MSTPublications: July 2017
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:
A Predictive Mathematical Modeling Approach for the Study of Doxorubicin Treatment in Triple Negative Breast Cancer.
McKenna MT, Weis JA, Barnes SL, Tyson DR, Miga MI, Quaranta V, Yankeelov TE.
Sci Rep. 2017 Jul 18;7(1):5725. doi: 10.1038/s41598-017-05902-z.
The potency, efficacy, and mechanism of action of cytotoxic agents have been studied for years. However, these pharmacologic properties are inherently insufficient to predict the spatiotemporal response of individual tumors to treatment. In this paper, we show that a combined pharmacokinetic/pharmacodynamic (PK/PD) modeling approach allows for prediction of the in vitro response of a panel of TNBC cell lines to doxorubicin therapy. This work enables cell line-specific model parameters to be estimated from experimental data, revealing phenotypic heterogeneity in PK/PD properties not previously quantified. More generally, this work provides a template for studies quantitatively investigating treatment response and a scalable approach toward predictions of tumor response in vivo. (By Matthew McKenna, M3)
Antibacterial photosensitization through activation of coproporphyrinogen oxidase.
Surdel MC, Horvath DJ Jr, Lojek LJ, Fullen AR, Simpson J, Dutter BF, Salleng KJ, Ford JB, Jenkins JL, Nagarajan R, Teixeira PL, Albertolle M, Georgiev IS, Jansen ED, Sulikowski GA, Lacy DB, Dailey HA, Skaar EP.
Proc Natl Acad Sci U S A. 2017 Jul 24. pii: 201700469. doi: 10.1073/pnas.1700469114. [Epub ahead of print]
Gram-positive bacteria cause the majority of skin and soft tissue infections (SSTIs), resulting in the most common reason for clinic visits in the United States. Recently, it was discovered that Gram-positive pathogens use a unique heme biosynthesis pathway, which implicates this pathway as a target for development of antibacterial therapies. We report here the identification of a small-molecule activator of coproporphyrinogen oxidase (CgoX) from Gram-positive bacteria, an enzyme essential for heme biosynthesis. Activation of CgoX induces accumulation of coproporphyrin III and leads to photosensitization of Gram-positive pathogens. In combination with light, CgoX activation reduces bacterial burden in murine models of SSTI. Thus, small-molecule activation of CgoX represents an effective strategy for the development of light-based antimicrobial therapies. (By Matthew Surdel, M3)
Co-authorships, Clinical Studies, and Reviews:
IL-6 variant is associated with metastasis in breast cancer patients.
Abana CO, Bingham BS, Cho JH, Graves AJ, Koyama T, Pilarski RT, Chakravarthy AB, Xia F.
PLoS One. 2017 Jul 21;12(7):e0181725. doi: 10.1371/journal.pone.0181725. eCollection 2017.
Misdiagnosis: CNS Erdheim-Chester disease mimicking CLIPPERS.
Berkman J, Ford C, Johnson E, Malow BA, Aulino JM.
Neuroradiol J. 2017 Jan 1:1971400917710251. doi: 10.1177/1971400917710251. [Epub ahead of print]
Instrumented fusion in a 12-month-old with atlanto-occipital dislocation: case report and literature review of infant occipitocervical fusion.
Hale AT, Dewan MC, Patel B, Geck MJ, Tomycz LD.
Childs Nerv Syst. 2017 Jul 6. doi: 10.1007/s00381-017-3497-8. [Epub ahead of print]
A salt-sensing kinase in T lymphocytes, SGK1, drives hypertension and hypertensive end-organ damage.
Norlander AE, Saleh MA, Pandey AK, Itani HA, Wu J, Xiao L, Kang J, Dale BL, Goleva SB, Laroumanie F, Du L, Harrison DG, Madhur MS.
JCI Insight. 2017 Jul 6;2(13). pii: 92801. doi: 10.1172/jci.insight.92801. [Epub ahead of print]