Dr. Alicia Meléndez
Ph.D., Columbia University
Office: NSB D338 Tel: 718 997-4580
Laboratory: NSB D311, D315 Tel: 718-997-3435
E-mail: alicia.melendez @ qc.cuny.edu
The focus of my research is to understand the molecular mechanisms that affect the cellular process of autophagy, and how autophagy is regulated in multicellular organisms. Autophagy is the major cellular pathway for degrading long-lived proteins and cytoplasmic organelles. It involves the rearrangement of subcellular membranes to sequester cargo for delivery to the lysosome where sequestered material is degraded and recycled. Recent studies have implicated a direct role for autophagy in the aging process of multicellular organisms, including the nematode C. elegans. In this organism, several conserved longevity pathways and processes are known to affect lifespan, including insulin/IGF-1 signaling, food intake (also referred to as dietary restriction), protein translation and mitochondrial respiration. Interestingly, mutants with reduced insulin/IGF-1 signaling and dietary-restricted animals have elevated levels of autophagy and require genes involved in autophagy to live long.
We use a combination of genetic, molecular and cellular biological approaches in the genetically tractable model organism C. elegans. In particular, our lab aims to: 1) determine the role of autophagy genes in development, aging, and fat accumulation; 2) understand the mechanism(s) by which autophagy extends lifespan; 3) identify new evolutionarily conserved genes that regulate autophagy; and 4) address whether the autophagy function of such novel genes is conserved in other animals. We began our characterization of autophagy genes by studying bec-1 in C. elegans. Its human homolog, beclin 1 was identified as the first autophagy gene in humans and shown to be monoallelically deleted in up to 75% of various human cancers. Therefore, any insights on the function of bec-1 is likely to advance our molecular understanding of important signaling pathways relevant to aging, and age-related disorders, including diabetes and cancer.
Sources of Funding:
National Science Foundation Research Initiation Grant
Ellison Medical Foundation New Scholar Award in Aging
National Institutes of Health – “Genetic Bases of Sarcopenia and Muscle Healthspan in C. elegans”
Lapierre, L. R., Meléndez, A., and M. Hansen, 2011. Autophagy links lipid metabolism to longevity. Autophagy, 8:1. 1-3.
J. Yang, D. Chen, Yani He, A. Meléndez, Z. Feng, Q. Hong, X. Bai, Q. Li, G. Cai, J. Wang, X. Chen, 2011. mir-34 modulates lifespan extension in C. elegans via autophagy-related proteins Atg4 and Atg9. AGE,.
LaPierre, L. R., S. Gelino, S., Meléndez, A., and M. Hansen, 2011. Autophagy and lipid metabolism coordinately modulate lifespan in C. elegans, Current Biology, 21, 1507-1514.
Fernando, T., Flibotte, S., Yin, J., Yzeiraj, E., Moerman, D.G., Meléndez, A., and C. Savage-Dunn. 2011. C. elegans ADAMTS ADT-2 regulates body size by modulating TGFb signaling and cuticle collagen organization. Developmental Biology 352(1): 92-103.
Ruck, A., J. Attonito, J., K. T. Garces, K. T., L. Núnez, L., Palmisano, N. J., Z. Rubel, Z., Z. Bai, Z., K. C. Q. Nguyen, K. C. Q., Sun, L., B. D. Grant, B. D., D. H. Hall, D. H. and A. Meléndez, 2011. The C. elegans bec-1 gene has a role in retrograde trafficking, Autophagy 7: 4, 1-15.
Meléndez, A. and Beth Levine, “Autophagy in C. elegans,” (June 12, 2009), WormBook, ed. The C. elegans Research Community, WormBasedoi/10.1895/wormbook1.147.1, http://www.wormbook.org
Meléndez, A., D.H. Hall and M. Hansen, 2008. Monitoring the role of autophagy in C. elegans aging, Methods in Enzymology, Vol 451: 493-520.
Meléndez, A. and T. Neufeld, 2008. The cell biology of autophagy, a developing story. Development 135, 2347-2360.
Zakeri, Z., Meléndez, A. and Lockshin, R., 2008. Detection of autophagy in cell death. Methods in Enzymology, Vol 442, 289-306.
Melendez, A., Talloczy, Z., Seaman, M., Eskelinen, E.L., Hall, D.H., Levine, B. Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science. 2003 Sep 5; 301(5638):1387-91.
Melendez, A., Greenwald, I. Caenorhabditis elegans lin-13, a member of the LIN-35 Rb class of genes involved in vulval development, encodes a protein with zinc fingers and an LXCXE motif. Genetics. 2000 Jul; 155(3):1127-37.
Melendez, A., Li, W., Kalderon, D. Activity, expression and function of a second Drosophila protein kinase A catalytic subunit gene. Genetics. 1995 Dec; 141(4):1507-20.