October 2019: Dr. Sarkar co-organized a symposium “Bioinformatics: Research & Application” symposium, Texas A&M University,
Overview of Research Projects
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.
Circadian Rhythm & Tumor Microenvironment:
The circadian clock regulates mammary gland homeostasis by coordinating rhythmic gene expression involved in metabolism, immunity, and tissue remodeling. Our research investigates how chronic circadian rhythm disruption (CRD), caused by shift work or jet lag, promotes breast cancer by remodeling the tumor immune microenvironment. We discovered that CRD disrupts mammary gland architecture, accelerates tumor initiation and metastasis, and creates an immunosuppressive ("cold") tumor microenvironment characterized by increased regulatory T cells, M2 macrophages, and myeloid-derived suppressor cells, together with reduced CD8⁺ T cells and dendritic cells. We identified LILRB4 as a key mediator linking CRD to immune suppression and metastatic progression, and demonstrated that LILRB4 blockade significantly reduces metastasis (Ogunlusi, O. et al. Oncogene, 2025). In addition, our work revealed that CRD reprograms tumor metabolism and the intratumoral microbiome, generating immunosuppressive metabolites that further promote immune evasion and tumor progression (Sarkar, M. et al. BMC Cancer, 2026). Our laboratory aims to define how circadian disruption reshapes the tumor immune microenvironment during breast cancer initiation, progression, and therapeutic resistance.
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 single-cell spatial transcriptomics (Ogunlusi, O. et al, MS Submitted), 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 (Carter, K. et al, MS submitted).
Identifying the regulators of PD-L1 in aggressive breast cancers: TNBC and metastatic invasive ductal carcinoma cells (mIDC) frequently express high levels of Programmed Death Ligand 1 (PD-L1), which binds to Programmed Death-1 (PD-1) receptor on T-cells, enabling tumors to directly suppress the host immune response by inhibiting T-cell proliferation and function. Using genome-wide CRISPR screening, next-gen sequencing, we have recently identified novel regulators of PD-L1. The overall goal is to investigate and identify the novel regulator and the mechanism of PD-L1 regulation in aggressive breast cancers (Patent submitted).
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:
1. Investigating the anti-cancer properties of novel nanomaterial (Nguyen, T el.al., 2023, Nguyen, C. et al, MS Submitted)
2. Investigating the anti-cancer properties of novel metabolite/vitamin derivative