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.

Dr. Bunz’s research objective is to understand how stress-activated signaling pathways affect the cellular responses to anti-cancer therapy. A longstanding interest is p53, a central node within a complex network of DNA damage-response pathways involved in tumor suppression. It is well-known that cancer associated p53 mutations impact the efficacy of DNA damage-based anticancer therapies, such as radiotherapy. It is now apparent that p53 also controls immune recognition, and thereby influences the efficacy of immune-based therapies. Recent work in the lab is focused on understanding the mechanistic basis for these effects, and on the development of therapeutic viral agents that can stimulate neoantigen-specific anti-cancer immune responses. The long-term goal is to better understand how current therapies work, and to develop new and improved cancer treatments.

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.

Jennifer Elisseeff’s initial research efforts focused on the development of biomaterials for studying stem cells and designing regenerative medicine technologies for application in orthopedics, plastic and reconstructive surgery, and ophthalmology. In clinical translation of these technologies, the group recognized the importance of the immune response in regenerative medicine responses. This led to a significant shift in research efforts to biomaterials-directed regenerative immunology and leveraging the adaptive immune system to promote tissue repair. The group is now characterizing the immune and stromal environments of healing versus non-healing wounds and tumors. Biomaterials are now being applied to model and manipulate tissue environments and studying the impact of systemic and environmental factors such as aging and senescent cells, sex differences, and infection/microbiome on tissue repair and homeostasis.

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.

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 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.

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.

Dr. Pienta is involved in research to study prostate cancer metastases and tumor resistance. Research projects utilize ecological principles to understand how cancer cells interact with the other cancer cells and host cells in the tumor microenvironment. The lab is currently focusing its efforts on understanding the role of polyaneuploid cancer cells in metastasis and therapeutic resistance.

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.

Malaria, a disease caused by protozoan parasites, is one of the most dangerous infectious diseases, claiming millions of lives and infecting hundreds of millions of people annually. Malaria parasites contain an essential organelle called the apicoplast that is thought to have arisen through endosymbiosis of an algal cell which had previously incorporated a cyanobacterium. Due to its prokaryotic origin, the apicoplast contains a range of metabolic pathways that differ significantly from those of the human host. We are 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. We are interested in these cofactors, how they are acquired, how they are used, and whether they are essential for the growth of blood stage or liver stage malaria parasites. We 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. 

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.

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.

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.