The Brennen laboratory takes a rigorous, multi-disciplinary, team-based approach towards developing innovative therapeutic and prognostic strategies for prostate cancer with an emphasis on exploiting vulnerabilities within the tumor microenvironment towards this goal. To accomplish this goal, we are strategically pursuing novel therapeutic platforms, including stromal-targeted prodrugs, protoxins, and radiolabeled antibodies, in addition to cell-based therapy and drug delivery; all of which are designed to reduce toxicity to peripheral non-target tissue (i.e. side effects) while maximizing anti-tumor efficacy (i.e. therapeutic benefit). Currently, many of these strategies are focused on overcoming stromal barriers to anti-tumor immune responses such that men suffering from prostate cancer can share in the immense, revolutionary power of immunotherapy that is transforming care for many with advanced disease in other tumor types previously thought to be unmanageable using conventional ap...proaches. Unfortunately, prostate cancer has largely proven refractory to these powerful approaches thus far and requires novel mono- or combinatorial treatment strategies to unleash the full potential of the immune system and generate personalized anti-tumor responses with the capability of producing long-term durable responses or even cures in these men.view more
Work in the Cynthia Sears Laboratory focuses on the bacterial contributions to the development of human colon cancer and the impact of the microbiome on other cancers and the therapy of cancer. The current work involves mouse and human studies to define how enterotoxigenic Bacteroides fragilis, pks+ Escherichia coli, Fusobacterium nucleatum, biofilms and the colonic microbiota induce chronic colonic inflammation and colon cancer. Prospective human studies of the microbiome and biofilms in screening colonoscopy are in progress as are studies to determine if and how the microbiome impacts the response of individuals with cancer to immunotherapy and other cancer therapies.
The Pardoll Lab focuses on the regulation of antigen-specific T cell responses and studies approaches to modify these responses for immunotherapy. Pardoll has a particular interest in cancer immunology and his lab’s studies on basic immunologic mechanisms have led to the development and design of a number of cancer vaccines and discovery of key checkpoint ligands and receptors, such as PD-L2, LAG-3 and neuritin, many of which are being targeted clinically.
Our primary pursuits are discovering and elucidating new molecules that regulate immune responses, investigating the biology of regulatory T cells, and better understanding the specific biochemical signatures that allow a patient’s T cells to selectively target cancer cells.
Barbara Slusher, M.A.S., Ph.D., leads a 20-member veteran drug discovery team of medicinal chemists, assay developers, pharmacologists, toxicologists and pharmacokinetic/drug metabolism experts, who identify novel drug targets arising from JHU faculty’s research and translate them into new, small molecule drug therapies.
Her team collaborates extensively with faculty at the Bloomberg~Kimmel Institute for Cancer Immunotherapy and leads the BKI immunotherapy drug discovery core, aimed at developing new immune-targeting drug therapies for laboratory and clinical testing at Johns Hopkins.
The Shenderov Lab focuses on the elucidation of the mechanisms of immune response and resistance to immunotherapy in Prostate Cancer. This has led to clinical and basic research investigating the presumptive checkpoint inhibitor B7-H3.
In pursuit of understanding biomarkers or resistance and response, and regulatory molecules of immune response, we utilize artificial intelligence, immunogenomics, and spatial proteomics and transcriptomics in the laboratory and at the bedside using clinical trial correlative samples.
The Franck Housseau Lab focuses on the role of the microbiome in colorectal tumorigenesis and on developing a better understanding of the tumor immune microenvironment. The lab is currently working to define the biomarkers of a pre-existing antitumor immune response in metastatic colorectal cancer to define a population of patients eligible for checkpoint blockade therapies.
The Ivan Borrello Lab focuses on the development of a novel approach of adoptive T cell therapy utilizing marrow-infiltrating lymphocytes (MILs) as a more tumor-specific T cell approach. This has led to establishing the first adoptive T cell trials at Johns Hopkins and an exploration of this approach in other diseases, including nonhematologic malignancies. The lab also examines strategies for treating minimal residual disease (MRD) in myeloma with the combination of immune modulation and whole cell-based vaccines.
The Jody Tversky Lab studies dendritic cells in allergy and immunotherapy; cluster immunotherapy clinical observations and immune tolerance; and clinical diagnostic sensitivity of 10 allergy skin prick devices.
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.
Zheng’s research focuses on two R01-funded projects; first, the group has developed a pancreatic cancer immunotherapy research program on a neoadjuvant therapy platform as well as a number of preclinical models of pancreatic cancer for developing innovative immunotherapy strategies. The group has applied the knowledge gained from pancreatic cancer immune-based therapies to the development of a colorectal cancer GVAX vaccine. Second, the group is aimed at understanding the mechanistic roles of the tumor microenvironment in cancer development and metastasis and identifying new targets for pancreatic cancer therapies by dissecting the tumor microenvironment of pancreatic cancer.
The Maureen Horton Lab conducts research on pulmonary fibrosis through the use of both preclinical models and human trials. Our studies have helped to develop novel, genetic, tissue-specific models of immune dysfunction, which have aided in defining the immune regulation of fibrosis and in the development of treatment strategies. We have used T-cell skewing immunotherapy to prevent and reverse chemical-induced lung fibrosis and have conducted clinical trials for idiopathic pulmonary fibrosis (IPF), which led to one of the first treatments that helped to improve quality of life in IPF patients.
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 b...ased 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.view more
Dr. Anders’ laboratory focuses on the basic processes that lead to cancer. His team approaches these questions through the use of both experimental models and examination of human tissues. His team is specifically interested in interrogating the immune microenvironment of cancer, detecting circulating cancer cells and preventing cancer metastasis.
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 lab currently focuses on identifying genetic alterations in cancer affecting sensitivity and resistance to targeted therapies, and connecting such changes to key clinical characteristics and novel therapeutic approaches. We have recently developed methods that allow noninvasive characterization of cancer, including the PARE method that provided the first whole genome analysis of tumor DNA in the circulation of cancer patients. These analyses provide a window into real-time genomic analyses of cancer patients and provide new avenues for personalized diagnostic and therapeutic intervention.