Life, as we know it, is a dynamic network of metabolic reactions that take nutrients from the environment and convert them into the building blocks and energy that cells need to grow and function. Each cell has a unique set of biosynthetic and energetic demands that must be met to ensure normal homeostasis. As a result, cells must establish distinct metabolic states to meet those demands. Disruption of these mechanisms can lead to severe developmental disorders and promote the progression of diseases such as cancer, neurodegeneration, and reproductive disorders. Our primary goal in the lab is to understand the dynamic changes in metabolic programs that support developmental and disease progression. Using a combination of genetics, molecular biology, and system based approaches (metabolomics, proteomics, and transcriptomics) we are investigating metabolic mechanisms that support reproduction and development in Drosophila and mammalian tissues. Our work focuses on three key areas:
- Defining the metabolic mechanisms that underlie cellular quiescence and reactivation.
- Examining how dynamic changes in the mitochondrial metabolism support growth and differentiation.
- Examining how changes in metabolism and dietary nutrients influence the regulation of conserved pathways that control development and disease progression.
- Characterizing how changes in metabolic states drive development and disease.
- Defining the role of cellular metabolic mechanisms in the regulation of conserved developmental signaling pathways
- Examining the relationship between mitochondrial metabolism and the ubiquitin proteasome system (UPS) in development and cancer recurrence
- Investingating how changes in mitochondrial metabolism drive growth and differentiation
- Understanding the metabolic basis for infertility
- The role of metabolic states in development and disease.
- Sieber MH, Spradling AC Curr. Opin. Genet. Dev. 2017 Aug 45 58-68
- Electron Transport Chain Remodeling by GSK3 during Oogenesis Connects Nutrient State to Reproduction.
- Sieber MH, Thomsen MB, Spradling AC Cell 2016 Jan 164 3 420-32
- Steroid Signaling Establishes a Female Metabolic State and Regulates SREBP to Control Oocyte Lipid Accumulation.
- Sieber MH, Spradling AC Curr. Biol. 2015 Apr 25 8 993-1004
- Coordination of triacylglycerol and cholesterol homeostasis by DHR96 and the Drosophila LipA homolog magro.
- Sieber MH, Thummel CS Cell Metab. 2012 Jan 15 1 122-7
- The DHR96 nuclear receptor controls triacylglycerol homeostasis in Drosophila.
- Sieber MH, Thummel CS Cell Metab. 2009 Dec 10 6 481-90
- Coordinated metabolic transitions during Drosophila embryogenesis and the onset of aerobic glycolysis.
- Tennessen JM, Bertagnolli NM, Evans J, Sieber MH, Cox J, Thummel CS G3 (Bethesda) 2014 Mar 4 5 839-50
- The Caenorhabditis elegans aristaless orthologue, alr-1, is required for maintaining the functional and structural integrity of the amphid sensory organs.
- Tucker M, Sieber M, Morphew M, Han M Mol. Biol. Cell 2005 Oct 16 10 4695-704
- Monomethyl branched-chain fatty acids play an essential role in Caenorhabditis elegans development.
- Kniazeva M, Crawford QT, Seiber M, Wang CY, Han M PLoS Biol. 2004 Sep 2 9 E257
- Suppression of the ELO-2 FA elongation activity results in alterations of the fatty acid composition and multiple physiological defects, including abnormal ultradian rhythms, in Caenorhabditis elegans.
- Kniazeva M, Sieber M, McCauley S, Zhang K, Watts JL, Han M Genetics 2003 Jan 163 1 159-69
Honors & Awards
- Carnegie Institution for Science Postdoctoral Innovation and Excellence Award
- Jane Coffin Childs Memorial Fund
Postdoctoral fellowship (2012-2015)
- Hamon Center for Regenerative Science and Medicine (2018)
- Simmons Comprehensive Cancer Center (2020)