Dr. Yegnasubramanian directs a Laboratory of Cancer Molecular Genetics and Epigenetics at the Sidney Kimmel Comprehensive Cancer Center (SKCCC), and is also the Director of the SKCCC Next Generation Sequencing Center. Our lab research is focused on understanding the complex interplay between genetic and epigenetic alterations in carcinogenesis and disease progression, and to exploit this understanding in developing novel biomarkers for diagnosis and risk stratification as well as in identifying targets for therapeutic intervention.

The Jonathan Zenilman lab conducts research related to sexually transmitted diseases (STDs). We are working to develop biological markers for sexual behavior to use in other research. The lab studies sexual risk behaviors in highly vulnerable populations and studies datasets from the Baltimore City Health Department to understand STD trends and behaviors. Additionally, we study nosocomial infections at Johns Hopkins Bayview Medical Center, with a focus on developing an antimicrobial control program. We also conduct clinical research related to the natural history and microbiology of chronic wounds in the outpatient setting.

The Kenneth J. Pienta laboratory has championed the concept that cancer tumorigenesis and metastasis can best be understood utilizing the principles of Ecology. As a result, the Pienta laboratory is working to develop new treatments for cancer utilizing network disruption.

Our Molecular Oncology lab seeks to understand the genomic wiring of response and resistance to immunotherapy through integrative genomic, transcriptomic, single-cell and liquid biopsy analyses of tumor and immune evolution. Through comprehensive exome-wide sequence and genome-wide structural genomic analyses we have discovered that tumor cells evade immune surveillance by elimination of immunogenic mutations and associated neoantigens through chromosomal deletions. Additionally, we have developed non-invasive molecular platforms that incorporate ultra-sensitive measurements of circulating cell-free tumor DNA (ctDNA) to assess clonal dynamics during immunotherapy. These approaches have revealed distinct dynamic ctDNA and T cell repertoire patterns of clinical response and resistance that are superior to radiographic response assessments. Our work has provided the foundation for a molecular response-adaptive clinical trial, where therapeutic decisions are made not based on imaging but based on molecular responses derived from liquid biopsies. Overall, our group focuses on studying the temporal and spatial order of the metastatic and immune cascade under the selective pressure of immune checkpoint blockade with the ultimate goal to translate this knowledge into “next-generation” clinical trials and change the way oncologists select patients for immunotherapy.

The Pathak lab is within the Division of Cancer Imaging Research in the Department of Radiology and Radiological Science. We develop novel imaging methods, computational models and visualization tools to ‘make visible’ critical aspects of cancer, stroke and neurobiology. Our research broadly encompasses the following areas: Functional and Molecular Imaging; Clinical Biomarker Development; Image-based Systems Biology and Visualization and Computational Tools. We are dedicated to mentoring the next generation of imagers, biomedical engineers and visualizers. Additional information can be found at www.pathaklab.org or by emailing Dr. Pathak.

Allen Everett, M.D., and his colleagues are identifying new biomarkers — measurable, physical signs — to help in identifying pediatric heart disease. Everett is the program leader at Johns Hopkins in pediatric biomarker discovery, initially in sickle cell disease and subsequently in other pediatric clinical conditions (birth injury, congenital heart disease repair, ECMO, prematurity and pulmonary hypertension).

The Jean Kim Laboratory performs translational research in the area of chronic rhinosinusitis, with a niche interest in the pathogenesis of hyperplastic nasal polyposis. Studies encompass clinical research to basic wet laboratory research in studying the underlying immune and autoimmune mediated mechanism of polyp growth and perpetuation of disease. Human cell and tissue culture models are used. Techniques in the laboratory include cell and tissue culture, real time PCR, immunoblot, ELISA, flow cytometry, immunohistochemistry, electron microscopy, gene array analysis, and other molecular approaches including genetic knockdowns. Approaches used in Dr. Kim’s clinical study designs include prospective and retrospective analysis of patient outcomes and clinical biomarkers, as wells controlled clinical trials.

The main research interests of the James Hamilton Lab are the molecular pathogenesis of hepatocellular carcinoma and the development of molecular markers to help diagnose and manage cancer of the liver. In addition, we are investigating biomarkers for early diagnosis, prognosis and response to various treatment modalities. Results of this study will provide a molecular classification of HCC and allow us to identify targets for chemoprevention and treatment. Specifically, we extract genomic DNA and total RNA from liver tissues and use this genetic material for methylation-specific PCR (MSP), cDNA microarray, microRNA microarray and genomic DNA methylation array experiments.

Dr. Ross and his research team have focused on Huntington's disease and Parkinson's disease, and now are using insights from these disorders to approach more complex diseases such as schizophrenia and bipolar disorder. They use biophysical and biochemical techniques, cell models, and transgenic mouse models to understand disease processes, and to provide targets for development of rational therapeutics. These then can provide a basis for developing small molecule interventions, which can be used both as probes to study biology, and if they have favorable drug-like properties, for potential therapeutic development. We have used two strategies for identifying lead compounds. The first is the traditional path of identification of specific molecular targets, such as enzymes like the LRRK2 kinase of Parkinson’s disease. Once structure is known, computational approaches or fragment based lead discovery, in collaboration, can be used. The second is to conduct phenotypic screens using cell models, or in a collaboration, natural products in a yeast model. Once a lead compound is identified, we use cell models for initial tests of compounds, then generate analogs, and take compounds that look promising to preclinical therapeutic studies in animal models. The ultimate goal is to develop therapeutic strategies that can be brought to human clinical trials, and we have pioneered in developing biomarkers and genetic testing for developing strategies.

The Bigos Lab focuses on a Precision Medicine approach to the treatment of psychiatric illness. In addition, this lab employs functional neuroimaging and genetics as biomarkers in neuropsychiatric drug development. A recent study used functional MRI to test the neural effects of a drug with the potential to treat cognitive dysfunction in schizophrenia. Other studies aim to identify patient-specific variables including sex, race, and genetics that impact drug clearance and clinical response to better select and dose antipsychotics and antidepressants.