Dr. Hua's research has centered on the development of novel MRI technologies for in vivo functional 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.

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.

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 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.

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.

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 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 goal of the lab's research is to identify molecular abnormalities that can improve the outcome of patients with pancreatic cancer and those at risk of developing this disease. Much of our work is focused on translational research evaluating markers and marker technologies that can help screen patients with an increased risk of developing pancreatic cancer. Thus, marker efforts have been focused mostly on identifying markers of advanced precancerous neoplasia (PanINs and IPMNs) that could improve our ability to effectively screen patients at risk of developing pancreatic cancer. We lead or participate in a number of clinical research protocols involved in the screening and early detection of pancreatic neoplasia including the CAPS clinical trials. We maintain a large repository of specimens from cases and controls with and without pancreatic disease and use this repository to investigate candidate markers of pancreatic cancer for their utility to predict pancreatic cancer risk. In addition, we have been working to identify familial pancreatic cancer susceptibility genes and identified BRCA2 as a pancreatic cancer susceptibility gene in 1996. We participate in the PACGENE consortium and the familial pancreatic cancer sequencing initiative. My lab also investigates pancreatic cancer genetics, epigenetics, molecular pathology, tumor stromal interactions and functional analysis of candidate genes and miRNAs. Dr. Goggins is the principal investigator of a phase I/II clinical trial evaluating the Parp inhibitor, olaparib along with irinotecan and cisplatin for patients with pancreatic cancer.