NanoRacks-The Investigation of Countermeasures to Modulate and Augment the Immune System (NanoRacks-ISS University Research (UR) - 1) - 09.27.17

Overview | Description | Applications | Operations | Results | Publications | Imagery

ISS Science for Everyone

Science Objectives for Everyone
Crew members are exposed to radiation and microgravity during space missions, which harms their immune systems and causes other negative health effects. NanoRacks-The Investigation of Countermeasures to Modulate and Augment the Immune System (NanoRacks-ISS University Research (UR)-1) studies a chemical compound that fights some of these ill effects by enhancing immune cells. The immune-boosting compound, called benzofuran-2-carboxylic acid, also shows promise for improving treatment in cancer patients on Earth.
Science Results for Everyone
Microgravity and radiation exposure in space suppress human immune systems. Previous studies report that benzofuran-2-carboxylic acid and its derivatives (KMEG) may provide protection from radiation and restore normal immune function. In this study, microgravity exposure changed expression of 78 lymphocyte genes. Subsequent treatment with KMEG induced upregulation of six genes involved in T cell early response, lymphocyte activation, growth, and proliferation, and downregulation of five genes involved in tumor progression and metastasis. These findings suggest KMEG diminishes microgravity induced immune dysfunction, advancing development of countermeasures to mitigate risks to crews.

The following content was provided by Alamelu Sundaresan, Ph.D., and is maintained in a database by the ISS Program Science Office.
Experiment Details

OpNom: NanoRacks Module-9 Ext (S/N 1001)

Principal Investigator(s)
Alamelu Sundaresan, Ph.D., Texas Southern University, Houston, TX, United States

Karla-Sue C. Marriott, Ph.D., Savannah State University, Savannah, GA, United States
Richard Wilkins, Ph.D., Prairie View A&M University, Prairie View, TX, United States
Jinghe Mao, Ph.D., Tougaloo College, Tougaloo, MS, United States
Shakhawat Bhuiyan, Ph.D., Jarvis Christian College, Hawkins, TX, United States

NanoRacks, LLC, Webster, TX, United States

Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)

Sponsoring Organization
Human Exploration and Operations Mission Directorate (HEOMD)

Research Benefits
Information Pending

ISS Expedition Duration
March 2014 - September 2014

Expeditions Assigned

Previous Missions
Information Pending

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Experiment Description

Research Overview

  • Microgravity and radiation exposure experienced during space flights result in immune system suppression.
  • NanoRacks-The Investigation of Countermeasures to Modulate and Augment the Immune System (NanoRacks-ISS University Research (UR) – 1) is contributory toward the development of solutions to immune system and radiation risks that have plagued NASA and its crew members for years and includes the study of the effects of radiation and microgravity in these phenomena since they are the most significant impediments to humans on long term exploration missions.
  • The initial findings on the efficacy of these compounds reveal inhibitive properties for cancer cell proliferation and restorative properties for immune cells exposed to radiation. Further, preliminary results indicated that the combination of benzofuran-2-carboxylic acid derivatives with radiation significantly enhanced the killing of lymphoblastoid cells (TK6) more effectively in comparison to synthetic benzofuran-2-carboxylic acid derivatives alone or radiation alone. These findings support the potential use of the compounds in the treatment of cancer and the restoration of the immune system.


The goal of this project is to study and understand the role and mechanisms of benzofuran-2-carboxylic acid derivatives supplementation in the prevention of immunosuppression observed in the space flight environment. It is hypothesized that benzofuran-2-carboxylic acid derivatives possess anti-cancer effects and/or enhance the sensitivity of immune cancer cells to radiation exposure.
NanoRacks-The Investigation of Countermeasures to Modulate and Augment the Immune System (NanoRacks-ISS University Research (UR) – 1) begins with the development and refinement of a synthetic pathway for efficient production of synthetic benzofuran-2-carboxylic acid derivatives on the ground. The compounds are provided to mix with the cell culture media for the treatment of human Lymphocytes and TK6 Lymphoblastoids during ground preparation for flight.
In the International Space Station (ISS) environment, the cells, cultured with the synthesized ligands (benzofuran-2-carboxylic acids), are exposed to microgravity and radiation. Radiation Area Monitors (RAMs) are strategically placed on the NanoRacks unit to capture radiation energy. The data captured is used to assess and characterize the ability of the synthesized ligands to augment immune parameters in human lymphocytes and TK6 Lymphoblastoids by evaluation of cellular and molecular mechanisms after supplementation of benzofuran-2-carboxylic acid derivatives and exposure to microgravity and radiation.
Preliminary results indicated augmentation of lymphocyte proliferation and increase in corresponding cytokines upon lymphocyte treatment with benzofuran-2-carboxylic acid derivatives in modeled microgravity and radiation protection of normal lymphocytes with radiation treatment (gamma). Further, the effects of radiation exposure to the signal transduction pathway on mitogen-activated protein (MAP) kinases that regulate various cellular activities were studied. Our preliminary results indicate that the combination of benzofuran-2-carboxylic acid derivatives with radiation significantly enhanced the killing of lymphoblastoid cells (TK6) more effectively in comparison to synthetic benzofuran-2-carboxylic acid derivatives alone or radiation alone.
In order to characterize the ISS radiation environment, NanoRacks-ISS University Research (UR) – 1 places two NASA RAM devices (radiation dosimeters), one internally and one externally on the Module. Data obtained is used to:
a. Determine the local radiation environment for the ISS biological experiment(s) which gives investigators information that can be used to assess damage and degradation to cells and animal tissue.
b. Compare the local radiation measurements to onboard radiation measurements from existing dosimeters.
c. Compare the local radiation measurements to model calculations of local radiation dose for that particular location on ISS. These comparisons help validate the models.
d. Compare radiation dosimetry measurements to ground based experiments.

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Space Applications
Drugs made from a chemical known as benzofuran-2-carboxylic acid could be used to enhance astronauts’ immune systems during spaceflight. Previous research shows the chemical could be used to boost immune cells that were exposed to simulated microgravity and radiation. A drug that could counteract these negative effects would benefit current and future space missions.

Earth Applications
Previous research on benzofuran-2-carboxylic acid shows that drugs derived from this chemical compound could suppress cancer cells and increase immune cells. More detailed research on these compounds may someday improve cancer treatment on Earth.

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Operational Requirements and Protocols

Crew time is required to handle the logistics associated with the conduct of the experiment (i.e., administration of fixative). Cell culture requirements are: late load for +4°C transport to ISS, warm to ambient temperature, growth in 6.5% CO2 (as provided by the silicon tubes, deactivation after two weeks, return by 30 days from mission end.

Ten tubes, each enclosed in two polyethylene bags filled with a 6.5% CO2 environment, are contained in a NanoRack 2.5U module. Upon arrival to the ISS, the NanoRacks module and its contents are stored at +4<°C for 3 days until placement in the BioServe CGBA. The silicon tubes are utilized by crew to allow sample growth in a 6.5% CO2 environment and for release of a fixative at 7 days ops (no less than 6 days). After the NanoRacks module, with tubes, is removed from the BioServe CGBA, the clamps on each tube are released to allow the mixing of the fixative. The tubes are shaken to assure proper distribution of the fluids in the tube. After the release of the fixative, the tubes must be stored as follows until return to the investigator: Tubes 1, 2, 5, 7, 8 at at +4°C; Tubes 3, 4, 6, 9, 10 at -80°C. RAM dosimeters are strategically positioned internal and external to the NanoRacks Module-9 Ext. Upon termination of the experiment on the ISS, both RAMs are stored with the cells at +4°C until return to the investigator.

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Decadal Survey Recommendations

Information Pending

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Results/More Information

This study evaluated the effect of benzofuran-2-carboxylic acid and its derivatives (KMEG) on global gene expression in microgravity. Past literature has reported that, in microgravity simulations, KMEG can protect from radiation and restore normal immune function. Lymphocytes exposed to microgravity for 6 days showed that 78 genes were differentially expressed relative to ground controls. Treatment with KMEG for microgravity lymphocytes induced a significant upregulation of 6 genes related to T cell proliferation; namely, CDCA 7, RAB 17, RPSA, YME1L-1, LY96, and AIF1, as well as the downregulation of 5 genes; namely, ANKHD1, AVP, TINAG L1, CDK5RA 2, and FYN. Some of the upregulated genes are involved in early response, lymphocyte activation, growth, and proliferation. More specifically, membrane trafficking, cell adhesion, differentiation, migration, signaling and anti-inflammatory effects. Some of the downregulated genes are involved in tumor progression that provides signals for cell survival, increased mitosis, invasion, and metastasis. These findings suggest that KMEG diminishes the immune dysfunction prompted by a microgravity environment. This research advances the development of countermeasures to mitigate the medical and physiological risks posed to crew members.

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Results Publications

    Okoro E, Mann V, Ellis I, Mansoor E, Olamigoke L, Marriott KC, Denkins P, Williams W, Sundaresan A.  Immune modulation in normal human peripheral blood mononuclear cells (PBMCs) (Lymphocytes) in response to benzofuran-2-carboxylic acid derivative KMEG during spaceflight. Microgravity Science and Technology. 2017 August; 29(4): 331-336. DOI: 10.1007/s12217-017-9551-z.

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Ground Based Results Publications

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ISS Patents

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Related Publications

    Martinelli LK, Russomano T, dos Santos MA, Falcao FP, Bauer ME, Machado A, Sundaresan A.  Effect of microgravity on immune cell viability and proliferation. IEEE Aerospace and Electronic Systems Magazine. 2009 July; 28(4): 85-90. DOI: 10.1109/MEMB.2009.933572.

    Marriott KC, Bartee R, Morrison AZ, Stewart L, Wesby J.  Expedited Synthesis of Benzofuran-2-Carboxylic Acids via Microwave-Assisted Perkin Rearrangement Reaction. Tetrahedron Letters. 2012 June 27; 53(26): 3319-3321. DOI: 10.1016/j.tetlet.2012.04.075.

    Zwieb C, Bhuiyan S.  Archaea Signal Recognition Particle Shows the Way. Archaea. 2010; 2010: 1-11. DOI: 10.1155/2010/485051.

    Hada M, Gersey B, Saganti PB, Wilkins R, Cucinotta FA, Wu H.  mBAND analysis of chromosome aberrations in human epithelial cells induced by γ-rays and secondary neutrons of low dose rate. Mutation Research - Genetic Toxicology and Environmental Mutagenesis. 2010 August 14; 701(1): 67-74. DOI: 10.1016/j.mrgentox.2010.03.009. PMID: 20338263.

    Sundaresan A, Pellis NR.  Cellular and Genetic Adaptation in Low-gravity Environments   . Annals of the New York Academy of Sciences. 2009 April; 1161(1): 135-146. DOI: 10.1111/j.1749-6632.2009.04085.x.

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Related Websites

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The NanoRacks Module-9 Ext Hardware contains the NanoRacks-ISS University Research (UR) – 1 investigation. Image courtesy of NanoRacks, LLC. 

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