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.

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.

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.

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.

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. Jaffee’s laboratory focuses on mechanisms of sensitivity and resistance to immune based therapies in mouse models and human models of pancreatic cancer. Areas of specific interest include understanding the inflammatory responses that are associated with cancer development and progression in pre-clinical and clinical models, and development of interventions to bypass specific inflammatory signals. Current projects aim to understand the pancreatic cancer tumor micro-environment and the inflammation that helps shape the tumor micro-environment early, beginning with the pre-malignant changes that are linked to the driver gene changes known to initiate pancreatic cancers (mutated Kras and p53). Her work is driving the discovery of pancreatic cancer immunobiology, and these findings are quickly being translated into immunotherapies that are showing promise for this previously immune resistant cancer. Further, she is using state of the art technologies to dissect the tumor microenvironment in mice and pancreatic cancer patients.

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 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.
 

Our primary research interest lies at the interface between chemistry, biology, and medicine. We employ high-throughput screening to identify modulators of various cellular processes and pathways that have been implicated in human diseases from cancer to autoimmune diseases. Once biologically active inhibitors are identified, they will serve both as probes of the biological processes of interest and as leads for the development of new drugs for treating human diseases.

Among the biological processes of interest are cancer cell growth and apoptosis, angiogenesis, calcium-dependent signaling pathways, eukaryotic transcription and translation.

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.

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.

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.

My laboratory studies how the gut microbiota influences disease pathogenesis. Our two areas of focus are determining how specific bacteria or communities of bacteria contribute to colon cancer and responses to immune checkpoint immunotherapy. As a pathogenesis laboratory, we use multiple approaches to achieve our goals including studies in humans and mouse models, microbiology, bioinformatics and immunologic methods. We also have an increasing interest in metabolites influencing host:microbial interactions. We hope to contribute to ways to prevent colon cancer and to improve immunotherapy outcomes for patients.  

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.  

Dr. Smith’s lab focuses on defining the functional programming of tumor-specific CD4+ and CD8+ T cells as it relates to response to immunotherapy. Owing to her interest and expertise in this area, her lab has collaborated with many clinicians within Johns Hopkins and at outside institutions on immunotherapy clinical trials aimed at improving treatment options, preventing disease recurrence, and understanding the predictors of response to treatment in both early and advanced-stage disease.

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.

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.