About

Meera V. Sundaram, Ph.D, is a Professor of Genetics at the University of Pennsylvania's Perelman School of Medicine. Her research utilizes the nematode C. elegans as a model system to study the cell biology and developmental roles of the apical extracellular matrix (aECM). Her lab focuses on understanding how the aECM shapes developing epithelia, including tubes of various sizes, and its role in protecting the organism from pathogens and environmental insults. Dr. Sundaram's work involves visualizing components of the aECM in live worms using fluorescent tags, and studying the complex and dynamic nature of this matrix, which is produced and assembled by different cell types. Her research has identified conserved protein families involved in matrix formation and has contributed to understanding the structural patterns and trafficking mechanisms of matrix components, advancing knowledge of epithelial tube development and extracellular matrix biology.

Research topics

• Biology
• Cell biology
• Genetics
• Chemistry
• Anatomy

Selected publications

• Pre-cuticle DPY-6 acts as a blueprint for aECM periodic organization in <i>C. elegans</i>

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-23 · 1 citations

  articleOpen access

  cuticle, a model aECM that undergoes morphogenesis during each of the worm's four larval molts, requires periodic circumferential furrows for structural integrity and immune regulation. Here, we show that furrow collagens must be cleaved from their N-terminal transmembrane domain for secretion and depend on the mucin-like pre-cuticle protein DPY-6 for their periodic assembly. While DPY-6 is dispensable for initial embryonic furrow formation, it acts as a mold during subsequent molts, ensuring pattern replication via its C-terminal cysteine cradle domain. These results reveal a central role for a transient matrix factor in organizing a complex periodically structured aECM. Author Summary: In multicellular organisms, the extracellular matrix (ECM) provides structural support and regulates tissue function. Using the free-living worm Caenorhabditis elegans, we investigated how its apical ECM, the cuticle, forms a precise, repeating pattern of ridges called furrows. The cuticle is rebuilt at each of the worm's four larval stages, providing a unique opportunity to study matrix morphogenesis in real time. We discovered that a transient protein, DPY-6, acts as a molecular mold to guide the self-organization of the matrix outside the epidermal cells. DPY-6 ensures that newly secreted proteins assemble into the correct periodic pattern during each rebuilding phase. Without DPY-6, the furrows lose their organization, leading to structural defects and immune system activation. Our findings reveal how a temporary scaffold can template the assembly of a complex, self-organizing structure. This work provides new insights into how biological matrices are built and maintained, with broader implications for understanding ECM assembly in health and disease.

  PublisherDOI

• RAP-2-independent roles for C. elegans MIG-15

  microPublication · 2026-04-16

  articleOpen access

  MIG-15 is the sole <i>Caenorhabditis elegans</i> member of the GCK-IV subfamily of Ste20 kinases. In mammals and <i>in vitro</i>, MIG-15-like kinases can function as effectors of the small GTPase Rap2. To test this model <i>in vivo</i>, we compared phenotypes of <i>mig-15</i> and <i>rap-2</i> mutants. <i>mig-15</i> mutants displayed severe defects in vulval morphogenesis, cell positioning, and locomotion. In contrast, <i>rap-2</i> mutants were largely indistinguishable from wild type. These findings indicate that several developmental roles of MIG-15 occur independently of RAP-2, suggesting that additional upstream regulators, including other small GTPases or adhesion-related pathways, control MIG-15 activity in specific developmental contexts.

  PublisherDOI

• Author Reply to Peer Reviews of Opposing roles for lipocalins and a CD36 family scavenger receptor in apical extracellular matrix-dependent protection of narrow tube integrity

  2025-10-16

  peer-reviewSenior author
  PublisherDOI

• FGF-dependent, polarized SOS activity orchestrates directed migration of <i>C. elegans</i> muscle progenitors independently of canonical effectors <i>in vivo</i>

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-14 · 2 citations

  preprintOpen access

  Summary Directed cell migration is essential for animal development, tissue maintenance, regeneration, and disease states. Cells often migrate towards, or away from, sources of secreted signaling proteins that impart spatial information. How migrating cells interpret extracellular signals to orient and navigate within living animals is a fundamental question in biology. Receptor Tyrosine Kinase (RTK) signaling plays critical roles in cell migration, and aberrant RTK pathway activity is a key driver of multiple types of cancers. Yet, how RTKs control cell migration in living animals remains unclear, in part due to essential, pleiotropic roles of key proteins in development. To elucidate how RTK signaling controls cell migration in vivo , we dissected spatial and temporal requirements for key signal transduction and cytoskeletal regulatory proteins using C. elegans muscle progenitor migration as a tractable model. Cell type-specific depletion of endogenously tagged proteins revealed that homologs of FGFR, GRB2, SOS, and Ras control cell migration independently of their canonical ERK, PI3K, Akt, mTOR, and PLCψ effectors. Instead, we found that FGF-dependent, polarized SOS-1 orients migrating cells towards an FGF source, and mislocalizing SOS activity within migrating cells severely disrupts migration independent of ERK. Cell type-specific, gain-of-function experiments demonstrated that activated Ras is largely permissive for anterior migration in this context, and an intragenic revertant identified in a screen for suppressors of activated Ras/let-60 revealed that signal transduction in migrating muscle progenitors can be genetically uncoupled from Ras-ERK-dependent developmental processes. We found that conserved regulators of branched actin assembly control SM protrusive dynamics but are not essential for accurate, FGF-directed migration. Our findings provide a novel mechanism for RTK-directed cell migration in vivo and highlight the importance of cell type-specific approaches to elucidate signal transduction mechanisms in physiologically relevant contexts. Our work also outlines a comprehensive framework for investigating RTK-dependent processes in a multicellular organism and introduces a versatile genetic toolkit for dissecting spatial and temporal signaling dynamics fundamental to development, homeostasis, and disease.

  PublisherOA PDFDOI

• Opposing roles for lipocalins and a CD36 family scavenger receptor in apical extracellular matrix-dependent protection of narrow tube integrity

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-07-28

  preprintOpen accessSenior authorCorresponding

  Abstract All exposed epithelial surfaces, including the walls of internal tubes, are lined by a lipid and glycoprotein-rich apical extracellular matrix (aECM) that helps shape and protect the apical domain. Secreted lipocalins are lipid transporters frequently found within apical compartments. We show that loss of the C. elegans lipocalin LPR-1 disrupts the assembly of another lipocalin, LPR-3, within the pre-cuticle aECM that protects and shapes the narrow excretory duct and pore tubes. LPR-1 is apically secreted and colocalizes with LPR-3 in intracellular vesicles and lysosomes, but unlike LPR-3 it does not detectably incorporate into the aECM. Forward genetic screens for lpr-1 suppressors identified mutations in scav-2, which encodes a transmembrane protein of the CD36 scavenger receptor B family. Loss of scav-2 restored LPR-3 matrix localization and suppressed the lpr-1 tube shaping defect, as well as the tube-shaping defects of a subset of pre-cuticle mutants, but not lpr-3 mutants. A SCAV-2 fusion accumulated at apical surfaces of interfacial epithelial tubes, including the excretory duct and pore, and both tissue-specific suppression of lpr-1 matrix defects and tissue-specific rescue experiments support a local role for SCAV-2 within these tubes. These data demonstrate that LPR-1 and SCAV-2 have opposing effects on narrow tube integrity by altering the content and organization of that tube’s luminal aECM, possibly by acting as transporters of an LPR-3 cofactor. These results have broadly relevant implications regarding the importance of lipocalins and scavenger receptors for aECM organization and integrity of the narrowest tubes in the body.

  PublisherOA PDFDOI

• Opposing roles for lipocalins and a CD36 family scavenger receptor in apical extracellular matrix-dependent protection of narrow tube integrity

  Development · 2025-11-26

  articleOpen accessSenior author

  All exposed epithelial surfaces, including the walls of internal tubes, are lined by a lipid and glycoprotein-rich apical extracellular matrix (aECM) that helps shape and protect the apical domain. Secreted lipocalins are lipid transporters frequently found within apical compartments. We show that loss of the Caenorhabditis elegans lipocalin LPR-1 disrupts the assembly of another lipocalin, LPR-3, within the pre-cuticle aECM that protects and shapes the narrow excretory duct and pore tubes. Loss of SCAV-2, a CD36 family scavenger receptor, restored LPR-3 matrix localization and suppressed the tube shaping defects of lpr-1 and a subset of pre-cuticle mutants, but not lpr-3 mutants. SCAV-2 accumulates at duct and pore apical surfaces and functions locally within these tubes. These data demonstrate that LPR-1 and SCAV-2 have opposing effects on narrow tube integrity by altering the content and organization of the luminal aECM of the tube, possibly by acting as transporters of LPR-3 or an LPR-3 cofactor. These results have broadly relevant implications regarding the importance of lipocalins and scavenger receptors for aECM organization and integrity of the narrowest tubes in the body.

  PublisherDOI

• <i>idh-1</i> neomorphic mutation confers sensitivity to vitamin B12 via increased dependency on one-carbon metabolism in <i>Caenorhabditis elegans</i>

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-03-14

  preprintOpen access

  Abstract The isocitrate dehydrogenase neomorphic mutation ( idh-1neo ) generates increased levels of cellular D-2-hydroxyglutarate (D-2HG), a proposed oncometabolite. However, the physiological effects of increased D-2HG and whether additional metabolic changes occur in the presence of an idh-1neo mutation are not well understood. We created a C. elegans model to study the effects of the idh-1neo mutation in a whole animal. Comparing the phenotypes exhibited by the idh-1neo to Δdhgd-1 (D-2HG dehydrogenase) mutant animals, which also accumulate D-2HG, we identified a specific vitamin B12 diet-dependent vulnerability in idh-1neo mutant animals that leads to increased embryonic lethality. Through a genetic screen we found that impairment of the glycine cleavage system, which generates one-carbon donor units, exacerbates this phenotype. Additionally, supplementation with an alternate source of one-carbon donors suppresses the lethal phenotype. Our results indicate that the idh-1neo mutation imposes a heightened dependency on the one-carbon pool and provides a further understanding how this oncogenic mutation rewires cellular metabolism.

  PublisherOA PDFDOI

• The Caenorhabditis elegans Dispatched ortholog, CHE-14, is dispensable for apical secretion of the Hedgehog-related proteins GRL-2 and WRT-10

  PubMed · 2024-08-20

  articleOpen accessSenior author

  ortholog for the Hedgehog transporter Dispatched, was necessary for the secretion of two tagged Hh-r proteins: WRT-10 and GRL-2 . We report that CHE-14 is dispensable for the apical localization of GRL-2 and WRT-10 . We also show that animals lacking CHE-14 and another redundant PTR protein DAF-6 also secrete WRT-10 , suggesting neither are required for secretion of these specific Hh-r proteins.

  PublisherOA PDFDOI

• <i>idh-1</i>neomorphic mutation confers sensitivity to vitamin B12 in<i>Caenorhabditis elegans</i>

  Life Science Alliance · 2024-07-15 · 5 citations

  articleOpen access

  In humans, a neomorphic isocitrate dehydrogenase mutation ( idh-1neo ) causes increased levels of cellular D-2-hydroxyglutarate (D-2HG), a proposed oncometabolite. However, the physiological effects of increased D-2HG and whether additional metabolic changes occur in the presence of an idh-1neo mutation are not well understood. We created a Caenorhabditis elegans model to study the effects of the idh-1neo mutation in a whole animal. Comparing the phenotypes exhibited by the idh-1neo to ∆dhgd-1 (D-2HG dehydrogenase) mutant animals, which also accumulate D-2HG, we identified a specific vitamin B12 diet-dependent vulnerability in idh-1neo mutant animals that leads to increased embryonic lethality. Through a genetic screen, we found that impairment of the glycine cleavage system, which generates one-carbon donor units, exacerbates this phenotype. In addition, supplementation with alternate sources of one-carbon donors suppresses the lethal phenotype. Our results indicate that the idh-1neo mutation imposes a heightened dependency on the one-carbon pool and provides a further understanding of how this oncogenic mutation rewires cellular metabolism.

  PublisherOA PDFDOI

• Author Reply to Peer Reviews of idh-1 neomorphic mutation confers sensitivity to vitamin B12 via increased dependency on one-carbon metabolism in Caenorhabditis elegans

  2024-06-25

  peer-review
  PublisherDOI

Recent grants

• NIH Grant R01DK077182

  NIH · $633k · 2012

• NIH Grant R01CA087512

  NIH · $892k · 2005

• Ras Signaling and Tubulogenesis in the C. elegans Excretory (renal) System

  NIH · $5.3M · 2000–2021

• C. elegans lipocalin function in growth factor signaling

  NSF · $590k · 2013–2017

• Building and shaping the apical extracellular matrix

  NIH · $4.7M · 2020–2030

Frequent coauthors

• Jennifer D. Cohen

  Harvard University

  16 shared

• Min Han

  Weifang University

  9 shared

• David H. Hall

  9 shared

• Alexandra Belfi

  University of Pennsylvania

  8 shared

• Yanping Zhang

  Anhui Agricultural University

  7 shared

• Christian E. Rocheleau

  7 shared

• Nicholas D Serra

  University of Pennsylvania

  5 shared

• John I. Murray

  California University of Pennsylvania

  5 shared

Labs

• Sundaram labPI

Education

• PhD, Molecular Biology

  Princeton University

  1992

• BA, Biology

  Mount Holyoke College

  1986