The first lab of Pimm’s new series turned out to be the Bernstein Laboratory at the University of California, San Francisco focusing on heart muscle regeneration. Unlike other professors, Harold Bernstein is extra fast, he answered my questions within 8 hours. This web-availability, rare within academic circles, positively correlates with the design and functionality of the Bernstein lab webpage, which was the first candidate of the lab website competition. I especially like that it is not a lab site built around the PI only, but it focuses on the team at work which is quite big (more than 30 members, 8 postdocs). The lab got a $2,229,140.00 California ESC grant (first year $531,888) on Modeling Myocardial Therapy with Human Embryonic Stem Cells.
The answers of professor Harold Bernstein’s are as follows:
1. What is your scientific background and how did you get immersed into stem cell research? What was the motivation behind that?
I trained in human genetics, receiving a Ph.D. Toward the end of my graduate studies, I realized that I wanted to know more about human biology, and so I entered medical school, and subsequently received an M.D. I have always been interested in the regulation of cell proliferation versus differentiation, since that is a key decision point in the formation of many mammalian tissues. Especially in some organs, such as brain, muscle and heart, the paradigm has been that once the decision to differentiate has been made, there is no turning back, hence, “terminal differentiation.” Stem cells seemed like the most likely model system in which to pursue our questions, and the advent of human ES cell technology has provided an unprecedented opportunity to examine human tissue development.
2. Who were your masters and supervisors?
Leonard Nash and Jeremy Knowles, Harvard University, Cambridge, MA
Robert Desnick, Mount Sinai School of Medicine, NY
Shaun Coughlin, UCSF, CA
3. What are the current research projects in your lab?
Hopefully, our website answers this: 1) characterization and manipulation of myogenic precursor cells; 2) mechanisms of cell cycle withdrawal during differentiation; 3) the role of cell cycle machinery in post-mitotic cellular responses; and, 4) CDC5-mediated control of cell division.
4. What are the crucial methods do you use?
Human ES cell culture, Mouse tissue stem cell culture, in vitro differentiation, transgenic modeling, in vivo tissue remodeling
5. What is the financial background of the lab, what grants are behind?
NHLBI, American Heart Association (but not for the human ES cell work), the Pollin Foundation, the California Institute for Regeneration Medicine (we just received one of their first Comprehensive Research Grants for $2.3 million) (Sources of support)
6. How functional is your lab homepage and how regularly is it updated?
I like to think it’s quite functional. We update it fairly regularly, especially with new personnel and publications.
7. What is the most important problem of recent stem cell biology?
Trying to figure out the relative contributions of inherent genetic programming and the tissue environment in directing stem cell fate.
8. What is the decisive mechanism behind stem cell’s remarkable regenerative potential? Differentiation, fusion, paracrine factors…How tissue dependent it is?
That remains to be seen.
9. How would you define the endogenous regenerative potential of a tissue/organ, say skeletal muscle?
Skeletal muscle has some capacity for repair, through resident precursor cells, i.e., satellite cells. There is much debate about whether cardiac muscle has a similar stem cell reservoir. Some investigators believe this “stem cell niche” is functional, while others believe it represents a vestige of development. The fact that patients who suffer a heart attack do not recover significant organ function argues for the latter, while the presence of ongoing, low-level apoptosis among cardiac myocytes, as seen in some studies, suggests there may be a mechanism that supports new myocyte formation.
10. In which medical sectors will stem cell therapie likely to be disruptive treatments in the next decade…knee implants, sports medicine, heart muscle….?
I like to think that what we learn about cardiac myocyte differentiation both in vitro and in vivo will result in cell-based therapies for myocardial insufficiency (i.e., heart failure) over the next decade. That’s why we’re doing what we do.