Research & Scholarship
My primary area of research is the Biology of Aging. Aging is influenced by a complex interaction between genes and environment that isn’t yet fully understood. Many environmental factors such as lifestyle and diet are thought to have a significant role in the aging process. In addition, many molecular pathways that result in telomere shorting, apoptotic cell death, advanced glycation end-products, and protein misfolding/aggregation are all thought to play a role in the aging process as well. Despite many decades of study, however, the relative contribution of each of these processes to aging and how this translates into the multitude of aging-associated phenotypes seen in people remains largely unknown.
Many of the primary advances in our understanding of basic mechanisms of aging over the past several years have come from studies in invertebrate organisms. My research focuses on the nematode, Caenorhabditis elegans. Studies in C. elegans, and other invertebrate organisms have yielded many clues about aging mechanisms that are conserved across a multitude of organisms.
The best characterized conserved mechanism of longevity control is Dietary Restriction, the reduction of calories without malnutrition. DR has been observed to increase life span in a variety of organisms, including yeast, nematodes, flies, mice, and rats. Although it remains unclear whether DR also promotes longevity in humans, initial indications are that DR improves health and survival in primates. My current research focuses on using C. elegans to understand the genetic controls of DR.
PUBLICATIONS
Mehta, R., *Chandler-Brown, D., Ramos, F.J., Shamieh, L.S., and Kaeberlein, M. Regulation of mRNA Translation as a Conserved Mechanism of Longevity Control. Department of Pathology, University of Washington, Seattle, WA Adv Exp Med Biol. 694:14-29 (2010).
The Role of TOR Signaling in Aging. Matt Kaeberlein and Lara S. Shamieh, Department of Pathology, University of Washington, Seattle, WA.
Chapter in: “The Comparative Biology of Aging", Norman S. Wolf, editor. Springer Publishers, Inc. 2010
Regulation of mRNA Translation as a Conserved Mechanism of Longevity Control. Mehta, R., *Chandler-Brown, D., Ramos, F.J., Shamieh, L.S., and Kaeberlein, M. Department of Pathology, University of Washington, Seattle, WA
Chapter in: “Protein Metabolism and Homeostasis in Aging”, Nektarios Tavernarakis, editor. Landes Biosciences, 2010.
Stanfel, M.N., Shamieh, L.S., Kaeberlein, M., and Brian K. Kennedy. The TOR pathway comes of age. Biochim Biophys Acta. 1790(10): 1067-74 (2009).
Mehta, R., Steinkraus, K.A., Sutphin, G.L., Ramos, F.J., Shamieh, L.S., *Huh, A., *Davis, C., *Chandler-Brown, D., and Matt Kaeberlein. Proteasomal regulation of the hypoxic response modulates aging in C. elegans. Science. 324(5931):1196-8 (2009).
Chatterji, A., Ochoa, W., Shamieh, L.S., Salakian, S.P., Wong, S.M., Clinton, G., Ghosh, P., Lin, T., and Johnson, J.E. Chemical conjugation of heterologous proteins on the surface of Cowpea mosaic virus. Bioconjug. Chem. 15(4): 807-13 (2004)
Shamieh, L.S., Evans, A.J., Denton, M.C., and Clinton, G.M. Receptor binding specificities of herstatin and its intron 8-encoded domain. FEBS Lett. 568(1-3): 163-6 (2004)
* = Undergraduate Student
POSTERS AND PRESENTATIONS
*Klum, S., *Schneider, H.S., Shamieh, L.S., and Kaeberlein, M. (2011) UV-Induced toxicity of ethosuximide, a known longevity compound. The Department of Pathology Annual Retreat. University of Washington.
*Grygotis, E., Kaeberlein, M., and Shamieh, L.S. (2011) Investigating the role of mediator protein MDT-15 on lifespan extension by dietary restriction. Amgen Research Forum. University of Washington.
*McCarthy, E., *Schneider, H.S., *Chandler-Brown, D., *Karnes, L.L., Shamieh, L.S. and Kaeberlein, M. (2011). UV-Induced toxicity of ethosuximide, a known longevity compound. Mary Gates Undergraduate Student Research Forum. University of Washington.
Shamieh, L.S., *Chandler-Brown, D., *McCarthy, E.M., *Karnes, L.L, and Kaeberlein, M. (2010) UV-Induced toxicity of ethosuximide, a known longevity compound. The Department of Pathology Annual Retreat. University of Washington.
*Chandler-Brown, D., Shamieh, L.S., *Karnes, L.L., and Kaeberlein, M. (2010) UV mediated toxicity of a known longevity compound. The Mary Gates Undergraduate Research Symposium. The University of Washington.
Shamieh, L.S., *Karnes, L.L., *Chandler-Brown, D., and Kaeberlein, M. (2009) UV mediated toxicity of a known longevity compound. The Department of Pathology Annual Retreat. The University of Washington.
*Chandler-Brown, D., Shamieh, L.S., Pendergrass, B.R., and Kaeberlein, M. (2009) Lifespan extension via reduced protein synthesis in C. elegans. The Mary Gates Undergraduate Research Symposium. The University of Washington.
Shamieh, L.S., Steinkraus, K.A., Pendergrass, B.R., McKay, V.L., Mehta, R., *Chandler-Brown, D., and Kaeberlein, M. (2008) Translation, degradation, and aging in C. elegans. The Department of Pathology Annual Retreat. The University of Washington.
Shamieh, L.S., Carroll, J.M., Clinton, G.M., and Roberts, C.T. (2005) Modulation of insulin-like growth factor signaling by an alternatively spliced product of the HER-2 gene. The Endocrine Society Annual Meeting
Carroll, J.M., Shamieh, L.S., Clinton, G.M., and Roberts, C.T. (2005) Herstatin regulation of insulin receptor expression and action. The Endocrine Society Annual Meeting.
Shamieh, L.S., Carroll, J.M., Roberts, C.T., and Clinton, G.M. (2005) Herstatin, an autoinhibitor of the erbB receptor family, modulates IGF-1-induced proliferation and survival signaling in MCF7 breast cancer cells. DoD Era of Hope Meeting.
Shamieh, L.S., Denton, M., and Clinton, G.M. (2003). The intron 8-encoded domain of herstatin encodes a receptor binding module that is required for erbB receptor inhibition. American Association for Cancer Research Annual Meeting.
Guo, S., Evans, A.J., Denton, M., Shamieh, L.S., Rhodes, J., and Clinton, G.M. (2002) Recombinant herstatin inhibits growth of carcinoma cells that overexpress HER-2 and the EGF receptor. American Association for Cancer Research Annual Meeting.
*= Undergraduate Student