Grants We Funded

Abstract

Impact Statement: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare type of T-cell non-Hogdkin's lymphoma that can develop around breast implants. Till date, 733 cases of BIA-ALCL have been reported and 36 deaths implicated to this condition. There are 10 million women with breast implant worldwide who are at risk of developing this condition. Guided by our preliminary data, we hypothesize that biofilms present on the breast implant acts on breast fatty acids and leads to the formation of oxylipins. These biofilm derived oxylipins subsequently lead to the activation and multiplication of T cells present in breast adipose. Findings of this proposal will help to understand role of bacterial biofilms as a confounding factor in BIA-ALCL.

Project Summary: Breast implant associated- anaplastic large cell lymphoma (BIA-ALCL) is identified as a T cell, non–Hodgkin lymphoma. BIA-ALCL can manifest as a solid mass infiltrating the peri-prosthetic fibrotic capsule and soft tissues. It can also appear as a late peri-implant seroma within which tumor cells proliferate.This can occur to patients who underwent reconstructive surgery post mastectomy in breast cancer and augmentative surgery for cosmetic purposes. Till date, 656 cases of BIA-ALCL have been reported worldwide and 17 deaths implicated to this condition. Nevertheless, though the number is less, it is of grave concern as there are 10 million women with breast implant worldwide and harbor the risk of developing this condition. The role of bacteria and body microflora in oncogenic response and therapeutic regimen is gaining attention. Bacterial infection have been implicated to cause cancer (gastric cancer by Helicobacter pylori). Bacteria can be in planktonic form (commonly associated with infections) or can form dormant colonies encapsulated in extrapolymeric substance called as biofilm. In this mode, they are metabolically inert and become recalcitrant to antibiotics and host immune cells. The host-pathogen interaction of bacterial biofilms are different from those of planktonic bacteria. Oxylipins are lipophilic molecules derived from the oxidation of fatty acids. They are primarily involved in signal transduction. Oxilipins have been reported to contribute to differentiation of cancer cell lines. The breast is rich in adipose tissue. This proposal is based on the hypothesis that bacterial enzymes can oxidize the host lipids like Oleic acid to form oxylipins HOME and DiHOME. These oxylipins then lead to activation and clonal proliferation of T cells which can lead to BIA-ALCL. To test the hypothesis, we have proposed two specific aims Aim 1: Test the presence of biofilm generated metabolites post-breast implant insertion Aim 2: Determine the role of implant associated biofilm in activation and clonal proliferation of host T cells.

Biography
I am an Assistant Professor in the Department of Surgery at Indiana University School of Medicine, Indianapolis. My google scholar citation is 1000+ with h-index 14. My expertise is in bacterial biofilm mediated host–pathogen interaction and gene regulation during cellular reprograming and plasticity. Since starting my lab (end of 2018) as an independent PI, I have begun investigating role of bacterial biofilms in breast implant related complications. The focus of this lab is to study bacterial biofilm as a confounding factor towards complications like BIA-ALCL, capsular contracture and patient reported systemic immune responses termed as breast implant illness (BII). Implant associated complications have escalated into a serious concern in in cosmetic surgery and reconstructive surgery. Currently, there are more than 10 million women globally with implants. My background in bacterial biofilms and cellular reprogramming provides me expertise to investigate this pathological condition. My current position at the Division of Plastic Surgery provides me a very fertile environment to approach the problem. In addition to my research, I serve as the Associate editor of two journals namely, RNA Biology, IF 5.35 and Oxidative Medicine and Cellular Longevity, IF 5.07. I am serving as the youngest associate editor in both the journals. In addition, I am currently serving as a Forum Editor for special issue ‘Biofilm’ in Advances in Wound Care, IF 3.11.