MODULATING ALZHEIMER'S DISEASE BY MTORC1 INHIBITION TO AUGMENT LYSOSOMAL ACTIVITY - PROJECT SUMMARY/ABSTRAC…

Assistance award details

Assistance award identifier

ASST_NON_R00AG078342_075

FAIN

R00AG078342

Recipient

RUTGERS THE STATE UNIVERSITY OF NEW JERSEY

Awarding agency

Department of Health and Human Services

Funding agency

Department of Health and Human Services

Assistance listing (CFDA)

93.866

Total obligated

$493,020

Period

Sep 15, 2022 – Dec 31, 2027

Fiscal year

2025

Place of performance state

NJ

Source file

FY2025_All_Assistance_Full_20261006.zip

Description

MODULATING ALZHEIMER'S DISEASE BY MTORC1 INHIBITION TO AUGMENT LYSOSOMAL ACTIVITY - PROJECT SUMMARY/ABSTRACT: THIS PROPOSAL IS IN APPLICATION FOR A PATHWAY TO INDEPENDENCE AWARD FOR DR. TRAVIS LEAR AT THE AGING INSTITUTE AT THE UNIVERSITY OF PITTSBURGH. DR. LEAR HAS EXTENSIVE EXPERIENCE IN THE MOLECULAR BIOLOGY OF UBIQUITINATION IN AGING, INFLAMMATION, AUTOPHAGY, AND LYSOSOME BIOLOGY. THIS K99/R00 WOULD BE A CRUCIAL STEP FOR DR. LEAR AS PART OF HIS CAREER GOAL OF REACHING RESEARCH INDEPENDENCE. THE FOCUS OF DR. LEAR’S FUTURE LAB WILL BE TO STUDY THE MECHANISMS OF PROTEIN DEGRADATION AND LYSOSOMAL ACTIVITY IN NEURODEGENERATION IN PURSUIT OF UNCOVERING NEW THERAPEUTIC AVENUES. UNDER THIS K99/R00 AWARD, DR. LEAR WOULD HAVE PROTECTED TIME FOR ADDITIONAL TRAINING IN NEUROBIOLOGY TECHNIQUES AND AGING BIOLOGY, AND FOR CAREER DEVELOPMENT TO FACILITATE A SUCCESSFUL TRANSITION TO RESEARCH INDEPENDENCE. THIS MENTORSHIP TEAM OF EXPERTS IN AGING, LYSOSOMAL, AND NEUROBIOLOGY COMBINED WITH THE SCIENTIFIC ENVIRONMENT AT THE AGING INSTITUTE WILL BE IDEAL FOR DR. LEAR’S TRAINING. THE SCIENTIFIC EXPERTISE TRAINING WILL ENTAIL 1) IN VITRO PRIMARY TISSUE CULTURE SKILL, 2) STUDY OF IPSC DEVELOPMENT, DIFFERENTIATION, AND GENE-EDITING, 3) GENERATION AND PHENOTYPIC CHARACTERIZATION OF MOUSE MODELS OF NEURODEGENERATION. DR. LEAR’S LEADERSHIP TRAINING WILL FOCUS ON 1) INTEGRATION TO SCIENTIFIC COMMUNITY THROUGH NETWORKING, 2) ENHANCING HIS MENTORING SKILLS, 3) IMPROVING GRANTSMANSHIP. SUCCESSFUL COMPLETION OF THE PROPOSED RESEARCH AND TRAINING PLAN WILL PROVIDE THE KNOWLEDGE AND EXPERIENCE NECESSARY TO PROGRESS TOWARD DR. LEAR’S CAREER GOAL OF BECOMING AN INDEPENDENT INVESTIGATOR STUDYING NEURONAL AGING AND ALZHEIMER’S DISEASE (AD). TO ACCOMPLISH THIS, DR. LEAR PROPOSES TO STUDY A NEW MECHANISM OF PROTEOLYTIC CONTROL OF LYSOSOMAL ACTIVATION TO AUGMENT PROCESSING OF PATHOGENIC TAU PROTEIN AGGREGATES IN MODELS OF AD. SPECIFICALLY, DR. LEAR HAS ELABORATED A MODEL IN WHICH A KEY MTORC1