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Isabel L. Jackson, PhD

Academic Title:

Associate Professor

Primary Appointment:

Radiation Oncology

Administrative Title:

Deputy Director Of The Division Of Translational Radiation Sciences (DTRS) In The Department Of Radiation Oncology

Location:

685 West Baltimore Street, MSTF 700-B

Phone (Primary):

410-706-5141

Fax:

410-706-2666

Education and Training

2006      B.S., Microbiology, North Carolina State University

2012      Ph.D., Pathology, Duke University, Durham, NC 

Biosketch

Dr. Isabel “Lauren” Jackson is the Deputy Director of the Division of Translational Radiation Sciences within the Department of Radiation Oncology. Dr. Jackson is a subject matter expert in the field of tumor and normal tissue radiobiology, with specialized expertise in medical countermeasure (MCM) development for acute radiation sickness and delayed effects of acute radiation exposure. Her expertise extends to model development, new target identification, biomarker discovery, schedule optimization, application of disease progression modeling to drug development, and product approval through the U.S. Food and Drug Administration (FDA) Animal Rule regulatory pathway. Studies conducted in Dr. Jackson’s laboratory are performed in compliance with the FDA’s Good Laboratory Practice regulations.

Dr. Jackson is currently a principal or collaborating investigator on a number of industry and federally sponsored contracts and research grants totalling more than $30 million, and serves as Director for the BARDA RadNuc Animal Model Development indefinite-deliverable/indefinite-quantity contract at the UMSOM. Her academic research is focused on improving the ability to translate findings from preclinical models to clinical radiation therapy. Her research takes a systems biology approach to interrogate and understand the mechanisms underlying late radiation tissue effects and identify biomarkers that correlate with tissue damage and recovery or failure in patients using state-of-the-art molecular biology techniques, classic radiobiology approaches, “omics” technologies, and computational biology. She has published extensively on the characterization and refinement of animal models of radiation-induced normal tissue injury that recapitulate the response in humans. Models developed in Dr. Jackson’s laboratory have gone on to receive FDA concurrence as appropriate for use in MCM screens for radiation pneumonitis/fibrosis and have since been used to screen MCMs for industry, the National Institutes of Allergy and Infectious Disease (NIAID)/National Institutes of Health (NIH) and Biomedical Advanced Research and Development Authority (BARDA)–sponsored contracts. 

Dr. Jackson has participated in more than a dozen pre-IND and IND meetings related to MCM development through the FDA Animal Rule. She serves as a member of the University of Maryland Baltimore Institutional Review Board, as an interviewer for the UM SOM admissions committee, and lecturer in the Department of Radiation Oncology board review course for radiation oncology residents and the annual Radiation Biology and Physics review courses. Dr. Jackson has presented her findings at national and international scientific conferences, academic institutions, NIH-sponsored workshops, and to the FDA. She is the senior editor for biology for Advances in Radiation Oncology, a journal of the American Society of Therapeutic Radiation Oncology, and serves as an ad hoc reviewer for peer-reviewed journals including Neuro-Oncology; the International Journal of Radiation Oncology, Biology, Physics; Cancer Research; Radiation Research; the International Journal of Radiation Biology; and the American Journal of Respiratory Cell and Molecular Biology. She is the author of several book chapters on normal tissue tolerance to radiation, mechanisms of injury, and potential therapeutic interventions.

Research/Clinical Keywords

Acute Radiation Sickness (ARS), Delayed Effects of Acute Radiation Exposure, Pulmonary Inflammation, Fibrosis, Medical Countermeasures, Radiomitigators, Late Normal Tissue Toxicity

Highlighted Publications

Jackson IL, Vujaskovic Z, Down J. Revisiting strain-related differences in radiation sensitivity of the mouse lung: recognizing and avoiding the confounding effects of pleural effusions. Radiat Res 2010;173:10–20. PMCID: PMC2818983.

Williams JP, Jackson IL, Shah JR, Czarniecki CW, Maidment BW, DiCarlo AL. Animal models and medical countermeasures development for radiation-induced lung damage: Report from an NIAID workshop. Radiat Res 2012;177(5):e0025–e0039. PMID: 22468702.

Jackson IL, Zhang X, Hadley C, et al. Temporal expression of hypoxia associated genes in lungs following thoracic irradiation. Free Radical Biology Medicine. 53(2):337-346. 2012

Jackson IL, Xu PX, Nguyen G, Down JD, Johnson CS, Katz BP, Hadley C, Vujaskovic Z. Characterization of the dose response relationship for lung injury following acute radiation exposure in three well established murine strains: developing an interspecies bridge to link animal models with human lung. Health Phys. 2014;106(1):48-55. PMID: 24276549.

Jackson IL, Zhang Y, Bentzen SM, Hu J, Zhang A, Vujaskovic Z. Pathophysiological mechanisms underlying phenotypic differences in pulmonary radioresponse. Scientific Reports. 2016.  Nov 15;6:36579. doi: 10.1038/srep36579

Jackson IL, Baye F, Goswami C, Katz BP, Zodda A, Pavlovic R, Gurung G, Winans D, Vujaskovic Z. Gene expression profiles among murine strains segregate with distinct differences in the progression of radiation-induced lung disease. Disease Models and Mechanisms. 2017. [Epub ahead of print]

Additional Publication Citations

Jackson, I.L., Batinic-Haberle, I., Sonveaux, P., Dewhirst, M.W., Vujaskovic, Z.,ROS production and angiogenic regulation by macrophages in response to heat therapy. Int J Hyperthermia 2006 June; (4) 263-73

Jackson, I.L, Chen, L., Batinic-Haberle, I., Vujaskovic, Z., Superoxide dismutase mimetic reduces hypoxia induced O2.-, TGF-beta, and VEGF production by macrophages.  Free Radical Research 2007 Jan; 41 (1): 8-14 

Fleckenstein K, Gauter-Fleckenstein, B., Jackson, I.L., Rabbani, Z.N., Anscher, M., Vujaskovic, Z., Using Biological Markers to Predict Risk of Radiation Injury. Seminars in Radiation Oncology 2007. April; 17 (2): 89-98. Review

Fleckenstein, K., Zgonjanin, L., Chen, L., Rabbani Z., Jackson I.L, Thrasher B., Kirkpatrick J., Foster W.M., Vujaskovic, Z., Temporal onset of hypoxia and oxidative stress after pulmonary irradiation. Int J Rad Onc Biol Phys 2007 68 (1): 196-204

Vujaskovic Z., Thrasher B., Jackson I.L., Brizel M.B., Brizel D. Evaluation of amifostine mediated esophageal radioprotection in a preclinical model. Int J Rad Onc Biol Phys 2007 Oct 1; 69(2): 534-40.

Rabbani ZN, Mi J, Zhang Y, Delong M, Jackson IL, Fleckenstein K, Salahuddin FK, Zhang X, Clary B, Anscher MS, Vujaskovic Z. Hypoxia inducible factor 1a signaling in fractionated radiation induced lung injury: Role of oxidative stress and tissue hypoxia. Radiation Research, 173(2):165-74, 2010.

Jackson I.L., Vujaskovic Z, Down J. Revisiting Strain-Related Differences in Radiation Sensitivity of the Mouse Lung: Recognizing and Avoiding the Confounding Effects of Pleural Effusions. Radiation Research.173 (1): 10-20, 2010.

Yakovlev VA, Rabender CS, Sankala H, Gauter-Fleckenstein B, Fleckenstein K, Jackson IL, Vujaskovic Z, Anscher MS, Mikkelsen RB, Graves PR. Temporal proteomic analysis of radiation-induced protein changes in rat lung: modulation by the superoxide dismutase mimetic MnTE-2-PyP. Int J Radiat Oncol Biol Phys. 2010.

Jackson IL, Vujaskovic Z, Down, JD. A Further comparison of pathologies following thoracic irradiation among different mouse strains: finding the best preclinical model for evaluating therapies directed against radiation induced lung damage. Radiation Research. 175(4):510-18. 175(4): 510-18, 2011.

Beketic-Oreskovic L, Ozretic P, Rabbani ZN, Jackson IL, Sarcevic B, Levanat S, Maric P, Babic I, Vujaskovic Z. Prognostic significance of carbonic anhydrase IX (CA-IX), Endoglin (CD105), and 8-hydroxy-2’deoxyguanosine (8-OHdG) in breast cancer patients. Pathology & Oncology Research. 17(3): 593-603, 2011.

Kelsey C, Jackson L, Langdon S, Owzar K, Hubbs J, Vujaskovic Z, Das S, Marks LB A polymorphism within the promoter of the TGF1 gene is associated with radiation sensitivity using an objective radiologic endpoint. International Journal Radiation Oncology Biology Physics. 82(2): 247-255, 2012

Zhang Y, Zhang X, Rabbani Z, Jackson IL, Vujaskovic Z. Oxidative Stress mediates radiation lung injury by inducing apoptosis. Accepted August 10, 2011. Int J Radiat Oncol Biol Phys. 2012 Jun 1;83(2):740-8

Kimura M, Rabbani Z, Zodda A, Yan H, Jackson IL, Polascik TJ, Donatucci CF, Moul JW, Vujaskovic Z, Koontz BF. Role of Oxidative Stress in a Rat Model of Radiation-Induced Erectile Dysfunction. Journal of Sexual Medicine. 2012 Jun;9(6):1535-49.

DiCarlo A.L, Jackson IL, Shah J, Czarniecki C, Maidment B, Williams J, Commentary: Development and Licensure of Medical Countermeasures to treat Lung Damage Resulting from a Radiological or Nuclear Incident. Radiation Research. 177(5):717-721. 2012

Williams JP, Jackson IL, Shah JR, Czarniecki CW, Maidment BW, DiCarlo AL. Animal Models and Medical Countermeasures Development for Radiation-Induced Lung Damage: Report from an NIAID Workshop. Radiation Research. 177 (5):e0025-39

Jackson IL, Zhang X, Hadley C, et al. Temporal expression of hypoxia associated genes in lungs following thoracic irradiation. Free Radical Biology Medicine. 53(2):337-346. 2012

Jackson IL, Xu P, Hadley C, Katz BP, McGurk R, Down JD, Vujaskovic Z. A preclinical rodent model of radiation-induced lung injury for medical countermeasure screening in accordance with the FDA animal rule. Health Physics. 2012. 103(4): 463-473.

McGurk R, Hadley C, Jackson IL, Vujaskovic Z. Development and dosimetry of a small animal lung irradiation platform. Health Physics. 2012. 103(4):454-462

Kelsey CR, Jackson IL, Langdon S, Owzar K, Hubbs J, Vujaskovic Z, Das S, Marks LB. Analysis of single nucleotide polymorphisms and radiation sensitivity of the lung assessed with an objective radiologic endpoint. Clin Lung Cancer 2013;14:267–274. PMID: 23313170.

Zhou S, Nissao E, Jackson IL, Leong W, Dancy L, Cuttitta F, Vujaskovic Z, Sunday ME. High-dose ionizing radiation-induced lung injury is mitigated by blockade of gastrin-releasing peptide. Am J Pathol 2013;182:1248–1254. PMID: 23395092.

Down JD, Medhora M, Jackson IL, Cline JM, Vujaskovic Z. Do Variations in Mast Cell Hyperplasia Account for Differences in Radiation-Induced Lung Injury among Different Mouse Strains, Rats and Nonhuman Primates? Radiat Res. 2013 Aug; 180(2):216-21. PMID: 23819595

Jackson IL, Xu PX, Nguyen G, Down JD, Johnson CS, Katz BP, Hadley C, Vujaskovic Z. Characterization of the dose response relationship for lung injury following acute radiation exposure in three well established murine strains: developing an interspecies bridge to link animal models with human lung. Health Phys. 2014 Jan; 106(1):48-55. PMID: 24276549

Jones JW, Scott AJ, Tudor G, Xu PT, Jackson IL, Vujaskovic Z, Booth C, MacVittie TJ, Ernst RK, Kane MA. Identification and quantification of biomarkers for radiation-induced injury via mass spectrometry. Health Phys. 2014 Jan; 106(1):106-19. PMID: 24276554

Kimura M, Zodda AR, Mahmood J, Das SK, Nguyen GB, Jackson IL, Vujaskovic Z. Pilot study evaluating a rat model of radiation-induced erectile dysfunction using a image guided microirradiator. Urology. 2015 May; 85(5):1214.e1-6.

Murigi F, Mohindra P, Hung C, Salimi S, Goetz W, Pavlovic R, Jackson IL, Vujaskovic Z. Dose optimization study of AEOL 10150 as a mitigator of radiation induced lung injury in CBA/J mice. Radiation Research.  2015. Oct;184(4):422-32.

Antonic V, Rabbani ZN, Jackson IL, Vujaskovic Z. Bovine SOD attenuates radiation induced lung damage in rats. Free Radic Res. 2015 Oct;49(10):1259-68.

Zhang X, Hadley C, Jackson IL, Rabbani ZN, Zhang A, Batinic-Haberle I, Vujaskovic Z. Hypo-CpG methylation controls PTEN expression and cell apoptosis in irradiated lung. Free Radical Research. 2016Aug;50(8):875-86.

Xu P-T, Maidment III, Jackson IL, Das S, Zoda A, Zhang X, Antonic V, Seal S, Vujaskovic Z. Cerium oxide nanoparticles: a potential medical countermeasure to mitigate radiation induced lung injury in CBA/J mice. Radiation Research. 2016. May 2. [Epub ahead of print]

Dabjan M, Buck C, Jackson IL, Vujaskovic Z, Marples B, Down JD. A survey of changing trends in modeling radiation lung injury in mice: bringing out the good, the bad, and the uncertain. Review. Laboratory Investigation. 2016 Aug 1.doi:10.1038/labinvest.2016.76. [Epub ahead of print]

Mahmood J, Shamah A, Creed M, Pavlovic R, Matsui H, Kimura M, Molitoris J, Shukla H, Jackson IL, Vujaskovic Z. Radiation Induced Erectile Dysfunction: Recent Advances and Future Directions. Advances in Radiation Oncology.  May 23, 2016. Accepted.

Jackson IL, Zhang Y, Bentzen SM, Hu J, Zhang A, Vujaskovic Z. Pathophysiological mechanisms underlying phenotypic differences in pulmonary radioresponse. Scientific Reports. 2016.  Accepted.

Jones JW, Carter CL, Li F, Pierzchalski K, Jackson IL, Vujaskovic Z, Kane MA. Ultraperformance convergence chromatography-high resolution tandem mass spectrometry for lipid biomarker profiling and identification. Biomed Chromatogr. 2016 Aug 24. [Epub ahead of print].

Awards and Affiliations

  • 2006: New Investigator Award, Society for Thermal Medicine
  • 2006: Scholar-In-Training Travel Award, Radiation Research Society
  • 2007: Scholar-In-Training Travel Award, 13th International Congress of Radiation Research
  • 2008: Scholar-In-Training Travel Award, Radiation Research Society
  • 2010: Scholar-In-Training Travel Award, Radiation Research Society
  • 2011: Sponsored by National Institutes of Allergy and Infectious Disease to attend the 14th Inter. Congress Rad Res.
  • 2015: Young Investigators Travel Award, 15th International Congress of Radiation Research

Grants and Contracts

RTOR-RADNUC-1002 (Base)            Vujaskovic/Jackson (CoPIs)                         
BARDA ID/IQ   HHS0100201 50 0009I    
8/2/16 - 12/31/17                              

Establishment of a Preclinical Model of Ionizing Radiation-induced Thrombocytopenia, Coagulopathies and Measures of Associated Vascular and Organ Injury

The objective is to establish a disease progression model for total body irradiation-induced thrombocytopenia, vascular injury and associated etiologies (ex. consumption coagulopathy)across a radiation dose-range to induce the hematopoietic acute radiation syndrome (H-ARS).

HHS0100201100007C                      Jackson (PI)                                              
Aeolus Pharmaceuticals, Inc.                                             
12/1/13 -12/31/16

Amendment 10:  Therapeutic efficacy screening of AEOL10150 in a small animal model: Determining duration, timing, natural history, and mechanism of action  CLIN007

AEOLUS Advanced Development of a AEOL10150 as a Medical Countermeasure of Pulmonary Injury Associated with ARS and DEARE. The overall objective is to bring AEOL 10150 from TRL 7 to FDA Approval as a Medical Countermeasure for Pulmonary Injury Associated with ARS and DEARE.

RTOR-RADNUC-1005                        Vujaskovic/Jackson (Co-PI)                  
BARDA ID/IQ   HHS0100201 50 0009I
09/26/16 - 3/31/18
                                 

A Large Animal Model Study of Host Biomarker Expression Due to In-homogeneous Ionizing Radiation Exposure

The objective is to irradiate a large animal model using four irradiation geometries: 1) bilateral (parallel-opposed) TBI, 2) unilateral (single-field) TBI, 3) upper-torso unilateral (single-field) partial-body irradiation (PBI), and 4) lower torso unilateral (single-field) PBI. Blood samples will be collected at the prescribed time points and shipped to five BARDA designated laboratories for biodosimetric analysis.

R43 AI127113                                   Kaytor/Jackson (multi PI/PD)           
SBIR/NIH; Sub with Humanetics Corp.                                       
09/1/16-8/31/18    

Development of BIO300 as a MCM for lethal radiation pneumonitis/fibrosis

The objective of this technical proposal is to complete early stage drug development for BIO 300 as a mitigator of radiation induced normal tissue injury.

BAA NIAID-DAIT-NOIHAIAI2015042   Jackson (PI)
NIH; Sub with Chrysalis Biotherapeutics   
9/1/16-8/31/19  

Development of TP508 as a mitigator of the hematopoietic subsyndrome of the acute radiation syndrome.

The objective of this technical proposal is to advance the development of TP508 towards FDA approval and licensure under the animal rule for the indication of the mitigation of leukopenia, thrombocytopenia, and vascular injury to improve survival following acute radiation exposure

Varian Medical Systems                         Jackson (PI)                 
12/15/16-12/14/17                                                                                                                           

 

N/A                                                         Jackson (PI)                                              
Departmental Seed Grant 2016
07/1/16-6/30/17                                                 

Use of non-toxic gentamicin to increase expression of p53 in malignancies and selectively increase radiosensitization

In this project, we outline pilot experiments to test a novel mechanism of radiosensitization that would specifically target tumor cells and not normal tissues. 

U01 AI107361                                  Vujaskovic (PI)                               
NIAID (NIH)
05/15/13 - 04/30/18                                                                                

Mitigation of Radiation-Induced Pulmonary Injury with Nrf2 activator

The objective of this proposal is to bring TMC towards pivotal efficacy studies under GLP guidelines in rodent and non-human primates for Investigational New Drug (IND) application and FDA approval under the Animal Rule.

Professional Activity

Institutional Service – University of Maryland School of Medicine

Faculty Interviewer, School of Medicine Admissions Committee

Mentor, Summer Bioscience Internship Program (SBIP)

Member, University of Maryland Institutional Review Board (IRB)

 

National/International Service

Senior Editor - Biology, Advances in Radiation Oncology

Reviewer, International Journal of Hyperthermia

Reviewer, International Journal Radiation Biology

Reviewer, Cancer Research

Reviewer, International Journal of Radiation Biology Oncology Physics

Reviewer, Radiation Research

Reviewer, SpringerPlus

Reviewer, Health Physics

Reviewer, Neuro-Oncology

Reviewer, American Journal of Respiratory Cell and Molecular Biology

Lab Techniques and Equipment

Environment – Contribution to Success

The facility space dedicated to the Division of Translational Radiation Sciences (DTRS) was designed and completely renovated to accommodate the unique needs of preclinical studies conducted in compliance with the U.S. Food and Drug Administration GLP regulations. The layout, furnishings, and equipment selected for the offices, wet lab space, and animal suite areas were all chosen to ensure efficiency of communication and maximize productivity.  The comprehensive resources available in the DTRS facility are complimented by the specialized expertise and technology available through the core services at the University of Maryland, School of Medicine.  Support provided by the internal Veterinary Resources program and various University Offices work in concert with DTRS policies and practices to ensure a safe work environment for both animals and personnel, with an emphasis on integrity and compliance.

Test and Control Article Preparation

The Division’s drug preparation suite is located behind a card-access door and has all of the necessary tools, safety controls, procedures, and documentation practices for mixing test and control articles.

 Small and Large Animal Irradiation Sources

  • 3 - Orthovoltage X-RAD 320 irradiators (Precision X-Ray, Inc.)
  • 1 - Small Animal Radiation Research Platform with onboard CT (X-Strahl)
  • 1 - 21EX Trilogy Linear Accelerator (LINAC) by Varian Medical Systems (+3 clinical back-up LINAC)

 Physiology

  • 2 - Fifteen chamber Buxco Whole Body Plethysmography Systems (Data Sciences International)
  • 1 - Vevo 2100 Small Animal Imaging System, with rodent anesthetic system (VisualSonics, Inc.)
  • 1 - CX 50 Ultrasound System for large animals
  • 1 - GE Medical Systems Model Lightspeed 2.X CT Scanner with 2 MIM workstations for CT analysis
  • Multiple Pulse Oximeters (large and small animals)

 Pathology and Histology

  • 1- Grosslab Pathology Workstation (Thermo Scientific)
  • 1- Axio Imager M2 microscope with AxioCam MRc (Carl Zeiss Microscopy LLC)
  • 2- HM355 Microtome (Thermo Scientific)
  • 2- Nikon Eclipse 50i microscopes
  • 1- Aperio ScanScope CS Slide Digitizer

 Molecular Biology

  • Multiple MasterCycler Pros for RT-PCR (Eppendorf)
  • 1- 96 and 384-well CFX RT- PCR system with automator (Bio-Rad)
  • 2- HT Multi-Detection Microplate Reader (Biotek)
  • 2- Nanodrop spectrophotometer (Thermo Scientific)
  • 1- ChemiDoc MP Gel Imaging System (Bio-Rad)
  • 1- MaxQ500 Shaker (Thermo Scientific)
  • Multiple Sorvall ST16 Centrifuge (Thermo Scientific)
  • Multiple Refrigerated Centrifuge (Eppendorf)
  • 1- PCR Workstation (Thermo Scientific)

 Tissue Culture

  • Multiple Air-Jacketed CO2 Incubator (Nuaire)
  • Multiple Heracell Dual Chamber Incubator (Thermo Scientific)
  • 1- Cell Counter (Beckman Coulter)
  • 3- inverted microscopes (2 Olympus CK2, 1 Nikon TE2000-S with image capture capability),

 Clonogenic Assay

  • Colony Counter and Scanner (Synoptics)

 Clinical Chemistry and Hematology:

  • 3- Beckman Coulter (BC) AcT diff2 hematology analyzer
  • Multiple BC Allegra x-15 centrifuge
  • 1- Hematek automated slide stainer
  • 1- GammaCell Elite 1000 blood irradiator
  • General equipment such as electronic and standard balance, vortex, water bath
  • 1- Alfa Wassermann ACE clinical chemistry analyzer

 Flow Cytometry:

  • 2- BD FACSCalibur with FACSflow supply system

 Other

  • Smart-Vue Wireless Temperature Monitoring and Alarm System (Thermo Scientific)
  • Analytical Balance 220g (Mettler Toledo)
  • Tabletop autoclaves
  • Water baths, vortex mixers, etc. 

Podcast

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Dr. Lauren Jackson discusses radiation exposure, including the effects of a nuclear strike.

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