Bio

Clinical Focus


  • Gastroenterology

Academic Appointments


Professional Education


  • Residency:Beth Israel Deaconess Medical Center (2005) MA
  • Board Certification: Gastroenterology, American Board of Internal Medicine (2009)
  • Fellowship:Beth Isreal Deaconess Medical Center (2009) MA
  • Board Certification: Internal Medicine, American Board of Internal Medicine (2005)
  • Internship:Beth Israel Deaconess Medical Center (2003) MA
  • Medical Education:Albert Einstein College of Medicine (2002) NY

Publications

All Publications


  • Ex Vivo Neurogenesis within Enteric Ganglia Occurs in a PTEN Dependent Manner PLOS ONE Becker, L., Peterson, J., Kulkarni, S., Pasricha, P. J. 2013; 8 (3)

    Abstract

    A population of multipotent stem cells capable of differentiating into neurons and glia has been isolated from adult intestine in humans and rodents. While these cells may provide a pool of stem cells for neurogenesis in the enteric nervous system (ENS), such a function has been difficult to demonstrate in vivo. An extensive study by Joseph et al. involving 108 rats and 51 mice submitted to various insults demonstrated neuronal uptake of thymidine analog BrdU in only 1 rat. Here we introduce a novel approach to study neurogenesis in the ENS using an ex vivo organotypic tissue culturing system. Culturing longitudinal muscle and myenteric plexus tissue, we show that the enteric nervous system has tremendous replicative capacity with the majority of neural crest cells demonstrating EdU uptake by 48 hours. EdU(+) cells express both neuronal and glial markers. Proliferation appears dependent on the PTEN/PI3K/Akt pathway with decreased PTEN mRNA expression and increased PTEN phosphorylation (inactivation) corresponding to increased Akt activity and proliferation. Inhibition of PTEN with bpV(phen) augments proliferation while LY294002, a PI3K inhibitor, blocks it. These data suggest that the ENS is capable of neurogenesis in a PTEN dependent manner.

    View details for DOI 10.1371/journal.pone.0059452

    View details for Web of Science ID 000317562100136

    View details for PubMedID 23527198

  • Divergent fate and origin of neurosphere-like bodies from different layers of the gut AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY Becker, L., Kulkarni, S., Tiwari, G., Micci, M., Pasricha, P. J. 2012; 302 (9): G958-G965

    Abstract

    Enteric neural stem cells (ENSCs) are a population of neural crest-derived multipotent stem cells present in postnatal gut that may play an important role in regeneration of the enteric nervous system. In most studies, these cells have been isolated from the layer of the gut containing the myenteric plexus. However, a recent report demonstrated that neurosphere-like bodies (NLBs) containing ENSCs could be isolated from mucosal biopsy specimens from children, suggesting that ENSCs are present in multiple layers of the gut. The aim of our study was to assess whether NLBs isolated from layers of gut containing either myenteric or submucosal plexus are equivalent. We divided the mouse small intestine into two layers, one containing myenteric plexus and the other submucosal plexus, and assessed for NLB formation. Differences in NLB density, proliferation, apoptosis, neural crest origin, and phenotype were investigated. NLBs isolated from the myenteric plexus layer were present at a higher density and demonstrated greater proliferation, lower apoptosis, and higher expression of nestin, p75, Sox10, and Ret than those from submucosal plexus. Additionally, they contained a higher percentage of neural crest-derived cells (99.4 ± 1.5 vs. 0.7 ± 1.19% of Wnt1-cre:tdTomato cells; P < 0.0001) and produced more neurons and glial cells than those from submucosal plexus. NLBs from the submucosal plexus layer expressed higher CD34 and produced more smooth muscle-like cells. NLBs from the myenteric plexus layer contain more neural crest-derived ENSCs while those from submucosal plexus appear more heterogeneous, likely containing a population of mesenchymal stem cells.

    View details for DOI 10.1152/ajpgi.00511.2011

    View details for Web of Science ID 000303593900007

    View details for PubMedID 22361728

  • Stem cell transplantation in neurodegenerative disorders of the gastrointestinal tract: future or fiction? GUT Kulkarni, S., Becker, L., Pasricha, P. J. 2012; 61 (4): 613-621

    Abstract

    Current advances in our understanding of stem and precursor cell biology and in the protocols of stem cell isolation and transplantation have opened up the possibility of transplanting neural stem cells for the treatment of gastrointestinal motility disorders. This review summarises the current status of research in this field, identifies the major gaps in our knowledge and discusses the potential opportunities and hurdles for clinical application.

    View details for DOI 10.1136/gut.2010.235614

    View details for Web of Science ID 000300955000020

    View details for PubMedID 21816959

  • Gut-derived factors promote neurogenesis of CNS-neural stem cells and nudge their differentiation to an enteric-like neuronal phenotype AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY Kulkarni, S., Zou, B., Hanson, J., Micci, M., Tiwari, G., Becker, L., Kaiser, M., Xie, X. (., Pasricha, P. J. 2011; 301 (4): G644-G655

    Abstract

    Recent studies have explored the potential of central nervous system-derived neural stem cells (CNS-NSC) to repopulate the enteric nervous system. However, the exact phenotypic fate of gut-transplanted CNS-NSC has not been characterized. The aim of this study was to investigate the effect of the gut microenvironment on phenotypic fate of CNS-NSC in vitro. With the use of Transwell culture, differentiation of mouse embryonic CNS-NSC was studied when cocultured without direct contact with mouse intestinal longitudinal muscle-myenteric plexus preparations (LM-MP) compared with control noncocultured cells, in a differentiating medium. Differentiated cells were analyzed by immunocytochemistry and quantitative RT-PCR to assess the expression of specific markers and by whole cell patch-clamp studies for functional characterization of their phenotype. We found that LM-MP cocultured cells had a significant increase in the numbers of cells that were immune reactive against the panneuronal marker ?-tubulin, neurotransmitters neuronal nitric oxide synthase (nNOS), choline acetyltransferase (ChAT), and neuropeptide vasoactive intestinal peptide (VIP) and showed an increase in expression of these genes, compared with control cells. Whole cell patch-clamp analysis showed that coculture with LM-MP decreases cell excitability and reduces voltage-gated Na(+) currents but significantly enhances A-current and late afterhyperpolarization (AHP) and increases the expression of the four AHP-generating Ca(2+)-dependent K(+) channel genes (KCNN), compared with control cells. In a separate experiment, differentiation of LM-MP cocultured CNS-NSC produced a significant increase in the numbers of cells that were immune reactive against the neurotransmitters nNOS, ChAT, and the neuropeptide VIP compared with CNS-NSC differentiated similarly in the presence of neonatal brain tissue. Our results show that the gut microenvironment induces CNS-NSC to produce neurons that share some of the characteristics of classical enteric neurons, further supporting the therapeutic use of these cells for gastrointestinal disorders.

    View details for DOI 10.1152/ajpgi.00123.2011

    View details for Web of Science ID 000295253900006

    View details for PubMedID 21817062

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