I am interested in cutaneous squamous cell carcinoma, the second most common malignancy with 800,000 cases diagnosed in the US each year. These tumors are the most common malignancy arising in solid organ transplant recipients and more aggressive in immunosuppressed patients. As a practicing dermatologic surgeon, I collect tumors from my patients to aid in the study of the molecular mechanisms of this cancer.

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 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.

Our laboratory studies the molecular and cellular mechanisms underlying the perception of pain under healthy conditions and in the setting of pathology. Towards this goal, we utilize a wide spectrum of approaches including behavioral analysis, in vivo and in vitro imaging and electrophysiology, genome editing, image analysis, transcriptomics, biochemistry, and cell biology. We have four topics of study. First, the identification of mechanisms underlying pain in a diverse collection of rare hereditary skin conditions known as palmoplantar keratodermas. Second, how injured and uninjured neurons interact and change their behavior following a peripheral nerve injury, and how these changes relate to neuropathic pain. Third, the role of RNA binding proteins as regulators of the development and maintenance of neuropathic pain. And forth, using synthetic biology approaches to re-engineer signal transduction pathways in order to convert signals that would have promoted pain into analgesic signals.

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. 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.

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.

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 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.

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.

Research in my laboratory focuses on understanding the cellular and molecular mechanisms that control immune responses, with a particular emphasis on how metabolism governs this process. Currently our work is focused on the role of metabolism in T cell differentiation and function, as well as in regulating other immune cell types, such as macrophages. My laboratory is committed to using a wide variety of approaches to address key questions in immune cell metabolism in vitro and in vivo, and how this impacts protective immunity to infection and cancer. We hope that our work will allow us to develop new ways to target immune cell longevity, differentiation, and function through metabolism, with a long-term goal of mitigating human disease.

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.

The Rebecca laboratory focuses on understanding genetic and non-genetic mechanisms of therapy resistance and metastasis leveraged by cancer cells, using acral lentiginous melanoma as a paradigm. Their particular focus is on stem cell-like tumor cell subpopulations of melanoma cells that “hijack” developmental signaling cassettes to drive transient metastatic and drug resistant cell states. Their studies encompass quantitative tools, genetic editing, molecular biology, in vivo patient-derived xenograft therapy trials and bioinformatic analyses to arrive at a comprehensive understanding of actionable vulnerabilities for stem cell-like subpopulations of cancer cells.

Dr. Sharma’s laboratory focuses on elucidating the molecular mechanisms underlying breast cancer initiation and progression and developing various preventive and treatment strategies using mouse models and human samples. Areas of specific interest include understanding the molecular connections between breast cancer and obesity, racial disparities, and microbial dysbiosis. Better mechanistic understanding regarding various aspects of cancer initiation and metastatic progression can pave the way to reduce breast cancer related mortality.  

The Sinnis Laboratory studies the sporozoite stage of Plasmodium, the infectious stage of the malaria parasite, inoculated by mosquitoes into the mammalian host. 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 proteomics, 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 elucidating how the dNTPase and DNA/RNA binding activities of the enzyme SAMHD1 lead to HIV-1 restriction in macrophages, anticancer drug resistance, and cellular DNA repair. Our long-range goal is to design novel small molecules that inhibit or activate the various activities of SAMHD1 in cells for antiviral, anticancer, and anti-inflammatory therapeutic uses.

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.

My laboratory focuses on trying to unravel the molecular mechanisms that lead to metastatic progression and therapy resistance. We are investigating the link between changes in the tumor microenvironment and melanoma progression, and further, how these changes may affect response to therapy. More recently, we have become very interested in how the aging microenvironment guides changes leading to increased metastasis and therapy resistance, as well as cell-autonomous aspects of therapy resistance, and have demonstrated that normal age-related changes in the microenvironment can contribute to multiple aspects of melanomagenesis and therapy resistance.

Dr. Wirtz studies the biophysical properties of healthy and diseased cells, including interactions between adjacent cells and the role of cellular architecture on nuclear shape and gene expression. He has developed and applied particle tracking methods to probe the micromechanical properties of living cells in normal conditions and disease state. His lab conducts groundbreaking research in the areas of cell motility, tumorigenesis and cancer metastasis, extracellular vesicles, digital pathology, machine learning applications to biological images, and immunology.