Primary Submission Contact

Shilpa Dhar

Faculty Sponsor

Laura Rowe

Faculty Sponsor Email Address

Laura.Rowe@valpo.edu

College

Arts and Sciences

Department/Program

Chemistry

Document Type

Poster Presentation

Date

Fall 10-28-2016

Abstract

BRCA1 mutation carriers are predisposed to breast and ovarian cancer. Chemotherapy is a common treatment used in breast cancer patients. However, chemotherapy can cause damage to bone marrow. Bone marrow is responsible for the production of white blood cells, namely neutrophils, which are the first line of defense in the innate immune system2. When an infectious or inflammatory challenge presents itself, neutrophils are used up in large quantities, and the hematopoietic system in the body has to rapidly adapt to increased demands by switching from the process of steady-state granulopoeisis to emergency granulopoeisis3. Evidence has shown that BRCA1 mutation carriers who have undergone chemotherapy treatment experience low counts of neutrophils1. Additional evidence has shown that the Fanconi gene pathway contributes to genomic stability during emergency granulopoeisis, and increased Fanconi C (Fancc) gene expression contributes to emergency granulopoeisis4. Since the BRCA1 gene is downstream of the FANCC gene, a myeloid leukemia cell line (U937) was tested to determine whether BRCA1 deficiency contributes to emergency granulopoeisis as well. Different concentrations of the protein IL-1Beta was added to the cells in order to mimic the emergency granulopoeisis response, and both FANCC and BRCA1 gene expression was measured. The general trend for the expression of both genes was found to be different than has previously been reported4.

  1. Shanley S et al. Clin Cancer Res. 2006; 12(23): 7033-7038.
  2. Kolaczkowzka E et al. Nat Rev Immunol. 2013; 13(3): 159-175.
  3. Manz M et al. Nature Reviews Immunology. 2014; 14: 302-314.
  4. Hu L et al. J Clin Invest. 2013; 123(9): 3952-3966.

Biographical Information about Author(s)

Shilpa Dhar is a junior chemistry major at Valparaiso University. This project was completed as part of a SURF (summer undergraduate research fellowship) program at the University of Texas Southwestern Medical Center.

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