Research in the David Sack Lab focuses on enteric infections. Our team has worked to develop laboratory detection methods to better understand the epidemiology of these agents. We also work to create appropriate clinical management strategies, such as antibiotics and rehydration methods, for enteric infections. Our work has included participating in the development of vaccines for a range of bacterial infections, including rotavirus, cholera and enterotoxigenic E. coli.

The David Celentano Lab studies behavioral and social epidemiology by integrating behavioral science theory and research with epidemiology methods. Our team directs epidemiological investigations and stages preventive interventions targeting HIV/AIDS and other sexually transmitted infections.

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.

Our research focuses on the biology of the peptidoglycan of Mycobacterium tuberculosis, the organism that causes tuberculosis, and Mycobacteroides abscessus, a related bacterium that causes opportunistic infections. We study basic mechanisms associated with peptidoglycan physiology but with an intent to leverage our findings to develop tools that will be useful in the clinic to treat mycobacterial infections. Peptidoglycan is the exoskeleton of bacteria that not only provides structural rigidity and cell shape but also several vital physiological functions. Breaching this structure is often lethal to bacteria. We are exploring fundamental mechanisms by which bacteria synthesize and preserve their peptidoglycan. Although our lab uses genetic, biochemical and biophysical approaches to study the peptidoglycan, we pursue questions irrespective of the expertise required to answer those questions. It is through these studies that we identified synergy between two beta-lactam antibiotics against select mycobacteria.