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.

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.

At the brain tumor laboratory, Henry Brem, M.D. and Betty Tyler, along with more than 350 trainees, 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.

The goal of the Johns Hopkins Brain Cancer Biology and Therapy Laboratory is to locate the genetic 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.

Led by Dr. Chetan Bettegowda and Dr. Jordina Rincon-Torroella, our lab uses genetic analysis, biomarkers and patient outcome data 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.

The Bert Vogelstein Laboratory seeks to develop new approaches to the prevention or treatment of 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.

Dr. Bhujwalla’s lab promotes preclinical and clinical multimodal imaging applications to understand 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.

The mission of the Lemberg research group is to understand metabolism in childhood/young adult cancers in order to develop a better understanding of how these cancers develop, how they respond to treatments, and how children can go on to live healthy lives with or after a cancer history. We aim to investigate how tumors and the surrounding physiologic environments interact to drive nutrient use so that the tumor can grow and spread, and how the presence of a cancer affects the development of the whole child. Our ultimate goal is to improve outcomes for children and young adults with cancer.

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.