The Alison Moliterno Lab studies the molecular pathogenesis of myeloproliferative disorders (MPDs), including polycythemia vera, essential thrombocytosis and idiopathic myelofibrosis. Our research is focused on the genetic and epigenetic lesions associated with MPDs, with the goal of improving diagnosis and treatment for these disorders.

Research in the Josef Coresh Lab focuses on cardiovascular epidemiology, kidney disease and genetic epidemiology. Our team uses innovative methods to quantify disease burden and consequences in the population; studies the causes and consequences of vascular disease in the heart, kidneys and brain; and works to develop a strong scientific basis for quantifying the burden, causes and consequences of kidney disease. Working in collaboration with leading laboratories and specialists, we also aim to quantify the interplay of genes and environment in health and disease.

The James Hamilton laboratory performs pre-clinical experiments and basic studies investigating liver inflammation, fibrosis, and nuclear receptor signaling. In close collaboration with Dr Svetlana Lutsenko in Physiology, their team performs detailed studies of hepatocyte and non-parenchymal cell isolation, culture, biology and genetic manipulation. Working with models of Wilson disease, a disorder of copper overload, they discovered that hepatic nuclear receptor mediated control of lipid metabolism is a preferential and early target of copper toxicity. Furthermore, targeting nuclear receptors with pharmacologic agonists prevents and reverses liver inflammation and fibrosis.

The Constance Monitto Lab conducts clinical research on pediatric pain management as well as basic science studies on chemotherapy resistance. In our pediatric pain management research, we work to assess the impact of low-dose opioid antagonism on opioid-related side effects, such as nausea and vomiting. We also analyze data on current methods of pediatric pain management in the United States. In addition, our team uses basic science studies to assess the success of epigenetic gene regulation on the development of resistance to chemotherapeutic agents in cancer.

The GI Biomarkers Laboratory studies gastrointestinal cancer and pre-cancer biogenesis and biomarkers. The lab is led by Dr. Stephen Meltzer, who is known for his research in the molecular pathobiology of gastrointestinal malignancy and premalignancy. Research in the lab has led to several groundbreaking genomic, epigenomic and bioinformatic studies of esophageal and colonic neoplasms, shifting the gastrointestinal research paradaigm toward genome-wide approaches.

The Cammarato Lab is located in the Division of Cardiology in the Department of Medicine at the Johns Hopkins University School of Medicine. We are interested in basic mechanisms of striated muscle biology. We employ an array of imaging techniques to study “structural physiology” of cardiac and skeletal muscle. Drosophila melanogaster, the fruit fly, expresses both forms of striated muscle and benefits greatly from powerful genetic tools. We investigate conserved myopathic (muscle disease) processes and perform hierarchical and integrative analysis of muscle function from the level of single molecules and macromolecular complexes through the level of the tissue itself. Anthony Ross Cammarato, MD, is an assistant professor of medicine in the Cardiology Department. He studies the identification and manipulation of age- and mutation-dependent modifiers of cardiac function, hierarchical modeling and imaging of contractile machinery, integrative analysis of striated muscle performance and myopathic processes.

The Brown Lab is focused on the function of the cerebral cortex in the brain, which underlies our ability to interact with our environment through sensory perception and voluntary movement. Our research takes a bottom-up approach to understanding how the circuits of this massively interconnected network of neurons are functionally organized, and how dysfunction in these circuits contributes to neurodegenerative diseases like amyotrophic lateral sclerosis and neuropsychiatric disorders, including autism and schizophrenia. By combining electrophysiological and optogenetic approaches with anatomical and genetic techniques for identifying cell populations and pathways, the Brown Lab is defining the synaptic interactions among different classes of cortical neurons and determining how long-range and local inputs are integrated within cortical circuits. In amyotrophic lateral sclerosis, corticospinal and spinal motor neurons progressively degenerate. The Brown Lab is examining how abnormal activity within cortical circuits contributes to the selective degeneration of corticospinal motor neurons in an effort to identify new mechanisms for treating this disease. Abnormalities in the organization of cortical circuits and synapses have been identified in genetic and anatomical studies of neuropsychiatric disease. We are interested in the impact these abnormalities have on cortical processing and their contribution to the disordered cognition typical of autism and schizophrenia.

The Wang lab focuses on the signals that direct the differentiation of pluripotent stem cells, such as induced-pluripotent stem (iPS) cells, into hematopoietic and cardiovascular cells. Pluripotent stem cells hold great potential for regenerative medicine. Defining the molecular links between differentiation outcomes will provide important information for designing rational methods of stem cell manipulation.

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.