We have three major research areas in our laboratory:

1.  How do disseminated tumor cells (DTCs) remain dormant at metastatic sites?

Cancer cells disseminate from the primary tumor and seed in distant organs, remaining dormant for many years before metastases become detectable. How do DTCs remain dormant? We are exploring the concept of “niche construction” to understand how DTC sustain dormancy-supportive niches. By using ECM-enriched proteomics we have found that dormant tumor cells secrete a specific set of ECM and ECM remodeling matrisome proteins,“the quiesome”, that are lost upon break from dormancy. We have identified a group of ECM molecules, that contribute to tumor dormancy through the formation of a pro-quiescence ECM niche that when disrupted restore the growth of dormant cells. We are focus on understanding the biology and related mechanism on how tumor-derived ECM regulates tumor dormancy.


Di Martino et al., 2019. PMC6839695
Di Martino et al., 2021. PMC8507703
Di Martino et al., 2022. PMC8818089

In vivo 3D reconstruction of the tumor extracellular matrix.

2. How do DTCs regulate proliferative/invasive programs?

While cancer progression is seen as a process of uncontrol growth, cancer dissemination may require the coordination and proper balance of proliferative and invasive programs. We are exploring the mechanisms balancing proliferation/invasion programs and how by interfering with those signaling nodes tumor growth and dissemination are affected. We have found that cells that undergo dormancy downregulate RhoGTPase regulators GAPs (GTPase activating proteins). By using intravital microscopy and quiescence biosensors we are characterizing the role of GAPs molecules on the regulation of the dormant state of breast cancer cells.


Mondal et al., 2021. PMC8246644
Mondal et al., Imaging cell adhesion and migration (in press)
Mondal et al., forthcoming

Breast cancer cells degrading extracellular matrix

3. How does the aged microenvironment regulates mammary tumor development and metastatic dormancy?

Aging is a major risk factor for breast cancer. Accumulation of protein damage is a common feature of most tissues in aging organisms. Compromised quality control with age contributes to altered protein homeostasis and cancer progression. Autophagy is a self-degradative cellular process that plays a major role as part of the proteostasis network in maintenance of cellular homeostasis. Chaperone-Mediated Autophagy (CMA) is a selective form of autophagy capable that decrease with age. In collaboration with the laboratories of Dr. Cuervo (Cuervo Lab) and Dr. Arias (Arias Lab) at Albert Einstein College we have developed and characterized a novel transgenic reporter mouse model that allows dynamic measurement of CMA activity in vivo (Dong et al., Nature Communications 2020). In this model, we are characterizing the spatiotemporal changes in CMA activity during mammary gland and mammary tumor development and the impact of an aged microenvironment and CMA deficiency on breast progression and tumor dormancy.


Dong et al, 2020. PMC6994528

In vivo 3D reconstruction of a mammary gland duct (Green: epithelial cells/Red: Collagen matrix)