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        <ExplanationTxt>KOREA ADVANCED INSTITUTE OF SCIENCE &amp; TECHNOLOGY (KAIST): THE GRANT TO KAIST WILL SUPPORT EUNHO CHOI, WHO IS ENGINEERING A NEW TYPE OF PROBIOTIC THAT CAN SPECIFICALLY TARGET AND ELIMINATE GROUP B STREPTOCOCCUS (GBS), A DANGEROUS BACTERIUM THAT CAN CAUSE INFECTIONS IN NEWBORNS AND ADULTS. THIS ENGINEERED PROBIOTIC WILL BE TESTED USING A "COLON-ON-A-CHIP" MODEL, WHICH MIMICS THE HUMAN GUT AND ALLOWS SCIENTISTS TO STUDY HOW THE TREATMENT WORKS WITHOUT USING ANIMALS. THE GOAL IS TO CREATE A SAFE AND EFFECTIVE TREATMENT FOR GBS INFECTIONS WHILE PRESERVING THE BALANCE OF HEALTHY GUT BACTERIA. THIS PROJECT COULD ALSO REDUCE THE NEED FOR ANIMAL TESTING IN THE FUTURE AND IMPROVE OUR UNDERSTANDING OF HOW BACTERIA INTERACT IN THE HUMAN BODY. MASARYK UNIVERSITY: A GRANT WAS GIVEN TO MASARYK UNIVERSITY TO SUPPORT ELISKA REHURKOVA'S WORK TO CREATE A HUMAN-RELEVANT MODEL TO UNDERSTAND THE STAGES OF MALE SEX HORMONE PRODUCTION WITHIN THE TESTES, RECOGNIZING THE ROLE ENVIRONMENTAL POLLUTANTS AND DRUGS PLAY IN DISRUPTING THEIR LEVELS DURING DEVELOPMENT. ELISKA WILL DIFFERENTIATE HUMAN INDUCED PLURIPOTENT STEM CELLS INTO LEYDIG CELLS, CELLS OF THE TESTES THAT PRODUCE ANDROGENS, AND TRANSITION THE CELLS INTO 3D CELL CULTURE. SHE WILL CHARACTERIZE THE MODEL, VALIDATE IT WITH SELECT REFERENCE CHEMICALS, AND COMPARE HER FINDINGS TO THOSE OF OTHER EXISTING MODEL SYSTEMS. HER PROJECT REPRESENTS A CRUCIAL ADVANCEMENT IN MALE REPRODUCTIVE TOXICOLOGY, AS SHE IS DEVELOPING A SYSTEM THAT CAN ALLOW FOR THE TESTING OF ENVIRONMENTAL POLLUTANTS AND CHEMICALS ON TESTICULAR STEROIDOGENESIS IN A HUMAN-RELEVANT, ANIMAL-FREE CELL MODEL.</ExplanationTxt>
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        <FormAndLineReferenceDesc>SCHEDULE I PART II COLUMN H</FormAndLineReferenceDesc>
        <ExplanationTxt>CORNELL UNIVERSITY (NEW YORK): THE GRANT WAS GIVEN TO CORNELL UNIVERSITY IN NEW YORK TO SUPPORT THE RESEARCH CONDUCTED BY YANSONG (HARRY) PENG. HARRY'S RESEARCH FOCUSES ON "A TISSUE-ENGINEERED PANCREATIC CANCER MODEL FOR DISSECTING THE ROLES OF LYMPHATIC VESSELS IN TUMOR IMMUNITY." DUKE UNIVERSITY (NORTH CAROLINA): THE GRANT WAS GIVEN TO DUKE UNIVERSITY TO SUPPORT THE RESEARCH CONDUCTED BY MINGZHI XU, "AN INTEGRATED MICROFLUIDIC SYSTEM WITH ENGINEERED BLOOD VESSEL MIMIC AND SKELETAL MUSCLE TO INVESTIGATE THE RELATION BETWEEN RHEUMATOID ARTHRITIS AND ATHEROSCLEROSIS." RHEUMATOID ARTHRITIS (RA) IS A CHRONIC INFLAMMATORY AUTOIMMUNE DISEASE THAT PRIMARILY TARGETS THE JOINTS, BUT ALSO SYSTEMICALLY PROMOTES INFLAMMATION. PATIENTS WITH RA EXPERIENCE MUSCLE WEAKNESS AND ELEVATED INFLAMMATORY CYTOKINES IN THEIR CIRCULATION HAVE INCREASED ATHEROSCLEROSIS, WHICH LEADS TO A HIGHER CARDIOVASCULAR DISEASE (CVD) RISK. SYSTEMIC INFLAMMATION PLAYS AN IMPORTANT ROLE IN ATHEROSCLEROSIS, AND AUTOIMMUNE DISEASES SUCH AS RA ACCELERATE ATHEROSCLEROSIS DUE TO ELEVATED SYSTEMIC INFLAMMATION. ANIMAL MODELS AVAILABLE FOR EITHER ATHEROSCLEROSIS OR RHEUMATOID ARTHRITIS HAVE LIMITATIONS, WITH PHENOTYPES THAT ARE COMPLICATED TO PRODUCE AND TAKE A LONG TIME TO DEVELOP. IN THIS PROPOSAL, MINGZHI WILL LINK TISSUE ENGINEERED BLOOD VESSELS (TEBV) AND ENGINEERED SKELETAL MUSCLE MYOBUNDLES MADE WITH HUMAN CELLS TO PRODUCE AN INTEGRATED SYSTEM. THIS SYSTEM WILL BE USED TO INVESTIGATE THE INTERACTION OF BLOOD VESSELS AND MUSCLE IN RA TO IDENTIFY THERAPEUTICS THAT LACK TOXICITY AND DEMONSTRATE EFFICACY IN HUMANS. JOHNS HOPKINS UNIVERSITY: A GRANT WAS GIVEN TO JOHNS HOPKINS TO SUPPORT THE RESEARCH CONDUCTED BY DOWLETTE-MARY ALAM EL DIN, "DEVELOPING COGNITION-IN-A-DISH TO INVESTIGATE THE IMPACT OF CHRONIC LOW DOSE DOMOIC ACID EXPOSURE ON NERUONAL DEVELOPMENT AND FUNCTION." DOMOIC ACID (DA) IS A NEUROTOXIN PRODUCED BY ALGAE BLOOMS THAT CAN CONTAMINATE SHELLFISH AND LEAD TO CELLULAR AND STRUCTURAL BRAIN DAMAGE IN EXPOSED HUMANS. ITS PRESENCE IN COASTAL AREAS HAS BECOME MORE FREQUENT DUE TO CLIMATE CHANGE CAUSING AN INCREASE IN THE NUMBER OF HARMFUL ALGAE BLOOMS. MOST STUDIES INVESTIGATING THE ROLE OF DA IN COGNITIVE IMPAIRMENT HAVE BEEN CONDUCTED IN ANIMAL MODELS, BUT DO NOT PROVIDE A BIOLOGICALLY RELEVANT MODEL FOR HUMAN COGNITIVE DEVELOPMENT. IN THIS PROPOSAL, DOWETTE PLANS TO DEVELOP A COGNITION-IN-A-DISH MODEL USING A HUMAN BRAIN ORGANOID TO INVESTIGATE THE EFFECTS OF CHRONIC LOW-DOSE DA EXPOSURE NEURODEVELOPMENTAL EVENTS, FUNCTIONAL NEURAL NETWORK FORMATION, AND COGNITIVE FUNCTIONS. IDENTIFICATION OF THE PATHWAYS THROUGH WHICH DA DISRUPTS COGNITIVE FUNCTION WILL IMPACT HUMAN HEALTH AND SAFETY BY INFORMING REGULATORY GUIDELINES FOR EXPOSURE. HARVARD UNIVERSITY: THE GRANT TO HARVARD IS IN SUPPORT OF ZEKE BENSHIRIM'S PROJECT, IN WHICH HE IS DEVELOPING A METHOD TO ENHANCE THE STRUCTURAL INTEGRITY OF BRAIN ORGANOIDS, WHICH CURRENTLY LOSE THEIR ORGANIZATION OVER TIME, LIMITING THEIR ABILITY TO ACCURATELY MIMIC HUMAN BRAIN DEVELOPMENT AND DISEASES LIKE EPILEPSY AND ALZHEIMER'S. TO ADDRESS THIS, ZEKE WILL REPLICATE THE NATURAL PROCESS OF NEURAL TUBE INFLATION BY CAREFULLY/PRECISELY INJECTING FLUID INTO THE CORE OF THE ORGANOID, MAINTAINING ITS STRUCTURE, AND PROMOTING PROPER GROWTH. THIS RESEARCH COULD LEAD TO MORE RELIABLE MODELS FOR STUDYING NEUROLOGICAL DISEASE AND TESTING TREATMENTS, OFFERING A POWERFUL ALTERNATIVE TO ANIMAL TESTING. NEW YORK UNIVERSITY: THE GRANT TO NEW YORK UNIVERSITY WILL SUPPORT LUNAN LIU'S PROJECT TO DEVELOP A HUMAN ORGAN-ON-ACHIP/ORGANOID SYSTEM TO INVESTIGATE PANCREATIC CANCER, A HIGHLY MALIGNANT CANCER THAT RESPONDS POORLY TO DRUGS AND IMMUNOTHERAPIES. TO MORE ACCURATELY REPRESENT COMPLEXITY SEEN IN VIVO, LUNAN WILL GENERATE CHIP MODELS THAT INCLUDE STROMAL, IMMUNE AND BLOOD VESSEL COMPONENTS, IN ADDITION TO ORGANOIDS DERIVED FROM THE CELLS OF DIFFERENT PANCREATIC CANCER PATIENTS TO BETTER UNDERSTAND HOW AND WHY THE CANCER IS DIFFICULT TO TREAT WITH IMMUNOTHERAPIES, AND WHY DIFFERENT PATIENTS HAVE DIFFERENT RESPONSES TO TREATMENTS. IN ADDITION TO BEING MORE HUMAN-RELEVANT, THE MODEL CAN PRODUCE MORE DATA AND DO SO MORE QUICKLY THAN ANIMAL MODELS WHILE BETTER REPRESENTING THE DIVERSITY OF THE HUMAN POPULATION THAN INBRED MOUSE MODELS TYPICALLY USED TO STUDY THE CONDITION. UNIVERSITY OF CALIFORNIA LOS ANGELES: WITH THE GRANT TO UCLA, CLAUDIA NGUYEN IS PLANNING TO STUDY HUMAN BRAIN DEVELOPMENT USING ORGANOIDS AND WILL SPECIFICALLY EXAMINE HOW THE THALAMUS INFLUENCES GENE EXPRESSION AND CELL TYPES OF THE CORTEX. IN THIS PROJECT, CLAUDIA WILL CREATE ORGANOIDS OF BOTH BRAIN REGIONS AND FUSE THEM TOGETHER AND MONITOR CHANGES ACROSS THREE TIME POINTS DURING DEVELOPMENT, COMPARED TO A CONTROL IN WHICH ONLY CORTICAL ORGANOIDS ARE FUSED. IMPORTANTLY, SHE WILL COMPARE THE DATA OBTAINED FROM HER ORGANOID MODEL TO DATA COLLECTED FROM HUMAN CORTEX AND THALAMUS TISSUES AT DIFFERENT STAGES OF DEVELOPMENT. THIS APPROACH WILL REDUCE RELIANCE ON ANIMALS, WHICH ARE COMMONLY USED IN NEUROSCIENCE RESEARCH, WHILE ALSO PROVIDING A BASELINE OF EVENTS THAT TAKE PLACE DURING TYPICAL BRAIN DEVELOPMENT, WHICH WILL BE USEFUL FOR UNDERSTANDING NEURODEVELOPMENTAL AND NEUROPSYCHIATRIC DISORDERS. UNIVERSITY OF DELAWARE: THE GRANT WAS GIVEN TO THE UNIVERSITY OF DELAWARE TO SUPPORT THE DEVELOPMENT OF A CELL-BASED MODEL TO ACCURATELY MIMIC THE COMPLEX PHYSIOLOGICAL ENVIRONMENT OF THE CERVICOVAGINAL REGION OF THE FEMALE REPRODUCTIVE TRACT, WHICH IS A COMMON SITE OF INVASION FOR SECUALLY TRANSMITTED PATHOGENS, INCLUDING GONORRHEA. FILIPA MARIA RIBEIRO SOEIRO DE CARVALHO WILL BE WORKING ON THIS PROJECT, WHICH PROPOSES TO DESIGN A MICROPHYSIOLOGICAL MODEL TO MIMIC THE STRUCTURE AND FUNCTION OF THIS TISSUE AND WILL INCORPORATE HUMAN-DERIVED CELLS AND SCAFFOLD MATERIALS. THE MODEL WILL BE SUBJECT TO INFECTION WITH GONORRHEA TO VALIDATE INFECTION PATHOGENESIS AND ADVANCE OUR UNDERSTANDING OF SEXUALLY TRANSMITTED INFECTIONS, AND REDUCE RELIANCE ON ANIMAL MODELS, INCLUDING NONHUMAN PRIMATES AND RODENTS, WHICH ARE COMMONLY USED FOR THIS PURPOSE. UNIVERSITY OF MARYLAND-COLLEGE PARK (MARYLAND): THE GRANT WAS GIVEN TO THE UNIVERSITY OF MARYLAND-COLLEGE PARK TO SUPPORT THE RESEARCH CONDUCTED BY IAN SMITH, "A SPHEROID ANTIOGENIC VASCULARIZATION MIDROFLUIDIC DEVICE TO REPLACE METASTASIS-BASED MOUSE MODELS." TUMORS COMMONLY CAUSE THE FORMATION OF A NETWORK OF CAPILLARIES AND THE RESULTING INVASION OF CANCERS CELLS INTO BLOOD OR LYMPH VESSELS RESULTS IN THE SPREAD OF CANCER TO OTHER PARTS OF THE BODY. CURRENT IN VITRO MODELS HAVE DIFFICULTIES IN OBSERVING REAL-TIME CELLULAR BEHAVIORS, FAIL TO PROVIDE RELEVANT DATA REGARDING THE MECHANISM UNDERLYING THESE CELLULAR BEHAVIORS, AND OFTEN OVERSIMPLIFY THE COMPLEXITIES FOUND IN VIVO. IN THIS PROPOSAL, IAN PLANS TO VALIDATE A COMPETITIVE IN VITRO MODEL TO REPLACE THE CURRENT IN VIVO MODELS. IAN'S LAB HAS DEVELOPED A SPHEROID ANGIOGENIC VASCULARIZATION MICROFLUIDIC DEVICE (SAVD) THAT INCORPORATES RELEVANT STRUCTURES FOUND IN VIVO, WHILE ALLOWING FOR REAL TIME OBSERVATION ACROSS DIFFERENT IMAGING MODALITIES. HE WILL VALIDATE THE EFFICACY OF THIS DEVICE AND USE IT TO IDENTIFY THE UNDERLYING MECHANISMS OF CANCER CELL INTRAVASATION INTO BLOOD VESSELS AND DEVELOP A TREATMENT REGIME TO MITIGATE THIS PROCESS. UNIVERSITY OF ROCHESTER (NEW YORK): THE GRANT WAS GIVEN TO THE UNIVERSITY OF ROCHESTER TO SUPPORT THE RESEARCH CONDUCTED BY KAIHUA (CHLOE). CHLOE'S RESEARCH FOCUSES UPON "IN VITRO STUDIES OF BIOPHYSICAL AND MOLECULAR DETERMINANTS OF THE BLOOD-BRAIN BARRIER DURING SEPSIS AND SYSTEMIC INFLAMMATION." THE GOAL OF THIS PROJECT IS THE IN VITRO STUDY OF BIOPHYSICAL AND MOLECULAR DETERMINATES OF THE BLOOD BARRIER DURING SEPSIS AND SYSTEMIC INFLAMMATION. SEPSIS IS A POTENTIALLY LIFE-THREATENING CONDITION THAT TAKES PLACE WHEN THE BODY RESPONDS TO AN INFECTION BUT DAMAGES ITS OWN TISSUES DURING THE PROCESS. SURVIVORS OF SEVERE SEPSIS OFTEN HAVE COGNITIVE LOSS AND MENTAL PROBLEMS BELIEVED TO BE LINKED TO BRAIN INJURY RESULTING FROM THE DESTRUCTION OF THE BLOOD BRAIN BARRIER AND TRANSPORT OF SEPTIC FACTORS THROUGH BLOOD FLOW. ALTHOUGH MICE ARE COMMONLY USED TO MODEL SEPSIS, THEY DO NOT GIVE RESPONSE PROFILES RESEMBLING THOSE OF HUMANS. IN THIS PROPOSAL, CHLOE PLANS TO DEVELOP A HUMAN CELL-BASED MODEL TO STUDY BRAIN INJURY DURING SEPSIS. HER MODEL WILL INCLUDE THE THREE CELL TYPES COMPRISING THE NEUROVASCULAR VIRGINIA TECH/WAKE FOREST UNIVERSITY: VIKRAM SURENDRAN IS VALIDATING A 3D LUNG MODEL TO BETTER STUDY LUNG FIBROSIS, A LIFE-THREATENING DISEASE WITH NO CURE. HIS MODEL RECREATES THE NATURAL INTERFACE BETWEEN AIR AND LUNG, PROVIDING A MORE ACCURATE PLATFORM TO UNDERSTAND FIBROSIS PROGRESSION AND EVALUATE THE EFFECTIVENESS OF POTENTIAL TREATMENTS. BY VALIDATING THIS MODEL AND TESTING REAL-WORLD DRUGS, VIKRAM AIMS TO DEMONSTRATE ITS RELIABILITY FOR PREDICTING DRUG RESPONSES, WHICH IS CRUCIAL FOR RAPIDLY ADOPTING NON-ANIMAL MODELS.</ExplanationTxt>
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        <FormAndLineReferenceDesc>FORM 990, PART VI, SECTION C, LINE 19</FormAndLineReferenceDesc>
        <ExplanationTxt>THE FORM 990, AND ALL OTHER GOVERNING DOCUMENTS ARE MADE AVAILABLE TO THE PUBLIC UPON THEIR REQUEST. THE FORM 990 FOR THE CURRENT YEAR AND FOR PRIOR YEARS ARE AVAILABLE ON THE WEBSITE IRS.GOV.</ExplanationTxt>
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        <FormAndLineReferenceDesc>FORM 990, PART XI, LINE 9:</FormAndLineReferenceDesc>
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