Past Profiles ‑ Dr. Kishore Pasumarthi
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Profile on Dr. Kishore Pasumarthi
After a heart attack, the heart muscle is permanently damaged in the area formerly supplied by a blocked artery. The damaged muscle cannot be repaired, scar tissue is formed and the heart simply doesn’t work as well as it did before. Dr. Kishore Pasumarthi and his cardiac regeneration research group are working to change this fact and heal cardiac damage.
“Generally, heart muscle cells don’t regenerate but it is still possible in lower vertebrate animals like zebrafish and newts. So if we cut open their chest and resect the heart a little bit, they can grow that tissue back,” says Pasumarthi. “If we can find a way of repairing damaged heart muscle in people that would be wonderful. That is our goal.”
Pasumarthi is a full professor in the Department of Pharmacology at Dalhousie Medical School. He has been at Dalhousie since 2003 but started his cardiac regeneration journey back in 1991 during his Ph.D. studies at the University of Manitoba. “I became fascinated in the subject,” says Pasumarthi, “and stayed with it forever.”
Pasumarthi’s work aims to benefit people who suffer from declining heart function and eventual heart failure. His research looks at two different strategies for cardiac regeneration: cell transplantation and the division of heart muscle cells.
At Indiana University during his post-doc, Pasumarthi worked with embryonic stem cells, with promising results. “The heart is an organ where cell-to-cell communication is very important in terms of synchronizing contraction,” says Pasumarthi. “We were the first to show that transplanted embryonic muscle cells can effectively communicate with the recipient heart muscle tissue.”
Now almost any cell can be reprogrammed back to a master stem cell, which can then be differentiated into heart muscle. But there are many steps between making master stem cells and actually using them to repair damaged heart muscle.
“The problem with this approach is that you can never get 100 per cent pure muscle cells,” says Pasumarthi. “In this process, you can generate a number of undesirable cell types that can cause troubles in the long run. So, we are looking at how best to identify and isolate the cardiac precursor cells.”
Cardiac precursor cells are one step more differentiated than the stem cells but are not yet mature heart cells. Pasumarthi says the benefit of identifying and transplanting this cell stage is that they can multiply. If you implant one precursor cell it can become two or four or six cells and heal more area.
Although the precursor cells only make heart muscle cells they can be one of two types: contracting cells and pace-making cells. “We don’t want to grow the pace-making cells,” says Pasumarthi. They can cause arrhythmia (an irregular heartbeat) and damage the heart that way. These are the types of roadblocks constantly encountered on the research path.
Pasumarthi and his team are in the midst of defining the cellular pathways used to form the two cell types, so that they can eventually control the process and form only the contracting cells.
The other approach used by Pasumarthi and his team to attempt cardiac regeneration is to cause heart muscle cell division. “We are still interested in making muscle cells divide,” he says. “We have discovered a protein that can do that, a cell division control protein, Cyclin-D2.”
They have shown in an animal model that using Cyclin-D2 can increase the number of new heart muscle cells. They were able to make one per cent of muscle cells around a heart attack scar divide, replacing the scar by 25 to 30 per cent with new muscle cells over a six-month period.
“But in humans, we want a better therapy that is going to be immediate. If we are going to use medications or gene-based approaches, they had better be very good,” says Pasumarthi. “So that is the goal, how do we make the rest of the muscle cells that are not dividing also divide?”
For Pasumarthi, his research is not about miraculous developments, it is about staying the course: “I see constant small changes and improvements and things that we could do,” he says. “These are all small pieces of the puzzle.”