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Julio Lahoz Beneytez

Julio Lahoz-Beneytez

Early Stage Researcher / PhD student

Bayer AG
BTS-TD-ET-SPO
Building B106, G101
51368 Leverkusen, Germany

November 2013 - November 2016

 

Biography

Julio Lahoz-Beneytez studied a five year degree in Pharmaceutical Sciences (Miguel Hernandez University, Spain) followed by an MSc in Systems Biology (University of Warwick, UK). Over that period he got involved in several projects, thus obtaining a strong background in experimental immunology, experimental pharmacology and modelling and simulation. Currently he is pursuing a PhD at the Computational Systems Biology group of Bayer Technology Services in collaboration with the Imperial College London. Here he is merging his main research interests: Systems Biology, Immunology and PBPK modelling.

QuanTI research project

Physiologically based models applied to stable isotope experiments and leukocyte dynamics.

"Our working hypothesis is that the spatial structure, the processes that govern cellular dynamics and ADME (administration, distribution, metabolism and elimination) processes of labelling compounds impact on the estimation of cell turnover rates measured using stable isotope labelling. We propose to model the ADME processes of exogenous labelled glucose and to implement a physiologically based model of immune cell distribution with the final aim to reliably estimate the turnover parameters of immune cells.

Stable isotope compounds are seen as a breakthrough in order to trace cellular proliferation and death in humans [6,7]. However, different labelling yield different proliferation estimates that vary as much as 10-fold, even for the same compound [4,8]. This is the case of deuterium labelled glucose. A prominent issue might be the poor description of label exposure and its pharmacokinetics [8]. Based on the rapid turnover of glucose, conventional approaches [9] assume that label availability can be described by a "square wave". However, meal intakes, unbalanced sampling (i.e. majority of points taken during the day), the existence of a delabelling phase and recycling of label via hepatic glucose metabolism means that the "square wave" approximation may be invalid [8]. This could have led to an underestimation of label availability which could become more significant the shorter the labelling period is.

Additionally, immune cell turnover and distribution are complex processes that involve a spatial hierarchy. For instance, naïve T cells proliferate both in thymus and secondary lymphoid organs (SLO) and recirculate between blood, lymph and SLO whereas memory cells are characterised by more heterogeneous trafficking behaviour which include trafficking through tissues and proliferation in the periphery. In addition, samples are typically only taken from peripheral blood [6,7] and sampling in different locations would entail important ethical problems."

Extracted and adapted from Julio Lahoz-Beneytez research plan.

  1. Mohri H, Perelson AS, Tung K, Ribeiro RM, Ramratnam B, et al. (2001) Increased turnover of T lymphocytes in HIV-1 infection and its reduction by antiretroviral therapy. The Journal of experimental medicine 194: 1277-1288.
  2. Macallan DC, Asquith B, Irvine AJ, Wallace DL, Worth A, et al. (2003) Measurement and modeling of human T cell kinetics. European journal of immunology 33: 2316-2326.
  3. Vrisekoop N, den Braber I, de Boer AB, Ruiter AF, Ackermans MT, et al. (2008) Sparse production but preferential incorporation of recently produced naive T cells in the human peripheral pool. Proceedings of the National Academy of Sciences 105: 6115-6120.
  4. Westera L, Drylewicz J, Den Braber I, Mugwagwa T, Van Der Maas I, et al. (2013) Closing the gap between T-cell life span estimates from stable isotope-labeling studies in mice and humans. Blood 122: 2205-2212.
  5. Asquith B, Debacq C, Macallan DC, Willems L, Bangham CR (2002) Lymphocyte kinetics: the interpretation of labelling data. Trends in immunology 23: 596-601.
  6. Busch R, Neese RA, Awada M, Hayes GM, Hellerstein MK (2007) Measurement of cell proliferation by heavy water labeling. Nature protocols 2: 3045-3057.
  7. Macallan DC, Asquith B, Zhang Y, de Lara C, Ghattas H, et al. (2009) Measurement of proliferation and disappearance of rapid turnover cell populations in human studies using deuterium-labeled glucose. Nature protocols 4: 1313-1327.
  8. Ahmed R, Westera L, Drylewicz J, Elemans M, Zhang Y, et al. Reconciling estimates of cell proliferation from stable isotope labeling experiments. Submitted.
  9. Macallan DC, Asquith B, Zhang Y, de Lara C, Ghattas H, et al. (2009) Measurement of proliferation and disappearance of rapid turnover cell populations in human studies using deuterium-labeled glucose. Nat Protoc 4: 1313-1327.

Supervisors

Dr Christoph Niederalt, Systems Pharmacology Oncology, Bayer Technology Services (BTS) GmbH, Germany

Dr Becca Asquith, Department of Medicine, Imperial College London (ICL), UK

Publications

Lahoz-Beneytez, J., Schnizler, K., & Eissing, T. (2015). A pharma perspective on the systems medicine and pharmacology of inflammation. Mathematical biosciences, 260, 2-5.

Pozo, Ó. J., Ibáñez, M., Sancho, J. V., Lahoz-Beneytez, J., Farré, M., Papaseit, E., ... & Hernández, F. (2015). Mass Spectrometric Evaluation of Mephedrone In Vivo Human Metabolism: Identification of Phase I and Phase II Metabolites, Including a Novel Succinyl Conjugate. Drug Metabolism and Disposition, 43(2), 248-257.





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Last update: 11 June 2017