Overview

The High mobility group box (HMGB) proteins are a family of four DNA-binding proteins that regulate chromatin structure. We have recently shown that HMGB3 is involved in the cancer cell plasticity of neuroendocrine tumors. Cancer plasticity is defined as the ability of cancer cells to transit from one cell state to another by adopting new phenotypic and molecular characteristics. Our unpublished data and published studies indicate that HMGB3 is also involved in the progression of other cancer types, making it an attractive drug target. 

How does HMGB3 regulate chromatin structure? What are the HMGB3 protein-protein interactions? Is HMGB3 druggable? These are some of the questions we try to address. 

This project is headed by Dr. Nilakshi Kulathunga, a postdoctoral fellow in the Michael lab.

Saghafinia, S. et al. Cancer cells retrace a stepwise differentiation program during malignant progression. Cancer Discov 11, candisc.1637.2020 (2021).

Neuroendocrine tumors arise due to the malignant transformation of bona fide neuroendocrine cells located in various organs and via neuroendocrine transdifferentiation of epithelial tumors. Our group is primarily interested in the neuroendocrine tumors of the gastroenteropancreatic system. As part of our research strategy, we also examine whether our findings are relevant to other neuroendocrine tumors, such as small-cell lung cancer and prostate neuroendocrine tumors.

Our research currently focuses on dissecting the molecular heterogeneity of small bowel and pancreatic neuroendocrine tumors, identifying pathways involved in metastasis and elucidating the neuron-cancer interactions.

Zoey Wang is using omics approaches to elucidate the NET heterogeneity and the molecular pathways involved in cancer cell plasticity.

William You is using CRISPR approaches to identify the mechanisms of liver metastasis of gastroenteropancreatic neuroendocrine tumours.

Perren, A. et al. What is the origin of pancreatic endocrine tumors? In Zen Y “The Pancreas: An Integrated Textbook of Basic Science, Medicine, and Surgery” 4th edition Wiley Press. Sept 2023.

Michael, I. P. et al. A set of microRNAs coordinately controls tumorigenesis, invasion, and metastasis. Proc National Acad Sci 116, 24184–24195 (2019).

Saghafinia, S. et al. Cancer cells retrace a stepwise differentiation program during malignant progression. Cancer Discov 11, candisc.1637.2020 (2021).

The brain is one of the main organs of cancer metastasis from various primary tumor sites, such as breast, lung, and melanoma. Recent studies have unveiled the importance of the interaction of cancer cells with neurons during brain metastasis. Our lab is interested in elucidating the signaling pathways involved in the cancer-neuron cross-talk. 

How do cancer cells interact with the various neuron types? Do cancer cells from different primary tumors interact with the same neuron types? What is the role of miRNAs during the cancer-neuron interactions?

Areeba Qureshi is exploring the role of miR-181/HMGB3 axis in the cancer-neuron interactions during brain metastasis. 

Michael, I.P. et al. ALK7 Signaling Manifests a Homeostatic Tissue Barrier That Is Abrogated during Tumorigenesis and Metastasis. Dev Cell 2019 May 6;49(3):409-424.e6.

Zeng, Q. et al. Synaptic proximity enables NMDAR signalling to promote brain metastasis. Nature 573, 526–531 (2019).