Bikul Das, MD, PhD
Associate Research Investigator
Biomedical research and altruism are not often linked. Although altruism is considered a deep evolutionary mechanism of survival in microbial life, the characteristic has not yet been studied in human cells. In fact, survival of the fittest is a concept that is far more prevalent. Bikul Das has identified unusual altruistic behavior in stem cells. This research has great potential for both cancer and regenerative medicine.
Das’ research has shown that in times of stress, human embryonic stem cells (hESCs), produce molecules that benefit themselves and also help nearby stem cells survive. On the surface this sounds beneficial. However, the altruistic cells are also more prone to mutations—a sign that they could lead to cancers. Additionally, altruistic stem cells may be hijacked by both cancer and microbes to survive and persist in hostile environment. Das’ research has already shown that Mycobacteria tuberculosis, which causes the dreaded disease TB, hide in human stem cells of bone marrow niche. Das is now focusing on understanding the cellular interaction between altruistic stem cells, cancer, and pathogenic microbes like TB.
“I am interested in the deep evolutionary link between stem cells, cancer and microbes,” said Das. “If we can learn how to control the altruistic behavior of stem cells, we will have a new weapon in our disease fighting arsenal.”
Das has developed an in vitro model to study stem cell altruism. The preliminary results described in a human embryonic stem cell model indicate that during hypoxia/oxidative stress, a rare fraction of stem cells could reprogram to a robust phenotype of regenerative activity. The reprogrammed cells exhibited an altered p53/MDM2 oscillation, and underwent apoptosis/differentiation (loss of fitness), while the rest of the population was protected (gain of fitness) from the reactive oxygen species generated during the hypoxia/oxidative stress. In the next phase of this work, Das is investigating whether adult stem cells also exhibit altruistic reprogramming. The goal of this work is to develop insight, which will enable more effective regenerative medicine techniques.
In addition to examining the role these cells play in regeneration, Das is interested in both microbial and cancer cell interaction with altruistic stem cells. Specifically, he is interested in finding out if cancer stem cells and microbes hijack the altruistic stem cell reprogramming mechanism to persist in our body for years. For these goals, Das has identified cancer stem cell markers for neuroblastoma, small cell cancer and sarcomas. He is now developing in vitro and in vivo models to study the interaction between altruistic stem cells and cancer stem cells.
Das is also working to identify oral cancer stem cells in collaboration with the Indian laboratory, KaviKrishna Laboratory, Indian Institute of Technology Complex, Guwahati, Assam. This collaboration is an extension of the work he did last year, along with Antonio Campos-Neto, which found that Tuberculosis lies dormant in stem cells – providing new knowledge of how the bacteria can stay dormant in the human body and later resurface as active disease. Das is now studying whether TB bacteria may reprogram its host stem cells to altruistic phenotype for bacterial long-term dormancy.
Das’ work has been supported by the Laurel Foundation by a Grant Challenge Award from the Bill & Melinda Gates Foundation.
Gauhati University, India, MD, 1993, Internal Medicine
University of Toronto, Toronto, PhD, 2007, Medicine/Oncology