2025-04-11T14:45:55+00:00 2024-06-30 346565596 ERNST & YOUNG US LLP 101 E WASHINGTON ST PHOENIX AZ 85004 990 2023-07-01 952160097 The Salk Institute for Biological Studies SALK 8584534100 10010 N TORREY PINES ROAD LA JOLLA CA 920371002 KIMBERLY M CASTILLO CFO 8584534100 2025-04-11 true true Steven T Rutti P00775456 6023223000 2025-04-11 2023 2025-03-06 01:10:19Z GERALD JOYCE 10010 N TORREY PINES ROAD LA JOLLA CA 920371002 448822367 false X WWW.SALK.EDU X 1960 CA BASIC RESEARCH IN THE FOLLOWING: MOLECULAR BIOLOGY & GENETICS, NEUROSCIENCE, AND PLANT BIOLOGY. 28 24 1144 24 -1432732 0 150813576 139394431 0 21763570 22040070 1075216 -268031 173652362 161166470 0 0 91143114 93365130 0 6599611 76263720 83864106 167406834 177229236 6245528 -16062766 805255578 822778011 172966503 173371281 632289075 649406730 UNLOCKING THE SECRETS OF LIFE ITSELF IS THE DRIVING FORCE BEHIND THE SALK INSTITUTE. OUR TEAM OF WORLD-CLASS, AWARD-WINNING SCIENTISTS PUSHES BOUNDARIES OF KNOWLEDGE IN AREAS SUCH AS NEUROSCIENCE, CANCER RESEARCH, AGING, IMMUNOBIOLOGY, PLANT BIOLOGY, COMPUTATIONAL BIOLOGY, AND MORE. FOUNDED BY JONAS SALK, DEVELOPER OF THE FIRST SAFE AND EFFECTIVE POLIO VACCINE, THE INSTITUTE IS AN INDEPENDENT, NONPROFIT RESEARCH ORGANIZATION AND ARCHITECTURAL LANDMARK: SMALL BY CHOICE, INTIMATE BY NATURE, AND FEARLESS IN THE FACE OF ANY CHALLENGE. false false 147208206 0 0 SEE SCHEDULE O 147208206 true true false true false false false false true true true false false true true true false false false true false false false true false false false false true false false false true false false false false true false false false false true true false false false true 149 0 true 1144 true true true false false false false true true false false false false false false X 28 24 false false false false true true true true true false false false true true true true true true true false CA CO CT DC FL GA AL HI IL KS KY ME AK MD MA MI MN MS MO NH NJ NM NY NC ND OH OK OR PA RI SC TN TX UT VA AR WA WV WI X X KIMBERLY CASTILLO 8584534100 10010 N TORREY PINES ROAD LA JOLLA CA 920371002 GERALD JOYCE MD PHD PRESIDENT / PROFESSOR 50.0 X X 761791 0 56240 MARKUS REINHARD VICE CHAIR 2.0 X X 0 0 0 MARNA C WHITTINGTON PHD CHAIR 2.0 X X 0 0 0 RICHARD A HEYMAN PHD VICE CHAIR 2.0 X X 0 0 0 REUBEN SHAW PHD TRUSTEE/PROFESSOR 50.0 X X 408448 0 53564 ALAN D GOLD TRUSTEE (OUTGOING NOV 2023) 0.5 X 0 0 0 AMY JACOBS TRUSTEE 0.5 X 0 0 0 BENJAMIN H LEWIS TRUSTEE 0.5 X 0 0 0 CAROL GALLAGHER PHARMD TRUSTEE 0.5 X 0 0 0 CORINNE MENTZELOPOULOS TRUSTEE 0.5 X 0 0 0 DANIEL C LEWIS TRUSTEE 0.5 X 0 0 0 DANIEL TIERNEY TRUSTEE 0.5 X 0 0 0 DAVID DOLBY TRUSTEE 0.5 X 0 0 0 DENNIS DRIVER TRUSTEE (OUTGOING JULY 2023) 0.5 X 0 0 0 EDWIN K HUNTER TRUSTEE 0.5 X 0 0 0 ERIC SAGERMAN TRUSTEE 2.0 X 0 0 0 FREDERICK J DOTZLER TRUSTEE 0.5 X 0 0 0 FREDERIK PAULSEN PHD TRUSTEE 0.5 X 0 0 0 HAEYOUNG KONG TANG PHD TRUSTEE 2.0 X 0 0 0 HOWARD H NEWMAN PHD TRUSTEE 0.5 X 0 0 0 IRVING WEISSMAN MD TRUSTEE 0.5 X 0 0 0 IRWIN M JACOBS SM SCD CHAIR EMERITUS (OUTGOING NOV 2023) 2.0 X 0 0 0 JANELLE AYRES PHD TRUSTEE/PROFESSOR 50.0 X 269237 0 40484 JAY FLATLEY TRUSTEE 2.0 X 0 0 0 LYN HUTTON TRUSTEE 2.0 X 0 0 0 MARK KNICKREHM TRUSTEE 0.5 X 0 0 0 MARY JANE SALK TRUSTEE 0.5 X 0 0 0 SANJAY K JHA PHD TRUSTEE 0.5 X 0 0 0 TATYANA SHARPEE PHD TRUSTEE/PROFESSOR (OUTGOING MAR 2024) 50.0 X 259119 0 45248 TERRY ROSEN PHD TRUSTEE 2.0 X 0 0 0 TIMOTHY M SCHOEN TRUSTEE 2.0 X 0 0 0 WOLFGANG BUSCH PHD TRUSTEE/PROFESSOR 50.0 X 349121 0 49249 JULIA A MILLER JD SECRETARY/GENERAL COUNSEL 50.0 X 414822 0 62210 KIM E WITMER TREASURER/SVP FINANCE & ADMN 50.0 X 523931 0 48414 KIMBERLY CASTILLO CHIEF FINANCIAL OFFICER 50.0 X 325608 0 56562 BRYAN ROBINSON VP, EXTERNAL RELATIONS 50.0 X 500110 0 47465 FRED GAGE PHD PROFESSOR 50.0 X 585895 0 58365 RONALD EVANS PHD PROFESSOR 50.0 X 435269 0 35772 SAMUEL PFAFF PHD PROFESSOR 50.0 X 379480 0 57673 5212831 0 611246 167 false true false RUDOLPH & SLETTEN INC 7584 METROPOLITAN DR STE 100 SAN DIEGO CA 92108 CONSTRUCTION SERVICE 2266704 EAST END ADVISORS LLC 610 FIFTH AVENUE SUITE 506 NEW YORK NY 10020 INVESTMENT ADVISOR 1926342 UNIVERSITY OF CALIFORNIA SAN DIEGO 9500 GILMAN DRIVE LA JOLLA CA 92093 TRNG PROGRAM/SUBCONT 1339024 AO REED & CO 4777 RUFFIN STREET SAN DIEGO CA 92111 CONSTRUCTION SERVICE 976361 SHOW IMAGING INC 1125 JOSHUA WAY VISTA CA 92081 ENTERTAINMENT SERVICE 742603 16 920400 82929715 55544316 2882637 139394431 0 0 0 0 0 9038204 -1432732 10470936 1011800 1011800 0 0 299192646 286190780 13001866 0 13001866 13001866 153300 920400 1465117 -1311817 -1311817 ROYALTIES 900099 1183 1183 A/R RECHARGE ALLOWANCE 900099 28806 28806 REVENUE SHARE-HOST VEHICLE CHARGING STAT 900099 1997 1997 0 0 0 0 31986 161166470 0 -1432732 23204771 0 0 0 0 0 0 0 0 3109959 1236676 1784936 88347 0 0 0 0 71543965 59576885 8306292 3660788 4874763 4095746 525735 253282 8664051 7280929 934589 448533 5172392 4345812 557834 268746 394545 65000 329545 0 979867 252352 727515 0 276990 0 276990 0 3100 0 3100 0 0 0 2870948 0 2870948 0 13741606 12298542 825907 617157 27535 7153 7323 13059 752066 222101 404540 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139394431 766475518 0 0 160545802 176855692 138798417 150881176 139394431 766475518 12874606 753600912 4322033 6807160 9621065 6721516 10050004 37521778 0 3315 1945 4857 2864 31986 44967 804042263 0 0.9373 0.9455 X Schedule A, Part II, Line 10 Other Income DESCRIPTION - ROYALTIES, COLUMN A - 1093.0, COLUMN B - 993.0, COLUMN C - 2851.0, COLUMN D - 1781.0, COLUMN E - 1183.0, COLUMN F - 7901.0; DESCRIPTION - REVENUE SHARING-HOST VEHICLE CHARGING STATION, COLUMN A - 1228.0, COLUMN B - 952.0, COLUMN C - 2006.0, COLUMN D - 1083.0, COLUMN E - 1997.0, COLUMN F - 7266.0; DESCRIPTION - NET GIFT SHOP SALES, COLUMN A - 994.0, COLUMN B - 0.0, COLUMN C - 0.0, COLUMN D - 0.0, COLUMN E - 0.0, COLUMN F - 994.0; DESCRIPTION - AR RECHARGE ALLOWANCE, COLUMN A - 0.0, COLUMN B - 0.0, COLUMN C - 0.0, COLUMN D - 0.0, COLUMN E - 28806.0, COLUMN F - 28806.0; RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED false false false false false false false false true 3100 3100 false Schedule C, Part II-B, Line 1 DETAILED DESCRIPTION OF THE LOBBYING ACTIVITY PAID MEMBERSHIP DUES TO RESEARCH AND BIOMEDICAL ORGANIZATIONS, A PORTION OF WHICH ARE CONSIDERED LOBBYING. ASSOCIATION OF INDEPENDENT RESEARCH INSTITUTES - $1,500, NATIONAL ASSOCIATION FOR BIOMEDICAL RESEARCH - $1,200, BIOCOM - $400. 351101623 4828947 31788749 16900459 370818860 345211760 4585120 17999745 16695002 351101623 375050161 1603261 -15394543 16047119 345211760 299166085 14926831 74973285 14016040 375050161 286834762 6580341 17530495 11779513 299166085 0.0387 0.6951 0.2662 false false 1153930 1153930 64209980 56127835 8082145 100100412 70489610 29610802 120527559 82860875 37666684 931947 923392 8555 76522116 ALTERNATIVE INVESTMENTS 486545877 F STOCKS NOT-PUBLICLY TRADED <5% 3011 C LIMITED PARTNERSHIP INTEREST 28955451 F 515504339 4585 DEFERRED RETIREE MEDICAL OBLIG 4129876 LEASE LIABILITY 5015491 9149952 X 167039603 33334875 -26288749 7046126 159993477 2637713 -1464720 1172993 161166470 176056640 1465117 1465117 174591523 2637713 0 2637713 177229236 Schedule D, Part XI, Line 2(d) INVESTMENT RETURN IN EXCESS OF AMOUNT DESIGNATED FOR CURRENT OPERATIONS UNDER SPENDING POLICY ($26,141,913) AND CHANGE IN VALUE OF DEFERRED GIFTS ($146,836) Schedule D, Part XI, Line 4(b) FUNDRAISING EXPENSES ($1,073,700) AND ROUNDING $397 Schedule D, Part XII, Line 2(d) FUNDRAISING EVENTS EXPENSE $1,073,700 Schedule D, Part XII, Line 4(b) ROUNDING $1 Schedule D, Part V, Line 4 Intended uses of endowment funds ENDOWMENT INCOME INTENDED TO BE USED FOR AND TO SUPPORT RESEARCH, OPERATIONS, AND LECTURESHIP EXPENSES. Schedule D, Part X, Line 2 FIN 48 (ASC 740) footnote INCOME TAXES - THE INSTITUTE HAS NO UNRECOGNIZED TAX BENEFITS AS OF JUNE 30, 2024 AND 2023. Schedule D, Part XI, Line 2(d) Other revenues in audited financial statements not in form 990 INVESTMENT INCOME IN EXCESS OF AMOUNT DESIGNATED FOR CURRENT OPERATIONS - -26141913 CHANGE IN VALUE OF DEFERRED GIFTS - -146836 Schedule D, Part XI, Line 4(b) Other revenues in form 990 not in audited financial statements FUNDRAISING EXPENSES - -1465117 ROUNDING - 397 Schedule D, Part XII, Line 2(d) Other expenses in audited financial statements not in form 990 FUNDRAISING EXPENSES - 1465117 Europe (Including Iceland and Greenland) 0 0 Program Services SCIENTISTS TRAVEL TO FOREIGN COUNTRIES TO ATTEND CONFERENCES. WE DO NOT DEEM THESE ACTIVITIES TO CONSTITUTE WORKING IN THE REGION. 288481 North America (Canada & Mexico only) 0 0 Program Services SCIENTISTS TRAVEL TO FOREIGN COUNTRIES TO ATTEND CONFERENCES. WE DO NOT DEEM THESE ACTIVITIES TO CONSTITUTE WORKING IN THE REGION. 44461 South Asia 0 0 Program Services SCIENTISTS TRAVEL TO FOREIGN COUNTRIES TO ATTEND CONFERENCES. WE DO NOT DEEM THESE ACTIVITIES TO CONSTITUTE WORKING IN THE REGION. 6203 East Asia and the Pacific 0 0 Program Services SCIENTISTS TRAVEL TO FOREIGN COUNTRIES TO ATTEND CONFERENCES. WE DO NOT DEEM THESE ACTIVITIES TO CONSTITUTE WORKING IN THE REGION. 67580 Middle East and North Africa 0 0 Program Services SCIENTISTS TRAVEL TO FOREIGN COUNTRIES TO ATTEND CONFERENCES. WE DO NOT DEEM THESE ACTIVITIES TO CONSTITUTE WORKING IN THE REGION. 2797 South America 0 0 Program Services SCIENTISTS TRAVEL TO FOREIGN COUNTRIES TO ATTEND CONFERENCES. WE DO NOT DEEM THESE ACTIVITIES TO CONSTITUTE WORKING IN THE REGION. 25071 Central America and the Caribbean 0 0 Investments 215382133 Europe (Including Iceland and Greenland) 0 0 Investments 37220916 North America (Canada & Mexico only) 0 0 Investments 1188844 0 0 0 0 0 0 254226486 0 254226486 true false true true true false Schedule F, Part I, Line 3 Method used to account for expenditures on org's financial statements CENTRAL AMERICA AND THE CARIBBEAN-Accrual; EAST ASIA AND THE PACIFIC-Accrual; EUROPE (INCLUDING ICELAND AND GREENLAND)-Accrual; MIDDLE EAST AND NORTH AFRICA-Accrual; NORTH AMERICA (CANADA & MEXICO ONLY)-Accrual; SOUTH AMERICA-Accrual; SOUTH ASIA-Accrual CONCERT 1073700 920400 153300 71903 620088 773126 0 0 1073700 920400 153300 71903 620088 773126 1465117 -1311817 X true true X X X X X false false false false false false false false false GERALD JOYCE MD PHD PRESIDENT / PROFESSOR 751123 0 0 0 10668 0 39600 0 16640 0 818031 0 0 0 REUBEN SHAW PHD TRUSTEE/PROFESSOR 261343 0 0 0 147105 0 39600 0 13964 0 462012 0 0 0 JANELLE AYRES PHD TRUSTEE/PROFESSOR 263290 0 0 0 5947 0 32175 0 8309 0 309721 0 0 0 TATYANA SHARPEE PHD TRUSTEE/PROFESSOR (OUTGOING MAR 2024) 240373 0 0 0 18746 0 31394 0 13854 0 304367 0 0 0 WOLFGANG BUSCH PHD TRUSTEE/PROFESSOR 217250 0 0 0 131871 0 37284 0 11965 0 398370 0 0 0 KIM E WITMER TREASURER/SVP FINANCE & ADMN 506663 0 0 0 17268 0 39600 0 8814 0 572345 0 0 0 JULIA A MILLER JD SECRETARY/GENERAL COUNSEL 385649 0 0 0 29173 0 39600 0 22610 0 477032 0 0 0 KIMBERLY CASTILLO CHIEF FINANCIAL OFFICER 315835 0 0 0 9773 0 39600 0 16962 0 382170 0 0 0 FRED GAGE PHD PROFESSOR 568480 0 0 0 17415 0 39600 0 18765 0 644260 0 0 0 RONALD EVANS PHD PROFESSOR 406745 0 0 0 28524 0 33000 0 2772 0 471041 0 0 0 SAMUEL PFAFF PHD PROFESSOR 306990 0 0 0 72490 0 38688 0 18985 0 437153 0 0 0 BRYAN ROBINSON VP, EXTERNAL RELATIONS 470601 0 0 0 29509 0 33000 0 14465 0 547575 0 0 0 Schedule J, Part I, Line 1a First-class or charter travel FIRST-CLASS OR CHARTER TRAVEL: FRED GAGE, PH.D., PROFESSOR - $16,705; JANELLE AYRES, PH.D., PROFESSOR - $7,632; JAN KARLSEDER, PH.D., PROFESSOR - $7,312; WOLFGANG BUSCH, PH.D., PROFESSOR - $4,115. NOT TAXABLE - ACCOUNTABLE PLAN. REUBEN SHAW PROFESSOR HOME LOAN X 700000 274164 false true true TATYANA SHARPEE PROFESSOR HOME LOAN X 30140 30140 false true true 304304 X 84 2882637 Market value 0 false true false Schedule M, Part I Explanations of reporting method for number of contributions Securities - Publicly traded - THE AMOUNT REPORTED REPRESENTS THE NUMBER OF CONTRIBUTIONS RECEIVED. Form 990, Part III, Line 4a continued1 PREYING ON HUNGRY, ANXIOUS WORMS-THE LIFE OF THE TINY WORM CALLED C. ELEGANS CONSISTS MOSTLY OF LOOKING FOR FOOD, EATING FOOD, AND LAYING EGGS. SO, WHEN ANY OF THESE BEHAVIORS IS DISRUPTED, THERE'S CAUSE FOR CONCERN. IN A NEW STUDY, SALK RESEARCHERS DISCOVERED THAT THE "FEEL GOOD" BRAIN CHEMICAL DOPAMINE REGULATES ANXIOUS WORM BEHAVIOR IN THE PRESENCE OF NIPPING PREDATORS. THE FINDINGS ILLUMINATE HOW THIS DOPAMINE-REGULATED BRAIN PATHWAY MAY BE RELATED TO ANXIETY AND COULD PROVIDE INSIGHT INTO HUMAN CONDITIONS, SUCH AS POST-TRAUMATIC STRESS DISORDER (PTSD). THE STUDY WAS LED BY PROFESSOR SREEKANTH CHALASANI AND PUBLISHED IN ELIFE ON JULY 11, 2023. REVEALING HIV DRUG-RESISTANCE MECHANISMS THROUGH PROTEIN STRUCTURES-SALK SCIENTISTS, IN COLLABORATION WITH THE NATIONAL INSTITUTES OF HEALTH, DISCOVERED THE MOLECULAR MECHANISMS BY WHICH THE HUMAN IMMUNODEFICIENCY VIRUS (HIV) BECOMES RESISTANT TO DOLUTEGRAVIR, ONE OF THE MOST EFFECTIVE, CLINICALLY USED ANTIVIRAL DRUGS FOR TREATING THE INFECTION. THE NEW STUDY REVEALS HOW CHANGES TO THE 3D STRUCTURES OF INTEGRASE, AN HIV PROTEIN, CAN LEAD TO DOLUTEGRAVIR RESISTANCE AND HOW OTHER COMPOUNDS MAY BE ABLE TO OVERCOME THIS RESISTANCE. THE STUDY WAS LED BY ASSOCIATE PROFESSOR DMITRY LYUMKIS AND PUBLISHED IN SCIENCE ADVANCES ON JULY 21, 2023. WHY WE LOSE FAT AND MUSCLE DURING INFECTION-A SALK TEAM DISCOVERED THE WASTING RESPONSE-LOSS OF FAT AND MUSCLE-TO INFECTION WITH THE BACTERIA T. BRUCEI IN MICE OCCURS IN TWO PHASES, EACH REGULATED BY DIFFERENT T CELL SUBTYPES. WHILE FAT LOSS DID NOT BENEFIT THE FIGHT AGAINST INFECTION, MUSCLE LOSS DID-A SURPRISING CLUE THAT SOME WASTING MAY HELP MANAGE ILLNESS. THE FINDINGS CAN INFORM THE DEVELOPMENT OF MORE EFFECTIVE THERAPEUTICS THAT SPARE PEOPLE FROM WASTING AND INCREASE OUR UNDERSTANDING OF HOW WASTING INFLUENCES SURVIVAL AND MORBIDITY ACROSS INFECTIONS, CANCERS, CHRONIC ILLNESSES, AND MORE. THE STUDY WAS LED BY PROFESSOR JANELLE AYRES AND PUBLISHED IN CELL REPORTS ON JULY 24, 2023. USING THE BODY'S "INVISIBLE SCALPEL" TO REMOVE BRAIN CANCER-SALK RESEARCHERS FOUND THAT HELPER T CELLS PLAY A CRUCIAL ROLE IN THE SUCCESS OF THE IMMUNOTHERAPY TREATMENT ANTI-CTLA-4 IN MICE WITH GLIOBLASTOMA, THE MOST COMMON AND DEADLY FORM OF BRAIN CANCER. THE IMMUNOTHERAPY'S SUCCESS DEPENDED ON HELPER T CELLS PAIRING UP WITH BRAIN-RESIDENT IMMUNE CELLS CALLED MICROGLIA-DEMONSTRATING THE VALUE OF THE IMMUNE SYSTEM'S QUILTED CONNECTIONS. THE FINDINGS SHOW THE BENEFIT OF HARNESSING THE BODY'S OWN IMMUNE CELLS TO FIGHT BRAIN CANCER AND COULD LEAD TO MORE EFFECTIVE IMMUNOTHERAPIES FOR TREATING BRAIN CANCER IN HUMANS. THE STUDY WAS LED BY PROFESSOR SUSAN KAECH AND PUBLISHED IN IMMUNITY ON AUGUST 11, 2023. HIGH-FAT DIETS ALTER GUT BACTERIA, BOOSTING COLORECTAL CANCER RISK IN MICE-THE PREVALENCE OF COLORECTAL CANCER IN PEOPLE UNDER THE AGE OF 50 HAS RISEN IN RECENT DECADES. ONE SUSPECTED REASON: THE INCREASING RATE OF OBESITY AND HIGH-FAT DIETS. NOW, SALK SCIENTISTS, IN COLLABORATION WITH UC SAN DIEGO, DISCOVERED EXACTLY HOW HIGH-FAT DIETS CAN CHANGE GUT BACTERIA AND ALTER DIGESTIVE MOLECULES CALLED BILE ACIDS, PREDISPOSING MICE TO COLORECTAL CANCER. THE FINDINGS HELP SCIENTISTS BETTER UNDERSTAND COLORECTAL CANCER AND HOW TO POTENTIALLY PREVENT IT. THE STUDY WAS LED BY PROFESSOR RONALD EVANS AND PUBLISHED IN CELL REPORTS ON AUGUST 22, 2023. "SUPER-ENHANCER" SUPER-CHARGES PANCREATIC TUMOR GROWTH-PANCREATIC CANCERS ARE AMONG THE MOST AGGRESSIVE, DEADLY TUMOR TYPES AND FOR YEARS RESEARCHERS HAVE STRUGGLED TO DEVELOP EFFECTIVE DRUGS AGAINST THE TUMORS. A SALK TEAM IDENTIFIED A NEW SET OF MOLECULES THAT FUEL THE GROWTH OF TUMORS IN PANCREATIC DUCTAL ADENOCARCINOMA (PDAC), THE MOST COMMON TYPE OF PANCREATIC CANCER. THE NEW RESEARCH EXPLAINS HOW CERTAIN GENE MUTATIONS TRIGGER OUT-OF-CONTROL GROWTH IN PANCREATIC CANCER BY ACTIVATING A "SUPER-ENHANCER" THAT TURNS ON OTHER GENES. THEY ALSO SHOW THE EFFECTIVENESS OF A NEW DRUG THAT PUTS THE BRAKES ON PANCREATIC CANCER GROWTH BY BLOCKING THE EFFECTS OF THAT SUPER-ENHANCER. THE STUDY WAS LED BY PROFESSOR RONALD EVANS AND PUBLISHED IN NATURE COMMUNICATIONS ON SEPTEMBER 6, 2023. REDUCING STRESS ON T CELLS MAKES THEM BETTER CANCER FIGHTERS-EVEN FOR KILLER T CELLS-SPECIALIZED IMMUNE CELLS-SEEKING AND DESTROYING CANCER CELLS AROUND THE CLOCK CAN BE EXHAUSTING. IN A NEW STUDY, SALK SCIENTISTS DISCOVERED THE BODY'S SYMPATHETIC STRESS RESPONSE ("FIGHT-OR-FLIGHT") HORMONES CAN EXHAUST KILLER T CELLS IN VARYING CANCER TYPES IN MOUSE AND HUMAN TISSUE SAMPLES-AND THAT EXHAUSTION CAN BE INHIBITED WITH BETA-BLOCKERS. THEIR DISCOVERY DEMONSTRATES THE POTENTIAL BENEFIT OF PAIRING BETA-BLOCKERS WITH EXISTING IMMUNOTHERAPIES TO IMPROVE CANCER TREATMENT BY BOLSTERING KILLER T CELL FUNCTION. THE STUDY WAS LED BY PROFESSOR SUSAN KAECH AND PUBLISHED IN NATURE ON SEPTEMBER 20, 2023. REWIRING TUMOR MITOCHONDRIA ENHANCES THE IMMUNE SYSTEM'S ABILITY TO RECOGNIZE AND FIGHT CANCER-IMMUNOTHERAPY, WHICH USES THE BODY'S OWN IMMUNE SYSTEM TO FIGHT CANCER, IS AN EFFECTIVE TREATMENT OPTION, YET MANY PATIENTS DO NOT RESPOND TO IT. THUS, CANCER RESEARCHERS ARE SEEKING NEW WAYS TO OPTIMIZE IMMUNOTHERAPY SO THAT IT IS MORE EFFECTIVE FOR MORE PEOPLE. RESEARCHERS AT SALK FOUND THAT MANIPULATING AN EARLY STEP IN ENERGY PRODUCTION IN MITOCHONDRIA-THE CELL'S POWERHOUSES-REDUCES MELANOMA TUMOR GROWTH AND ENHANCES THE IMMUNE RESPONSE IN MICE. IN THE FUTURE, THIS MANIPULATION OF MITOCHONDRIA ENERGY PRODUCTION MAY BE LEVERAGED TO CREATE NEW CANCER THERAPEUTICS THAT ARE LESS HARMFUL FOR MITOCHONDRIA AND CELLS. THE STUDY WAS LED BY PROFESSORS SUSAN KAECH AND GERALD SHADEL AND PUBLISHED IN SCIENCE ON SEPTEMBER 21, 2023. UNLEASHING THE POWER OF AI TO TRACK ANIMAL BEHAVIOR-MOVEMENT OFFERS A WINDOW INTO HOW THE BRAIN OPERATES AND CONTROLS THE BODY. METHODS FOR TRACKING HUMAN AND ANIMAL MOVEMENT HAVE COME A LONG WAY, WITH CURRENT CUTTING-EDGE METHODS UTILIZING ARTIFICIAL INTELLIGENCE TO AUTOMATICALLY TRACK PARTS OF THE BODY AS THEY MOVE. HOWEVER, TRAINING THESE MODELS IS STILL TIME-INTENSIVE AND LIMITED BY THE NEED FOR RESEARCHERS TO MANUALLY MARK EACH BODY PART HUNDREDS TO THOUSANDS OF TIMES. A SALK TEAM CREATED GLOWTRACK, A NONINVASIVE MOVEMENT-TRACKING METHOD THAT USES FLUORESCENT DYE MARKERS TO TRAIN ARTIFICIAL INTELLIGENCE. GLOWTRACK IS ROBUST, TIME-EFFICIENT, AND HIGH DEFINITION-CAPABLE OF TRACKING A SINGLE DIGIT ON A MOUSE'S PAW OR HUNDREDS OF LANDMARKS ON A HUMAN HAND. THE STUDY WAS LED BY ASSOCIATE PROFESSOR EIMAN AZIM AND PUBLISHED IN NATURE COMMUNICATIONS ON SEPTEMBER 26, 2023. "A NEW ERA IN BRAIN SCIENCE": UNVEILING HUMAN BRAIN CELL ATLAS-SALK COLLEAGUES AND GLOBAL COLLABORATORS ANALYZED MORE THAN HALF A MILLION BRAIN CELLS FROM THREE HUMAN BRAINS TO ASSEMBLE AN ATLAS OF HUNDREDS OF CELL TYPES THAT MAKE UP A HUMAN BRAIN IN UNPRECEDENTED DETAIL. THE MASSIVE SCIENTIFIC COLLABORATION IS A PART OF THE NATIONAL INSTITUTES OF HEALTH'S BRAIN INITIATIVE, AN EFFORT LAUNCHED IN 2014 TO DESCRIBE THE FULL PLETHORA OF CELLS IN MAMMALIAN BRAINS. MORE DETAILED WORK ON A LARGER NUMBER OF BRAINS, ECKER SAYS, WILL PAVE THE WAY TOWARD A BETTER UNDERSTANDING OF HOW CERTAIN BRAIN CELL TYPES CAN MALFUNCTION IN BRAIN DISORDERS AND DISEASES. THE STUDY WAS LED BY PROFESSOR JOSEPH ECKER AND RESEARCH PROFESSOR MARGARITA BEHRENS AND WAS PUBLISHED IN SCIENCE ON OCTOBER 13, 2023. GENETIC ARCHITECTURE MAY BE KEY TO USING PEACEKEEPING IMMUNE CELLS TO TREAT AUTOIMMUNITY OR FIGHT CANCER-REGULATORY T CELLS ARE SPECIALIZED IMMUNE CELLS THAT SUPPRESS THE IMMUNE RESPONSE AND PREVENT THE BODY FROM ATTACKING ITS OWN CELLS. UNDERSTANDING HOW THESE CELLS WORK IS KEY TO DETERMINING HOW THEY MIGHT BE MANIPULATED TO ENCOURAGE THE DESTRUCTION OF CANCER CELLS OR PREVENT AUTOIMMUNITY. CELL BEHAVIOR IS INFLUENCED BY CHROMATIN ARCHITECTURE (THE 3D SHAPE OF CHROMOSOMES) AND WHICH GENES ARE ACCESSIBLE TO PROTEINS-LIKE FOXP3, WHICH PROMOTES REGULATORY T CELL DEVELOPMENT. SALK RESEARCHER REVEALED THAT FOXP3 IS ESSENTIAL FOR CREATING THE UNIQUE CHROMATIN ARCHITECTURE OF REGULATORY T CELLS AND, IN TURN, PROMOTING THEIR IMMUNE SUPPRESSIVE FUNCTION. THE STUDY WAS LED BY PROFESSOR YE ZHENG AND ASSISTANT PROFESSOR JESSE DIXON AND PUBLISHED IN NATURE COMMUNICATIONS ON NOVEMBER 6, 2023. REPAIRING NERVE CELLS AFTER INJURY AND IN CHRONIC DISEASE-EACH YEAR IN THE UNITED STATES THERE ARE MORE THAN 3 MILLION CASES OF PERIPHERAL NEUROPATHY, WHEREIN NERVES OUTSIDE OF THE BRAIN AND SPINAL CORD ARE DAMAGED AND CAUSE PAIN AND LOSS OF FEELING IN THE AFFECTED AREAS. SALK RESEARCHERS HAVE NOW UNCOVERED IN MICE A MECHANISM FOR REPAIRING DAMAGED NERVES DURING PERIPHERAL NEUROPATHY. THE FINDINGS HAVE THE POTENTIAL TO INSPIRE NOVEL THERAPEUTICS THAT BOLSTER REPAIR FUNCTION AND HEAL PERIPHERAL NEUROPATHY CAUSED BY DIABETES, INJURY, GENETICALLY INHERITED DISEASE, INFECTION, AND MORE. THE STUDY WAS LED BY PROFESSOR SAMUEL PFAFF AND PUBLISHED IN CELL REPORTS ON NOVEMBER 28, 2023. Form 990, Part III, Line 4a continued2 HOW DRUGS CAN TARGET THE THICK "SCAR TISSUE" OF PANCREATIC CANCER-PANCREATIC CANCER IS ONE OF THE DEADLIEST CANCERS-ONLY ABOUT ONE IN EIGHT PATIENTS SURVIVES FIVE YEARS AFTER DIAGNOSIS. THOSE DISMAL STATISTICS ARE IN PART DUE TO THE THICK, NEARLY IMPENETRABLE, WALL OF FIBROSIS, OR SCAR TISSUE, THAT SURROUNDS MOST PANCREATIC TUMORS AND MAKES IT HARD FOR DRUGS TO ACCESS AND DESTROY THE CANCER CELLS. SALK RESEARCHERS HAVE NOW DISCOVERED HOW A CLASS OF ANTI-CANCER DRUGS CALLED HDAC INHIBITORS CAN HELP TREAT PANCREATIC CANCER BY MODULATING THE ACTIVATION OF FIBROBLASTS-THE CELLS THAT MAKE UP THAT WALL OF SCAR TISSUE. THE STUDY WAS LED BY PROFESSOR RONALD EVANS AND PUBLISHED IN NATURE COMMUNICATIONS ON DECEMBER 6, 2023. SALK TEAMS ASSEMBLE FIRST FULL EPIGENOMIC CELL ATLAS OF THE MOUSE BRAIN-AS PART OF A WORLDWIDE INITIATIVE TO REVOLUTIONIZE SCIENTISTS' UNDERSTANDING OF THE BRAIN, SALK SCIENTISTS HELPED ANALYZE MORE THAN 2 MILLION BRAIN CELLS FROM MICE TO ASSEMBLE THE MOST COMPLETE ATLAS EVER OF THE MOUSE BRAIN. THEIR WORK NOT ONLY DETAILS THE THOUSANDS OF CELL TYPES PRESENT IN THE BRAIN BUT ALSO HOW THOSE CELLS CONNECT AND THE GENES AND REGULATORY PROGRAMS THAT ARE ACTIVE IN EACH CELL. THE EFFORTS WERE COORDINATED BY THE NATIONAL INSTITUTES OF HEALTH'S BRAIN RESEARCH THROUGH ADVANCING INNOVATIVE NEUROTECHNOLOGIES (BRAIN) INITIATIVE, WHICH ULTIMATELY AIMS TO PRODUCE A NEW, DYNAMIC PICTURE OF MAMMALIAN BRAINS. THE FOUR SALK-AUTHORED STUDIES INCLUDED IN THE SPECIAL NATURE ISSUE PUBLISHED DECEMBER 13, 2023, WERE LED BY PROFESSOR EDWARD CALLAWAY, PROFESSOR JOSEPH ECKER, AND RESEARCH PROFESSOR MARGARITA BEHRENS. UNCOVERING KEY BRAIN PATHWAY MEDIATING PANIC DISORDER SYMPTOMS-CREATING A MAP OF THE REGIONS, NEURONS, AND CONNECTIONS IN THE BRAIN THAT MEDIATE PANIC ATTACKS CAN PROVIDE GUIDANCE FOR DEVELOPING MORE EFFECTIVE PANIC DISORDER THERAPEUTICS. SALK SCIENTISTS HAVE BEGUN TO CONSTRUCT SUCH A MAP, DESCRIBING A CIRCUIT OF SPECIALIZED NEURONS THAT SEND AND RECEIVE A NEUROPEPTIDE-A SMALL PROTEIN THAT SENDS MESSAGES THROUGHOUT THE BRAIN-CALLED PACAP. WHAT'S MORE, THEY DETERMINED THAT PACAP AND THE NEURONS THAT PRODUCE ITS RECEPTOR ARE POSSIBLE DRUGGABLE TARGETS FOR NEW PANIC DISORDER TREATMENTS. THE STUDY WAS LED BY ASSOCIATE PROFESSOR SUNG HAN AND PUBLISHED IN NATURE NEUROSCIENCE ON JANUARY 4, 2024. A STEP TOWARDS CLINIC-READY PATIENT-DERIVED ORGANOIDS-PANCREATIC CANCER HAS THE HIGHEST MORTALITY RATE OF ALL MAJOR CANCERS AND IS ESPECIALLY DIFFICULT TO TREAT BECAUSE THE TUMORS GROW SO QUICKLY AND ARE CONSTANTLY EVOLVING-BUT PATIENT-DERIVED ORGANOIDS COULD CHANGE ALL THAT. A SALK STUDY PROVIDED CRITICAL INSIGHTS INTO THE ROBUSTNESS OF THESE LAB-GROWN MINI-ORGANS AS A CLINICAL MODEL OF PANCREATIC CANCER. THEY FOUND THE ORGANOIDS' GENE EXPRESSION AND DRUG RESPONSES WERE NOT AFFECTED BY THE BRAND OF EXTRACELLULAR MATRIX USED IN THE CELL CULTURE, AND THAT ONE BRAND EVEN SPED UP THE GROWTH OF TUMOR ORGANOIDS-MAKING THEM WELL-SUITED FOR FAST PACED CANCER TREATMENT PROTOCOLS. DATA LIKE THIS INCREASES CONFIDENCE THAT CLINICAL CONCLUSIONS ARE RELIABLE ACROSS DIFFERENT LABS AND BATCHES OF ORGANOIDS. THE STUDY WAS LED BY ASSISTANT PROFESSOR DANNIELLE ENGLE AND PUBLISHED IN JCI INSIGHT ON JANUARY 9, 2024. IRON INFLUENCES PLANT IMMUNITY AND MAY PROMOTE RESILIENCY AGAINST CLIMATE CHANGE-PLANTS AND ANIMALS ALIKE RELY ON IRON FOR GROWTH AND REGULATION OF MICROBIOMES-COLLECTIONS OF BACTERIA, FUNGI, AND MORE THAT CO-EXIST IN PLACES LIKE THE HUMAN GUT OR THE SOIL AROUND A PLANT'S ROOTS. PLANTS FACE A SPECIAL CHALLENGE WHEN ACQUIRING IRON, SINCE THE STRATEGIES PLANTS USE TO INCREASE IRON AVAILABILITY ALTER THE ROOT MICROBIOME AND CAN INADVERTENTLY BENEFIT HARMFUL SOIL-DWELLING BACTERIA. SALK SCIENTISTS DISCOVERED HOW PLANTS MANAGE IRON DEFICIENCY WITHOUT HELPING "BAD" BACTERIA THRIVE-BY ELIMINATING IMA1, THE MOLECULAR SIGNAL FOR IRON DEFICIENCY IN ROOTS AT RISK OF BACTERIAL ATTACK. ADDITIONALLY, THEY FOUND THAT THIS IRON DEFICIENCY SIGNALING PATHWAY AND THE PLANT IMMUNE SYSTEM ARE DEEPLY INTERTWINED. THE STUDY WAS LED BY PROFESSOR WOLFGANG BUSCH AND PUBLISHED IN NATURE ON JANUARY 10, 2024. LUNG CANCER HIJACKS IMMUNE CELL METABOLISM TO FUEL ITS OWN GROWTH-LUNG ADENOCARCINOMA IS THE MOST COMMON LUNG CANCER AND THE CAUSE OF MOST CANCER-RELATED DEATHS IN THE UNITED STATES. ONE WAY LUNG ADENOCARCINOMA ARISES IS A MUTATION IN A PROTEIN CALLED EGFR (EPIDERMAL GROWTH FACTOR RECEPTOR). MODERN IMMUNOTHERAPIES DON'T WORK AGAINST EGFR-DRIVEN LUNG ADENOCARCINOMA, AND WHILE SOME DRUGS TO TREAT THE CANCER DO EXIST, PATIENTS TYPICALLY DEVELOP A RESISTANCE TO THEM WITHIN JUST A FEW YEARS. SALK COLLEAGUES AND COLLABORATORS AT YALE UNIVERSITY AND UC LOS ANGELES DISCOVERED THAT EGFR-DRIVEN LUNG ADENOCARCINOMA HIJACKS A SPECIALIZED LUNG-RESIDENT IMMUNE CELLS CALLED MACROPHAGES, PULLING THEM INTO THE TUMOR AND TURNING THEM INTO CANCER FUEL-SUPPLIERS. THE FINDINGS COULD INSPIRE NEW LUNG ADENOCARCINOMA INTERVENTIONS THAT DISRUPT THIS TUMOR CELL-MACROPHAGE RELATIONSHIP, AS WELL AS SUGGEST EGFR INHIBITOR TREATMENTS MAY BE MORE SUCCESSFUL WHEN PAIRED WITH STATINS, A CLASS OF DRUGS USED TO LOWER CHOLESTEROL LEVELS. THE STUDY WAS LED BY PROFESSORS SUSAN KAECH AND CHRISTIAN METALLO AND PUBLISHED IN CANCER DISCOVERY ON JANUARY 25, 2024. FAULTY DNA DISPOSAL SYSTEM CAUSES INFLAMMATION-CELLS IN THE HUMAN BODY CONTAIN POWER-GENERATING MITOCHONDRIA, EACH WITH THEIR OWN UNIQUE SET OF GENETIC INSTRUCTIONS CALLED MTDNA. WHEN MTDNA REMAINS INSIDE MITOCHONDRIA, IT SUSTAINS BOTH MITOCHONDRIAL AND CELLULAR HEALTH, BUT IF IT LEAVES THE MITOCHONDRIA, IT CAN INITIATE AN IMMUNE RESPONSE THAT PROMOTES INFLAMMATION. SALK RESEARCHERS AND COLLABORATORS AT UC SAN DIEGO AND UNIVERSITY OF VIRGINIA HAVE DISCOVERED A MECHANISM THAT MOVES IMPROPERLY FUNCTIONING MTDNA FROM THE MITOCHONDRIA INTO THE REST OF THE CELL. WHEN THIS HAPPENS, THE MTDNA GETS FLAGGED AS FOREIGN DNA AND ACTIVATES A CELLULAR PATHWAY TO PROMOTE INFLAMMATION-A PROMISING TARGET FOR NEW THERAPEUTICS THAT DISRUPT INFLAMMATION AND MITIGATE ITS NEGATIVE EFFECTS DURING AGING AND DISEASES LIKE LUPUS OR RHEUMATOID ARTHRITIS. THE STUDY WAS LED BY PROFESSOR GERALD SHADEL AND PUBLISHED IN NATURE CELL BIOLOGY ON FEBRUARY 8, 2024. CONTROLLING ROOT GROWTH DIRECTION COULD HELP SAVE CROPS AND MITIGATE CLIMATE CHANGE-ROOT SYSTEMS ARE CENTRAL TO PLANT SURVIVAL AND PRODUCTIVITY, DETERMINING THE PLANT'S ACCESS TO NUTRIENTS AND WATER AND, THEREFORE, THE PLANT'S ABILITY TO WITHSTAND NUTRIENT DEPLETION AND EXTREME WEATHER LIKE DROUGHT. A SALK TEAM REVEALED FOR THE FIRST TIME THAT THE COMMON PLANT HORMONE ETHYLENE IS INVOLVED IN REGULATING THE LATERAL ROOT ANGLES THAT SHAPE ROOT SYSTEMS. RESEARCHERS IN SALK'S HARNESSING PLANTS INITIATIVE NOW PLAN TO TARGET THE ETHYLENE SIGNALING PATHWAY IN THEIR EFFORTS TO ENGINEER PLANTS AND CROPS THAT CAN WITHSTAND THE ENVIRONMENTAL STRESSES OF CLIMATE CHANGE AND DROUGHT. THE STUDY WAS LED BY PROFESSOR WOLFGANG BUSCH AND PUBLISHED IN CELL REPORTS ON FEBRUARY 13, 2024. SALK SCIENTISTS DISCOVER NEW TARGET FOR REVERSIBLE, NON-HORMONAL MALE BIRTH CONTROL-SURVEYS SHOW MOST MEN IN THE UNITED STATES ARE INTERESTED IN USING MALE CONTRACEPTIVES, YET THEIR OPTIONS REMAIN LIMITED TO UNRELIABLE CONDOMS OR INVASIVE VASECTOMIES. NEW APPROACHES TO MALE CONTRACEPTION ARE NEEDED, BUT BECAUSE SPERM DEVELOPMENT IS SO COMPLEX, RESEARCHERS HAVE STRUGGLED TO IDENTIFY PARTS OF THE PROCESS THAT CAN BE SAFELY AND EFFECTIVELY TINKERED WITH. IN A SALK STUDY, RESEARCHERS DEMONSTRATED THAT TREATING MALE MICE WITH AN EXISTING CLASS OF DRUGS, CALLED HDAC (HISTONE DEACETYLASE) INHIBITORS, CAN INTERRUPT THE FUNCTION OF THIS PROTEIN COMPLEX AND BLOCK FERTILITY WITHOUT AFFECTING LIBIDO. THE TEAM HOPES TO SOON SEE THIS THERAPEUTIC APPROACH IN DEVELOPMENT FOR HUMAN CLINICAL TRIALS. THE STUDY WAS LED BY PROFESSOR RONALD EVANS AND PUBLISHED IN PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (PNAS) ON FEBRUARY 20, 2024. MORE THAN JUST NEURONS: A NEW MODEL FOR STUDYING HUMAN BRAIN INFLAMMATION-NEURONS ONLY MAKE UP HALF OF THE HUMAN BRAIN, WITH THE OTHER HALF-ROUGHLY 85 BILLION CELLS-CONSISTING OF OTHER CELLS CALLED GLIA. THE MOST COMMON TYPE OF GLIAL CELLS ARE ASTROCYTES, WHICH ARE IMPORTANT FOR SUPPORTING NEURONAL HEALTH AND ACTIVITY. SALK RESEARCHERS HAVE CREATED THE FIRST 3D ORGANOIDS THAT MIMIC FEATURES OF THE HUMAN BRAIN TO CONTAIN MATURE, FUNCTIONAL ASTROCYTES. WITH THIS ASTROCYTE-RICH MODEL, RESEARCHERS WILL BE ABLE TO STUDY STRESS AND INFLAMMATION IN AGING AND ALZHEIMER'S DISEASE WITH GREATER DEPTH AND CLARITY THAN EVER BEFORE. ALREADY, THE RESEARCHERS HAVE USED THE NEW ORGANOIDS TO REVEAL A RELATIONSHIP BETWEEN ASTROCYTE DYSFUNCTION AND INFLAMMATION, AS WELL AS A POTENTIALLY DRUGGABLE TARGET FOR DISRUPTING THAT RELATIONSHIP. THE STUDY WAS LED BY PROFESSOR RUSTY GAGE AND PUBLISHED IN NATURE BIOTECHNOLOGY ON FEBRUARY 28, 2024. Form 990, Part III, Line 4a continued3 MODELING THE ORIGINS OF LIFE: NEW EVIDENCE FOR AN "RNA WORLD"-SCIENTISTS IN THE 1960S, INCLUDING SALK FELLOW LESLIE ORGEL, PROPOSED THAT LIFE BEGAN WITH THE "RNA WORLD"-A HYPOTHETICAL ERA IN WHICH SMALL, STRINGY RNA MOLECULES RULED THE EARLY EARTH AND ESTABLISHED THE DYNAMICS OF DARWINIAN EVOLUTION. NEW SALK RESEARCH PROVIDES FRESH INSIGHTS ON THE ORIGINS OF LIFE, PRESENTING COMPELLING EVIDENCE SUPPORTING THE RNA WORLD HYPOTHESIS. THE RECENT STUDY UNVEILED AN RNA ENZYME THAT CAN MAKE ACCURATE COPIES OF OTHER FUNCTIONAL RNA STRANDS, WHILE ALSO ALLOWING NEW VARIANTS OF THE MOLECULE TO EMERGE OVER TIME. THESE REMARKABLE CAPABILITIES SUGGEST THE EARLIEST FORMS OF EVOLUTION MAY HAVE OCCURRED ON A MOLECULAR SCALE IN RNA. THE STUDY WAS LED BY PROFESSOR AND SALK PRESIDENT GERALD JOYCE AND PUBLISHED IN PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (PNAS) ON MARCH 4, 2024. PROTECTING BRAIN CELLS WITH CANNABINOL-ONE IN EVERY 10 INDIVIDUALS ABOVE THE AGE OF 65 DEVELOPS AN AGE-RELATED NEUROLOGICAL DISORDER LIKE ALZHEIMER'S OR PARKINSON'S, YET TREATMENT OPTIONS FOR THIS POPULATION REMAIN SPARSE. CANNABINOIDS-COMPOUNDS DERIVED FROM THE CANNABIS PLANT, LIKE WELL-KNOWN THC (TETRAHYDROCANNABINOL) AND CBD (CANNABIDIOL)-MAY OFFER A SOLUTION. ONE CANNABINOID CALLED CBN (CANNABINOL) HAS RECENTLY PIQUED THE INTEREST OF RESEARCHERS, WHO HAVE BEGUN EXPLORING THE CLINICAL POTENTIAL OF THE MILDER, LESS PSYCHOACTIVE SUBSTANCE. SALK SCIENTISTS FOUND CBN PROTECTS THE BRAIN AGAINST AGING AND NEURODEGENERATION, THEN BEGAN DEVELOPING POTENTIAL THERAPEUTICS. THE STUDY WAS LED BY RESEARCH PROFESSOR PAMELA MAHER AND PUBLISHED IN REDOX BIOLOGY ON MARCH 29, 2024. ARTIFICIAL INTELLIGENCE HELPS SCIENTISTS ENGINEER PLANTS TO FIGHT CLIMATE CHANGE-SALK SCIENTISTS ARE DESIGNING CLIMATE-SAVING PLANTS USING A SOPHISTICATED NEW RESEARCH TOOL CALLED SLEAP-AN EASY-TO-USE ARTIFICIAL INTELLIGENCE (AI) SOFTWARE THAT TRACKS MULTIPLE FEATURES OF ROOT GROWTH. THE INTERDISCIPLINARY SALK TEAM HAVE OFFICIALLY DEBUTED A NEW PROTOCOL FOR USING SLEAP TO ANALYZE PLANT ROOT PHENOTYPES-HOW DEEP AND WIDE THEY GROW, HOW MASSIVE THEIR ROOT SYSTEMS BECOME, AND OTHER PHYSICAL QUALITIES THAT, PRIOR TO SLEAP, WERE TEDIOUS TO MEASURE. APPLYING SLEAP TO PLANTS HAS ALREADY ENABLED THE RESEARCHERS TO ESTABLISH THE MOST EXTENSIVE CATALOG OF PLANT ROOT SYSTEM PHENOTYPES TO DATE, GIVING SALK'S HARNESSING PLANTS INITIATIVE A POWERFUL BOOST. THE STUDY WAS LED BY SALK FELLOW TALMO PEREIRA AND PROFESSOR WOLFGANG BUSCH AND PUBLISHED IN PLANT PHENOMICS ON APRIL 12, 2024. UPGRADING BRAIN STORAGE: QUANTIFYING HOW MUCH INFORMATION OUR SYNAPSES CAN HOLD-TO UNDERSTAND HOW THE BRAIN LEARNS AND RETAINS INFORMATION, SCIENTISTS TRY TO QUANTIFY HOW MUCH STRONGER A SYNAPSE HAS GOTTEN THROUGH LEARNING, AND HOW MUCH STRONGER IT CAN GET. SYNAPTIC STRENGTH CAN BE MEASURED BY LOOKING AT THE PHYSICAL CHARACTERISTICS OF SYNAPSES, BUT IT IS MUCH MORE DIFFICULT TO MEASURE THE PRECISION OF PLASTICITY (WHETHER SYNAPSES GROW WEAKER OR STRONGER BY A CONSISTENT AMOUNT) AND THE AMOUNT OF INFORMATION A SYNAPSE CAN STORE. A NEW COMPUTATIONAL METHOD DEVELOPED AT SALK CAN DO ALL THREE, OPENING THE DOOR FOR NEW STUDIES ON HUMAN LEARNING AND MEMORY AND HOW THOSE PROCESSES EVOLVE OR DETERIORATE WITH AGE OR DISEASE. THE STUDY WAS LED BY PROFESSOR TERRENCE SEJNOWSKI AND PUBLISHED IN NEURAL COMPUTATION ON APRIL 23, 2024. THIS TIME, IT'S PERSONAL: ENHANCING PATIENT RESPONSE TO CANCER IMMUNOTHERAPY-FEWER THAN HALF OF ALL CANCER PATIENTS RESPOND TO CURRENT IMMUNOTHERAPIES, CREATING AN URGENT NEED TO IDENTIFY BIOMARKERS THAT CAN PREDICT WHICH PATIENTS ARE MOST LIKELY TO BENEFIT. SALK SCIENTISTS HAVE DONE JUST THAT, FINDING THAT MUTATIONS IN A GENE CALLED ARID1A MAKE PATIENTS MORE LIKELY TO RESPOND POSITIVELY TO IMMUNE CHECKPOINT BLOCKADE-A TYPE OF IMMUNOTHERAPY THAT WORKS BY KEEPING CANCER-FIGHTING IMMUNE CELLS TURNED "ON." THE ARID1A MUTATION PROMPTS AN ANTIVIRAL RESPONSE THAT PULLS MORE CANCER-FIGHTING IMMUNE CELLS INTO THE TUMOR, AND BECAUSE THE GENE IS PRESENT IN MANY CANCERS-ENDOMETRIAL, OVARIAN, COLON, GASTRIC, LIVER, AND PANCREATIC-THE BIOMARKER COULD HAVE A HUGE IMPACT IN IDENTIFYING PATIENTS FOR SPECIFIC IMMUNOTHERAPIES. THE FINDINGS ALSO ENCOURAGE THE DEVELOPMENT OF DRUGS THAT TARGET ARID1A AND RELATED PROTEINS AS A WAY OF SENSITIZING OTHER TUMORS TO IMMUNOTHERAPY. THE STUDY WAS LED BY PROFESSOR DIANA HARGREAVES AND PUBLISHED IN CELL ON MAY 15, 2024. KEY NUTRIENTS HELP PLANTS BEAT THE HEAT-BECAUSE PLANTS CANNOT REGULATE THEIR OWN TEMPERATURES, THEY ARE ESPECIALLY SENSITIVE TO CLIMATE CHANGE-RELATED TEMPERATURE CHANGES. SALK SCIENTISTS HAVE DISCOVERED THAT PLANT'S TYPICAL RESPONSE TO HIGH TEMPERATURES CAN ULTIMATELY REDUCE LEVELS OF TWO IMPORTANT NUTRIENTS-NITROGEN AND PHOSPHORUS-IN THE PLANT, MAKING THEM LESS NUTRITIOUS WHEN CONSUMED. AT THE SAME TIME, IF THE SOIL CONTAINS LOW AMOUNTS OF THESE NUTRIENTS, PLANTS SLOW ROOT GROWTH AND DON'T RESPOND ADEQUATELY TO THE HIGHER TEMPERATURES. THE NEW MOLECULAR DETAILS OF THIS INTERACTION BETWEEN ROOT GROWTH AND NUTRIENT AVAILABILITY IN THE FACE OF HIGH TEMPERATURES WILL INFORM THE ENGINEERING OF SALK IDEAL PLANTS. THE STUDY WAS LED BY PROFESSOR WOLFGANG BUSCH AND PUBLISHED IN NATURE COMMUNICATIONS ON JUNE 1, 2024. COOPERATIVE PROTEINS HELP THE IMMUNE SYSTEM IDENTIFY AND ATTACK INVADERS-AT THE FRONT LINE OF THE HUMAN IMMUNE RESPONSE ARE CELLS CALLED MACROPHAGES, WHICH ARE RESPONSIBLE FOR CORRECTLY IDENTIFYING INTRUDERS AND THEN DIRECTING HOW THE ENTIRE IMMUNE SYSTEM RESPONDS. ACTIVATING MACROPHAGES REQUIRES THE WORK OF THREE VERSIONS OF A PROTEIN COMPLEX CALLED SWI/SNF: CBAF, NCBAF, AND PBAF. SALK RESEARCHERS DISCOVERED THAT EACH VARIANT PLAYS A DISTINCT ROLE IN INITIATING MACROPHAGES' RESPONSES TO INTRUDERS AND, CONSEQUENTLY, HOW THE IMMUNE SYSTEM REGULATES INFLAMMATION. BY DELINEATING THESE SWI/SNF VARIANTS, THE TEAM HAS REVEALED NEW IMMUNE SYSTEM MECHANISMS THAT COULD BE TARGETED WITH THERAPEUTICS TO REGULATE INFLAMMATION ASSOCIATED WITH CONDITIONS LIKE SEPSIS, CYTOKINE STORM, COVID-19, AND MANY MORE. THE STUDY WAS LED BY ASSOCIATE PROFESSOR DIANA HARGREAVES AND PUBLISHED IN IMMUNITY ON JUNE 5, 2024. UNVEILING TELO-SEQ: A BREAKTHROUGH IN TELOMERE RESEARCH ON AGING AND CANCER-THERE IS A LOT OF INTEREST IN UNDERSTANDING EXACTLY WHEN AND HOW TELOMERES, THE ENDCAPS ON OUR CHROMOSOMES, SHORTEN OVER TIME AND HOW THAT MAY IMPACT HEALTH AND DISEASE, BUT EXISTING TECHNOLOGY ONLY ALLOWED SCIENTISTS TO MEASURE THE AVERAGE LENGTH OF ALL TELOMERES IN A CELL. IN COLLABORATION WITH OXFORD NANOPORE TECHNOLOGIES, A SALK TEAM DEVELOPED "TELO-SEQ"-A TOOL THAT COMBINES STATE-OF-THE-ART SEQUENCING, BIOCHEMISTRY, AND BIOINFORMATICS TECHNIQUES TO ACHIEVE UNPRECEDENTED RESOLUTION OF TELOMERE STRUCTURE AND COMPOSITION. THEIR FINDINGS WILL FACILITATE A SLEW OF NEW INSIGHTS INTO THE MOLECULAR DYNAMICS OF CANCER AND AGING, WHICH COULD LEAD TO NOVEL THERAPEUTICS TARGETING THESE TELOMERIC MECHANISMS. THE STUDY WAS LED BY PROFESSOR AND CSO JAN KARLSEDER AND PUBLISHED IN NATURE COMMUNICATIONS ON JUNE 18, 2024. Form 990, Part VI, Line 1a Delegate broad authority to a committee THE EXECUTIVE COMMITTEE SHALL ADVISE AND AID THE OFFICERS OF THE CORPORATION IN ALL MATTERS CONCERNING ITS INTERESTS, INCLUDING WITHOUT LIMITATION ALL MATTERS RELATING TO COMPENSATION AND BENEFITS, AND SHALL POSSESS AND MAY EXERCISE, DURING THE INTERVALS BETWEEN THE MEETINGS OF THE BOARD OF TRUSTEES, ALL THE POWERS AND AUTHORITY OF THE BOARD OF TRUSTEES IN THE MANAGEMENT OF THE BUSINESS AND AFFAIRS OF THE CORPORATION, INCLUDING THE POWER TO AUTHORIZE THE CORPORATE SEAL TO BE AFFIXED TO ANY AND ALL DOCUMENTS WHICH MAY REQUIRE THE SAME TO BE AFFIXED THERETO, INSOFAR AS SUCH SEEMS TO THE EXECUTIVE COMMITTEE FOR THE BEST INTERESTS OF THE CORPORATION, IN ALL CASES IN WHICH SPECIFIC DIRECTIONS SHALL NOT HAVE BEEN GIVEN BY THE BOARD OF TRUSTEES, EXCEPT THAT THE EXECUTIVE COMMITTEE SHALL HAVE NO POWER TO ADOPT, AMEND, OR REPEAL THE BY-LAWS. Form 990, Part VI, Line 6 Classes of members or stockholders MEMBERSHIP OF THE CORPORATION CONSISTS OF THE PERSONS ELECTED TO THE BOARD OF TRUSTEES AND THREE MEMBERS FROM AMONG THE RESIDENT AND NON-RESIDENT FELLOWS AND PROFESSORS CHOSEN AND ELECTED ANNUALLY BY THE RESIDENT AND NON-RESIDENT FELLOWS AND PROFESSORS. Form 990, Part VI, Line 7a Members or stockholders electing members of governing body THE MEMBERS OF THE CORPORATION ELECT THE TRUSTEES. Form 990, Part VI, Line 7b Decisions requiring approval by members or stockholders THE MEMBERS OF THE CORPORATION MAY ALTER, AMEND, OR REPEAL THE BY-LAWS BY VOTE. Form 990, Part VI, Line 11b Review of form 990 by governing body THE FORM 990 IS PREPARED BY THE INSTITUTE, INTERNALLY REVIEWED BY THE CHIEF FINANCIAL OFFICER AND EXTERNALLY REVIEWED BY THE TAX DEPARTMENT OF A PUBLIC ACCOUNTING FIRM. PRIOR TO ELECTRONIC FILING, A COPY OF THIS FORM 990 IS PROVIDED TO AND DISCUSSED IN THE EXECUTIVE SESSION OF THE BOARD OF TRUSTEES. Form 990, Part VI, Line 12c Conflict of interest policy ANNUALLY, THE CONFLICT OF INTEREST DISCLOSURE STATEMENT IS SENT OUT FOR COMPLETION BY THE MEMBERS OF THE BOARD OF TRUSTEES, SENIOR MEMBERS OF ADMINISTRATION AND RESEARCHERS. THE DESIGNATED OFFICIAL FOR EACH GROUP REVIEWS THE COMPLETED FORMS AND BRINGS ANY POTENTIAL CONFLICT OF INTEREST TO THE RESPECTIVE COMMITTEES FOR REVIEW. UPON DETERMINATION THAT A CONFLICT OF INTEREST EXISTS, THE FOLLOWING CONDITIONS OR RESTRICTIONS MAY BE IMPOSED: A. MONITORING OF ACTIVITIES GENERATING THE CONFLICT BY ANOTHER MEMBER; B. DISQUALIFICATION FROM PARTICIPATION IN THE ACTIVITIES GIVING RISE TO THE CONFLICT; C. MODIFICATION OF RESPONSIBILITIES TO AVOID CONFLICTS; D. PUBLIC DISCLOSURE OR DIVESTITURE OF SIGNIFICANT FINANCIAL INTERESTS; E. MODIFICATION OF THE RESEARCH PLAN OR REMOVAL OF THE AFFECTED RESEARCHER FROM THE RESEARCH; F. SEVERANCE OF RELATIONSHIP THAT CREATES ACTUAL OR POTENTIAL CONFLICTS; G. TERMINATION OF EMPLOYMENT. Form 990, Part VI, Line 15a Process to establish compensation of top management official A COMPREHENSIVE MARKET ASSESSMENT WAS COMPLETED IN APRIL 2024, BASED ON COMPENSATION DATA FROM A SELECTED PEER GROUP FOR SALK PRESIDENT AND EXECUTIVE LEADERSHIP ROLES. THIS ASSESSMENT WAS PROVIDED TO THE CHAIR AND CO-CHAIRS OF SALK'S BOARD OF TRUSTEES AND TO SALK'S PRESIDENT. SALK'S PRESIDENT AND THE INSTITUTE'S VICE-PRESIDENT PEOPLE & CULTURE DISCUSSED THE PERFORMANCE OF VICE-PRESIDENT-LEVEL EXECUTIVES AT A MEETING ON APRIL 17, 2024, WITH THE CHAIR AND CO-CHAIRS OF THE BOARD OF DIRECTORS; THE VICE-PRESIDENT PEOPLE & CULTURE WAS NOT PRESENT FOR DISCUSSION ABOUT HER PERFORMANCE. AFTER THIS MEETING, A SEPARATE DISCUSSION ABOUT THE COMPENSATION OF THE INSTITUTE PRESIDENT, RECOMMENDED CHANGES WERE PRESENTED TO AND APPROVED BY THE SALK BOARD OF TRUSTEES AT THE EXECUTIVE SESSION OF THE APRIL 19, 2024 BOARD OF TRUSTEES MEETING. Form 990, Part VI, Line 15b Process to establish compensation of other employees A COMPREHENSIVE MARKET ASSESSMENT WAS COMPLETED IN APRIL 2024, BASED ON COMPENSATION DATA FROM A SELECTED PEER GROUP FOR SALK PRESIDENT AND EXECUTIVE LEADERSHIP ROLES. THIS ASSESSMENT WAS PROVIDED TO THE CHAIR AND CO-CHAIRS OF SALK'S BOARD OF TRUSTEES AND TO SALK'S PRESIDENT. SALK'S PRESIDENT AND THE INSTITUTE'S VICE-PRESIDENT PEOPLE & CULTURE DISCUSSED THE PERFORMANCE OF VICE-PRESIDENT-LEVEL EXECUTIVES AT A MEETING ON APRIL 17, 2024, WITH THE CHAIR AND CO-CHAIRS OF THE BOARD OF DIRECTORS; THE VICE-PRESIDENT PEOPLE & CULTURE WAS NOT PRESENT FOR DISCUSSION ABOUT HER PERFORMANCE. AFTER THIS MEETING, A SEPARATE DISCUSSION ABOUT THE COMPENSATION OF THE INSTITUTE PRESIDENT, RECOMMENDED CHANGES WERE PRESENTED TO AND APPROVED BY THE SALK BOARD OF TRUSTEES AT THE EXECUTIVE SESSION OF THE APRIL 19, 2024 BOARD OF TRUSTEES MEETING. Form 990, Part VI, Line 19 Required documents available to the public UPON REQUEST, THE OFFICE OF THE CHIEF FINANCIAL OFFICER MAKES AVAILABLE TO THE PUBLIC THE INSTITUTE'S GOVERNING DOCUMENTS AND CONFLICT OF INTEREST POLICY. FINANCIAL STATEMENTS ARE AVAILABLE ON THE SALK WEBSITE. Form 990, Part VII, Section A DIRECTORS COMPENSATION THE FOLLOWING INDIVIDUALS WERE COMPENSATED FOR THE FOLLOWING SERVICES AND NOT PAID AS TRUSTEES: GERALD JOYCE, PH.D. - PRESIDENT/PROFESSOR; REUBEN SHAW, PH.D. - PROFESSOR; JANELLE AYRES, PH.D. - PROFESSOR; WOLFGANG BUSCH, PH.D. - PROFESSOR; TATYANA SHARPEE, PH.D. - PROFESSOR. Form 990, Part XI, Line 9 Other changes in net assets or fund balances POSTRETIREMENT BENEFIT CHANGES OTHER THAN NET PERIODIC BENEFIT COST - -7222; CHANGE IN VALUE OF DEFERRED GIFTS - -146836; ROUNDING - -396; SALK INSTITUTE COMMERCIAL SERVICES CORP 10010 N TORREY PINES ROAD LA JOLLA CA 920371002 232159172 MGMT SERVICES PA SALK INSTITUTE C Corporation 4 41143 1.0000 true CHARITABLE REMAINDER TRUSTS (4) SUPPORT CA NA Trust false false false false false false false false false false false false false true true false true false false