Dr. Swarnali Acharyya Research

Biography
Research Summary
Publications
Lab Members

Research Summary

The broad focus of our laboratory is exploring mechanisms of drug resistance and cancer metastasis. These are two major challenges that significantly limit anti-cancer therapy and claim millions of lives worldwide.

Metastasis originates from the Greek word meaning “change of place” and is the process by which cancer cells spread from their original site of origin to other parts of the body. Even if the primary tumor is diagnosed early, surgically removed or treated, cancer cells can remain in the body often culminating in aggressive metastatic disease, sometimes even after decades. Patients with metastatic disease often show poor response to conventional therapies and succumb to death.

The goal of our laboratory is to identify new mediators of metastasis and to develop strategies to sensitize these metastases to more effective therapies.

  • We utilize a combination of genetically engineered and xenograft mouse models to understand the process of metastasis (see Figures A and B).
  • We actively collaborate with clinical investigators to model the development and treatment of metastatic disease in preclinical models (see Figure B) and to validate our findings in patient-derived clinical samples.
  • We are particularly interested in investigating the tumor-microenvironment interactions that promote the growth and survival of metastasis and those that dictate therapeutic response (See Figure C).
  • Our primary focus lies on two types of solid tumors- metastatic breast cancer and lung cancer.


Figure A.
Rapid and non-invasive monitoring of metastatic cells in-vivo using whole body bioluminescence imaging. Cancer cells are engineered to express luciferase that can be monitored and quantified over time.


Figure B
Human breast cancer cells (brown cells stained with vimentin) that have metastasized to the lungs after injection in the mammary gland site are shown in an experimental xenograft model.

Figure C
We have previously identified a paracrine axis through TNF-α/CXCL1/2/S100A8/9 that acts as a mediator of both chemoresistance and metastasis in breast cancer (Acharyya et al., Cell, 150(1), 165-178, 2012). We have shown how chemotherapy drugs trigger a parallel stromal reaction in the tumor microenvironment leading to TNF-α production, which in turn amplifies the CXCL1/2/S100A8/9 survival axis between metastatic cells and myeloid cells in the tumor microenvironment. We have shown that the use of CXCR2 antagonists in combination with chemotherapy reduces lung metastatic burden in preclinical models. We will further expand our studies to determine the role of components of this axis in breast and lung cancer subtypes.