Meera V. Sundaram, Ph.D

faculty photo
Associate Professor of Genetics
Department: Genetics
Graduate Group Affiliations

Contact information
446A Clinical Research Building
415 Curie Boulevard
Philadelphia, PA 19104-6145
Office: 215-573-4527
Fax: 215-573-5892
Education:
B.A. (Biology)
Mount Holyoke College, magna cum laude , 1986.
Ph.D. (Molecular Biology)
Princeton University, 1993.
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Description of Research Expertise

Research Interests
Tubular organ development in C. elegans

Key words: C. elegans, signal transduction, Ras, genetics, tube development.

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 and subsequent morphogenesis, as well as proteins that modulate EGF signaling.

Lipocalin signaling and tubular morphogenesis
The tubular cells of the excretory system are an excellent model for studying mechanisms of intracellular lumen formation and tube connectivity. Through genetic screening, we discovered a lipocalin-dependent signaling mechanism that controls lumen connectivity. 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.

Epithelial junction integrity and remodeling
The tubular cells of the excretory system are also an excellent model for studying junction formation and remodeling. These cells undergo de novo epithelialization and junction formation during tubulogenesis, and the excretory pore cell later undergoes a programmed delamination and loss of epithelial identity. We identified a family of apically localized transmembrane "eLRRon" proteins that are required to organize the apical extracellular matrix and maintain junction connectivity. Current studies are examining the link between apical matrix and junctions, and testing whether modulation of apical matrix contributes to programmed junction remodeling.

Rotation Projects
Please see Meera about possible projects

Lab personnel:
Hasreet Gill (undergraduate assistant, 2012-present)
Emily Pu (postdoctoral fellow, 2012-present)
Fabien Soulavie (postdoctoral fellow, 2013-present)
Rachel Forman-Rubinsky (research specialist, 2014-present)
Senait Bekele (undergraduate assistant, 2014-present)
Leah Ragno (undergraduate assistant, 2014-present)

Lab Alumni:
Ranjana Kishore (postdoc, 1998-2002), Staff scientist, Wormbase, Caltech
Nate Dudley (research specialist, 1998-2000), went on to PhD
David Garbe (research specialist, 1998-2001), went on to PhD
Robyn Howard Barfield (grad student, 1999-2004), Staff scientist, Redwood Biosciences
Gautam Kao, (postdoc, 1999-2004), Research Associate, Gothenburg U. Sweden
Laura Sherritt (research specialist, 2000-2001), went on to industry
Christian Rocheleau (postdoc 2000-2005), Assoc Professor, McGill U.
Kyunghee Koh (postdoc, 2001-2003), Asst Professor, Jefferson U.
Jeff Doto (research specialist, 2001-2004), went on to MS
Priti Batta (research specialist, 2002-2003), went on to MD
Yelena Bernstein (research specialist, 2002-2004), went on to pharm degree
David Raizen (postdoc, 2002-2007), Asst Professor, UPenn
Craig Stone (grad student, 2002-2008), Medical writer, EBSCO publishing
Kelly Kraus (research specialist, 2003-2004), went on to VMD
Kelly Howell (grad student, 2003-2010), Postdoc, Columbia U.
Olena Vatamaniuk (postdoc, 2004-2005), Assoc Professor, Cornell U.
Anne McKnight (research specialist, 2004-2006), went on to MPH
Kevin Cullison (research specialist, 2004-2008), went on to MD
Vincent Mancuso (grad student, 2004-2011), homemaker
Ariel Junio (research specialist, 2005-2006), went on to industry
Ishmail Abdus-Saboor (grad student, 2006-2012), Postdoc, Weill Cornell Med
Kate Palozola (research specialist, 2009-2011), PhD student, UPenn
Brian Gantick (research specialist, 2010-2011), went on to business
Jean Parry (postdoctoral fellow, 2010-2014), Asst Professor, Georgian Court U.
Jennifer Cohen (research specialist, 2012-2014), PhD student, UPenn
Jesus Ayala-Figuerosa (post-baccalaureate student, 2013-2014), Masters student UPR
Michelle Kanther (postdoctoral fellow, 2013-2014), research specialist, UPenn
and numerous undergraduates, not listed

Selected Publications

Jean M. Parry Meera V. Sundaram: A cell non-autonomous role for Ras signaling in C. elegans neuroblast delamination. Development in press, 2014.

Sundaram, M.V.: Canonical RTK-Ras-ERK signaling and related alternative pathways. Wormbook. www.wormbook.org, 2013.

Mancuso, V.P., Parry, J. M., Storer, L., Poggioli, C., Nguyen, K. C. Q., Hall, D.H. and Sundaram, M.V: Extracellular leucine-rich repeat proteins are required to organize the apical extracellular matrix and maintain epithelial junction integrity in C. elegans. Development 139: 979-990, March 2012.

Abdus-Saboor I, Stone CE, Murray JI, Sundaram MV: The Nkx5/HMX homeodomain protein MLS-2 is required for proper tube cell shape in the C. elegans excretory system. Dev Biol 366(2): 298-307, June 2012.

Abdus-Saboor, I., Mancuso, V.P., Murray, J.I., Palozola, K., Norris, C., Hall, D.H., Howell, K., Huang, K. and Sundaram, M.V: Notch and Ras promote sequential steps of excretory tube development in C. elegans. Development 138: 3545-3555, August 2011.

Howell, K., Arur, S., Schedl, T. and Sundaram, M. V.: EOR-2 is an obligate binding partner of the BTB-Zinc Finger protein EOR-1 in Caenorhabditis elegans. Genetics 184: 899-913, April 2010.

Stone, C. E., Hall, D. H., and Sundaram, M. V.: Lipocalin signaling controls unicellular tube development in the Caenorhabditis elegans excretory system. Developmental Biology 329: 201-211, 2009.

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Last updated: 09/30/2014
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