J. Tyson McDonald, PhD
Adjunct Researcher
Center of Cancer Systems Biology
Mailing Address:
39 Tyler Street, Room 200
Cancer Research Center, Hampton University
Hampton, VA 02668 USA
Email: john.mcdonald [at] hamptonu.edu
Education and Training:
• PhD in Biomedical Physics, University of California Los Angeles
• BS in Nuclear Engineering, University of Michigan Ann Arbor
Research Description:
The classic outcomes of radiation exposure — like cell cycle arrest, apoptosis, and senescence — may form barriers to the introduction of genomic instability and cancer, but these are sometimes circumvented by cellular resistance mechanisms that may be up-regulated to enhance the probability of survival. Ionizing radiation is an exogenous stress that has powerful effects on cell death and multiple signaling pathways. The pathways that are activated within the signaling network therefore serve as targets for interventions aimed at controlling responses in potentially harmful environments. My research is focused on the long-term molecular effects of actue and chronic exposures to high and low-dose ionizing radiation.
Along with using commercially
available cell cultures for in vitro studies, my research
includes normal tissues from clinically indicated robotic-assisted
laparoscopic radical prostatectomies. Tissues were grossly
identified, sectioned into frozen or formalin fixed samples, and
processed as primary cultures. Normal epithelial and fibroblast
primary cell cultures were derived from regions of normal tissue,
as confirmed by analysis on adjacent tissues by hematoxylin and eosin
staining, and were exposed to actue doses of radiation from a Cesium-137
source (0.5cGy per min.) or chronic irradiation using a Cobalt-57
source (1–2cGy per day). The result of this research aims to uncover
an appreciation of cell–cell signaling within a tissue
microenvironment that is critical to understanding cellular response
to low-dose ionizing radiation outside the realm of cell death.
Publications:
(click on title to go to manuscript abstract)
- Beheshti A, Wage J, McDonald JT, Lamont C, Peluso M,
Hahnfeldt P, Hlatky L. Tumor-host signaling interaction reveals a
systemic, age-dependent splenic immune influence on tumor
development. Oncotarget. 2015 Oct 21. DOI:
10.18632/oncotarget.6214. [Epub ahead of print] [Open Access]
- Beheshti A, Benzekry S, McDonald JT, Ma L, Peluso M,
Hahnfeldt P, Hlatky L. Host age is a systemic regulator of gene expression
impacting cancer progression. Cancer Res. 2015 Mar
15;75(6):1134-43. Epub 2015 Mar
2. PMCID: PMC4397972.
- Sasi S, Song J, Park D, Enderling H, McDonald JT,
Gee H, Garrity B, Shtifman A, Yan X, Walsh K, Natarajan M,
Kishore R, Goukassian DA. TNF-TNFR2/p75 signaling inhibits early and
increases delayed non-targeted effects in bone marrow-derived
endothelial progenitor cells. J Biol Chem. 2014 May
16;289(20):14178-93. Epub 2014 Apr 7. PMCID: PMC4022885. [Open Access]
- Gao X, McDonald JT, Naidu M, Hahnfeldt P, Hlatky L. A proposed quantitative index for assessing the potential
contribution of reprogramming to cancer stem cell kinetics. Stem
Cells Int. 2014 May 12;2014:249309. Epub 2014 Apr
17. PMCID: PMC4052692. [Open Access]
- McDonald JT, Briggs C, Szelag H, Peluso M, Schneider D,
Perepletchikov A, Klement GL, Tuerk I, Hlatky L. Chronic low dose-rate radiation down-regulates
transcription related to mitosis and chromosomal movement similar
to acute high dose in prostate cells. Int J Radiat Biol. 2014
Mar;90(3):231-40. Epub 2014 Jan 8.
- Beheshti A, Pinzer BR, McDonald JT, Stampanoni M,
Hlatky L. Early tumor development captured through nondestructive, high resolution differential phase contrast X-ray imaging. Radiat
Res. 2013 Nov;180(5):448-54. Epub 2013 Oct 14. PMCID: PMC3925470.
- Gao X, McDonald JT, Hlatky L, Enderling H. Acute and
fractionated irradiation differentially modulate glioma stem cell
division kinetics. Cancer Res. 2013 Mar 1;73(5):1481-90. Epub 2012
Dec 26. PMCID: PMC3594421. [Open Access]
- Rietman EA, McDonald JT, Hlatky L. Organism mutation
stability and cancer. In: Shoja MM, Agutter PS, Tubbs RS, Ghanei M,
Ghabili K, Harris A, Loukas M (eds). Hypotheses
in Clinical Medicine. Nova Science Publishers, Inc.;
2013:135-46.
- Gao X, McDonald JT, Hlatky L, Enderling H. Cell-Cell
Interactions in Solid Tumors — the Role of Cancer Stem Cells. In: D'Onofrio A, Cerrai P, Gandolfi A (eds). New Challenges for Cancer Systems
Biomedicine. Milan, Italy: Springer, 2012:191-204. In
Series: SIMAI Springer Series: Bellomo N, Formaggia L, Bangerth W,
Nobile F, Pareschi L, Tercero PP, Tosin A, Zubelli JP (series eds).
- McDonald JT, Kim K, Norris AJ, Vlashi E, Phillips TM,
Lagadec C, Della Donna L, Ratikan J, Szelag H, Hlatky L, McBride
WH. Ionizing radiation activates the Nrf2 antioxidant
response. Cancer Res. 2010 Nov 1;70(21):8886-95. Epub 2010 Oct
12. PMCID: PMC2970706. [Open Access]
- Kim K, Pollard JM, Norris AJ, McDonald JT, Sun Y,
Micewicz E, Pettijohn K, Damoiseaux R, Iwamoto KS, Sayre JW,
Price BD, Gatti RA, McBride WH. High-throughput screening
identifies two classes of antibiotics as radioprotectors:
tetracyclines and fluoroquinolones. Clin Cancer Res. 2009 Dec
1;15(23):7238-45. Epub 2009 Nov 17. PMCID: PMC2787903. [Open Access]
- Vlashi E, Kim K, Lagadec C, Donna LD, McDonald JT,
Eghbali M, Sayre JW, Stefani E, McBride W, Pajonk F. In vivo
imaging, tracking, and targeting of cancer stem cells. J Natl
Cancer Inst. 2009 Mar 4;101(5):350-9. Epub 2009 Feb 24. Erratum
in: J Natl Cancer Inst. 2009 Jun 3;101(11):833. PMCID:
PMC2727141. [Open
Access]
- Brush J, Lipnick SL, Phillips T, Sitko J, McDonald
JT, McBride WH. Molecular mechanisms of late normal tissue
injury. Semin Radiat Oncol. 2007 Apr;17(2):121-30.