Dr John E. Pearl

My approach to research and teaching reflects my own background -- I've lived and worked in several countries and am a passionate advocate for travel, adventure and cultural exchange. My core philosophy is an extension of this experience where I believe the purpose of science is to serve and better humanity. This collective service has the potential to improve health, welfare and our environment. I apply this approach by trying to make our research experience fun, supportive, collaborative and social.

I graduated with a Bachelor of Science in Microbiology from Colorado State University. While at Colorado State, I trained in the Mycobacterial Research Labs, an internationally recognized centre for investigation of mycobacterial diseases and pathogens. At Colorado State, I developed what would become a life-long interest in the taxonomic family of Mycobacteriaceae, which contains a range of notable human and animal pathogens, including the causative agent for Tuberculosis.  Following this, I worked for a veterinary biotech company and then moved into commercial research and development for a small biotech instrumentation company. In 2002, I relocated to the Trudeau Institute, a private research organization focusing on pulmonary pathogens, to continue my work with models of Tuberculosis and other mycobacterial pathogens. While at the Trudeau Institute, I earned a Ph.D. from the University of Porto in Portugal with a mechanistic focus on how infection with Mycobacterium avium modulates host immunity.

Before moving to Leicester, I held two academic appointments where I taught environmental microbiology and medical microbiology. During this formative period, I developed my approach to teaching which leverages the student's interests and experiences to enhance engagement.

In my work in Leicester, I'm an advocate of research-focused teaching where I believe that the best science arises from a highly diverse and international group of students who become invested in the scientific endeavour through working in a lab and participating in research. In this regard, we emphasize hypothesis development, experimental design and formal hypothesis testing which culminates in various forms of scientific communication. Simply stated, for a student to succeed and to maximize their potential, every student needs to be able to bring their whole self to work.

Science is social and science is fun!

My primary research interest at the University of Leicester is investigating the strategies by which mycobacteria modulate the immune response of the infected host. This is a critical question that is crucial to vaccine development for Tuberculosis, to treatment of Non-tuberculous mycobacterial [NTM] infections and prevention of opportunistic disease in people with pre-existing conditions, such as diabetes and cystic fibrosis. In addition, we have a strong interest in the environmental impact of these bacteria as contaminants of water distribution systems and medical devices such as endoscopes. Our focus is to better understand how mycobacteria perceive and respond to physiological stress which leads to bacterial adaptation to and modulation of of their changing environment.

I'm an active member of the Leicester Microbial Sciences and Infectious Diseases Centre [LeMID] where my research supports the strategic goal of better understanding antibiotic resistance and stress responses. You can read more about my research here.   

I have an enduring commitment to the ethical and responsible use of animals in research. One of the considerations that lead to my move to England is it's status as one of the world's most progressive nations in terms of it's legal protection for animals -- search UK.gov: Animals (Scientific Procedures) Act 1986 (ASPA). I serve as the deputy chair of the University of Leicester's Animal Welfare and Ethical Review Board [AWERB] and chair the sub-committee that conducts welfare and scientific evaluation of all research involving animals at the UoL.

Because of the complexities and the legal framework involved in conducting animal research in the UK I also serve as the manager of scientific collaboration and contract research for our animal facility. In this role I assist commercial or academic organizations with accessing our world-class animal facility in order to perform ethically-approved high quality experimental work. See: https://le.ac.uk/dbs.

1.            PHOSP-COVID Collaborative Group, Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study. Lancet Respir Med, 2022.

2.            Sulman, S., et al., Balance between Protection and Pathogenic Response to Aerosol Challenge with Mycobacterium tuberculosis (Mtb) in Mice Vaccinated with TriFu64, a Fusion Consisting of Three Mtb Antigens. Vaccines (Basel), 2021. 9(5).

3.            Evans, R.A., et al., Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study. Lancet Respir Med, 2021. 9(11): p. 1275-1287.

4.            Pearl, J.E., M. Das, and A.M. Cooper, Immunological roulette: Luck or something more? Considering the connections between host and environment in TB. Cell Mol Immunol, 2018. 15(3): p. 226-232.

5.            Torrado, E., et al., Interleukin 27R regulates CD4+ T cell phenotype and impacts protective immunity during Mycobacterium tuberculosis infection. The Journal of experimental medicine, 2015. 212(9): p. 1449-63.

6.            Pearl, J.E., Free Radicals in Mycobacterial Disease, in Oxidative Stress: Diagnostics, Prevention, and Therapy Volume 2. 2015, American Chemical Society. p. 503-539.

7.            Torrado, E., et al., Differential and site specific impact of B cells in the protective immune response to Mycobacterium tuberculosis in the mouse. PloS one, 2013. 8(4): p. e61681.

8.            Pearl, J.E., et al., Nitric oxide inhibits the accumulation of CD4+CD44hiTbet+CD69lo T cells in mycobacterial infection. European journal of immunology, 2012. 42(12): p. 3267-79.

9.            Khader, S.A., et al., IL-23 is required for long-term control of Mycobacterium tuberculosis and B cell follicle formation in the infected lung. Journal of immunology, 2011. 187(10): p. 5402-7.

10.          Robinson, R.T., et al., Mycobacterium tuberculosis infection induces il12rb1 splicing to generate a novel IL-12Rbeta1 isoform that enhances DC migration. The Journal of experimental medicine, 2010. 207(3): p. 591-605.

11.          Khader, S.A., et al., In a murine tuberculosis model, the absence of homeostatic chemokines delays granuloma formation and protective immunity. Journal of immunology, 2009. 183(12): p. 8004-14.

12.          Reiley, W.W., et al., ESAT-6-specific CD4 T cell responses to aerosol Mycobacterium tuberculosis infection are initiated in the mediastinal lymph nodes. Proceedings of the National Academy of Sciences of the United States of America, 2008. 105(31): p. 10961-6.

13.          Mayer, K.D., et al., Cutting edge: T-bet and IL-27R are critical for in vivo IFN-gamma production by CD8 T cells during infection. Journal of immunology, 2008. 180(2): p. 693-7.

14.          Khader, S.A., et al., IL-23 and IL-17 in the establishment of protective pulmonary CD4+ T cell responses after vaccination and during Mycobacterium tuberculosis challenge. Nature immunology, 2007. 8(4): p. 369-77.

15.          Khader, S.A., et al., Interleukin 12p40 is required for dendritic cell migration and T cell priming after Mycobacterium tuberculosis infection. The Journal of experimental medicine, 2006. 203(7): p. 1805-15.

16.          Cruz, A., et al., Cutting edge: IFN-gamma regulates the induction and expansion of IL-17-producing CD4 T cells during mycobacterial infection. Journal of immunology, 2006. 177(3): p. 1416-20.

17.          Khader, S.A., et al., IL-23 compensates for the absence of IL-12p70 and is essential for the IL-17 response during tuberculosis but is dispensable for protection and antigen-specific IFN-gamma responses if IL-12p70 is available. Journal of immunology, 2005. 175(2): p. 788-95.

18.          Florido, M., et al., Gamma interferon-induced T-cell loss in virulent Mycobacterium avium infection. Infection and immunity, 2005. 73(6): p. 3577-86.

19.          Pearl, J.E., et al., IL-27 signaling compromises control of bacterial growth in mycobacteria-infected mice. Journal of immunology, 2004. 173(12): p. 7490-6.

20.          König, S., et al., Protein Expression Analysis, in Analysing Gene Expression. 2004, Wiley-VCH Verlag GmbH & Co. KGaA. p. 623-702.

21.          Hancock, W.W., et al., Intact type 1 immunity and immune-associated coagulative responses in mice lacking IFN gamma-inducible fibrinogen-like protein 2. Proceedings of the National Academy of Sciences of the United States of America, 2004. 101(9): p. 3005-10.

22.          Turner, J., et al., CD8- and CD95/95L-dependent mechanisms of resistance in mice with chronic pulmonary tuberculosis. American journal of respiratory cell and molecular biology, 2001. 24(2): p. 203-9.

23.          Pearl, J.E., et al., Inflammation and lymphocyte activation during mycobacterial infection in the interferon-gamma-deficient mouse. Cellular immunology, 2001. 211(1): p. 43-50.

24.          Pearl, J.E., I.M. Orme, and A.M. Cooper, CD95 signaling is not required for the down regulation of cellular responses to systemic Mycobacterium tuberculosis infection. Tubercle and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 2000. 80(6): p. 273-9.

25.          Cooper, A.M., et al., Expression of the nitric oxide synthase 2 gene is not essential for early control of Mycobacterium tuberculosis in the murine lung. Infection and immunity, 2000. 68(12): p. 6879-82.

I’m keen to recruit and supervise a diverse range of talented and ambitious students. Among the projects that I am actively working on:

• Non-culture detection of mycobacteria in the environment to understand the metabolic configuration and respiratory state associated with their capacity to survive and persist.
• Investigation of phenotypic development in NTM as a response to challenging environments with an emphasis on metabolic remodelling and respiration.
• Development of constraints-based genome scale models of mycobacteria to understand bacterial fitness within the context of challenging environments using the COBRA toolbox and MATLAB.
• The interaction between the environment and mycobacteria during aerosolization to better understand what factors are important for airborne transmission. In this regard, we are developing tools to quantify environmental parameters using low-cost sensors based on a single-board computer.
• Airflow measurement and computational fluid dynamic modelling of experimental aerosol exposure to predict lower airway particulate deposition.
• Production engineering of an anatomically realistic mouse training device for intravenous and intraperitoneal injection skill development.

I teach in two programs within the College of Life Sciences and supervise a range of research-focussed students.

For the undergraduate Natural Sciences program, I facilitate workshops related to life sciences in astrobiology [NT2001] and I convene the associated multidisciplinary lab [NT2003]. The highlight of my work with these students is an open-ended laboratory experience in which we try to determine whether life is contained within a sample returned from a notational planetary body. This is especially challenging because we have to develop a testable definition life and then infer it's presence or absence based on a limited number chemical assays and observational studies. 

For post-graduate students, I convene two MSc courses: Infection and Immunity and Chronic Disease and Immunity. I lecture on a variety of topics including:

• scientific communication
• data analysis and presentation
• the ethics of animal research 
• experimental design using animal models
• selected topics in immunology and inflammation

My most impactful teaching, however, is performed in my lab where I work in collaboration with undergrad and graduate students to develop their skill and scientific acumen to prepare them for their next educational or career goal. When a student participates in real scientific discovery, they gain the ability to imagine their own futures as scientists. When combined with our strong commitment to international education where we recruit from a global pool of applicants, we truely are training global citizens of change.