Current Research Interests
My research is evolving into a common theme: the deep evolutionary link between stem cells, cancer and microbes.
Research Interest 1: CANCER and STEMNESS
Cancer is considered as a disease of cellular evolution to reach a state of self-sufficiency and immortality. The final stage of this evolution is the appearance of aggressive and metastatic cancer cells. These aggressive cancer cells exhibit some molecular and cellular features of embryonic stem cells. During my clinical practice in India and Bhutan, while treating cancer patients, an important and disturbing question came to my mind: why should a cancer cell, towards the end of its evolution to become an aggressive cell exhibit features of embryonic stem cells? After all, embryonic stem cell creates life, whereas aggressive cancer cell kills life. During my PhD and fellowship training in Toronto (Hospital for Sick Children), I found that exposure of cancer cells to oxidative stress could induce embryonic stem cell like state (the stemness state) to cancer cells (Das B et al. Stem Cells, 2008). My current interpretation of the finding is that oxidative stress-induced stem cell like cancer cell state (cancer stemness state) has a deep evolutionary history of unicellular life survival in the early pre-cambrian era, when earth was mostly hypoxic. In this interpretation, stemness is a type of defense system of ancient unicellular life form. Thus, one possible explanation of why cancer cell switch to an embryonic stem cell like state is that there are two kind of stemness states: stable or balanced state (life-supporting), and an unstable state of aggression (life-destroying). Cancer cell may evolve into the unstable stemness state, a kind of atavistic re-programming mechanism, the tumor stemness reprogramming (Das B et al. Stem Cells, 2012; and Das B, http://www.semm.it/pastevents_research/material/01_csc_05/wCSC_scientific_program.pdf)
Research Interest 2: ALTRUISTIC STEM CELLS
While writing a book on antioxidant, "The Science Behind Squalene" (Published in the year 2000), one idea came to my mind, about "cytoprotection" or altruism as commonly known in microbiology as well as social science. Is it possible that stem cells are altruistic? Finally, after 12 years of thinking and research, now I have a model to work on this elusive idea on stem cell altruism. The preliminary results are now published in Stem Cells, June 2012. The results indicate that my ideas on tumor stemness switch as well as stem cell altruism are converging towards one single idea: when we are dealing with cancer, we are dealing with a potent regenerative force of billion years of evolution hard wired in those tiny cancer cells. It is a sad story, because, if what we found is true, the cure for cancer is going to be tougher than what we could imagine. It is a tough goal, but there must be some easy solution out there that we have probably missed so far.
Research Interest 3: STEM CELLS AND MICROBES
Since my early days of medical practice in India and Bhutan, I have a strong interest to understand how bacteria remain dormant and then reactivate to cause disease like tuberculosis. My hypothesis is that adult stem cell niche may play a role in latency, and reactivation of tuberculosis. I have been awarded with a Gates foundation grant to explore the potential role of bone marrow stem cell nihce in tubercular latency. The project was completed and the results are published in Science Translational Medicine, January 30, 2013 issue. The findings indicate a potential deep evolutionary link between stem cells and microbes. My next step is to explore this hypothetical evolutionary link by using the stem cell/TB bacteria as a model. I hope that this approach will help me to find a way to understand how life evolved in extreme stressful environment of deep history, and if those survival mechanisms of life have been re-evoked by stem cells, cancer and microbes to persist in extreme environment
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