The Systems Pharmacology group uses theoretical models in close collaboration with experimentalists and clinicians to explore how we could use both within-host and population-wide drug treatment strategies to minimize human morbidity and mortality. Our focus is bacterial population dynamics, specifically pathogen population dynamics of anti-infective therapy. The focus of our research is rationalizing antibiotic treatment by bridging the gap between intracellular reaction kinetics and bacterial population dynamics to improve dosing regimens in tuberculosis therapy. We link single cell analyses (John McKinney, EPFL Lausanne) to clinical studies (TB Alliance, Martin Boeree, & Rob Arnoutse, Radboud University) and are funded by the Bill & Melinda Gates foundation. These models are also employed to develop new extended release technologies together with gastroenterologists at Harvard Medical School and MIT (Giovanni Traverso and Andrew Bellinger). In collaboration with researchers at the Department for Systems Pharmacology, Harvard Medical School (Adam Palmer), and Simon Fraser University, Vancouver (Leonid Chindelevitch), we explore how resistance mechanisms affect bacterial susceptibility. In addition, we recently developed a method to infer pathogen population dynamics with researchers at Harvard Medical School (Sören Abel, now NCMM) and work on resistance evolution in nosocomial infections and tuberculosis.
Alireza Shams (shared with Yale School of Public Health)
Ted Cohen, Yale School of Public Health
Sören Abel, University Tromsø, Harvard Medical School & NCMM
Matthew Waldor, Harvard Medical School
Giovanni Traverso & Andrew Bellinger, MIT & MGH/Harvard Medical School
Helen Jenkins, Boston University
Khisi Mdluli & Carl Mendel, TB Alliance
John McKinney & Neeraj Dhar, EPFL Lausanne
Adam Palmer, Harvard Medical School
Leonid Chindelevitch, Simon Fraser University, Vancouver
Dominique Cadosch & Sebastian Bonhoeffer, ETH Zürich
Roger Kouyos, University Hospital Zürich
Jan Engelstädter, University of Queensland
A Kunkel*, P Abel zur Wiesch*, RR Nathavitharana, FM Marx, HE Jenkins, T Cohen
BMC infectious diseases 16 (1), 282
Hubbard PT, Chao MC, Abel S, Blondel CJ, Abel zur Wiesch P, Zhou X, Davis BM, and Waldor MK.
PNAS (2016) published ahead of print doi:10.1073/pnas.1601718113.
Cadosch D, Abel zur Wiesch P, Kouyos RD, and Bonhoeffer, S.
PLOS Computational Biology (2016) 12 (3):e1004749.
Salvatore P, Becerra M, Abel zur Wiesch P, Hinkley T, Kaur D, Sloutsky A, Cohen T
Fitness costs of drug-resistance mutations in multidrug resistant M. tuberculosis: a household-based case-control study.
J. Infect. Dis. (2015) pii: jiv347. [Epub ahead of print]
Abel S, Abel zur Wiesch P, Davis BM, and Waldor MK
Analysis of bottlenecks in experimental models of infection.
PLOS PATHOGENS (2015) 11(6):e1004823
Abel zur Wiesch P#, Abel S, Gkotzis S, Ocampo P, Engelstädter J, Hinkley T, Magnus C, Waldor MK, Udekwu K, and Cohen T
Classic reaction kinetics can explain complex patterns of antibiotic action.
SCI. TRANSL. MED. (2015) 7(287):287ra73
Abel S, Abel zur Wiesch P, Chang H-H, Davis BM, Lipsitch M, and Waldor MK
Sequence tag-based analysis of pathogen population dynamics.
Nature Methods (2015) 12(3):223-6
Kouyos RD, Metcalf CJE, Birger R, Klein EY, Abel zur Wiesch P, Ankomah P, et al.
The path of least resistance: aggressive or moderate treatment?
Proceedings of the Royal Society B: Biological Sciences (2014) 281(1794):20140566
Ocampo PS, Lazar V, Bogos B, Arnoldini M, Abel zur Wiesch P, Busa-Fekete R, Fekete G, Pal C, Ackermann M and Bonhoeffer S
Antagonism is prevalent between bacteriostatic and bactericidal antibiotics.
Antimicrobial Agents and Chemotherapy (2014) 58(8):4573-82
Abel zur Wiesch P#*, Kouyos RD*, Abel S, Viechtbauer W, and Bonhoeffer S
Optimal antibiotic treatment in hospitals: meta-analysis and models.
PLOS Pathogens (2014) 10(6):e1004225
Abel S, Bucher T, Nicollier M, Hug I, Kaever V, Abel zur Wiesch P, Jenal U
Bi-modal Distribution of the Second Messenger c-di-GMP Controls Cell Fate and Asymmetry during the Caulobacter Cell Cycle.
PLOS Genetics (2013) 9(9):e1003744
Kouyos RD*, Abel zur Wiesch P*, Bonhoeffer S
On being the right size: the impact of population size and stochastic effects on the evolution of drug resistance in hospitals and the community.
PLOS Pathogens (2011) 7(4):e1001334.
Kouyos RD, Abel zur Wiesch P, Bonhoeffer S
Informed Switching Strongly Decreases the Prevalence of Antibiotic Resistance in Hospital Wards.
PLOS Computational Biology (2011) 7(3):e1001094.
Abel zur Wiesch P*, Kouyos R*, Engelstädter J, Regoes R, Bonhoeffer S
Population biological principles of resistance evolution in infectious diseases.
Lancet Infectious Diseases (2011) 11(3):236-247.
Bonhoeffer S, Abel zur Wiesch P, and Kouyos RD
Rotating antibiotics does not minimize selection for resistance.
Mathematical Biosciences and Engineering (2010) 7(4):919-922.
Schulz zur Wiesch P#, Engelstädter J, and Bonhoeffer S
Compensation of Fitness Costs and Reversibility of Antibiotic Resistance Mutations.
Antimicrobial Agents and Chemotherapy (2010) 54(5):2085-95
Priser og utmerkelser
ETH medal for outstanding PhD thesis
Fellowships and Grants:
Nov. 2016: Work package leader JPIAMR (total grant: 1.8 Mio EUR, 350000 EUR to PzW)
Nov. 2016: Work package leader Horizon 2020 (total grant: 5.82 Mio EUR, 644000 EUR to PzW)
Dec 2015: Co-PI research grant Helse Nord (main PI: Soren Abel)
Dec 2015: Co-PI research grant FRIPRO (main PI: Soren Abel)
Sep ‘14 Research grant Bill & Melinda Gates foundation ($374,312, Co-PI w/Ted Cohen)
Apr ‘13 Swiss National Science Foundation ($220,000)
Apr ‘12 Fellowship by German Academic Exchange Service ($72,800)
June ‘11 Swiss National Science Foundation ($54,000)
June ’10 Scholarship, Summer Institute Modeling in Infectious Diseases
Aug ‘08-May ’11 E-fellows scholarship
Jul-Oct ‘03 Travel scholarship Foundation of German Business (SDW)
May ‘03-Oct ’04 Fellowship Foundation of German Business (SDW)