Cells are bounded by a plasma membrane, which is composed of bilayer forming phospholipids. Although phospholipids are integral structural components of cells, they are not inert or static. Membrane phospholipids are dynamically reorganized and biochemically remodeled in response to signaling pathways and changing cellular behaviors. Recently, technological advances in mass spectrometry have shed new light on the detailed molecular composition of membrane phospholipids, revealing hundreds of different phospholipid species per cell, which differ in their headgroups, length of their fatty acid chains, and degree of unsaturation. It is not clear why cells require so many different phospholipid species. Perhaps different species play subtly different physiological roles in the lives of cells. Phospholipids also can be cleaved to release potent lipid signaling molecules (mediators), which can initiate signal transduction cascades. Perhaps the variety of phospholipid species is due to the variety of stored mediator precursors. There is still much to be discovered about phospholipid metabolism and remodeling in vivo. My research focuses on the Lands Cycle, a phospholipid metabolism pathway important both for lipid signal release and for phospholipid molecular remodeling, in the fruit fly Drosophila melanogaster.
The Lands Cycle uses phospholipase A2 (PLA2) to break down phospholipids into fatty acids and lysophospholipids. Both of these products can be converted into potent lipid mediators, e.g., free arachidonic acid can be made into prostaglandins. Acyltransferases (ATs) reverse this reaction, resynthesizing phospholipids from fatty acyl coAs and lysophospholipids. These enzymes are conserved in Drosophila, but their functions are not known. We generated the first Drosophila mutations in ATs oysgedart (oys) and nessy (nes). Flies lacking oys and nes do not make functional sperm, implicating phospholipid remodeling in male fertility. We found that a cyclooxygenase-like enzyme, Pxt, also is required for spermatogenesis, while other enzymes in phospholipid biosynthetic pathways are not. Together, our data suggest that lipid signals may be important for spermatogenesis.
The current focus of the lab is the PLA2 enzymes. We have mutated the Drosophila calcium-independent iPLA2-beta, and we are characterizing its roles in development and physiology. iPLA2-beta (also known as PLA2G6 and PARK14) is a disease locus for neurodegeneration in humans, and mutant flies show an age related decline in motor activity, consistent with analogous functions in the insect model. We are investigating how iPLA2-beta protects cells from death and why certain cells are more sensitive to its absence.
The Steinhauer lab is powered by undergraduates. The classical genetic approaches used are ideally suited for students of many different levels, and the research provides students with an immersive experience in the scientific process.
This research is supported by funding from the Yeshiva University Provost's Office and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
-The Steinhauer lab, in collaboration with the Jenny lab at Einstein, publishes in Development! Read the paper here.
-To graduating senior Liam Eliach, the class of '19 valedictorian!
-Dr. Steinhauer consulted for the NY Times on a video about vaccine misinformation.
-To senior Yoni Schwartz, for receiving the Victoria Finnerty undergraduate travel award to attend the national Drosophila conference 2018! Yoni was featured on the YU blog.
-Dr. Steinhauer was interviewed about Genetics education in Trends in Genetics.
-Along with scientists from Memorial Sloan Kettering Cancer Center, Cold Spring Harbor Laboratory, Cornell University, and the Japanese National Institute of Genetics, the Steinhauer lab published a paper on the evolution of genes and the activity of newly evolved genes in the male reproductive system. Read a comment on their work here.
-To the 2017 Nobel Prize Winners in Physiology or Medicine (Jeffrey Hall and Michael Rosbash of Brandeis University, and Michael Young of Rockefeller University), for their studies on circadian rhythms in Drosophila!
-Huge thanks to Dr. Ruth Lehmann, director of the Skirball Institute for Biomolecular Medicine, for coordinating the donation of a confocal microscope through Zeiss, Inc to the Steinhauer lab!! Read about it here.
-The lab was featured on the Genetics Society of America blog.
-To senior Shlomo Friedman, for receiving a 2016-2017 Kressel Fellowship.
-To lab alumnus Benny Statman, for being chosen for the best Honors thesis in the Natural Sciences for 2015.
-To graduating senior Yosef Frenkel, for being chosen as the class of '16 valedictorian.
-To lab alumni Geulah Ben-David and Eli Miller, for publication of their article 'Drosophila spermatid individualization is sensitive to temperature and fatty acid metabolism' in the peer-reviewed journal Spermatogenesis. Access the article here. This achievement was highlighted here.
-To undergraduate Yosef Frenkel, for being awarded a 2015-2016 Kressel Fellowship.
- Steinhauer J, Statman B*, Fagan J, Borck J*, Surabhi S, Yarikipati P, Edelman D*, Jenny A. Combover interacts with the axonemal component Rsp3 and is required for Drosophila sperm individualization. 2019. Development. Sep 2;146(17). doi: 10.1242/dev.179275.
- Kondo S, Vedanayagam J, Mohammed J, Eizadshenass S*, Pang N, Aradhya R, Siepel A, Steinhauer J, and Lai EC. 2017. New genes often acquire male-specific functions but rarely become essential in Drosophila. Genes and Development. 31:1841–1846.
- Steinhauer J. 2017. Co-culture activation of MAP kinase in Drosophila S2 cells. Methods in Molecular Biology: ERK signaling. 1487:235-241.
- Steinhauer J. 2015. Separating from the pack: molecular mechanisms of Drosophila spermatid individualization. Spermatogenesis. 5:2, e1041345.
- Ben-David G*, Miller E*, and Steinhauer J. 2015. Drosophila spermatid individualization is sensitive to temperature and fatty acid metabolism. Spermatogenesis. 5:1, e1006089. Cover photo.
- Steinhauer J, Liu HH, Miller E*, and Treisman JE. 2013. Trafficking of the EGFR ligand Spitz regulates its signaling activity in polarized tissues. Journal of Cell Science. 126(19): 4469-78.
- Legent K, Steinhauer J, Richard M, Treisman JE. 2012. A mosaic screen of the X chromosome identifies Casein kinase 1 alpha as an essential negative regulator of Wingless signaling. Genetics. 190(2):601-16.
- Steinhauer J, Gijón MA, Riekhof W, Voelker DR, Murphy RC, Treisman JE. 2009. Drosophila lysophospholipid acyltransferases are specifically required for germ cell development. Mol Biol Cell. 20(24): 5224-5235.
- Steinhauer J and Treisman JE. 2009. Lipid-modified morphogens: functions of fats. Curr Opin Genet Dev. 19: 1-7.
- Steinhauer J and Kalderon D. 2006. Microtubule polarity and axis formation in the Drosophila oocyte. Dev Dyn. 235(6): 1455-68.
- Steinhauer J and Kalderon D. 2005. The RNA-binding protein Squid is required for the establishment of anteroposterior polarity in the Drosophila oocyte. Development. 132(24): 5515-25. Featured in Faculty of 1000.
- Steinhauer J, Agha R, Pham T, Varga AW, Goldberg MB. 1999. The unipolar Shigella surface protein IcsA is targeted directly to the bacterial old pole: IcsP cleavage of IcsA occurs over the entire bacterial surface. Mol Microbiol. 32(2): 367-77.
*indicates student author
Full publication list available here.