Sunitha Nagrath
Principal Investigator
Dr. Nagrath's research goal is to bring the next generation of engineering tools to patient care, especially in cancer. Her major focus of research is to develop advanced MEMS tools for understanding cell trafficking in cancer through isolation, characterization and study of circulating cell in peripheral blood of cancer patients. Dr. Nagrath’s research on isolating and studying rare cells from cancer patients. She would like to focus her lab’s efforts on designing and developing smart chips using microfluidics and nanotechnology to make impact in medicine and life sciences. Her goal is to create cutting edge engineering solutions for clinical medicine with novel translational biomedical research tools. She strongly believes in building a team where engineers, biologists and clinicians will come together to solve the complex problems with better approaches.
https://che.engin.umich.edu/2021/02/15/sunitha-nagrath-elected-fellow-of-aimbe/
https://che.engin.umich.edu/2021/02/15/sunitha-nagrath-elected-fellow-of-aimbe/
Publications
Optimizing the Detection of Circulating Markers to Aid in Early Lung Cancer Detection, Cancers (2016)
Improving early detection of lung cancer is critical to improving lung cancer survival. Studies have shown that computerized tomography (CT) screening can reduce mortality from lung cancer, but this involves risks of radiation exposure and can identify non-cancer lung nodules that lead to unnecessary interventions for some. There is a critical need to develop alternative, less invasive methods to identify patients who have early-stage lung cancer. The detection of circulating tumor cells (CTCs) are a promising area of research, but current technology is limited by a low yield of CTCs. Alternate studies are investigating circulating nucleic acids and proteins as possible tumor markers. It is critical to develop innovative methods for early lung cancer detection that may include CTCs or other markers that are low-risk and low-cost, yet specific and sensitive, to facilitate improved survival by diagnosing the disease when it is surgically curable.
GM-CSF Mediates Mesenchymal-Epithelial Crosstalk in Pancreatic Cancer, Cancer Discovery (2016)
Pancreatic ductal adenocarcinoma (PDA) is characterized by a dense stroma consisting of a prevalence of activated fibroblasts whose functional contributions to pancreatic tumorigenesis remain incompletely understood. In this study, we provide the first identification and characterization of mesenchymal stem cells (MSCs) within the human PDA microenvironment, highlighting the heterogeneity of the fibroblast population. Primary patient PDA samples and low passage human pancreatic cancer associated fibroblast (CAF) cultures were found to contain a unique population of cancer associated MSCs (CA-MSCs). CA-MSCs markedly enhanced the growth, invasion and metastatic potential of PDA cancer cells. CA-MSCs secreted the cytokine GM-CSF that was required for tumor cell proliferation, invasion and transendothelial migration. Depletion of GM-CSF in CA-MSCs inhibited the ability of these cells to promote tumor cell growth and metastasis. Together, these data identify a population of MSCs within the tumor microenvironment that possesses a unique ability, through GM-CSF signaling, to promote PDA survival and metastasis.
The Marrow Niche Controls the Cancer Stem Cell Phenotype of Disseminated Prostate Cancer, Oncotarget (2016)
Dissemination of cancer stem cells (CSCs) serves as the basis of metastasis. Recently, we demonstrated that circulating prostate cancer targets the hematopoietic stem cell (HSCs) ‘niche’ in marrow during dissemination. Once in the niche, disseminated tumor cells (DTCs) may remain dormant for extended periods. As the major function of the HSC niche is to maintain stem cell functions, we hypothesized that the niche regulates CSC activities of DTCs. Here we show that DTCs recovered from marrow were significantly enriched for a CSC phenotype. Critically, the conversion of DTCs to CSCs is regulated by niche-derived GAS6 through the Mer/mTOR; molecules previously shown to regulate dormancy. The data demonstrate that the niche plays a significant role in maintaining tumor-initiating prostate cancer in marrow and suggests a functional relationship between CSCs and dormancy. Understanding how the marrow niche regulates the conversion of DTCs to CSCs is critical for the development of therapeutics specifically targeting skeletal bone metastasis and dormancy.
