The Zhu lab is focused on characterizing the activities of large collection of proteins, building signaling networks for better understanding the mechanisms of biological processes, and identifying biomarkers in human diseases and cancers. More specifically, our group is interested in analyzing protein posttranslational modifications, and identifying important components involved in transcription networks and host-pathogen interactions on the proteomics level, and biomarkers in human IBD diseases.

Prostate cancer is the most commonly diagnosed malignancy in men in the United States, although our understanding of the molecular basis for this disease remains incomplete. We are interested in characterizing consistent alterations in the structure and expression of the genome of human prostate cancer cells as a means of identifying genes critical in the pathways of prostatic carcinogenesis. We are focusing on somatic genomic alterations occurring in sporadic prostate cancers, as well as germline variations which confer increases in prostate cancer risk. Both genome wide and candidate gene approaches are being pursued, and cancer associated changes in gene expression analyses of normal and malignant prostate cells are being cataloged as a complementary approach in these efforts. It is anticipated that this work will assist in providing more effective methodologies to identify men at high risk for this disease, in general, and in particular, to identify new markers of prognostic and therapeutic significance that could lead to more effective management of this common disease.

Normal and neoplastic cells respond to genome integrity threats in a variety of different ways. Furthermore, the nature of these responses are critical both for cancer pathogenesis and for cancer treatment. DNA damaging agents activate several signal transduction pathways in damaged cells which trigger cell fate decisions such as proliferation, genomic repair, differentiation, and cell death. For normal cells, failure of a DNA damaging agent (i.e., a carcinogen) to activate processes culminating in DNA repair or in cell death might promote neoplastic transformation. For cancer cells, failure of a DNA damaging agent (i.e., an antineoplastic drug) to promote differentiation or cell death might undermine cancer treatment. Our laboratory has discovered the most common known somatic genome alteration in human prostatic carcinoma cells. The DNA lesion, hypermethylation of deoxycytidine nucleotides in the promoter of a carcinogen-defense enzyme gene, appears to result in inactivation of the gene and a resultant increased vulnerability of prostatic cells to carcinogens. Studies underway in the laboratory have been directed at characterizing the genomic abnormality further, and at developing methods to restore expression of epigenetically silenced genes and/or to augment expression of other carcinogen-defense enzymes in prostate cells as prostate cancer prevention strategies. Another major interest pursued in the laboratory is the role of chronic or recurrent inflammation as a cause of prostate cancer. Genetic studies of familial prostate cancer have identified defects in genes regulating host inflammatory responses to infections. A newly described prostate lesion, proliferative inflammatory atrophy (PIA), appears to be an early prostate cancer precursor. Current experimental approaches feature induction of chronic prostate inflammation in laboratory mice and rats, and monitoring the consequences on the development of PIA and prostate cancer.

The Raman laboratory is within the Division of Cancer Imaging Research in the Department of Radiology and Radiological Science. The focus of the laboratory is bench-to-bed side cancer research. We integrate molecular and cellular biology, developmental biology, cancer biology, molecular imaging techniques to study cancer formation and progression. Many of the projects in the lab investigate dysregulated genes in cancer and the translatability of this information to a clinical setting. One such project is to functionally decipher the role of a RNA helicase gene, DDX3, in the biogenesis of multiple cancer types such as breast, lung, brain, sarcoma, colorectal and prostate. Additionally, using a rational drug design approach, a small molecule inhibitor of DDX3 (RK-33) was synthesized and its potential for clinical translation is being investigated.

The lab currently focuses on identifying genetic alterations in cancer affecting sensitivity and resistance to targeted therapies, and connecting such changes to key clinical characteristics and novel therapeutic approaches. We have recently developed methods that allow noninvasive characterization of cancer, including the PARE method that provided the first whole genome analysis of tumor DNA in the circulation of cancer patients. These analyses provide a window into real-time genomic analyses of cancer patients and provide new avenues for personalized diagnostic and therapeutic intervention.

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.

Zheng’s research focuses on two R01-funded projects; first, the group has developed a pancreatic cancer immunotherapy research program on a neoadjuvant therapy platform as well as a number of preclinical models of pancreatic cancer for developing innovative immunotherapy strategies. The group has applied the knowledge gained from pancreatic cancer immune-based therapies to the development of a colorectal cancer GVAX vaccine. Second, the group is aimed at understanding the mechanistic roles of the tumor microenvironment in cancer development and metastasis and identifying new targets for pancreatic cancer therapies by dissecting the tumor microenvironment of pancreatic cancer.

Research in the Lee Bone Lab uses community-based participatory approaches to promote health in underserved urban African-American populations. We conduct randomized clinical trials on cardiovascular disease, diabetes and cancer detection and control in order to test the success of community interventions. We focus in particular on making interventions sustainable and on implementing electronic education to improve communication.

Our research results in effective and quality care which has led to the development of new therapies, medications and vaccines, including the HPV vaccine — the first vaccine to prevent gynecologic cancer. Our patient satisfaction scores are among the highest in the nation, due to our commitment to safety and quality.

The Kathryn Carson Lab investigates ways to improve medical research, particularly in the areas of brain and thyroid cancer, Alzheimer’s disease, atherosclerosis, hypertension, HIV and lupus. Our team seeks to help researchers optimize their studies through better study design, protocol and grant writing, data cleaning and analysis, and publication writing. We work with investigators from a wide range of departments through the Johns Hopkins Institute for Clinical and Translational Research.