476135 Systems Biology and Systems Pharmacology Approaches to HIV Infection and TB/HIV Co-Infection

Sunday, November 13, 2016
Continental 4 & 5 (Hilton San Francisco Union Square)
Elsje Pienaar, University of Michigan, Ann Arbor, MI

Systems biology and systems pharmacology approaches to HIV infection and TB/HIV co-infection

Elsje Pienaar, University of Michigan

Research Investigator

Research Interests:

I aim to establish a research group that uses computational approaches to study within-host dynamics and treatment of infectious diseases, such as tuberculosis (TB) and human immunodeficiency virus (HIV). My work will leverage my established collaborations with experts in animal models of HIV and TB-HIV co-infection. I will build multi-scale multi-compartment computational models of HIV infection to determine 1) the roles of cytokine and CD4+/CD8+ T cell imbalances, in the context of different CD4+ T cell levels, in driving immune-deficiency in HIV+ patients; 2) pharmacokinetics and viral dynamics in different physiological compartments which influence HIV treatment efficacy and the persistence of viral reservoirs, and 3) precision treatment options based on patient-specific data.

Ultimately, I will integrate this model with a host-scale model of tuberculosis (TB) infection and treatment to 1) study the natural progression of this globally devastating co-infection, and 2) evaluate different coordinated treatment strategies for TB and HIV.

Through my experience in infectious diseases (experimental and computational), systems biology, systems pharmacology, and productive collaborative experience with experimentalists, I am well positioned to achieve these goals.

Research Proposal Experience:

I have worked with current and past mentors to prepare successful NIH research proposals. I have submitted proposals for independent funding from the Simons Foundation. I am awaiting a decision on an NIH training grant (K01) and I am preparing an application for a PhRMA foundation research starter grant.

Teaching Interests:

My educational experiences include classroom teaching (guest lectures in chemical engineering and mathematical biology), student mentoring (graduate and undergraduate students in chemical engineering and microbiology) and formal training in pedagogy (Certificate in learning, instructing and knowledge (Linköping University, 2012)). I look forward to teaching any core Chemical Engineering courses, as well as developing specialty graduate courses in systems biology/systems pharmacology.

Academic Appointments

2015 – Present. Research investigator in Chemical Engineering, Microbiology and Immunology, University of Michigan, Ann Arbor, MI.

Grants

2011 Knut and Alice Wallenberg Travel Grant

2012 Microbiology and Immunology Postdoctoral Travel Grant

Honors and Awards

2014 BMES Innovation and Career Development Award

2010 Outstanding Doctoral Dissertation Award, UNL College of Engineering

2009 NIH-NIAID Scholarship Keystone Symposia

Education and Training

2012 – 2015 Research fellow. Chemical Engineering, Microbiology and Immunology, University of Michigan, Ann Arbor, MI. Advisors: Dr. Jennifer Linderman and Dr. Denise Kirschner.

2010 – 2012 Postdoctoral fellow. Medical Microbiology, Linköping University, Linköping, Sweden. Advisor: Dr. Maria Lerm.

2007 – 2010 PhD, Chemical and Biomolecular Engineering, Biological Sciences University of Nebraska-Lincoln, Lincoln, NE. Advisor: Dr. Hendrik Viljoen.

2005 – 2007 MSc, Chemical and Biomolecular Engineering, Biological Sciences University of Nebraska-Lincoln, Lincoln, NE. Advisor: Dr. Hendrik Viljoen.

2002 – 2004 BSc, Financial and Actuarial Mathematics, University of Pretoria, Pretoria, South Africa

Selected Publications

Pienaar E, Matern W, Linderman JJ, Bader JS, Kirschner DE. Multi-scale model of Mycobacterium tuberculosis infection maps metabolite and gene perturbations to granuloma sterilization predictions. Infection and Immunity. 2016:84(5):1650.

Pienaar E, Dartois V, Linderman JJ, Kirschner DE. In silico evaluation and exploration of antibiotic tuberculosis treatment regimens. BMC Systems Biology. 2015;9:79.

Linderman JJ, Cilfone N, Pienaar E, Gong C, and Kirschner DE. A Multi-scale Approach to Designing Therapeutics for Tuberculosis. Integrative biology. 2015; 7:591-609.

Pienaar E, Cilfone NA, Lin PL, Dartois V, Mattila JT, Butler JR, Flynn JL, Kirschner DE, Linderman JJ. A computational tool integrating host immunity with antibiotic dynamics to study tuberculosis treatment. J Theor Biol. 2015;367:166-179.

Raffetseder J*, Pienaar E*, Blomgran R, Eklund D, Patcha Brodin V, Andersson H, Stendahl O, Welin A, Lerm M. Replication Rates of Mycobacterium tuberculosis in Human Macrophages Do Not Correlate with Mycobacterial Antibiotic Susceptibility. PLoS One. 2014;9(11):e112426. *: co-first authors.

Pienaar E, Lerm M. A Mathematical Model of the Initial Interaction between Mycobacterium tuberculosis and Macrophages. J Theor Biol. 2014; 342:23-32.

Viljoen S, Pienaar E, Viljoen HJ. A state-time epidemiology model of tuberculosis: Importance of re-infection. Computational Biology and Chemistry. 2012;36(0):15-22.

Pienaar E, Fluitt AM, Whitney SE, Freifeld AG, Viljoen HJ. A model of tuberculosis transmission and intervention strategies in an urban residential area. Comput Biol Chem. 2010;34(2):86-96.

Pienaar E, Whitney SE, Viljoen HJ, van Rensburg NF. A model of the complex response of Staphylococcus aureus to methicillin. J Theor Biol. Apr 2009;257(3):438-445.

Pienaar E, Viljoen HJ. The tri-frame model. J Theor Biol. Apr 2008;251(4):616-627.

Pienaar E, Theron M, Nelson M, Viljoen HJ. A quantitative model of error accumulation during PCR amplification. Comput Biol Chem. Apr 2006;30(2):102-111.

Publications in preparation

Pienaar E, Sarathy J, Prideaux B, Dartois V, Kirschner DE and Linderman JJ. Systems Pharmacology Predicts Antibiotic Spatial Distribution And Efficacy In TB Granulomas.

Pienaar E, Kirschner DE and Linderman JJ. Mechanisms driving drug resistance emergence in TB granulomas.


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