Albany College Of Pharmacy And Health Sciences

DISRUPTION OF CAMPUS OPERATIONS DUE TO CORONAVIRUS-INSTITUTIONAL AID.

DISRUPTION OF CAMPUS OPERATIONS DUE TO CORONAVIRUS-STUDENT RELIEF AID.

REPRESSION OF INFLAMMASOME BY FRANCISELLA TULARENSIS

A MECHANISM FOR TNF INDUCED ENDOTHELIAL DYSFUNCTION

INVESTIGATING RNA POLYMERASE III DRIVEN MECHANISMS IN REGULATING HIV LATENCY - ABSTRACT RESTING CD4+ T CELLS HARBOR MAJORITY OF LATENT HUMAN IMMUNODEFICIENCY VIRUS (HIV) DURING INFECTION. ELIMINATION OF THIS RESERVOIR IS AN EXTREMELY CHALLENGING TASK BECAUSE OF INVOLVEMENT OF MULTIPLE MECHANISMS IN REGULATING HIV LATENCY. THEREFORE, PERHAPS, NONE OF THE CURRENTLY PROMISING LATENCY REVERSING AGENTS (LRAS) WERE ABLE TO REDUCE THE SIZE OF THE LATENT PROVIRAL RESERVOIR IN PATIENTS. HENCE, THERE IS A DIRE NEED TO FIND NOVEL MECHANISMS AND THERAPEUTIC TARGETS THAT CAN BE TARGETED TO PURGE THE HETEROGENOUS LATENT RESERVOIR. RNA POLYMERASE III (RNA POL III) APPEARS TO BE A MASTER REGULATOR WITH UNEXPLORED POTENTIAL OF REGULATING LATENCY VIA MEDIATING DISTINCT MECHANISMS, SUCH AS I) REGULATING THE EXPRESSION FROM NEIGHBORING RNA POL II GENE PROMOTERS AND II) TRANSCRIPTION OF NOVEL NONCODING RNAS WITH POTENTIAL TO REGULATE EXPRESSION OF CELLULAR/VIRAL GENES. OUR PRELIMINARY STUDIES SUGGEST THE ENRICHMENT OF POL III TRANSCRIBED NONCODING RNAS IN LATENT CELLS, NAMELY 7SK, 21A AND BC200 THAT ARE INTERSPERSED AMONG ALU REPEATS. THIS IS HIGHLY RELEVANT TO HIV LATENCY BECAUSE THE HIV GENOME IS FOUND TO PREFERENTIALLY INTEGRATE NEAR ALU REPEATS. CONSEQUENTLY, USE OF AN RNA POL III INHIBITOR, ML60218, RESULTED IN AN UNPRECEDENTED REACTIVATION (UP TO 90%) OF LATENT CELL LINES J89GFP AND THP89GFP, IN A DOSE- DEPENDENT MANNER (25 ΜM-50 ΜM). FURTHER, WE OBSERVED A HIGH DEGREE OF CELL DEATH SPECIFICALLY IN HIV INFECTED CELLS DUE TO VIRAL CYTOPATHIC EFFECTS, WHEREAS UNINFECTED CELLS MAINTAINED SURVIVAL EVEN AT A VERY HIGH CONCENTRATION OF RNA POL III INHIBITOR (100 ΜM). THESE EXCITING FINDINGS AND CORROBORATING REPORTS WILL BE LEVERAGED TO TEST THE HYPOTHESIS THAT RNA POL III PLAYS A CRUCIAL ROLE IN THE ESTABLISHMENT OF HIV LATENCY AND TARGETING NOVEL INTERMEDIATE EFFECTORS OF RNA POL III DRIVEN MECHANISMS MAY ENHANCE THE EFFICACY OF CURE STRATEGIES. THIS STUDY IS DIVIDED INTO TWO SPECIFIC AIMS THAT WILL BE FOCUSED ON INVESTIGATING RNA POL III DRIVEN DIRECT (BY GENOMIC OCCUPANCY) AND INDIRECT (BY NCRNAS) MECHANISMS THAT MAY REGULATE HIV LATENCY. IN AIM 1, EFFECT OF RNA POL III INHIBITION/KNOCKDOWN WILL BE TESTED IN EX VIVO CULTURED PRIMARY CD4+ T CELL MODEL. FURTHER IN AIM 1.2 WE WILL INVESTIGATE IF PHYSICAL PRESENCE OF RNA POL III IN PROXIMITY CAN MODIFY CHROMATIN LANDSCAPE AT HIV 5´ LTR. IN AIM 2, WE WILL IDENTIFY RNA POL III TRANSCRIBED NONCODING RNAS INVOLVED IN LATENCY BY EMPLOYING RNA-SEQ IN COMBINATION WITH RNA POL III CHIP-SEQ. FINALLY, GENE KNOCKDOWN STUDIES WILL BE PERFORMED FOR SELECT NONCODING RNAS ALONE OR IN COMBINATION TO INVESTIGATE THEIR ROLE IN PROMOTING REPRESSED CHROMATIN STATE AT HIV 5´ LTR. OUR STUDY IS HIGHLY INNOVATIVE AS WE AIM TO IDENTIFY NOVEL EPIGENETIC MODULATORS THAT CAN BE SYNCHRONOUSLY TARGETED TO OVERCOME CHALLENGES ASSOCIATED WITH SHOCK AND KILL STRATEGY OF HIV CURE. SUCCESSFUL COMPLETION OF THIS STUDY WILL PROVIDE CRITICAL MECHANISTIC INFORMATION WHICH MAY ADDRESS THE HETEROGENEITY AMONG LATENT RESERVOIRS.

MECHANISMS AND OUTCOMES OF ERYTHROCYTE NECROPTOSIS

A UNIQUE DOUBLE PHD FINGER AND BROMODOMAIN IN EPIGENETIC SIGNALING

PHARMACOLOGY OF CYCLOPHOSPHAMIDE AND OTHER ALKYLATORS

AN IN VITRO-IN VIVO CORRELATION MODEL TO PREDICT SERUM NON-TRANSFERRIN BOUND IRON

SIMULTANEOUS DETERMINATION OF FREE, TOTAL, AND NORMALIZED CONCENTRATIONS OF BIOACTIVE COMPOUNDS

SOLID PHASE MICROEXTRACTION AS A NEW TOOL FOR QUANTIFYING ANTIBODY DRUGS IN BREAST CANCER AND BUILDING PK-PD MODELS - MODERN DRUG ANALYSIS TECHNIQUES ARE AN INTEGRAL PART OF RESEARCH AND HEALTHCARE TODAY. REGRETTABLY, THE CURRENT APPROACH FOR SAMPLE COLLECTION CONSISTS OF LITERALLY REMOVING “A PIECE OF THE PATIENT OR EXPERIMENTAL ANIMAL” (WHETHER IT IS A BLOOD SAMPLE OR A TISSUE BIOPSY) THAT IS SENT TO THE LABORATORY FOR ANALYSIS. SUCH A PROCEDURE POSES ETHICAL ISSUES, HEALTH RISKS FOR THE MEDICAL PERSONNEL, AND INCONVENIENCE FOR THE INVESTIGATED BEING (PATIENT OR LAB ANIMAL). FURTHERMORE, ALTHOUGH IT HAS BEEN RECOGNIZED THAT TISSUE CONCENTRATIONS ARE MORE PREDICTIVE OF CLINICAL OUTCOME THAN PLASMA CONCENTRATIONS, THE ASSESSMENT OF DRUG DISTRIBUTION AND TARGET SITE PHARMACOKINETICS IS VERY DIFFICULT BECAUSE OF LACK OF APPROPRIATE METHODOLOGY. POINT-OF-CARE DEVICES FOR MEASURING ELECTROLYTES, CARDIAC MARKERS, AND SEVERAL SMALL MOLECULES NOW RESIDE IN EMERGENCY ROOMS AND EVEN AT PATIENT BEDSIDES - BUT THERE ARE NO CLINICAL DEVICES FOR FAST MONITORING OF DRUG LEVELS IN BODY FLUIDS AND TISSUES. THE NEED FOR SUCH DEVICES IS EVEN GREATER FOR DIFFICULT TO TREAT DISEASES SUCH AS NEOPLASMS. IN RESPONSE TO THE CURRENT CHALLENGES FACED BY DRUG ANALYSIS FOR PHARMACOKINETICS, PHARMACODYNAMICS, AND THERAPEUTIC DRUG MONITORING, WE ARE PROPOSING TO APPLY INNOVATIVE MICROSAMPLING APPROACHES TO MEASURE THERAPEUTIC ANTIBODY CONCENTRATIONS IN THE TUMORS WITHOUT COLLECTING A PHYSICAL SAMPLE FROM THE INVESTIGATED ORGANISM. THESE METHODS FEATURE RELIABLE CALIBRATION, FREEDOM FROM PUMPS, NO OSMOTIC EFFECTS, AND SIGNIFICANT IMPROVEMENTS IN SENSITIVITY. FURTHERMORE, THEY ARE FASTER AND MORE ECONOMICAL THAN CLASSICAL ONES. THE NEW METHODS WILL BE APPLIED FOR THE FIRST TIME TO MEASURE THE TUMOR CONCENTRATION OF IMMUNE CHECKPOINT INHIBITORS THAT ACT BY BLOCKING THE PROGRAMMED CELL DEATH RECEPTORS ON T CELLS. THE PROPOSED RESEARCH WILL UTILIZE BIOCOMPATIBLE SAMPLING DEVICES FOR DIRECT MICROEXTRACTION OF ANTIBODY DRUGS FROM TUMORS. THESE DEVICES WILL BE PREPARED BY COVERING FLEXIBLE MEDICAL-GRADE METAL WIRES WITH BIOCOMPATIBLE POLYMERS AND HIGH AFFINITY EXTRACTIVE PHASES. THE EXTRACTED ANALYTES WILL BE QUANTIFIED BY CHROMATOGRAPHY AND MASS SPECTROMETRY TO OFFER HIGH SPECIFICITY AND LOW LIMITS OF DETECTION. FOR QUANTITATION, SEVERAL CALIBRATION METHODS WILL BE APPLIED, SUCH AS EXTERNAL STANDARD, DIFFUSION-BASED CALIBRATION, AND KINETIC CALIBRATION. THE DATA WILL BE USED TO BUILD A PHARMACOKINETIC-PHARMACODYNAMIC MODEL FOR A REPRESENTATIVE THERAPEUTIC ANTIBODY, SUCH AS PEMBROLIZUMAB. THE NEW IN VIVO SAMPLING METHOD WILL BE VALIDATED BY COMPARISON WITH LARGE PORE MICRODIALYSIS. IT IS EXPECTED THAT MICROEXTRACTION WILL PROVIDE BETTER SENSITIVITY, ACCURACY, LESS TISSUE DAMAGE (DUE TO SMALLER SIZE), PORTABILITY, AND CONVENIENCE (NO PUMPS AND FLUIDS).

TARGETING SECRETED FACTORS IN ENDOCRINE RESISTANT BREAST CANCER THERAPY - ABSTRACT/SUMMARY: VARIOUS TYPES OF ENDOCRINE THERAPY HAVE BEEN USED FOR POSTMENOPAUSAL WOMEN WITH EARLY STAGE BREAST CANCER. THESE THERAPIES ARE SAFE AND EFFECTIVE, BUT INITIALLY RESPONSIVE BREAST TUMORS OFTEN DEVELOP RESISTANCE AND EVENTUALLY RECUR. SINCE A COMMUNICATION BETWEEN TUMOR AND TUMOR CIRCUMSTANCE PLAYS AN IMPORTANT ROLE TO GROW TUMOR AND SPREAD TUMOR TO SECONDARY ORGANS, WE EXAMINED THE COMMUNICATION OF ENDOCRINE RESISTANT BREAST CANCER WITH STROMA WHICH IS THE PART OF A TISSUE OR ORGAN THAT HAS A CONNECTIVE AND STRUCTURAL ROLE IN CANCER. WE ESTABLISHED FOUR DIFFERENT ENDOCRINE RESISTANT BREAST CANCER CELL LINES AND EXAMINED THE COMMUNICATION OF THESE CELLS WITH FOUR STROMAL CELLS. WE FOUND THAT CCL5 AND ENDOGLIN MIGHT PLAY AN IMPORTANT ROLE IN ENDOCRINE RESISTANT BREAST CANCER. THUS, WE WILL 1) INVESTIGATE THE ROLE OF CCL5 AND ENDOGLIN IN THE CROSSTALK BETWEEN ERBC CELLS AND STROMAL CELLS, 2) UNVEIL THE MECHANISM OF THE UPREGULATED CCL5 AND ENDOGLIN IN CROSSTALK BETWEEN ERBC AND STROMA, AND 3) DEVELOP THERAPEUTIC STRATEGIES TO BLOCK THE PARACRINE INTERACTION BETWEEN THE STROMAL CELL AND ERBC CELL. WE WILL INVESTIGATE WHICH SECRETED FACTORS COULD SERVE AS A KEY REGULATOR IN THE TRANSITION OF BREAST CANCER CELLS TO ENDOCRINE RESISTANCE AND GAINING OF AN AGGRESSIVE PHENOTYPE. FURTHER, SECRETED FACTORS FROM THE COMMUNICATION BETWEEN ENDOCRINE RESISTANT BREAST CANCER AND STROMA MIGHT PROVE TO BE AN ATTRACTIVE TARGET FOR BREAST CANCER DRUGS. MOST OF THE CANCER DRUGS IN USE CURRENTLY HAVE BEEN DEVELOPED TO DIRECTLY IMPACT TUMOR CELLS. THESE DRUGS DO NOT DO MUCH TO BLOCK SIGNALS COMING FROM TUMOR CIRCUMSTANCE. OUR PROPOSED INVESTIGATION WILL GIVE US A SMALL LIST OF THE MOST POTENT OF THESE SIGNALS. DRUGS, SOME OF WHICH WE WILL IDENTIFY HERE, AND OTHERS THAT WILL HAVE TO BE DEVELOPED, THAT BLOCK THESE SIGNALS COULD LIMIT THE ABILITY OF THE TUMORS TO SPREAD TO SECONDARY ORGANS, WHICH SHOULD RESULT IN OVERALL SURVIVAL GAINS FOR PATIENTS.

ACTIVATION OF TYPE I INTERFERON PRODUCTION IN HUMAN IMMUNE CELLS BY CELL-TO-CELL TRANSMISSION OF HIV-1 - ABSTRACT TYPE I INTERFERON (IFN) IS AN IMPORTANT CYTOKINE THAT NOT ONLY FUNCTIONS AS HOST INNATE IMMUNE RESPONSE AGAINST INFECTION BUT ALSO REGULATES INFLAMMATION AND IMMUNOPATHOGENESIS PROCESS. IFN PRODUCTION MEDIATED BY CGAS/STING SIGNALING PATHWAY, WHICH SENSES CYTOSOL DNA, IS ONE OF FUNDAMENTAL SYSTEMS FOUND IN A VARIETY OF VIRAL INFECTIONS. HOWEVER, MECHANISMS OF HOW HIV-1 INFECTION INDUCES PRODUCTION OF IFN IN IMMUNE CELLS HAS BEEN INCOMPLETELY UNDERSTOOD FOR DECADES. CLINICAL STUDIES HAVE DEMONSTRATED ELEVATED IFN ACTIVITY IN PEOPLE LIVING WITH HIV-1. IN SIMILAR, PERSISTENT IFN EXPRESSIONS WERE FOUND IN HIV/AIDS ANIMAL MODELS. HOWEVER, IN VITRO STUDIES USING CELL-FREE HIV-1 VIRUSES REPORTED POOR INDUCTION OF IFN PRODUCTION TRIGGERED BY CGAS/STING SIGNALING PATHWAY. INTERESTINGLY, IN A PILOT STUDY, WE FOUND THAT HIV-1 CELL ASSOCIATED INFECTION, A MODE OF VIRAL TRANSMISSION THROUGH DIRECT CELL TO CELL CONTACT THAT YIELDS RAPID VIRION TRANSFER AND MUCH EFFICIENT REPLICATION, ACTIVATED IFN EXPRESSION BY TRIGGERING CGAS-STING SIGNALING PATHWAY IN CULTURED MT2 CELLS. THEREFORE, IN THIS STUDY, WE HYPOTHESIZE THAT CELL-TO-CELL TRANSMISSION OF HIV-1 ACTIVATES PRODUCTIONS OF IFNS AND INFLAMMATORY CYTOKINES BY INDUCING CGAS/STING PATHWAYS. WE HAVE DEVELOPED TWO CELL BASED MODELS TO STUDY CELL-TO-CELL TRANSMISSION OF HIV-1 INDEPENDENT OF CELL FREE VIRUS INFECTION IN BOTH CULTURED AND PRIMARY HUMAN IMMUNE CELLS.WE PROPOSE TO TEST OUR HYPOTHESIS BY TWO SPECIFIC AIMS. AIM 1. TO INVESTIGATE WHETHER HIV-1 CELL-TO-CELL TRANSMISSION ACTIVATES IFN PRODUCTION BY INDUCING CGAS/STING/IRF-3 PATHWAY. WE WILL INVESTIGATE AND CONFIRM THE ACTIVATION OF THIS PATHWAY SPECIFICALLY BY CELL ASSOCIATED INFECTION. WE WILL FURTHER VERIFY THAT CGAS IS THE SENSOR OF THIS PATHWAY ACTIVATION AND IDENTIFY FACTORS THAT TRIGGERS THIS ACTIVATION UNDER UNIQUE VIROLOGICAL AND CELLULAR ENVIRONMENTS DURING CELL ASSOCIATED TRASMISSION OF HIV-1. AIM 2. TO INVESTIGATE WHETHER HIV- 1 CELL-TO-CELL TRANSMISSION TRIGGERS CGAS/STING/NF-ΚB PATHWAY. WE WILL EXAMINE CHANGES IN STATUS OF THIS SIGNALING PATHWAY ACTIVATION AFTER CELL-TO-CELL TRANSMISSION OF HIV-1. WE WILL ALSO INVESTIGATE IF CELL ASSOCIATED INFECTION REACTIVATES HIV-1 IN LATENCY THROUGH UPREGULATING NF-ΚB. UNDERSTANDING THE ROLE OF HIV- 1 CELL-TO-CELL TRANSMISSION IN THE ACTIVATION OF IFN WITH WELL CHARACTERIZED SIGNALING PATHWAYS WILL REPRESENT A NEW WAY TO FULFILL OUR UNDERSTANDING IN THE PATHOGENESIS OF HIV INFECTION AS WELL AS PROVIDING A POTENTIAL GUIDE TO THERAPEUTIC APPROACHES. THIS STUDY WILL ALSO PROVIDE GREAT OPPORTUNITY OF RESEARCH COLLABORATIONS AND EXTENSIVE LEARNING EXPERIENCE FOR STUDENTS AT ACPHS.

ROLE OF METHYLATION IN ETHANOL-INDUCED MICROGLIAL ACTIVATION

CODRUGS OF LIPOIC ACID AND TOCOPHEROL/TOCOPHERAMINE FOR USE AS PHOTOPROTECTIVE AG

SYNERGISTIC EXTRA AND INTRACELLULAR RECOGNITION OF F. TULARENSIS

NOVEL PROBES FOR SIRTUINS: A CHEMICAL BIOLOGY APPROACH

COLLABORATIVE RESEARCH: EPIIC: EMPOWERED -- BUILDING THE FUTURE WORKFORCE TOGETHER -THIS IS A COLLABORATIVE PROJECT ACROSS THE FOLLOWING INSTITUTIONS: HOBART AND WILLIAM SMITH COLLEGE, UNIVERSITY OF MAINE AT FARMINGTON, ALBANY COLLEGE OF PHARMACY & HEALTH SCIENCES, MONTGOMERY COLLEGE, BENJAMIN FRANKLIN CUMMINGS INSTITUTE OF TECHNOLOGY, AND OHIO WESLEYAN UNIVERSITY. ACCORDING TO THE US BUREAU OF LABOR STATISTICS, OVER THE NEXT DECADE, STEM OCCUPATIONS ARE FORECAST TO GROW FASTER THAN THE TOTAL FOR ALL OCCUPATIONS, LEAVE A TALENT SHORTAGE FOR INDUSTRIES TO FILL NEARLY 3.5 MILLION STEM JOBS BY 2029. IN ADDITION, THERE IS A GROWING DISCONNECT BETWEEN WHAT STEM STUDENTS LEARN IN COLLEGE AND WHAT EMPLOYERS EXPECT NEW GRADUATES TO BE ABLE TO DO. SOME EMPLOYERS FIND RECENT GRADUATES LACK SOFT SKILLS LIKE PROBLEM SOLVING, CRITICAL THINKING, AND WRITTEN AND ORAL COMMUNICATION; OTHERS FIND STUDENTS TO BE UNFAMILIAR WITH THE PRACTICAL AND TECHNICAL SKILLS NEEDED FOR THEIR DAY-TO-DAY WORK. THIS COLLABORATIVE EPIIC PROJECT DEFINES A PROCESS TO ADDRESS THESE ISSUES AT THE ACADEMIC INSTITUTIONS PARTICIPATING IN THIS PROJECT. COHORT INSTITUTIONS WILL WORK TOGETHER GROW INDUSTRY PARTNERSHIPS, IMPROVE ALIGNMENT OF PROGRAM CURRICULA WITH INDUSTRY NEEDS, AND ENHANCE FACULTY SKILLS AND KNOWLEDGE OF EMERGING TECHNOLOGIES. THROUGH THIS EPIIC PROJECT, THE COLLABORATING INSTITUTIONS WILL BUILD RELATIONSHIPS WITH INDUSTRY EXPERTS AND GOVERNMENT AGENCIES TO FIND OUT WHAT SKILLS AND KNOWLEDGE ARE NEEDED FOR STEM JOBS IN THEIR FIELDS. THE COHORT WILL USE THIS INFORMATION TO MODIFY AND ENHANCE COLLEGE COURSES AND CURRICULAR STRUCTURE WITH INDUSTRY NEEDS IN MIND SO STUDENTS ARE PREPARED FOR JOBS RIGHT OUT OF COLLEGE. AT THE SAME TIME, SKILLS TRAINING FOR FACULTY MUST BE PROVIDED SO INSTRUCTORS ARE PREPARED TO TEACH THE ENHANCED COURSE CONTENT AND MULTIPLE DEGREE PATHWAYS MUST BE CREATED SO STUDENTS WITH DIVERSE PREPARATION AND LIFE SITUATIONS WILL GRADUATE. PROJECT PARTICIPANTS WILL ALSO COMMUNICATE TO STUDENTS CLEARLY AND EFFECTIVELY ABOUT HOW AND WHY THEIR EDUCATION WILL PREPARE THEM FOR THE STEM CAREERS THEY WANT, THUS BUILDING THE WORKFORCE THIS COUNTRY NEEDS. EACH ACADEMIC INSTITUTION IN THE DIVERSE COHORT, WHICH INCLUDES TWO SMALL LIBERAL ARTS COLLEGES, TWO 2-YEAR TECHNICAL COLLEGES, A PRIMARILY UNDERGRADUATE STATE UNIVERSITY, AND A 4-YEAR COLLEGE OFFERING SPECIALIZED UNDERGRADUATE AND GRADUATE DEGREES, HAS DEVELOPED AN INDIVIDUALIZED PLAN TO IMPLEMENT THIS PROCESS. THE PARTICIPATING INSTITUTIONS WILL EXCHANGE INFORMATION AND WORK TOGETHER AS A COHORT TO ENHANCE EACH INSTITUTION'S CAPACITY FOR BUILDING EXTERNAL PARTNERSHIPS. THIS PROCESS WILL POSITION THE INSTITUTIONS TO FURTHER DEEPEN ENGAGEMENT WITH INDUSTRY AND ENHANCE THEIR CONTRIBUTIONS TO THEIR REGIONAL INNOVATION ECOSYSTEMS. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.- SUBAWARDS ARE NOT PLANNED FOR THIS AWARD.

SITE-DIRECTED CHEMOTHERAPY FOR BREAST CANCER USING NOVEL ANGIOGENESIS INHIBITOR

EXPERIMENTAL MODELS FOR TESTING NOVEL TARGETS FOR PANCREATIC CANCER CELL INVASION

THE ROLE OF THE SPLEEN IN THE FEBRILE REPONSE

HEALTH CARE AND OTHER FACILITIES

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