The Erika Matunis Laboratory studies the stem cells that sustain spermatogenesis in the fruit fly Drosophila melanogaster to understand how signals from neighboring cells control stem cell renewal or differentiation. In the fruit fly testes, germ line stem cells attach to a cluster of non-dividing somatic cells called the hub. When a germ line stem cell divides, its daughter is pushed away from the hub and differentiates into a gonialblast. The germ line stem cells receive a signal from the hub that allows it to remain a stem cell, while the daughter displaced away from the hub loses the signal and differentiates. We have found key regulatory signals involved in this process. We use genetic and genomic approaches to identify more genes that define the germ line stem cells' fate. We are also investigating how spermatogonia reverse differentiation to become germ line stem cells again.

The Espenshade Lab uses a multi-organismal and multidisciplinary approach to understand how eukaryotic cells measure insoluble lipids and dissolved gases. We have chosen cholesterol and oxygen as our model molecules, based on their essential roles in cell function and the importance of their proper homeostasis for human health.

The objective of the Xiao Group's research is to study the dynamics of cellular processes as they occur in real time at the single-molecule and single-cell level. The depth and breadth of our research requires an interdisciplinary approach, combining biological, biochemical and biophysical methods to address compelling biological problems quantitatively. We currently are focused on dynamics of the E. coli cell division complex assembly and the molecular mechanism in gene regulation.

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.

Work in the William B. Guggino Lab focuses on the structure of the cystic fibrosis transmembrane conductance regulator (CFTR) and water channels; the molecular structure of transport proteins in epithelial cell membranes; and gene therapies to treat cystic fibrosis (CF) patients. We are also working to identify CF’s specific defect in chloride channel regulation. One recent study showed that insulin-like growth factor 1 (IGF-1) enhances the protein expression of CFTR.

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 basic and translational studies looking at the effects of environmental exposures, including cigarette smoke and electronic cigarettes, on lung epithelial function. We are focused on mechanisms to reverse injury to promote lung health, primarily in the context of Chronic Obstructive Pulmonary Disease (COPD).

The Natalie West Lab collaborates with Noah Lechtzin’s lab to study cystic fibrosis, with a particular focus on new resistant bacteria and their effect on the lung function of people with cystic fibrosis.

The Nicholas Flavahan Lab primarily researches the cellular interactions and subcellular signaling pathways that control normal vascular function and regulate the initiation of vascular disease. We use biochemical and molecular analyses of cellular mediators and cell signaling mechanisms in cultured vascular cells, while also conducting physiological assessments and fluorescent microscopic imaging of signaling systems in isolated blood vessels. A major component of our research involves aterioles, tiny blood vessles that are responsible for controlling the peripheral resistance of the cardiovascular system, which help determine organ blood flow.

The Kalina Hristova Lab investigates the structure and assembly of biological membranes. Our team conducts research on the structural and thermodynamic principles that enable membrane protein folding and signal transduction across biological membranes. Part of our work has involved developing new tools to study the structure of thermally disordered fluid membranes and the energetics of biomolecular interactions in biological membranes. Through our studies, we have established a better understanding of the physical principles behind complex biological processes and the mechanisms of disease development in humans.