Dr. Stefan David

     Postdoc Fellow
    Division of Gastroenterology
    Department of Medicine
    The Johns Hopkins University School of Medicine

    1503 E. Jefferson St, Rm 143
    Tel :(410) 502-6057
    Fax: (410) 502-1329
    Email: sdavid9@jhmi.edu

    M.D., 2000 Carol Davila University, School of Medicine

Research Interest:

Perturbances of homeostasis with respect to the cells number results in disease. Generally, loosing specialized cell (either due to acute or chronic conditions) will result in a loss of function with consequences like degenerative diseases. On the contrary, increased cell numbers may result in neoplastic processes.

My research is focused on understanding the molecular mechanisms that govern cellular decisions (proliferation, cell death, migration and invasion) and the way they can be harnessed to detect, prevent and treat human diseases.

Esophageal adenocarcinoma (EAC) is one of the cancers with the fastest growing incidence in the western world. Barrett’s esophagus (BE) is the precursor lesion of EAC. Discerning which patients will progress from BE to EAC and identifying the factors driving neoplasia development are extremely important. An important factor involved is acid exposure due to gastroesophageal reflux disease (GERD). Interestingly, the inflammation triggered by GERD determines increased expression of both TNF alpha (member of the TNF superfamily involved in apoptosis induction), and NF-kB p65 (one of the five members of the NF-kB signaling pathway that could rescue tumor cells from apoptosis).                                                                                                                                         

My in vitro studies reveal that TNF is a potent apoptosis induction in EAC cell lines like SEG1 and Bic, while brief acid stimulation prior to the TNF exposure diminishes cell death while activating NF-kB p65 signaling in SEG1 cells. This could set a new threshold in the cell apoptotic commitment, enabling a survival tendency in EAC tumor cell. Finding the proper inhibitory means to restore the proper cellular response to apoptotic stimuli would result in prevention of neoplasia or even in an adjuvant treatment improving the response to current therapies.

                                              Last modified 09/01/2007