October 2019: Dr. Sarkar co-organized a symposium “Bioinformatics: Research & Application” symposium, Texas A&M University,
Overview of Research Projects
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Tumors develop in complex and dynamic microenvironments that influence their growth, invasion, and metastasis. The primary focus of our group is to utilize multidisciplinary approaches (molecular biology, bioinformatics, computational biology, nanotechnology, machine learning, and artificial intelligence) to understand the impact of the tumor microenvironment on tumor heterogeneity and the consequences for cancer cell plasticity, stemness, and therapy resistance.
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The Impact of Circadian disruption on Breast Tumorigenesis: In the breast, circadian clocks regulate the rhythmic expression of numerous genes. Circadian disruption is hypothesized to increase risk for breast cancer via disruption of central and peripheral clocks, resulting in widespread dysregulation of clock-controlled biological processes. Epidemiological studies have shown that circadian rhythm disruption (CRD) caused by shift work or frequent jet lag is associated with the risk of breast cancer development. However, the role of CRD in mammary gland morphology and aggressive mammary tumorigenesis and the molecular mechanisms underlying CRD and cancer risk remain unknown. We found that chronic CRD disrupted mouse mammary gland morphology and increased tumor burden and lung metastasis in a genetically engineered mouse model of aggressive breast cancer and induced an immunosuppressive tumor microenvironment by enhancing leukocyte immunoglobulin-like receptor 4a (LILRB4a or LILRB4) expression. Moreover, CRD increased the M2 macrophage (anti-inflammatory) and regulatory T-cell populations but decreased the M1 macrophage (proinflammatory) populations. These findings identify and implicate LILRB4a as a link between CRD and aggressive mammary tumorigenesis.
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The role of Cancer-associated fibroblasts in tumor progression and therapy resistance: Cancer-associated fibroblasts have been implicated in diverse roles including cancer invasion, metastasis, resistance to existing cancer therapeutics, angiogenesis, and tumor proliferation. Using scRNA seq, our recent study has been identified a specific population of CAF which is responsible for tumor progression. By using transgenic mice model, scRNA seq, single-cell spatial proteomics, our current study focuses on the role of CAFs on drug response and reprogramming of tumor metabolomics.We will use computational modeling of the crosstalk between CAFs and Tumor Cells the Tumor Microenvironment. This in silico system will help to acquire novel insights into designing effective therapeutic strategies aimed at cancer cells and/or CAFs.
EMT-induced cells participate in tumor angiogenesis: EMT enhances metastatic dissemination while partial EMT or reversal of EMT (MET or mesenchymal to epithelial transition) facilitates the growth of metastases. Our recent study showed that Carcinoma cells that have undergone an EMT differentiate into endothelial cells and contribute to tumor growth (Sphyris et al., 2021). Our findings link the stemness, conferred through EMT, to the acquisition of endothelial cell traits and the augmentation of tumor angiogenesis in an EMT-dependent manner. Currently, we are using in vitro as well as in vivo studies, to shed some light on the molecular mechanism of EMT-mediated endothelial transdifferentiation. EMT also plays a pivotal role in vasculogenic mimicry (a pattern of tumor microcirculation) formation. In reality, the coexistence of angiogenesis and VM is common within aggressive tumors. Angiogenesis inhibitors have little or even no effect on VM. Our study will identify the correlation between CSCs, EMT, and VM formation with a focus on breast cancer.
VM in MDA231 VM in SUM 159
Other projects:
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1. Investigating the anti-cancer properties of novel nanomaterial
2. Investigating the anti-cancer properties of novel metabolite/vitamin derivative
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