David J. Feola - Pharm.D., Ph.D., BCPS

Dr. Feola received his Doctor of Pharmacy degree and Ph.D. from the University of Kentucky College of Pharmacy. He also completed residencies in pharmacy practice and infectious diseases pharmacotherapy at the UK Chandler Medical Center (R258). His primary research focus area is immunology and infectious diseases pharmacotherapy, with specific projects investigating immunomodulatory and immunotoxic properties of drug exposure in animals and humans. Dr. Feola is building a translational research program through which he will utilize animal models and molecular and cellular investigations to generate investigator-initiated of clinical trials.

The main question being addressed by the Feola lab involves the immunotoxicity that occurs as a result of zidovudine (ZDV) plus sulfamethoxazole-trimethoprim (SMX-TMP) combined exposure. The dysfunction observed in the humoral immune response among patients infected with HIV has been underappreciated. It has been shown however, that intrinsic B cell dysfunction exists in this patient population, which causes a decreased ability to produce an antigen-specific antibody response upon infection and vaccination. Previous work by Dr. Feola's group has demonstrated that this drug combination causes a synergistic immunotoxicity in normal mice. B cells in the bone marrow undergo an increased rate of apoptosis, which leads to a decreased humoral response to infectious challenge. This has been confirmed in a pilot human trial, that demonstrated that HIV-infected subjects exposed to simultaneous ZDV and SMX-TMP exhibited a blunted antigen-specific antibody response to influenza vaccination. Therefore, the central question concerns the possibility that common drug regimens for HIV-infected patients are contributing to the B lymphocyte dysfunction that is observed. Dr. Feola is now addressing the following issues: the effect of this drug combination upon the peripheral B cell subsets, including rapidly dividing cells of the germinal center, long-lived plasma cells in the bone marrow, and memory B cells; animal and clinical investigation of ex vivo B cell function upon exposure to these agents; and, gene expression alterations that occur in the bone marrow of mice exposed to these immunotoxic agents. Additionally, a large clinical trial will be conducted in HIV-infected subjects to further evaluate the impact of ZDV plus SMX-TMP on antigen-specific antibody production.

Other projects in the lab include: immunomodulatory effects of azithromycin among pediatric patients with cystic fibrosis, the effect of trauma on B lymphocyte function, and the detection of quorum sensing genes for the diagnosis and monitoring of cerebrospinal fluid infections.

Selected Publications/Presentations

• Evans ME, Feola DJ, and Rapp RP. Polymyxin B sulfate and colistin: old antibiotics for emerging multiresistant gram-negative bacteria. Annals of Pharmacotherapy 1999;33:960-7.
• Feola DJ and Garvy BA. Zidovudine plus sulfamethoxazole-trimethoprim adversely affects B lymphocyte maturation in bone marrow of normal mice. International Immunopharmacology 2005 Dec;5(13-14):1881-94.
• Feola DJ, Thornton AC, and Garvy BA. Effects of antiretroviral therapy on immunity in patients infected with HIV. Current Pharmaceutical Design 2006;12(9):1015-22.
• Feola DJ and Garvy BA. Combination exposure to zidovudine plus sulfamethoxazole-trimethoprim diminishes B lymphocyte immune responses to Pneumocystis murina infection in healthy mice. Clinical and Vaccine Immunology 2006 Feb;13(2):193-201.