Meera Sundaram
Associate Professor, Dept of Genetics

Genetics and Gene Regulation Program

Address

445 Clinical Research Building
415 Curie Boulevard
Philadelphia, Pennsylvania 19104-6145

Office tel.: 215 573-4527
Lab tel.: 215 573-4528
Fax: 215 573-5892
E-mail: sundaram@mail.med.upenn.edu


Education

Mount Holyoke College, B.A. (Biology), 1986.

Princeton University, PhD (Molecular Biology), 1993.

University of Colorado, Boulder, post-doctoral research (Developmental Genetics), 1993-97.

Research Interests

• Tubular organ development in C. elegans

Key words: C. elegans, signal transduction, tubulogenesis, developmental genetics

Description of Research

During embryonic development, multipotent cells must choose among various possible fates, and then differentiate and join together with appropriate neighbors to form functional organ systems. My research utilizes the “excretory” or renal system of the nematode worm Caenorhabditis elegans as a model system for studying the formation of tubular organs. C. elegans has many advantages for such studies, including a very simple and well described anatomy that allows phenotypic analysis at a single-celled resolution – for example, the worm’s renal system consists of only three connected single-celled tubes! C. elegans also has a sequenced genome containing many of the same genes found in more complex organisms, and it is highly amenable to powerful forward and reverse genetic approaches to find genes involved in a process of interest. We are identifying genes important for cells to adopt renal fates, form unicellular tubes and connect with one another to form a functional renal conduit, as well as genes that modulate the signal transduction pathways that control these processes.

Ras signaling, Notch signaling and cell fate specification
Both the EGFR/Ras/ERK and Notch signaling pathways play important roles in specifying excretory system cell fates. These pathways also are used to control many other developmental events, and a major question concerns the downstream targets of these pathways, how cell-type appropriate targets are chosen, and how these targets act with other cell intrinsic factors to elicit specific responses. The lab has identified and is characterizing a number of potential ERK targets important for excretory duct cell fate specification, as well as scaffold proteins that modulate signaling in a cell-type specific manner.

Lipocalin signaling and tubular morphogenesis
The tubular cells of the excretory system are an excellent model for studying mechanisms of intracellular lumen formation and fusion. Through genetic screening, we have discovered a lipocalin-based signaling mechanism that controls intracellular lumen development. Lipocalins are secreted cup-shaped proteins that bind sterols, odorants and other small lipophilic molecules and deliver them to target cells via specific plasma-membrane bound receptors. Studies are underway to identify the signaling pathway and cellular mechanism through which the LPR-1 lipocalin is acting. These studies are likely to be relevant to development of capillaries in the mammalian microvasculature, which are also networks of single-celled tubes believed to form lumen through a hollowing process.

Recent Publications

Howard, R. M. and Sundaram, M. V. (2002). C. elegans EOR-1/PLZF and EOR-2 positively regulate Ras and Wnt signaling and function redundantly with LIN-25 and the SUR-2 Mediator component. Genes & Dev. 16, 1815-1827.

Sundaram, M. V. (2005). The love-hate relationship between Ras and Notch. Genes & Dev. 19, 1825-1839.

Sundaram, M. V. (2005). RTK/Ras/MAPK signaling in C. elegans. In Wormbook (edited by the Community of C. elegans Researchers). http://www.wormbook.org.

Raizen, D. M., Zimmerman, J. E., Maycock, M. H., Ta, U. D, Sundaram, M. V. and Pack, A. I. (2008). Lethargus is a Caenorhabditis elegans sleep-like state. Nature 451, 569-572.

Rocheleau, C. R., Cullison, K., Huang, K., Bernstein, Y., Spilker, A. C. and Sundaram, M. V. (2008). The Caenorhabditis elegans ekl (enhancer of ksr-1 lethality) genes include putative components of a germline small RNA pathway. Genetics 178, 1431-1443.

Search PubMed for more articles

Lab

Rotation Projects

Please speak to Meera about ongoing projects in which you could participate.

Lab personnel:

Ishmail Abdus-Saboor, Graduate Student
Kelly Howell, Graduate Student
Vincent Mancuso, Graduate Student
Craig Stone, Graduate Student
Kevin Cullison, Research Specialist
Philicia Moonsamy, Undergraduate Student