From left to right: Juan Chen, Nasim Anwar, Arun Chopra, Jim Cook, Jay Radke, Mahmood Ghassemi, Jiangping Deng, Zeba Siddiqui, Guiqing Zhao

Info

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
Email: jlcook@uic.edu

Areas of Research

Studies of innate immunity to infectious agents and neoplastic cells. Studies of adenovirus E1A oncogene regulation of mammalian cell responses to injury induced, proapoptotic cell death responses. Studies of the role of the macrophage in anthrax infection and fatal shock response.

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 Family Center for Infectious Diseases 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 educational programs are part of the National Tuberculosis Curriculum Consortium.

Research Programs

Two areas of research are focused on understanding the molecular pathways that control the mammalian cell response to various 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 oncogene 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, activated macrophages and cytotoxic T lymphocytes (CTL). 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 following cellular injury by chemotherapeutic drugs and irradiation. 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.

Another project area involves 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 include evaluation of infection-induced and toxin-triggered macrophage activation and cytotoxicity in the context of host factors and development of animal models of the anthrax-induced shock syndrome. Another area of anthrax-related study involves the use of cell and animal models to assess novel therapeutics being developed by collaborating investigators to treat anthrax infection and block anthrax toxin-mediated pathogenesis. This therapeutics project is part of a multi-laboratory program project grant in collaboration with investigators from the University's College of Pharmacy and Medicine.

Selected Publications

• Smith, D.S., Huitt, G., Heifets, L.B. and Cook, J.L.: Mycobacterium terrae: Case reports, literature review and in vitro susceptibility testing. Clinical Infectious Diseases 30:444-453, 2000.
• Routes, J.R., Ryan, S., Li, H., Steinke, J. and Cook J.L.: Dissimilar Immunogenicities of adenovirus E1A and human papillomavirus E7 proteins influence tumor development. Journal of Immunology 165:4522-4527, 2000.
• Morikawa, O., Walker , T.A., Nielsen, L.D., Pan, T., Cook, J.L. and Mason, R.J.: Effect of adenovector-mediated gene transfer of keratinocyte growth factor (KGF) on the proliferation of alveolar type II cells in vitro and in vivo. American Journal of Respiratory Cell and Molecular Biology. 23:626-635, 2000.
• Routes, J.R., Ryan, S., Clase, Amanda, Miura, T., Kuhl, A., Potter, T.A. and Cook, J.L.: Adenovirus E1A oncogene expression in tumor cells enhances killing by TNF-related apoptosis inducing ligand (TRAIL). Virology 277:48-57, 2000.
• 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. and Routes, J.M.: Role of the innate immune response in determining the tumorigenicity of neoplastic cells. Developments in Biologicals. 106:99-108, 2001.
• 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. Proceedings 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, sensitizes 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.
• Peloquin, C.P., Berning, S.E., Nitta, A.T., Simone, P.M., Goble, M., Huitt, G.A., Iseman, M.D., Cook, J.L. and Curran-Everett, D.: Aminoglycoside toxicity: Daily versus thrice-weekly dosing for treatment of mycobacterial diseases. Clinical Infectious Diseases 38:1538-1544, 2004.
• Rosenzweig , S.D. , Schaffer, A.A., Ding, Li, Sullivan, R., Enyedi, B., Yim, J.-J., Cook, J.L., Musser, J.M. and Holland , S.M.: Interferon- g receptor 1 promoter polymorphisms: population distribution and functional implications. Clinical Immunology 112:113-119, 2004.
• Cook, J.L. and Routes, J.M.: Adenovirus E1A gene-induced tumor rejection through cellular sensitization to immune and nonimmune apoptotic injuries. Frontiers in Bioscience 10:1396-1414, 2005.
• Kpodonu, J., Cook, J.L., Massad, M.G., and Snow, N.J.: Tuberculosis of the thymus: Case report and review of the literature. Current Respiratory Medicine Reviews 1:123-126, 2005.
• Miura, T.A., Ryan, S., Cook, J.L., T. Potter and Routes, J.M.: The interaction of adenovirus E1A with p300 family members modulates cellular gene expression to reduce tumorigenicity. Journal of Cellular Biochemistry. 2006.
• Slotar, D. and Cook, J.L.: Upper and Lower Respiratory Tract Infections. In Textbook of Diagnostic Microbiology. C. Mahon and G. Manuselis, Eds. W. B. Saunders Co., 3 rd edition, 2007.