Page 326 - 2014 Printable Abstract Book
P. 326
therapeutics that enhance mucosal integrity and thereby prevent infection. Part funded by US Federal
funds from NIAID, NIH, and DHHS: Contract No: HHSN272201000046C.
1
(PS6-03) MicroRNAs as Biomarkers for Radiation Biodosimetry. Molykutty J. Aryankalayil ; Adeola
2
1
1
1
2
Makinde ; Patricia Rivera-Solis ; Sanjeewani Palayoor ; Claire Vanpouille-Box ; Sandra Demaria ; and
2
Norman Coleman , National Cancer Institute, Bethesda, MD and New York University, New York, NY
1
1
Rapid and reliable methods for conducting biological dosimetry are a necessity in the event of a
large-scale nuclear event. Timely and accurate methods are thus critical in order to correctly evaluate and
identify radiation dose exposure and triage appropriately. Alterations in microRNAs (miRNAs), small non-
coding RNAs of 19-22 nucleotides, have been reported in cells/tumors subjected to radiation exposure,
implying that miRNAs play an important role in cellular stress response to radiation. To examine the
possibility of using microRNA as stable blood or plasma-based biomarkers for radiation response, we have
used microRNA microarray analysis. Differential microRNA expression pattern was evaluated (>1.5 fold
and p value <0.05) at 6, 24, 48 h and 7day time points in serum from mice exposed to 2, 4 and 8Gy
irradiation. More differentially expressed microRNAs (up and down) were seen after higher dose of
radiation and later time points. Among the significantly upregulated microRNAs, miR-193b-3p and mir-
92a-3p were consistently upregulated for all doses at earlier time points. Whereas miR-34a, which
regulates G1/S cell cycle checkpoint activation in response to radiation induced DNA damage, showed
consistent upregulation for both low and high doses at later time points up to one week after exposure.
Significant down regulation of miR-150-5p, miR-101, miR-140, miR-29b, miR-193b and miR-30 family of
microRNAs were seen for low and high doses of radiation for all time points up to 7day. Low dose radiation
(2Gy) exposure also resulted in down regulation of a group of microRNAs after one week; whereas these
microRNAs showed upregulation after high dose exposure (8Gy) up to one week. This dose and time
dependent differential microRNA expression pattern might be useful in evaluating radiation response
during and after therapeutic radiation treatment in patients. Ultimately, a combined approach of
identifying plasma-based biomarkers by assessing functional miRNA, target mRNAs and the resulting
proteins to assess radiation exposure after mass-casualty incidents could provide a valuable tool in
developing and implementing effective and timely medical countermeasures.
(PS6-04) Biodosimeter development process, progress and challenges. Lynne M.K. Wathen, PhD; Paul
Eder, PhD; Donna Boston, MS; Bonnie Shen; and Rodney Wallace, US Dept. of Health and Human Services,
Washington, DC
A large-scale radiological or nuclear incident in a large metropolitan setting would result in an
immediate critical need to assess potentially dangerous exposures received by tens of thousands of
individuals to allow for prompt triage and appropriate medical treatment decisions. Measuring the
individual absorbed dose levels will require system architecture or a system of platforms that
contains diverse, integrated diagnostic and dosimetric tools that are accurate and precise. For large-scale
incidents, precision, rapidity, and ease of screening are essential. The Biomedical Advanced Research and
Development Authority (BARDA) within the HHS Office of the Assistant Secretary for
Preparedness and Response coordinates and administers programs for the advanced development and
acquisition of emergency medical diagnostics. The Diagnostics and Medical Devices Division
324 | P a g e
funds from NIAID, NIH, and DHHS: Contract No: HHSN272201000046C.
1
(PS6-03) MicroRNAs as Biomarkers for Radiation Biodosimetry. Molykutty J. Aryankalayil ; Adeola
2
1
1
1
2
Makinde ; Patricia Rivera-Solis ; Sanjeewani Palayoor ; Claire Vanpouille-Box ; Sandra Demaria ; and
2
Norman Coleman , National Cancer Institute, Bethesda, MD and New York University, New York, NY
1
1
Rapid and reliable methods for conducting biological dosimetry are a necessity in the event of a
large-scale nuclear event. Timely and accurate methods are thus critical in order to correctly evaluate and
identify radiation dose exposure and triage appropriately. Alterations in microRNAs (miRNAs), small non-
coding RNAs of 19-22 nucleotides, have been reported in cells/tumors subjected to radiation exposure,
implying that miRNAs play an important role in cellular stress response to radiation. To examine the
possibility of using microRNA as stable blood or plasma-based biomarkers for radiation response, we have
used microRNA microarray analysis. Differential microRNA expression pattern was evaluated (>1.5 fold
and p value <0.05) at 6, 24, 48 h and 7day time points in serum from mice exposed to 2, 4 and 8Gy
irradiation. More differentially expressed microRNAs (up and down) were seen after higher dose of
radiation and later time points. Among the significantly upregulated microRNAs, miR-193b-3p and mir-
92a-3p were consistently upregulated for all doses at earlier time points. Whereas miR-34a, which
regulates G1/S cell cycle checkpoint activation in response to radiation induced DNA damage, showed
consistent upregulation for both low and high doses at later time points up to one week after exposure.
Significant down regulation of miR-150-5p, miR-101, miR-140, miR-29b, miR-193b and miR-30 family of
microRNAs were seen for low and high doses of radiation for all time points up to 7day. Low dose radiation
(2Gy) exposure also resulted in down regulation of a group of microRNAs after one week; whereas these
microRNAs showed upregulation after high dose exposure (8Gy) up to one week. This dose and time
dependent differential microRNA expression pattern might be useful in evaluating radiation response
during and after therapeutic radiation treatment in patients. Ultimately, a combined approach of
identifying plasma-based biomarkers by assessing functional miRNA, target mRNAs and the resulting
proteins to assess radiation exposure after mass-casualty incidents could provide a valuable tool in
developing and implementing effective and timely medical countermeasures.
(PS6-04) Biodosimeter development process, progress and challenges. Lynne M.K. Wathen, PhD; Paul
Eder, PhD; Donna Boston, MS; Bonnie Shen; and Rodney Wallace, US Dept. of Health and Human Services,
Washington, DC
A large-scale radiological or nuclear incident in a large metropolitan setting would result in an
immediate critical need to assess potentially dangerous exposures received by tens of thousands of
individuals to allow for prompt triage and appropriate medical treatment decisions. Measuring the
individual absorbed dose levels will require system architecture or a system of platforms that
contains diverse, integrated diagnostic and dosimetric tools that are accurate and precise. For large-scale
incidents, precision, rapidity, and ease of screening are essential. The Biomedical Advanced Research and
Development Authority (BARDA) within the HHS Office of the Assistant Secretary for
Preparedness and Response coordinates and administers programs for the advanced development and
acquisition of emergency medical diagnostics. The Diagnostics and Medical Devices Division
324 | P a g e
