The Glunde lab is within the Division of Cancer Imaging Research in the Department of Radiology and Radiological Science. The lab is developing mass spectrometry imaging as part of multimodal molecular imaging workflows to image and elucidate hypoxia-driven signaling pathways in breast cancer. They are working to further unravel the molecular basis of the aberrant choline phospholipid metabolism in cancer. The Glunde lab is developing novel optical imaging agents for multi-scale molecular imaging of lysosomes in breast tumors and discovering structural changes in Collagen I matrices and their role in breast cancer and metastasis.

Directed by Debraj “Raj” Mukherjee, MD, MPH, the laboratory focuses on improving access to care, reducing disparities, maximizing surgical outcomes, and optimizing quality of life for patients with brain and skull base tumors.

The laboratory achieves these aims by creating and analyzing institutional and national databases, developing and validating novel patient-centered quality of life instruments, leveraging machine learning and artificial intelligence platforms to risk-stratify vulnerable patient populations, and designing novel surgical trials to push the boundaries of neurosurgical innovation.

Our research also investigates novel approaches to improve neurosurgical medical education including studying the utility of video-based surgical coaching and the design of new operative instrumentation.

Research in the Mark Liu Lab explores several areas of pulmonary and respiratory medicine. Our studies primarily deal with allergic inflammation, chronic obstructive pulmonary disease (COPD) and asthma, specifically immunologic responses to asthma. We have worked to develop a microfluidic device with integrated ratiometric oxygen sensors to enable long-term control and monitoring of both chronic and cyclical hypoxia. In addition, we conduct research on topics such as the use of magnetic resonance angiography in evaluating intracranial vascular lesions and tumors as well as treatment of osteoporosis by deep sea water through bone regeneration.

The bony skeleton is one of the most common sites of metastatic spread of cancer and a significant source of morbidity in cancer patients, causing pain and pathological fracture, impaired ambulatory ability and poorer quality of life.

In our continuous investigation of the mechanism of metastasis in spine tumors and of developing animal models and treatments, our team seeks to understand how cancer cells metastasize to the bony spine.

Our laboratory develops novel techniques to evaluate our animal models of metastatic spine disease.

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.

Effective immune responses are critical for control of a variety of infectious disease including bacterial, viral and protozoan infections as well as in protection from development of tumors. Central to the development of an effective immune response is the T lymphocyte which, as part of the adaptive immune system, is central in achieving sterilization and long lasting immunity. While the normal immune responses is tightly regulated there are also notable defects leading to pathologic diseases. Inactivity of tumor antigen-specific T cells, either by suppression or passive ignorance allows tumors to grow and eventually actively suppress the immune response. Conversely, hyperactivation of antigen-specific T cells to self antigens is the underlying basis for many autoimmune diseases including: multiple sclerosis; arthritis; and diabetes. Secondary to their central role in a wide variety of physiologic and pathophysiologic responses my lab takes a broad-based approach to studying T cell responses.

Our lab is focused on using comprehensive gene expression, methylation and sequencing and metabolomics analysis to identify alterations in breast cancer, and exploiting these for early detection and therapy. Among deferentially expressed genes, our lab has focused on the HOX genes. HOX genes are intimately involved in the development of resistance to both chemotherapy and to agents targeting the estrogen receptor. Our work explores the alternate pathways that are activated by HOX proteins leading to this resistance and novel treatments to overcome resistance in both tissue culture and xenograft models. In addition, epigenetically silenced genes and a metabolic reprogramming in tumors also trigger novel early detection and therapeutic strategies. We are testing the utility of differentiation therapy through reactivating RAR-beta in breast cancer using histone deacetylase inhibitors with great success. Also, we are targeting enzymes involved in gluconeogenesis and glycolysis with small molecule FDA-approved antimetabolites to achieve antitumor effects.

Current projects include: The evaluation of mechanisms of immune tolerance to cancer in mouse models of breast and pancreatic cancer. We have characterized the HER-2/neu transgenic mouse model of spontaneous mammary tumors. This model demonstrates immune tolerance to the HER-2/neu gene product. This model is being used to better understand the mechanisms of tolerance to tumor. In addition, this model is being used to develop vaccine strategies that can overcome this tolerance and induce immunity potent enough to prevent and treat naturally developing tumors. More recently, we are using a genetic model of pancreatic cancer developed to understand the early inflammatory changes that promote cancer development. The identification of human tumor antigens recognized by T cells. We are using a novel functional genetic approach developed in our laboratory. Human tumor specific T cells from vaccinated patients are used to identify immune relevant antigens that are chosen based on an initial genomic screen of overexpressed gene products. Several candidate targets have been identified and the prevelence of vaccine induced immunity has been assessed . This rapid screen to identify relevant antigenic targets will allow us to begin to dissect the mechanisms of tumor immunity induction and downregulation at the molecular level in cancer patients. More recently, we are using proteomics to identify proteins involved in pancreatic cancer development. We recently identified Annexin A2 as a molecule involved in metastases. The analysis of antitumor immune responses in patients enrolled on vaccine studies. The focus is on breast and pancreatic cancers. We are atttempting to identify in vitro correlates of in vivo antitumor immunity induced by vaccine strategies developed in the laboratory and currently under study in the clinics.