James L. Cook, MD

Chief, Section of Infectious Diseases
Harry F. Dowling Professor of Infectious Diseases
Professor of Medicine, Microbiology and Immunology

Dept. of Medicine, University of Illinois College of Medicine
M/C-735, Room 888
808 S. Wood Street
Chicago, IL 60612

phone - (312) 996-6732
fax - (312) 413-1657
jlcook@uic.edu

 Area of Research: Mycobateria.

Laboratory, description of activities:

 Clinical Activities

Several patient care-related activities and educational programs focus on expertise in the field of mycobacterial diseases. For over a decade, patients with refractory mycobacterial infections have been seen from across the U.S. and from other countries for clinical consultation on disease management. Patients with such unusual and drug-resistant mycobacterial infections continue to be seen on a weekly basis in the University's Outpatient Care Center. In addition to patient care activities, educational programs are provided to students, residents, fellows and postdoctoral graduates on the epidemiology, microbiology, diagnosis and treatment of tuberculosis and nontuberculous mycobacterial infections. The TB-related programs are part of a national teaching consortium.

  Research Programs

Two areas of research are focused on understanding the regulation of mammalian cell responses to different types of proapoptotic injuries in the context of viral gene expression or bacterial infection.

One project area involves studies of viral gene regulation of mammalian cell responses to injuries inflicted by cellular components of the innate immune response. Mammalian cells expressing the E1A gene of human adenovirus types 2 or 5 are phenotypically changed from being resistant to immunological injuries to becoming highly susceptible to apoptotic death triggered by natural killer (NK) cells, cytotoxic T lymphocytes (CTL), activated macrophages and tumor necrosis factor alpha (TNF). The in vivo correlate of this observation is that E1A expression in neoplastic cells converts them from highly tumorigenic cells to cells that are easily rejected by immunocompetent (but not immunodeficient) animals. E1A-induced cellular sensitization to apoptotic injury is not unique to immunological injuries, but is also observed with selected chemical and physical injuries. This suggests that the mechanisms by which E1A sensitizes cells to apoptosis are not unique to interactions between immunological mediators and E1A-expressing cells but may involve one or more common pathways through which cells respond to diverse injuries. The objective of these studies is to define the molecular mechanisms and cellular pathways through which this viral transcriptional regulator gene mediates cellular conversion to the apoptosis sensitive phenotype.

The other project area involved studies of the role of macrophages in the host response to anthrax infection and anthrax lethal toxin-induced shock syndrome. Bacillus anthracis infection and toxin production during systemic infection are associated with a shock syndrome that appears to be triggered through cellular mechanisms that involve activated macrophages, among other host cells. Studies in this project area in the laboratory include evaluation of infection-induced and toxin-triggered macrophage activation and cytotoxicity and development of animal models of the anthrax-induced shock syndrome. The effects of anthrax infection and related toxin production on endothelial cell function are also being evaluated to better understand the mechanisms of anthrax-induced changes in vascular permeability as part of the pathogenesis of systemic infection. A third area of anthrax-related study involves development of cell and animal models to assess novel therapeutics aimed at controlling anthrax infection and blocking anthrax toxin-mediated pathogenesis. This therapeutics project involves a multi-laboratory collaborative interaction.

 Selected Publications

• Hazelton, T.R., Newell, J.D., Jr., Cook, J.L., Huitt, G.A. and Lynch, D.A.: CT findings in 14 patients with pulmonary Mycobacterium chelonae infection. American Journal of Roentgenology 175:413-416, 2000.
• Cook, J.L., Walker, T.A., Worthen, G.S. and Radke, J.R.: Role of the E1A Rb-binding domain in repression of the NF-kappa B-dependent defense against tumor necrosis factor alpha. Porceedings of the National Academy of Sciences 99:9966-9971, 2002.
• Miura, T.A., Morris, K, Ryan, S., Cook, J.L. and Routes, J.M.: Adenovirus E1A, but not human papillomavirus E7, senstizes tumor cells to lysis by macrophages through nitric oxide- and TNF-alpha-dependent mechanisms despite up-regulation of 70 kDa heat shock protein. Journal of Immunology 170:4119-4126, 2003.
• Cook, J.L., Miura, T.A., Ikle, D.N., Lewis, Jr., A.M. and Routes, J.M.: E1A oncogene-induced sensitization of human tumor cells to innate immune defenses and chemotherapy-induced apoptosis in vitro and in vivo. Cancer Research 63: 3435-3443, 2003.
• Cook, J.L.: Nontuberculous Mycobacterial Infections. In Therapy of Infectious Diseases. L. Baddour and S.L. Gorback, Eds. Saunders-Elseiver Science, pp. 547-575, 2003.