The Endicott Lab uses a combination of quantitative proteomics, biochemistry, microscopy, cell biology, and mouse studies to address fundamental questions pertaining to chaperone-mediated autophagy (CMA). CMA is a selective form of lysosomal proteolysis, which targets individual proteins for lysosomal degradation.
We are primarily interested in two major research questions:
1. How is CMA regulated at the endocrine, cellular, and sub-cellular levels?
2. What are the targets of CMA, and how does their degradation affect metabolism, health, and longevity?
Protein turnover via the lysosome/autophagy system is a crucial regulator of aging. Chaperone-mediated autophagy (CMA) is the most selective form of lysosomal proteolysis, where proteins bearing consensus motifs are individually selected for lysosomal degradation. CMA degrades proteins that are damaged or present in excess, maintaining a “clean” proteome, but CMA also regulates the abundance of proteins whose overaccumulation contributes to age-related diseases, including Parkinson’s disease, Alzheimer’s disease, fatty-liver disease, cancer, and others.. Our own work has shown that long-lived mutant mice with reduced growth hormone signaling have elevated CMA, with decreased abundance of several CMA-sensitive proteins. There is currently intense interest in characterizing the mechanisms of CMA regulation, with the long-term goal of identifying and refining interventions for activating CMA therapeutically.
We have recently reported that CMA is negatively regulated by the insulin (INS)/PI3K/AKT signaling pathway, and that clinically safe inhibitors of class I PI3K activate CMA in mice. Using a combination of quantitative proteomics, genetics, mouse studies, and cell biology, we are further characterizing the mechanisms through which the INS/PI3K/AKT pathway regulates CMA, and attempting to understand how enhanced CMA affects the proteome.
S. Joseph Endicott, Ph.D.
Assistant Professor, Department of Pathology
Email: sendicott@salud.unm.edu
LinkedIn: https://www.linkedin.com/in/joseph-endicott-870195144/
Dr. Endicott obtained his PhD in 2016 from Yale's Department of Genetics, where he trained with Martina Brueckner, studying the genetic and cellular underpinnings of left-right asymmetry in vertebrate organ placement. He then completed his postdoctoral training in Richard Miller's lab at the University of Michigan, studying changes to autophagy in long-lived mouse mutants. Dr. Endicott worked as a Research Investigator at the University of Michigan, until he accepted a job as Assistant Professor of Pathology at UNM HSC. He is currently interested in (1) the mechanisms through which the insulin/PI3K pathway regulates chaperone-mediated autophagy and (2) how changes to autophagy long-lived mice with reduced insulin signaling affect the proteome. In his spare time, he likes to exercise, grow orchids, and make ice cream.
Eduardo Hernandez Acosta, Ph.D.
Post-doctoral Fellow, Department of Pathology
Email: ehernandezacosta@salud.unm.edu
LinkedIn: www.linkedin.com/in/eduardo-hernández-acosta
Dr. Hernandez Acosta obtained his PhD from New Mexico State University in 2023, where he studied the effects of urban microclimate on vector borne disease transmission by Aedes mosquitoes under the mentorship of Dr. Kathryn Hanley. He then joined Dr. Alison Kell lab at University of New Mexico where he focused on studying the replication kinetics of Hantaviruses. After a shift of research interests, Dr. Hernandez Acosta now studies the effects of PTEN overexpression on the lysosomal proteome, with a specific focus on chaperone-mediated autophagy substrates. Outside of science, he is an avid gamer and couch musician.
Publications within the past five years include:
Endicott SJ, Boynton DN Jr, Beckmann LJ, Miller RA: Long-lived mice with reduced growth hormone signaling have a constitutive upregulation of hepatic chaperone-mediated autophagy, Autophagy 12: 1-14, 2020. PMID 32013718
Endicott SJ, Ziemba ZJ, Beckmann LJ, Boynton DN Jr, Miller RA: Inhibition of class I PI3K enhances chaperone-mediated autophagy, Journal of Cell Biology 219: e202001031, 2020. PMID 33048163
Endicott SJ, Monovich AC, Huang EL, Henry EI, Boynton DN Jr, Beckmann LJ, MacCoss MJ, Miller RA: Lysosomal targetomics in ghr KO mice reveals that chaperone-mediated autophagy degrades nucleocytosolic acetyl-coA production enzymes. Autophagy 18:1551-1571, 2021. PMID 34704522
Shi X, Endicott SJ, Miller RA: Regulation of mTOR complexes in long-lived growth hormone receptor knockout and Snell dwarf mice. Aging 14:2442-2461, 2022. PMID 35305083
Zhang KK, Burns CM, Skinner ME, Lombard DB, Miller RA, Endicott SJ: PTEN is both an activator and a substrate of chaperone-mediated autophagy. Journal of Cell Biology 222(9), 2023. PMID 37418003
Zhang KK, Zhang P, Kodur A, Erturk I, Burns CM, Kenyon C, Miller RA, Endicott SJ: LAMP2A, and other chaperone-mediated autophagy related proteins, do not decline with age in genetically heterogeneous UM-HET3 mice. Aging 15, 2023. PMID 37315291
Endicott SJ, Miller RA: PTEN activates chaperone-mediated autophagy to regulate metabolism. Autophagy, 2023. PMID 37669771
Burns CM, Miller RA, Endicott SJ: Histodenz separation of lysosomal subpopulations for analysis of chaperone-mediated autophagy. Current Protocols 4, 2023. PMID 38197533
Hager M, Chang P, Lee M, Burns CM, Endicott SJ, Miller RA, Li X: Recapitulation of anti-aging phenotypes by global overexpression of PTEN in mice. Geroscience 46, 2024. PMID 38114855
Joseph Endicott, Ph.D.
Department of Pathology
Fitz Hall, Room 305
University of New Mexico School of Medicine
Albuquerque, New Mexico 87131
Email: sendicott@salud.unm.edu
Phone: (505) 272-2318 (office)
Fax: (505) 272-8084
Research Lab: Fitz Hall, Room 332
Phone: (505) 272-2563 (lab)