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Biofilm-modified macrophage (BAM) phenotype and function in diabetic wounds
Summary Data Summary
Applicant Roy, Sashwati
E-Mail Address roysa@iu.edu
Project Title Biofilm-modified macrophage (BAM) phenotype and function in diabetic wounds
CBU ID 16GRU3717
External SubContract ID 30835-18
Diabetic Complication Wound Healing
Funding Program Group Pilot & Feasibility [PF2016]
Abstract About 85% of lower-limb amputations in patients with diabetes are preceded by
infected foot ulceration. Emerging studies highlight the significant risk that
biofilm infection poses to the non-healing diabetic ulcers. Macrophages (Mphi)
are highly plastic innate immune cells that play a central role in tissue
repair. These cells of innate immune system serve as the primary defenders
against infection. Bacterial pathogens have evolved multiple strategies to evade
and subvert host immune system. Emerging studies indicate a role of
methicillin-resistant SA (MRSA) biofilms in evading Mphi bacterial effector
mechanisms by transforming Mphi towards an alternatively activated M2 phenotype.
Strategies of modifying activation state of Mphi have been suggested to be
effective in developing anti-biofilm therapeutics. A thorough characterization
and phenotyping of chronic wound biofilm modified Mphi (BAMs) is warranted. We
seek to understand how does the diabetic wound environment influences BAM
phenotype and function. A fine balance between ECM synthesis and degradation is
essential to achieve optimal repair. An imbalance in either direction may result
in scarring or poor healing outcomes. M2 Mphi may exist as ECM promoting
(ECM-promote) vs ECM degrading (ECM-degrade) subpopulations. Striking
preliminary data using a preclinical burn biofilm model demonstrated that wounds
infected with biofilm overproducing stain of SA rexB- mutant resulted in a
massive loss of collagen in the healing granulation tissue compared to the low
biofilm producing SA SarA- mutant strain. To be able to pharmacologically
stimulate the right kind of behavior in wound ECM turnover, a thorough
characterization of ECM-promote vs ECM-degrade mphi is necessary, as well as an
understanding of the signals they require for ECM turnover. The following two
specific aims will be addressed: AIM 1. Determine if functionally active wmphi
isolated from biofilm-infected diabetic wounds show ECM-degrade phenotype
causing wound collagen degradation. AIM 2. Investigate whether increased
presence of ECM-degrade wound mphi phenotypes in biofilm-infected human diabetic
wounds are associated with educed wound collagen levels and increased wound
recurrence.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel
Salary Total Costs 26030
Supply Total Costs 12931
Equipment Total Costs 0
Travel/Other Total Costs 0
Direct Costs 38961
Indirect Costs Proposed 21039
Total Costs Proposed 60000
Total Costs Approved 60000
Start Date 10/1/2016
End Date 4/30/2018
IFO Name Burkett, Maria
IFO E-Mail Address burkett.83@osu.edu
IACUC/IRB No. 99999
IACUC/IRB Institution Ohio State University-Main Campus
Entity ID No. 31-6025986
Report Request Date 4/30/2018
T1D NO
TypeCount
Invoices 13
Progress Reports 2
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  16GRU371730835-18Ohio State University-Main Campus9/30/2017$191.99$103.67$295.66-View PDF
  View  16GRU371730835-18Ohio State University-Main Campus8/31/2017$1,650.04$891.03$2,541.07-View PDF
  View  16GRU371730835-18Ohio State University-Main Campus7/31/2017$4,334.78$2,340.78$6,675.56-View PDF
  View  16GRU371730835-18Ohio State University-Main Campus6/30/2017$3,589.43$1,938.31$5,527.74-View PDF
  View  16GRU371730835-18Ohio State University-Main Campus5/31/2018$10,661.32$5,757.11$16,418.43-View PDF
  View  16GRU371730835-18Ohio State University-Main Campus5/31/2017$2,897.71$1,564.78$4,462.49-View PDF
  View  16GRU371730835-18Ohio State University-Main Campus4/30/2017$3,277.14$1,769.71$5,046.85-View PDF
  View  16GRU371730835-18Ohio State University-Main Campus3/31/2018$7,850.04$4,239.03$12,089.07-View PDF
  View  16GRU371730835-18Ohio State University-Main Campus2/28/2018$3,740.58$2,019.91$5,760.49-View PDF
  View  16GRU371730835-18Ohio State University-Main Campus12/31/2017$191.99$103.67$295.66-View PDF
  View  16GRU371730835-18Ohio State University-Main Campus11/30/2017$191.99$103.67$295.66-View PDF
  View  16GRU371730835-18Ohio State University-Main Campus10/31/2017$191.99$103.67$295.66-View PDF
  View  16GRU371730835-18Ohio State University-Main Campus1/31/2018$191.99$103.67$295.66-View PDF
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