The Bert Vogelstein Laboratory seeks to develop new approaches to the prevention or treatment o...f cancers through a better understanding of the genes and pathways underlying their pathogenesis.

Our major focus is on cancers of the colon and rectum. We have shown that each colon neoplasm arises from a clonal expansion of one transformed cell. This expansion gives rise to a small benign colon tumor (called a polyp or adenoma). This clonal expansion and subsequent growth of the tumors appears to be caused by mutations in oncogenes and tumor suppressor genes, and the whole process is accelerated by defects in genes required for maintaining genetic instability. Mutations in four or five such genes are required for a malignant tumor to form, while fewer mutations suffice for benign tumorigenesis. As the mutations accumulate, the tumors become progressively more dangerous.

Current studies are aimed at the further characterization of the mechanisms through which these genes act, the identification of other genes that play a role in this tumor type, and the application of this knowledge to patient management. view more

The goal of the Johns Hopkins Brain Cancer Biology and Therapy Laboratory is to locate the gene...tic and genomic changes that lead to brain cancer. These molecular changes are evaluated for their potential as therapeutic targets and are often mutated genes, or genes that are over-expressed during the development of a brain cancer. The brain cancers that the Riggins Laboratory studies are medulloblastomas and glioblastomas. Medulloblastomas are the most common malignant brain tumor for children and glioblastomas are the most common malignant brain tumor for adults. Both tumors are difficult to treat, and new therapies are urgently needed for these cancers. Our laboratory uses large-scale genomic approaches to locate and analyze the genes that are mutated during brain cancer development. The technologies we now employ are capable of searching nearly all of a cancer genome for molecular alterations that can lead to cancer. The new molecular targets for cancer therapy are first located by large scale gene expression analysis, whole-genome scans for altered gene copy number and high throughput sequence analysis of cancer genomes. The alterations we find are then studied in-depth to determine how they contribute to the development of cancer, whether it is promoting tumor growth, enhancing the ability for the cancer to invade into normal tissue, or preventing the various fail-safe mechanisms programmed into our cells. view more

The lab explores the genetic underpinnings that drive the pathogenesis of a variety of primary ...central nervous system neoplasms. We are interested in exploiting genetic changes for both diagnostic and therapeutic purposes. Our lab is currently working on understanding the extreme responders and extreme clinical phenotypes of brain and spinal cord tumors to identify factors that may modulate responses to therapy. view more

At the brain tumor laboratory, Henry Brem, M.D. and Betty Tyler, along with more than 350 train...ees, have conducted scientific research, contributed to scientific literature, amended clinical practice, and illuminated new pathways for improving clinical outcomes.



The laboratory has advanced the understanding of gene therapy, angiogenesis, intracranial implantation of biodegradable polymers to treat malignant glioma, tumor genetics and proteomics, microchip drug delivery and drug resistance studies. Dr. Brem and his colleagues have designed and led many multi-institutional clinical trials to improve and expand the range of therapeutic options for patients with brain tumors. view more

Chordoma research is led by a comprehensive team including Gary Gallia, M.D., director of the N...eurosurgery Skull Base Tumor Center. The laboratory focuses on developing new therapies for brain and skull base tumors, and has established the first primary skull base chordoma xenograft mouse model. The team is also exploring high throughput drug screening using the chordoma model, and the molecular pathways responsible for tumor maintenance and growth. view more

Current projects include:

The evaluation of mechanisms of immune tolerance to cancer in m...ouse 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. view more

Dr. Zhou's research focuses on developing new in vivo MRI and MRS methodologies to study brain ...function and disease. His most recent work includes absolute quantification of cerebral blood flow, quantification of functional MRI, high-resolution diffusion tensor imaging (DTI), magnetization transfer mechanism, development of chemical exchange saturation transfer (CEST) technology, brain pH MR imaging, and tissue protein MR imaging. Notably, Dr. Zhou and his colleagues invented the amide proton transfer (APT) approach for brain pH imaging and tumor protein imaging. His initial paper on brain pH imaging was published in Nature Medicine in 2003 and his most recent paper on tumor treatment effects was published in Nature Medicine in 2011. A major part of his current research is the pre-clinical and clinical imaging of brain tumors, strokes, and other neurologic disorders using the APT and other novel MRI techniques. The overall goal is to achieve the MRI contrast at the protein and peptide level without injection of exogenous agents and improve the diagnostic capability of MRI and the patient outcomes. view more

Dr. Hua's research has centered on the development of novel MRI technologies for in vivo functi...onal and physiological imaging in the brain, and the application of such methods for studies in healthy and diseased brains. These include the development of human and animal MRI methods to measure functional brain activities, cerebral perfusion and oxygen metabolism at high (3 Tesla) and ultra-high (7 Tesla and above) magnetic fields. He is particularly interested in novel MRI approaches to image small blood and lymphatic vessels in the brain. Collaborating with clinical investigators, these techniques have been applied 1) to detect functional, vascular and metabolic abnormalities in the brain in neurodegenerative diseases such as Huntingdon's disease (HD), Parkinson's disease (PD), Alzheimer's disease (AD) and mental disorders such as schizophrenia; and 2) to map brain functions and cerebrovascular reactivity for presurgical planning in patients with vascular malformations, brain tumors and epilepsy. view more

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. view more

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. view more

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. view more

Our lab is focused on using comprehensive gene expression, methylation and sequencing and metab...olomics 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. view more

Effective immune responses are critical for control of a variety of infectious disease includin...g 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. view more

The bony skeleton is one of the most common sites of metastatic spread of cancer and a signific...ant 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. view more

The Johns Hopkins comprehensive Subependymoma and Ependymoma Research Center divideS its effort...s 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. view more

Led by Dr. Chetan Bettegowda, our lab uses genetic analysis, biomarkers and patient outcome dat...a to identify better ways to diagnose and treat disease. We research a variety of neurological conditions, including central nervous system tumors, trigeminal neuralgia and traumatic brain and spinal injuries. view more

Dr. Bhujwalla’s lab promotes preclinical and clinical multimodal imaging applications to unders...tand and effectively treat cancer. The lab’s work is dedicated to the applications of molecular imaging to understand cancer and the tumor environment. Significant research contributions include 1) developing ‘theranostic agents’ for image-guided targeting of cancer, including effective delivery of siRNA in combination with a prodrug enzyme 2) understanding the role of inflammation and cyclooxygenase-2 (COX-2) in cancer using molecular and functional imaging 3) developing noninvasive imaging techniques to detect COX-2 expressing in tumors 4) understanding the role of hypoxia and choline pathways to reduce the stem-like breast cancer cell burden in tumors 5) using molecular and functional imaging to understand the role of the tumor microenvironment including the extracellular matrix, hypoxia, vascularization, and choline phospholipid metabolism in prostate and breast cancer invasion and metastasis, with the ultimate goal of preventing cancer metastasis and 6) molecular and functional imaging characterization of cancer-induced cachexia to understand the cachexia-cascade and identify novel targets in the treatment of this condition. view more