"Human-Based Models to Study Effects of Space Radiation and Countermeasures”

TRISH Pre-Release WebinarSeptember 20, 2019

KRISTIN FABRE, SENIOR INNOVATION SCIENTISTSCIENCE OFFICETranslational Research Institute for Space Health

Goal for this Webinar

The primary objectives are to provide potentialproposers high-level information regarding the upcoming TRISH Radiation Program and fostercollaborations between experts in diverse fields.

Feedback and outcomes from this webinar will influence structure of the

solicitation

Staying Connected to TRISHSRAD2001 will replace BRASH2001 for this upcoming yearOther TRISH activities on the horizon:

Scientist Program – supporting outstanding researchers and scientists at all stagesPostdoctoral Fellowship: Academy of Bioastronautics

2 year with competitive third yearNext opportunity: Fall 2019

Research Opportunities for Future NASA Flight SurgeonsVisiting ScientistsSenior Science Managers

• Next BRASH2101 will be announced fall 2020• Topics are being considered now...send us your

ideas• Industry Program will start fall/winter 2019

Staying Connected to TRISHThe Orbit: use this network to connect and meet your goals

• Expertise exchange• Training opportunities• Resource sharing

Register: trish.force.com

Share an idea: http://go.pardot.com/l/777423/2019-06-25/4tq

• An overview of TRISH and our mission for reducing space radiation risk

• Concept of this radiation solicitation (SRAD 2001)• How to set up multi-disciplinary teams• Data sharing and data management• What will be a successful TRISH proposal• Timeline for the solicitation

Topics to Cover

Donoviel/SAB 2-27-19

SLIDE/DECK TITLE

www.bcm.edu/spacehealthPartnered with NASA and led by Baylor College of Medicine’s Center for Space Medicine, TRISH is a consortium with the California

Institute for Technology (Caltech) and the Massachusetts Institute for Technology (MIT). A virtual institute, TRISH maintains a small physical footprint in Houston’s Texas Medical Center. Leveraging partnerships with Caltech and MIT – each located in established

hotbeds of health technology – TRISH connects the dots for game changing space health countermeasures and technologies.

Donoviel/SAB 2-27-19

SLIDE/DECK TITLE

www.bcm.edu/spacehealthPartnered with NASA and led by Baylor College of Medicine’s Center for Space Medicine, TRISH is a consortium with the California

Institute for Technology (Caltech) and the Massachusetts Institute for Technology (MIT). A virtual institute, TRISH maintains a small physical footprint in Houston’s Texas Medical Center. Leveraging partnerships with Caltech and MIT – each located in established

hotbeds of health technology – TRISH connects the dots for game changing space health countermeasures and technologies.

Deep Space Exploration

• Delayed Communications• No Resupply + Limited Supplies• No Immediate Return• More Radiation• Confined space

The Translation Research Institute for Space Health (TRISH)

A partner to NASA HRP that takes risksFocused on translating disruptive approaches to reduce risk during deep-space exploration – Health and Performance

Committed to supporting a diverse and intellectually-rich expert community

A lean virtual institute

A Consortium

Funded through a Cooperative agreement with NASA to Baylor College of Medicine• 6-year performance period + 6 more?

In its 3rd year of operations (Established 10/1/16)

Endow our astronauts with tools and knowhow

Performself-reliant medical care

Maintain Physical and Behavioral Health

Mitigatedamage from space radiation and other

environmental hazards

Optimize human health &

performance

TRISH Delivers…KNOWLEDGE

SOFTWARE

HARDWARE

METHODS

PROCEDURES

THERAPEUTICS

TRAINED SCIENTISTS

COMMUNITY

NEW IDEAS EXTENDED REACH

TRISH Investments

Countermeasures & Technology Readiness Description

Countermeasures & Technology Readiness Level

Proof of Concept Market-ready

Risk

Research & Development

1 2 3 4 5 6 7 8 9

Exploring possibilities

Test Feasibility

Mature & Refine Research Technologies & Methods

Demonstration Operations

Implementation

Goals for the "Human-Based Models to Study Effects of Space Radiation and Countermeasures”

1.Determine if complex human in vitro models could be effective for space radiation studies

2.Identify effective countermeasures against high (Linear Energy Transfer) LET ionizing radiation

Determine if complex human in vitro models could be used as an analog for radiation response

• Models that would be selected have demonstrated previous level of characterization for robust, physiologically-relevant response

• Real-time, non-invasive readouts would be a plus• Organs of interest (but not limited to): Cerebrovascular, CV, GI, vascular, BM• Single organ model (deeper dive of tissue to radiation) or multi-organ

(organ-organ cross-talk, non-targeted IR effects)• Short-term (1-3 days) versus longer-term (28 days) studies • Computational biology to fit the pieces into the bigger story of the whole

human

Tissues and Readouts of Interest• Cerebrovascular

• Vascular integrity (barrier function, transporter function), electrophysiological capability, ischemia/hypoxia, inflammatory readouts, demyelination of nerves, edema, biomarkers for cell viability, morphology, microglial function/activation, neural transmitters, lipid processing/metabolism/structure

• Cardiac• Contractility (force, stress), t-tubules or cardiac structure (sarcomere architecture), beat rate, biomarkers (ex. troponins, FABP3,

creatine kinase-MB, BNP), viability, calcium signaling, inflammation, fibrosis, pericarditis, would cardiac node function be of interest?

• Vascular• Barrier function, vascular injury, inflammatory readouts, capillary/artery/vein, thrombosis, necrosis, loss of smooth muscle fibers,

fenestrae, transporter polarity

• Gastrointestinal• Barrier function, crypt structure, stem cell viability, differentiation capability, citrulline (SI mass), FABP, microbiome

• Bone Marrow• Stem cell population , differentiation, cell viability, lymphocyte/granulocyte tracking, apoptosis

• Other? Skin, lung

• ‘OMICS• Cytokine profile• Other tissue injury

biomarkers• Emphasize chronic

inflammation?

Identify Effective Countermeasures Against Ionizing Radiation

• This program will emphasize a variety of approaches to countermeasures… each application should include AT LEAST one non-pharmaceutical/nutritional countermeasure approach

• We are NOT seeking to fund development of new therapeutics• Pharmaceuticals

• Small molecule, biologics, nanoparticle vesicles • Nutritional

• Antioxidants, vitamins/foods• Microbiome

• Non-pharmaceutical/nutritional approaches (examples, but not limited to...)• Genetic editing• Maintaining stem cell populations• Shielding• Bio-electronics • Nanotechnology• Materials• Semi-hibernation (control over proliferation rate )

• Short-term (1-3 days) versus longer-term (28 days) • HIGH LET Ionizing radiation: gamma (control), proton, neutron, GCR• Dose response; low dose studies to match exposure in space

Grant StructurePhase 1• 2-4 Projects funded• Program-structured grant mechanism• Multi-disciplinary Team Grants

• MPS/3D• Radiation biology/physics • Pathology, physiologist • Stem cell• Expertise in countermeasures studied in your project• Computational biology• Modeling/simulation

• 3-year duration…3rd year depending on TRISH renewal• Budget: Year 1 up to $1M TOTAL, Year 2 up to $1M TOTAL, Year 3 up to $1.3M• Year 1: characterizing platform for radiation research • Year 2: countermeasure development and characterization• Year 3: complete countermeasure testing• Regular tag-ups (4-6 weeks)• 6 month (or annual in-person meetings), could it be tagged on to HRP IWS workshop in Jan.• Each year we will re-evaluate progress and help determine subsequent goals

Multidisciplinary Teams Each team must include experts in: radiation biology/physics, complex human in vitro models, computational biology, human stem cells, human pathophysiology and countermeasures

***A network to help you find your team***

Kristin Fabre spacehealthinfo@bcm.edu BCM Innovation Scientist Radiation, complex in vitro models innovation

Data Management

Goal: Build the larger story of the human response to radiation from modular tissue/organ projects supported

• TRISH will set up a secure data storage solution• Partner with PIs to categorizes data you generate that will lead to further

opportunities on developing of the TRISH organ-to-human radiation exposure effort

• Raw data, data glossary and context of the study

***Standardizing protocols and outputs...more to come during the December 1st Webinar

Timeline for the solicitation

Program Grant

SRad-2001 will be funded as a Program grant

Next Webinar

Will cover:• Early December• Standardizing radiation and output parameters• Additional detailed information regarding the

solicitation• Stakeholders for the TRISH radiation program

Q/A and Discussion