The David Graham Lab studies the consequences of HIV interactions with the immune system, the resulting pathogenesis and how to sabotage these interactions. We apply advanced technologies like mass spectrometry to dissect processes at the molecular level. We are also actively involved in cardiovascular research and studies the ways proteins are organized into functional units in different cell types of the heart. Major projects in our lab are organized into three major areas: (1) H/SIV pathogenesis and neuropathogenesis, (2) Cardiovascular disease, and (3) High technology development

The Gregg Semenza Lab studies the molecular mechanisms of oxygen homeostasis. We have cloned and characterized hypoxia-inducible factor 1 (HIF-1), a basic helix-loop-helix transcription factor. Current research investigates the role of HIF-1 in the pathophysiology of cancer, cerebral and myocardial ischemia, and chronic lung disease, which are the most common causes of mortality in the U.S.

Work in the Joel Blankson Lab explores the mechanism of control of HIV-1 replication in a cohort of patients known as elite controllers or elite suppressors. These patients are HIV-1 seropositive but maintain levels of viremia that are below the limit of detection of standard clinical assays. We feel that elite suppressors represent a potential model for a therapeutic HIV vaccine. Our central hypothesis is that many of these patients are infected with fully replication-competent HIV-1 isolates that are held in check by the immune system. To test this hypothesis, we are studying many different host and viral factors in these patients.

Research in the Joseph Margolick Lab focuses on the many effects of HIV/AIDS on human health. We are particularly interested in the mechanisms of T-cell loss and preservation among people infected with HIV and the evaluation of human immune functions.

The Clinical Laboratory and Biomarkers Cores will coordinate access to laboratory expertise, testing, training, specimen repositories and Good Clinical Laboratory Practices (GCLP). The goals of this core are to assure that all JHU HIV investigators have access to and utilize appropriate, validated and, where applicable, certified laboratory assays. The core will also maintain a biomarker specimen repository for storage cataloguing and utilization of biological specimens.

The Post Lab is involved in the Multi-Ethnic Study of Atherosclerosis (MESA), a collaborative study of the characteristics of subclinical cardiovascular disease (that is, disease detected non-invasively before it has produced clinical signs and symptoms) and the risk factors that predict progression to clinically overt cardiovascular disease or progression of the subclinical disease. As MESA researchers, we study a diverse, population-based sample of 6,814 asymptomatic men and women aged 45-84. Approximately 38 percent of the recruited participants are white, 28 percent African-American, 22 percent Hispanic, and 12 percent Asian, predominantly of Chinese descent. Participants were recruited from six field centers across the United States, including Johns Hopkins University. Each participant received an extensive physical exam to determine a number of conditions, including coronary calcification, ventricular mass and function, flow-mediated endothelial vasodilation, standard coronary risk factors, sociodemographic factors, lifestyle factors, and psychosocial factors. Selected repetition of subclinical disease measures and risk factors at follow-up visits have allowed study of the progression of disease. Participants are being followed for identification and characterization of cardiovascular disease events, including acute myocardial infarction and other forms of coronary heart disease (CHD), stroke, and congestive heart failure; for cardiovascular disease interventions; and for mortality. Wendy S. Post, MD, MS, is an associate faculty, Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, and a professor of medicine.

The Douglas Ball Lab conducts clinical trials and pre-clinical laboratory studies of thyroid cancer. Our clinical trials, performed in collaboration with research staff in the upper aero-digestive group in the Sidney Kimmel Comprehensive Cancer Center, have included protocols for advanced radioiodine-refractory differentiated thyroid cancer and medullary thyroid cancer. Our pre-clinical research, conducted with Dr. Nelkin, Dr. Agrawal and other Kimmel Cancer Center researchers, includes pathogenesis and mechanisms of treatment resistance in medullary thyroid cancer, and pathogenesis and immune-directed therapy of anaplastic thyroid cancer.

The David Thomas Lab oversees clinical research projects that aim to understand the natural history and pathogenesis of hepatitis C virus infection. A special area of clinical and research focus is liver disease in HIV-infected people.

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.

We are interested in understanding how innate immune responses regulate lung health. Innate immunity involves ancient, and well-conserved mediators and their actions regulate the balance between homeostasis and pathogenesis. In the lungs, innate immunity play a critical role in response to environmental exposures such as allergen and ambient particulate matter. My lab focuses on how these exposures can promote aberrant mucosal responses that can drive the development of diseases like asthma.