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.

We are interested in how immune responses occur in the cervix. The focus of our translational research is on developing immune therapies for disease caused by human papillomavirus (HPV). HPV infection causes more cancers than any other virus in the world. Cervical cancer is the most common cancer caused by HPV, and although we have known how to screen for it for over half a century, it remains the second most common cause of cancer death in women. Although the preventive vaccines are a public health milestone, they prevent HPV infections, but are not designed to make immune responses to treat HPV. We are testing different strategies to make immune responses that could treat HPV disease. Our dedicated researchers are working to extend the techniques used in HPV vaccine development to the creation of vaccines targeting other cancers with defined tumor antigens.

The Greider lab uses biochemistry to study telomerase and cellular and organismal consequences of telomere dysfunction. Telomeres protect chromosome ends from being recognized as DNA damage and chromosomal rearrangements. Conventional replication leads to telomere shortening, but telomere length is maintained by the enzyme telomerase. Telomerase is required for cells that undergo many rounds of divisions, especially tumor cells and some stem cells. The lab has generated telomerase null mice that are viable and show progressive telomere shortening for up to six generations. In the later generations, when telomeres are short, cells die via apoptosis or senescence. Crosses of these telomerase null mice to other tumor prone mice show that tumor formation can be greatly reduced by short telomeres. The lab also is using the telomerase null mice to explore the essential role of telomerase stem cell viability. Telomerase mutations cause autosomal dominant dyskeratosis congenita. People with this disease die of bone marrow failure, likely due to stem cell loss. The lab has developed a mouse model to study this disease. Future work in the lab will focus on identifying genes that induce DNA damage in response to short telomeres, identifying how telomeres are processed and how telomere elongation is regulated.

Johns Hopkins is a member of the Specialized Program of Research Excellence (SPORE) in Cervical Cancer. With a $11.5 million grant from the National Cancer Institute, we are conducting lab, translational and clinical studies to prevent and treat cervical cancers. Previous studies have identified connections between immune system genes and HPV16. Current projects include the development of next-generation HPV vaccines to control HPV-associated precursor lesions and invasive cancer. Our dedicated researchers are working to extend the techniques used in HPV vaccine development to the creation of vaccines targeting other cancers with defined tumor antigens.

The Artemov lab is within the Division of Cancer Imaging Research in the Department of Radiology and Radiological Science. The lab focuses on 1) Use of advanced dynamic contrast enhanced-MRI and activated dual-contrast MRI to perform image-guided combination therapy of triple negative breast cancer and to assess therapeutic response. 2) Development of noninvasive MR markers of cell viability based on a dual-contrast technique that enables simultaneous tracking and monitoring of viability of transplanted stems cells in vivo. 3) Development of Tc-99m and Ga-68 angiogenic SPECT/PET tracers to image expression of VEGF receptors that are involved in tumor angiogenesis and can be important therapeutic targets. 4) Development of the concept of “click therapy” that combines advantages of multi-component targeting, bio-orthogonal conjugation and image guidance and preclinical validation in breast and prostate cancer models.

The Best Laboratory focus on therapeutic vaccine development for HPV-related diseases by developing a murine model of papilloma analogous to Recurrent Respiratory Papillomatosis (RRP) for testing of DNA vaccine technology. We also work to understand the immunosuppressive tumor microenvironment that facilitates RRP development, and translate this work into novel therapies and clinical practice.

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.

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.

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.

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.