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The role of neuropilin 2 in urinary & gastrointestinal complications in diabetes
Summary Data Summary
Applicant Adam, Rosalyn
E-Mail Address rosalyn.adam@childrens.harvard.edu
Project Title The role of neuropilin 2 in urinary & gastrointestinal complications in diabetes
CBU ID 21AU4206
External SubContract ID 36305-5
Diabetic Complication Uropathy
Funding Program Group Pilot & Feasibility [PF2021]
Abstract Type 2 diabetes (T2D) is associated with significant complications that affect
the normal function of the urinary and gastrointestinal tracts. The impact of
aberrant bladder and/or gut motility ranges from discomfort in the case of
urinary incontinence and diarrhea to life-threatening situations such as
intestinal pseudo-obstruction. In spite of this significant healthcare burden,
the mechanisms that underlie the development of bladder and GI dysmotility in
diabetes, and the extent to which they can be reversed pharmacologically, are
incompletely understood. As a result, the development of treatments to address
smooth muscle dysmotility in diabetes has been hampered. Coordinated smooth
muscle activity is central to the normal function of the bladder and
gastrointestinal tracts, underlying both their storage and voiding/expulsion
capabilities. Data from our group have identified a new function for neuropilin
2 (Nrp2) in regulation of smooth muscle. Deletion of Nrp2 in led to an increase
in evoked contraction of bladder strips or colonic rings, but slower
gastrointestinal transit. In mice with diminished bladder contractility
secondary to partial bladder outlet obstruction, inducible SM-specific deletion
of Nrp2 was found to restore SM contractility relative to Nrp2-intact mice. In
this proposal, we hypothesize that Nrp2-regulated signaling is a novel,
accessible target to control dysregulated smooth muscle activity in diabetes. We
will test the hypothesis with the following Specific Aims: (1) Determine the
impact of Nrp2 targeting on bladder and gut contractility in diabetes. (2)
Interrogate neuropilin 2-regulated signaling networks in diabetes. We will
employ functional analyses of bladder and gastrointestinal contractility and
motility in mice with type II diabetes. We will delete Nrp2 in vivo using a
CreLox approach to understand how bladder and gut contractility are influenced
by Nrp2 deletion, in the context of diabetes. We will also employ a multiomics
approach to interrogate the molecular basis of the physiological alterations
observed in bladder and gut in diabetes. At the end of the project period, we
will understand the extent to which manipulation of Nrp2 signaling restores the
contractile capability of smooth muscle in the urinary and gastrointestinal
tracts in diabetes, and the associated signaling networks that lie downstream of
Nrp2. Successful completion of the studies would highlight the potential for
therapeutic targeting of Nrp2 and its effectors in the context of diabetes.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel Rosalyn Adam
Maryrose Sullivan
Salary Total Costs 43086
Supply Total Costs 20039
Equipment Total Costs 0
Travel/Other Total Costs 15000
Direct Costs 78125
Indirect Costs Proposed 21875
Total Costs Proposed 100000
Total Costs Approved 100000
Start Date 7/1/2021
End Date 6/30/2022
IFO Name Veras, Rosa
IFO E-Mail Address osp@childrens.harvard.edu
IACUC/IRB No. 20-03-4133R
IACUC/IRB Institution Boston Children's Hospital
Entity ID No. 042774441-A1
Report Request Date 6/30/2022
T1D NO
TypeCount
Invoices 13
Progress Reports 1
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  21AU420636305-5Boston Children's Hospital9/9/2022$5,381.09$1,506.71$6,887.80-View PDF
  View  21AU420636305-5Boston Children's Hospital8/11/2022$7,483.20$2,095.30$9,578.50-View PDF
  View  21AU420636305-5Boston Children's Hospital7/7/2022$7,618.44$2,133.17$9,751.61-View PDF
  View  21AU420636305-5Boston Children's Hospital6/14/2022$6,106.95$1,709.95$7,816.90-View PDF
  View  21AU420636305-5Boston Children's Hospital5/3/2022$3,913.20$1,095.70$5,008.90-View PDF
  View  21AU420636305-5Boston Children's Hospital5/18/2022$5,231.12$1,464.71$6,695.83-View PDF
  View  21AU420636305-5Boston Children's Hospital5/18/2022$4,130.20-$3,763.16-View PDF
  View  21AU420636305-5Boston Children's Hospital3/22/2022$5,441.09$3,047.00$8,488.09-View PDF
  View  21AU420636305-5Boston Children's Hospital12/16/2022$1,101.26$308.35$1,409.61-View PDF
  View  21AU420636305-5Boston Children's Hospital11/15/2022$6,069.57$1,699.48$7,769.05-View PDF
  View  21AU420636305-5Boston Children's Hospital10/11/2012$5,852.54$1,638.71$7,491.25-View PDF
  View  21AU420636305-5Boston Children's Hospital1/9/2023$332.72-$332.72-View PDF
  View  21AU420636305-5Boston Children's Hospital1/8/2022$19,536.39$5,470.19$25,006.58-View PDF


Reports
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