MSTPublications: February 2018
Congratulations to all of our MSTP students on their successful publications! Take a look at the great work our students are doing.
First Author Original Research:
Variable Cell Line Pharmacokinetics Contribute to Non-Linear Treatment Response in Heterogeneous Cell Populations.
McKenna MT, Weis JA, Quaranta V, Yankeelov TE.
Ann Biomed Eng. 2018 Feb 26. doi: 10.1007/s10439-018-2001-2. [Epub ahead of print]
We develop a combined experimental-mathematical framework to investigate heterogeneity in the context of breast cancer treated with doxorubicin. We engineer a cell line to over-express the multi-drug resistance 1 protein (MDR1), an ATP-dependent pump that effluxes intracellular drug. Co-culture experiments mixing the MDR1-overexpressing line with its parental line are evaluated via fluorescence microscopy. To quantify the impact of population heterogeneity on therapy response, these data are analyzed with a coupled pharmacokinetics/pharmacodynamics model. The proliferation and death rates of each line vary with co-culture condition (the relative fraction of each cell line at the time of seeding). For example, the death rate in the parental line under low-dose doxorubicin treatment is increased from 0.64 (± 0.22) × 10-2 to 1.46 (± 0.58) × 10-2 h-1 with increasing fractions of MDR1-overexpressing cells. The growth rate of the MDR1-overexpressing line increases 29% as its relative fraction is decreased. Simulations of the pharmacokinetics/pharmacodynamics model suggest increased efflux from MDR1-overexpressing cells contributes to the increased death rate in the parental cells. Experimentally, the death rate of parental cells is constant across co-culture conditions under co-treatment with an MDR1 inhibitor. These data indicate that intercellular pharmacokinetic variability should be considered in analyzing treatment response in heterogeneous populations. (By Matt McKenna, M3)
Co-authorships, Clinical Studies, and Reviews:
EMR-Radiological Phenotypes in Diseases of the Optic Nerve and their Association with Visual Function.
Chaganti S, Robinson JR, Bermudez C, Lasko T, Mawn LA, Landman BA.
Deep Learn Med Image Anal Multimodal Learn Clin Decis Support (2017). 2017;2017:373-381. doi: 10.1007/978-3-319-67558-9_43. Epub 2017 Sep 9.
NMR resonance assignments of RNase P protein from Thermotoga maritima.
Zeng D, Brown BP, Voehler MW, Cai S, Reiter NJ.
Biomol NMR Assign. 2018 Feb 15. doi: 10.1007/s12104-018-9806-7. [Epub ahead of print]
Novel FOXC2 Mutation and Distichiasis in a Patient With Lymphedema-Distichiasis Syndrome.
De Niear MA, Breazzano MP, Mawn LA.
Ophthal Plast Reconstr Surg. 2018 Feb 5. doi: 10.1097/IOP.0000000000001079. [Epub ahead of print]
Cardiomyocyte-specific deletion of GSK-3β leads to cardiac dysfunction in a diet induced obesity model.
Gupte M, Tumuluru S, Sui JY, Singh AP, Umbarkar P, Parikh SS, Ahmad F, Zhang Q, Force T, Lal H.
Int J Cardiol. 2018 Feb 2. pii: S0167-5273(17)37094-8. doi: 10.1016/j.ijcard.2018.01.013. [Epub ahead of print]
Discovery of human cell selective effector molecules using single cell multiplexed activity metabolomics.
Earl DC, Ferrell PB Jr, Leelatian N, Froese JT, Reisman BJ, Irish JM, Bachmann BO.
Nat Commun. 2018 Jan 2;9(1):39. doi: 10.1038/s41467-017-02470-8.
Outpatient Transarterial Chemoembolization of Hepatocellular Carcinoma: Review of a Same-Day Discharge Strategy.
Fritsche MR, Watchmaker JM, Lipnik AJ, Baker JC, Geevarghese S, Banovac F, Omary RA, Brown DB.
J Vasc Interv Radiol. 2018 Feb 23. pii: S1051-0443(17)31038-2. doi: 10.1016/j.jvir.2017.11.018. [Epub ahead of print]
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