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 Michael B. Streiff Lab conducts clinical and laboratory research of thrombophilia associated with malignancy. We are interested in the application of novel coagulation assays to explore the pathogenesis of thrombosis and the development of strategies to enhance the clinical management of anti-thrombotic agents.

Our lab currently focuses on three areas of immunotherapy research: gaining a deeper knowledge of the biological underpinnings of human autoimmune response; discovering biomarkers that will help us identify which patients and tumor types are most likely to respond to various immune therapies; and developing immune-based treatment combinations that could deliver a more powerful anti-tumor response than monotherapies.

The Johns Hopkins comprehensive Subependymoma and Ependymoma Research Center divideS its efforts into three areas: basic science, translational research and clinical practice. Each division works separately but shares findings and resources openly with each other and our collaborators. The goal of our united efforts is to optimize current treatments to affect the care received by patients with subependymomas and ependymomas. Also, our clinical, translational and basic science teams work to develop novel therapies to improve and extend the lives of those with these rare tumors.

The Radiopharmaceutical Therapy and Dosimetry (RTD) Lab has two missions: 1. Support clinical Radiopharmaceutical Therapy (RPT) trials by performing patient-specific dosimetry and developing novel methods that advance this field and illustrate the impact of a precision medicine approach to implementing treatment planning in RPT. This includes radiobiological modeling and microscale dosimetry calculations for alpha-particle emitter RPT. 2. Pre-clinical studies using novel alpha-emitter RPT agents with immune intact transgenic animal models that incorporate modeling and dosimetry to support the translation of novel targeted radionuclide therapy strategies to the clinic. In particular, identifying how to best combine RPT with complementary orthogonal-modality agents while also obtaining a basic understanding of how the treatment works and which variables have the greatest impact on efficacy and toxicity. The underlying objective is to utilize pre-clinical modeling and dosimetry to help identify an optimal therapeutic clinical trial design so as to reduce unnecessary human experimentation.

Research in the Howard and Georgeanna Seegar Jones Reproductive Endocrinology Lab supports a broad interest in reproductive conditions, but has a particular focus on endometriosis, uterine fibroids, polycystic ovary syndrome (PCOS) and genes causing infertility. PCOS and uterine fibroids are among the most prevalent conditions leading to infertility and diseases in women, but both remain poorly understood. Studying these areas may lead to the development of new treatments or preventative therapies.

The clinical development of novel immune and stem cell therapies calls for suitable methods that can follow the fate of cells non-invasively in humans at high resolution. The Bulte Lab has pioneered methods to label cells magnetically (using tiny superparamagnetic iron oxide nanoparticles) in order to make them visible by MR imaging. While the lab is doing basic bench-type research, there is a strong interaction with the clinical interventional radiology and oncology groups in order to bring the methodologies into the clinic.

Dr. Sohn's lab is interested in understanding how biological stress-sensors are assembled, detect danger signals and initiate stress response. Innate immunity is the first line of defense against invading pathogens in higher eukaryotes. We are using in vitro quantitative biochemical assays and mutagenesis and x-ray crystallography to investigate the underlying operating principles of inflammasomes, a component of the innate immune system, to better understand biological stress sensors.

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 Konig Lab focuses on chimeric T cell- and antibody-based strategies for the treatment of autoimmune rheumatic diseases and cancer. A primary goal of the translational research program is the development of antigen-specific and personalized immunotherapies for autoimmune diseases, with the intent to achieve sustained disease remission and functional cure. The lab further aims to establish precision T cell-targeting therapies for the treatment of various autoimmune diseases. Applying these tools to immuno-oncology, the lab utilizes cellular engineering strategies to augment the cytotoxic killing of solid cancers by the immune system.