Research in the Casero Laboratory is focused on the role of polyamines and polyamine metabolism in disease, including cancer. My laboratory studies polyamine metabolic enzymes that are important in disease etiology and drug response, and are the molecular links between inflammation, DNA damage, epigenetic changes, and carcinogenesis. My laboratory is also exploring the ability of combining polyamine depletion with epigenetically-targeted drugs to enhance antitumor immune response and our results indicate a promising new avenue to treat cancer. Finally, my laboratory is interested in genetic alterations in the polyamine pathway that lead to disease. One such disease is the X-linked Snyder-Robison Syndrome, which results in aberrant polyamine profiles. We have identified possible treatment strategies for this syndrome.

The Cai lab focuses on understanding how the transcription process is regulated in normal and cancer cells. We are intrigued by the discoveries in our lab that many transcription factors involved in cancers can form small, liquid-like condensates in the nucleus to activate transcription. Our results are consistent with an emerging and paradigm-shifting view in biology: many biochemical reactions inside the living cell are organized in liquid-like condensates formed by weak protein and nucleic acid interactions. This implies that the material states as well as the components of cellular assemblies matter for their functions. We develop and employ many cutting-edge imaging tools in the lab, such as super resolution microscopy, single particle tracking, and optogenetics. By studying these condensates, we hope to understand how transcription is differentially organized in normal and cancer cells, and how we can target these condensates for cancer therapies.

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 essential micronutrients for both microbial pathogens and their animal hosts, and during infection, a tug of war for these nutrients ensues at the host-pathogen interface. As part of our immune response, we withhold essential metals from pathogens and also bombard them with free radicals or so-called reactive oxygen species (ROS). 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 their animal hosts use weapons of metals and ROS at the infection battleground. Our current emphasis is on pathogenic fungi including the most prevalent human fungal pathogen, Candida albicans and the emerging “superbug” fungal pathogen, Candida auris.

The Dang lab contributed to defining the function of the MYC oncogene including establishing the first mechanistic link between MYC and cellular energy metabolism. This foundational concept that genetic alterations in cancers re-program fuel utilization by tumors provides a framework to develop novel strategies for cancer therapy. Current lab interests include seeking metabolic vulnerabilities of cancer and define how the circadian molecular clock influences cancer metabolism, immunity, tumorigenesis and therapeutic resistance. The molecular and metabolic basis for pancreatic cancer cell immune evasion is an ongoing area of investigation.

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. 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.

Dr. Fertig directs an NCI-funded hybrid computational and experimental lab in the systems biology of cancer and therapeutic response for a new predictive medicine paradigm. Her wet lab develops time course models of therapeutic resistance and performs single cell technology development. Her computational methods blend mathematical modeling and artificial intelligence to determine the biomarkers and molecular mechanisms of therapeutic resistance from multi-platform genomics data. These techniques have broad applicability beyond her resistance models, including notably to the analysis of clinical biospecimens, developmental biology, and neuroscience. 

Our lab is part of the Women’s Malignancy Program at the Johns Hopkins School of Medicine. Our research is focused on cancer metastasis. Of all deaths attributed to cancer, 90% are due to metastasis, and treatments that prevent or cure metastasis remain elusive. Emerging data indicate that low oxygen tension (hypoxia), which occurs in most solid tumors, alters the biophysical and biochemical parameters of the extracellular matrix within a tumor. Our work is focused on how these alterations provide cells with a license to metastasize. We are a dynamic and creative lab group that always likes a good challenge. We use 2D and 3D model systems for in vitro investigations. We have also generated novel transgenic mice for metastasis studies in vivo. Our goal is to prevent any future deaths due to breast cancer.

The ribosome is a complex molecular machine that translates the genetic code into functional polypeptides. Our research focuses on understanding how the ribosome functions at a molecular level and how changes in its activity lead to mRNA quality control and the induction of cellular stress responses. Work in the Green lab ranges widely in scope, from detailed mechanistic questions in ribosome rescue to surveying global changes in gene expression and dissecting the complex interplay of mammalian signaling pathways.

Dr. Stephanie Hicks’ research interests focus around developing statistical methodology, and open-source software for biomedical data analysis, which often contains noisy or missing data and systematic biases. Her research addresses statistical challenges in epigenomics, single-cell genomics, and spatial transcriptomics to improve quantification and understanding of biological variability. She has developed fast, accurate and widely used statistical methods and software for single-cell RNA-sequencing data analysis with applications that include investigating high-grade serous ovarian cancer, high-grade glioma childhood cancer, and chronic myeloid leukemia cancer.

The Jenkins-Lord Laboratory focuses on understanding the molecular consequences of breast cancer disparities in African American women. This is accomplished through investigating the interplay between the molecular, genetic, environmental, and social contributors to breast cancer risk, and how these impact cancer outcomes in this population. Additionally, we have a special interest in characterizing how the immune microenvironment and gene expression are modulated in breast cancer based on this increased socio-environmental risk.

Cancer is a leading cause of death and morbidity in the United States and this problem is expected to grow as our life expectancy increases. Our laboratory has focused on the genetics of human cancer with a particular emphasis on exploring how inherited and somatic mutations can improve the clinical management of cancer. We have identified over a dozen cancer driver genes and the hereditary basis of several cancer predisposition syndromes. We have also developed several novel technologies to facilitate our studies of cancer. In particular we have focused on the development of digital genomic methods for detecting trace levels of tumor DNA. Most recently, we have focused on applying the above advances to the early detection of cancer and cancer immunotherapy.

The Leung Lab studies gene regulation using multi-disciplinary and quantitative imaging, genomics and proteomics approaches, to uncover novel roles of RNA metabolism, biomolecular condensates, and post-translational modifications.

We develop technology, such as proteomic and single-molecule tools to dissect the roles of a post-translational modification called ADP-ribosylation. My lab seeks to translate our basic scientific findings to disease therapy, e.g., PARP inhibitors in cancers and macrodomain inhibitors to fight Chikungunya viral infection and COVID-19.

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 damage repair, nuclear import and export, and cell stress response pathways. We have studied 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 Nayar laboratory aims to understand the underlying mechanism(s) by which a tumor becomes resistant to targeted therapy, employing this subset of breast cancer as a model. In particular, the lab is interested in mechanisms underlying the emergence and maintenance of resistant subpopulations within tumors, genetic and epigenetic drivers of resistance, and the identification of new therapeutic vulnerabilities in targeted therapy-resistant tumors. To this end, the laboratory leverages cell and molecular biology, animal models, functional genomics tools, and high-throughput screening methodologies to understand resistance to targeted inhibitors in advanced metastatic breast cancer.

My laboratory investigates the fundamental impact of epigenomic context on genome maintenance and its contribution to malignant transformation and overall cell function. Using a combination of molecular biology, imaging, genomics, cell-based approaches, and mouse models, we have uncovered a critical role for the splicing-regulated macroH2A1 histone variant in DSB repair pathway choice, fragile site integrity and telomere maintenance. Our ongoing research aims to 1) dissect the implications of macroH2A1 splice variant imbalance – and chromatin context more generally – for genome integrity, malignant transformation and tumor cell sensitivity to genotoxic agents; and 2) examine the contribution of a newly emerging aspect of chromatin structure, the modification of nuclear RNAs, to DNA repair and genome instability.

My laboratory is interested in the molecular mechanisms by which cells interpret signals from their environment that instruct them to proliferate, differentiate, or die by apoptosis.  A particular focus of the lab is the regulation of NF-κB, a pleiotropic transcription factor that is required for normal innate and adaptive immunity and which is inappropriately activated in several types of human cancer.

My group currently focuses on identifying genetic alterations in cancer affecting sensitivity and resistance to targeted therapies, and connecting such changes to key clinical characteristics and novel therapeutic approaches. We have recently developed methods that allow non-invasive characterization of cancer, including the PARE method that provided the first whole genome analysis of tumor DNA in the circulation of cancer patients. These analyses provide a window into real-time genomic analyses of cancer patients and provide new avenues for personalized diagnostic and therapeutic intervention.

Our research focuses on the role of transcriptional and epigenetic regulators in normal and cancer development, and in therapeutic response. We are passionate about asking clinically relevant questions, translating basic laboratory findings into therapeutic applications to benefit cancer patients, and providing new insights into how epigenetic regulators regulate transcription and dictate cell identity. The Toska lab uses a multidisciplinary approach integrating biochemistry, cell signaling, genomics and epigenomics at bulk and single cell level, organoid technology, and mouse genetics.

Our laboratory is interested in investigating the signal transduction and gene regulation in bacterial infection- and genotoxic stress-associated colonic inflammation and tumorigenesis, using a combination of genetic, immunological, molecular, and cellular approaches. We are studying the molecular/cellular mechanisms and pathophysiological significance of the novel and critical pathogen-host interactions and DNA damage responses that can be mechanistically linked to colon cancer etiology in mice and humans. 

The Wang lab is interested in the biological basis for protein and RNA homeostasis in neurodegeneration. We hope to solve problems that not only have biological significance but also have important implications for understanding and treating disease. Our work focuses on three main areas: discovering key regulators of protein homeostasis, uncovering novel players in the regulation of RNA homeostasis, and revealing the mechanisms of neurodegenerative diseases including those caused by repeat expansions.

We are an interdisciplinary team using the tools of biophysics, biochemistry, genetics, molecular and structural biology to elucidate the structure and function of chromatin, the native state of the genome in association with proteins and RNAs. This ‘epigenome’ carries the blueprint of gene expression programs directing cell growth, homeostasis and differentiation throughout plant and animal life. Our basic studies are highly relevant to medicine as genetic mutations and dysfunctions of the epigenome underlie many human diseases.