growth during epithelial remodeling events. Dr. Coulombe’s research has led him to devise a therapeutic strategy for the treatment of epidermolysis bullosa simplex (EBS) and related disorders.
Research in the Culotta lab focuses on the role of metal ions and oxygen radicals in biology and disease. Metal ions such as copper, iron and manganese are not only trace nutrients but can be quite toxic. One mechanism of toxicity is through generation of free radicals or so-called reactive oxygen species (ROS) that have been implicated in numerous human disorders from neurodegeneration to cancer and aging to infectious disease. As part of our immune response we attack pathogens through metals and ROS, and successful pathogens have evolved clever ways to thwart these assaults by the host. Using a combination of biochemical, cell biology and molecular genetic approaches we are exploring how microbes and the animals the infect use weapons of metals and ROS at the host-pathogen battleground. Our current emphasis is on the Lyme disease bacterium Borrelia burdorferi and the opportunistic fungal pathogen, Candida albicans.
The Drummond-Barbosa lab investigates how whole-body physiology influences the activity of tissue-resident stem cells using the Drosophila ovary system. They are currently identifying adipocyte and brain factors that contribute to the control of germline stem cells and their differentiating progeny in response to changes in diet or other stimuli.
Dr. Ewald has spent the past decade developing imaging, genetic, and 3D organotypic culture techniques to enable real-time analysis of cell behavior and molecular function in breast cancer. As a graduate student in Scott Fraser’s Lab at Caltech he utilized his physics training to develop and apply novel light microscopy approaches to reveal cellular interactions within intact tissues in real-time. During Dr. Ewald’s postdoctoral studies in Zena Werb’s Lab at UCSF, he developed novel 3D organotypic culture and imaging techniques to reveal the cellular mechanisms and molecular regulation of morphogenesis in primary normal and neoplastic mammary epithelia. His laboratory seeks to understand how epithelial cancer cells escape their normal developmental constraints and acquire the ability to invade and disseminate into normal tissues.
Research in our laboratory is focused on the understanding of molecular mechanisms that regulate the mitochondrial contribution to programmed cell death and inflammation signaling. Both processes are fundamental to a variety of diseases, including cancer, neurodegeneration and infectious diseases. In this context we are specifically interested in mitochondrial autophagy and interorganellar interactions, including with the endolysosomal compartment. We are applying a combination of fluorescence microscopy, molecular and cell biological, and biochemical approaches. Our studies aim at uncovering novel cell biological insights that can be exploited to combat diseases.
Research in the Jordan laboratory focuses on understanding the molecular mechanisms regulating DNA repair, chromosome segregation and cell cycle progression. Their lab studies the importance of Structural Maintenance of Chromosomes (SMC) complexes and cell cycle kinases, particularly Polo-like (PLK) kinases and Aurora kinases. The Jordan lab uses mouse and human pluripotent stem cells to help define the function of these proteins within essential molecular pathways of the cell. They also use mouse as a model organism to study consequences of gene mutation and chromosome missegregation, which give rise to physical and mental developmental defects, infertility and cancer predisposition. Current research from the Jordan laboratory encompasses the following:
1) Gametogenesis (spermatogenesis and oogenesis)
2) Pluripotent stem cell preservation, proliferation, and differentiation
My laboratory aims to understand the molecular mechanisms regulating eukaryotic signaling of pathways. This knowledge provides the framework needed to interpret how alterations to a pathway, such as additional proteins, mutations to pathway components, or small molecules, modulate activity and could help guide targeted therapies. To achieve this, my lab employs a multi-prong approach that combines cell-based assays, biochemistry, enzymology, biophysics, and structural biology.
The Laiho lab seeks to understand the regulatory events that are derailed in cancers, and to detect and exploit cancer cell characteristics that could be used as basis of new cancer therapies. Our major focus is on RNA polymerase I transcription and new therapeutic agents targeting this abundantly deregulated process in cancers.
Laboratory of Gene Regulation
Gene regulation: Using multi-disciplinary and quantitative imaging, genomics and proteomics approaches, my lab uncovers novel roles of non-coding RNAs, non-membranous granules, and post-translational modifications.
Technology development: My lab develops proteomics and informatics tools to dissect the roles of a post-translational modification called ADP-ribosylation.
Disease focus: My lab seeks to translate our basic scientific findings to therapy, e.g., PARP inhibitor in cancers and Chikungunya viral infection.
Research in the Matunis laboratory is focused on understanding the molecular mechanisms regulating the modification of proteins by the small ubiquitin-related modifier (SUMO) and the consequences of SUMOylation in relation to protein function, cell behavior and ultimately, human disease. Particular interests include understanding how SUMOylation regulates cell cycle progression, DNA repair, nuclear import and export, and cell stress response pathways. We study SUMOylation in mammalian cells, yeast and the malaria parasite, P. facliparum using a variety of in vitro biochemical approaches, in vivo cellular approaches and genetics.
The Meeker laboratory is located at the Johns Hopkins University School of Medicine. Utilizing a combination of tissue-based, cell-based, and molecular approaches, our research goals focus on abnormal telomere biology as it relates to cancer initiation and tumor progression, with a particular interest in the Alternative Lengthening of Telomeres (ALT) phenotype. In addition, our laboratories focus on cancer biomarker discovery and validation with the ultimate aim to utilize these novel tissue-based biomarkers to improve individualized prevention, detection, and treatment strategies.
Malaria parasites contain an essential organelle called the apicoplast, which is thought to have stemmed from endosymbiosis of an algal cell, which previously incorporated a cyanobacterium. Due to its prokaryotic origin, the apicoplast contains a range of metabolic pathways that greatly differ from those of the human host. Dr. Prigge’s lab is investigating biochemical pathways found in the apicoplast, particularly those required for the biosynthesis and modification of fatty acids. This metabolism should require several enzyme cofactors such as pantothenate, lipoic acid, biotin and iron-sulfur clusters. Their focus is on these cofactors, how they are acquired, how they are used and whether they are essential for the growth of blood stage malaria parasites. Dr. Prigge and his team approach these questions with a combination of cell biology, genetic, biophysical and biochemical techniques.
My research work focuses on various aspects of breast carcinogenesis, particularly the molecular and hormonal mechanisms underlying breast tumor growth, epithelial-mesenchymal transition, invasion, migration and breast cancer prevention. My studies have established important markers for development of acquired tamoxifen resistance. We are actively investigating novel molecular targets and pathways involved in chemopreventive role of bioactive components.
The Sinnis Laboratory studies the sporozoite stage of Plasmodium, the causative agent of malaria. The impressive journey of sporozoites, from the midgut wall of the mosquito where they emerge from oocysts, to their final destination in the mammalian liver, is the major focus of our investigations. Using classic biochemistry, mutational analysis, intravital imaging, and other assays that we and others have developed, we aim to understand the molecular interactions between sporozoites and their mosquito and mammalian hosts that lead to the establishment of malaria infection.
My laboratory is broadly interested in how dNTP pool levels and composition influence genetic stability, adaptive and innate immunity, inflammation, carcinogenesis, cellular senescence and aging. Current work in the lab focuses on two key aspects of dNTP metabolism. We are elucidating how the uniquely high concentration of dUTP in resting immune cells is used as a potent HIV-1 restriction factor in macrophages. We are also interested in the epigenetic effects of uracil when it is present in DNA. Our long-range goal is to design novel small molecules that predictably alter the make up of nucleotide pools in cells for antiviral, anticancer, and anti-inflammatory therapeutic uses.
Neurodegeneration is a poorly understood biomedical phenomenon and a major public health challenge in our increasingly aging society. Our goal is to describe at the molecular and cellular levels how specific neurons degenerate, how protein folding and misfolding operate in the cell, and how protective systems fail at disease stages.
My research activities focus on defining the environmental and genetic determinants of allergic airway diseases such as asthma. My lab members and I have specifically explored the role of CD4+ Th2 cells and cytokines (IL-13), and innate immune pathways (complement activation pathways, TLRs, CLRs), in the pathogenesis of asthma. I have made substantial contributions to our understanding of the molecular mechanisms underlying allergenicity of common allergens-specifically how allergens and airborne pollutants activate innate immune pathways through molecular mimicry (Nature). More recently, I have turned my attention to how the gut microbiome alters susceptibility to allergen and PM-induced asthma.