TGIF stem cell & science news bites

The FDA warning letter to Richard Burt of Northwestern related to noncompliance issues with his stem cell clinic trial for MS has dominated the news recently, but some other notable things have happened as well on stem cells and more generally in science. I’ve posted some notable news bites below.

Q&A video with Paul Episode 2: stem cell & CRISPR questions answered

This is the second in a series of videos I’m doing where I answer questions about the stem cell field. You can see the Episode 1 video here.

Today I tackle more questions on the stem cell field. If you have more stem cell questions, let me know and I’ll try to answer them next time.

One reader asked me about stem cells for stroke and about one company, Athersys, in particular, but I haven’t had time to tackle that one in such a way as to do it justice so stay tuned on that good question.

I realized after the fact that regarding stem cell epigenetics I should have said broadly that this is a process of regulation of gene expression.

Stem cell headlines: half a genome, Australian snake oil, CRISPR patent battle

embryo human

Wikimedia Photo

There’s a lot going on in the world of stem cells making for many striking headlines lately.

Here are some stem cell headlines that caught my attention.

Haploid Stem Cells Created. Could these cells be used to make germ cells?

Charlatans and snake-oil salesmen ‘hijacking stem cell therapies’ in Australia

In the CRISPR patent fight, the Broad Institute gains edge. The CRISPR-Cas9 patent chess match continues and some think Broad has slight advantage at this point.

CIRM grant to fund proposed stem cell trials for ALS. Go CIRM 2.0.

Removing Epigenetic Post-it Notes Returns Stem Cells to Unprimed State. Epigenetics is a very cool field.

Kirk, Manchin, Collins Introduce REGROW ACT, which if passed would dangerously weaken FDA oversight of stem cells. Stay tuned for more on this bill later this week.

Knoepfler Lab 2015: Our mission and research

Knoepfler LabMany of this blog’s readers ask about my own lab’s research. What is the focus of the work in the Knoepfler Lab?

You can go check out our lab website, but I thought it might be time again to blog about what we are all about as a lab and what we have been up to most recently. I am fortunate to have an exceptional team of researchers in my lab.

Our mission is to advance knowledge toward two main goals: (1) the development of new, safe, and effective stem cell-based regenerative medicine therapies, and (2) catalyzing novel cancer therapies, particularly for childhood brain tumors and other pediatric neuronal cancers. Related to this, we are also investigating how the brain normally grows during development. In short, the research we do mainly converges towards the goal of advancing science to get new stem cell and cancer therapies off the ground. To this end we use innovative molecular, developmental, and cellular biological techniques as well as genetics and genomics approaches.

H3.3 testes

We are particularly interested in a field of science called epigenetics. We all know about the genome where our genes are coded, but the genome doesn’t do anything without the epigenome (global and specific epigenetic events), which consists primarily of DNA methylation and histone modifications. Each cell’s epigenomic state orchestrates the genes that are on and off, which in turn collectively controls how that cell behaves (e.g. how a stem cell stays a stem cell or differentiates) or in the case of cancer and other diseases, how it misbehaves. We recently published a review article on the connections between epigenetics, cancer, and stem cells.

As it turns out, stem cells and cancer cells are unfortunately highly related cell types, perhaps even cellular siblings. For example, we showed in a novel paper a couple years back that the process of cellular reprogramming to make iPS cells is in some ways remarkably similar to the process of turning normal cells into cancer cells. This paper has stirred quite a bit of discussion.

What else have we been up to lately?

Supported by NIH and Alex’s Lemonade Stand Foundation, we are working on three main areas and you can see these themes reflected in the list of our recent publications.

First, we have a long-standing interest in a cancer-related gene called MYC. Some have speculated that every human cancer in one way or another has some problem with MYC, usually too much of it. At the same time, however, Myc proteins are essential for normal stem cell function. As a result Myc ends up being quite the Dr. Jekyll and Mr. Hyde kind of character. As with any molecule or person for that matter, Myc does not act alone. Lately we’ve been getting more interested in a key cofactor of Myc called Miz-1.

Second, we are excited about a relatively newer area of epigenetic and chromatin research focused on a molecule called histone variant H3.3. Histones come in different forms and histone variants are cool and interesting because they don’t follow the normal rules for histones. Histone variants such as H3.3 can become part of chromatin (the combination of DNA and histones) basically any time in any kind of cells. For most histones their ability to do that is much more sharply constrained. This makes a variant such as H3.3 far more dynamic and important to decision-making processes by cells such as stem cells and cancer cells.

In the case of H3.3, two genes make the same identical H3.3 protein. We call these genes A and B, short, for H3f3a and H3f3b. In 2013 we reported in our Bush, et al. paper the phenotype of the first knockout of an H3.3-coding gene in mice with our knockout of the B gene. About half the time, mice lacking the B gene do not make it through development and have a host of problems including an inability to properly segregate their chromosomes during cell division that leads in turn  to DNA damage and apoptosis (cell death). The surviving B knockout mice are pretty much all infertile. It’s notable that mutations in H3.3 occur in humans and are strongly linked to childhood cancer. Last year we also published a review article in Cancer Cell on the H3.3-cancer connection, which involves two particularly disastrous tumors in children called glioblastoma and DIPG. We are excited about our new H3.3 paper on its function in germ cells, which I discuss in more depth here including its relevance for brain tumors. In the image above you can see H3.3 loss-of-function testes with unusual histone mark levels.

Third, we are studying two genes that also function in stem cells and cancer called DPPA4 and DPPA2. It is fascinating to think about how certain genes like these, H3.3, and Myc, can function normally in stem cells, but then with a monkey wrench in the system they can cause cancer. In the case of DPPA4 and DPPA2, they have long been known to be important stem cell genes, but it was only in 2013 that our lab discovered and published in the journal Stem Cells that they are also oncogenes. Surprisingly, it is still largely an open question how the Dppa4 and Dppa2 proteins actually work.

Overall one can see that we work at the interface of stem cells, cancer, and developmental tissue growth and investigate how epigenetic machinery orchestrates the regulatory events involved.

Finally, we are committed to educational outreach and advocacy for evidence-based innovative medical treatments and regenerative medicine therapies.

2015 Stem Cell Meetings, Conferences & Courses

Stem Cell Meetings 2015Below is a list of upcoming stem cell and regenerative medicine conferences and meetings in 2015.

If you do not see your meeting, please let me know and I will include it.

This list is meant to be as inclusive as possible, but by listing specific events I am not necessarily endorsing them.

Enjoy!

Genetic Engineering of Mammalian Stem Cells, Wellcome Trust, February 16-28, 2015, Hinxton, Cambridge, UK.

Gordon Research Conference: Stem Cells & Cancer. Exploring the Heterogeneity of Cancer Cells and Relevance to Therapy, Ventura, CA, February 14-15, 2015.

Keystone Heart Disease and Regeneration: Insights from Development, Copper Mountain, CO, March 1-6, 2015.

World Cord Blood Congress V and Innovative Cell Therapies, ESH Meeting, Monaco, March 5-8, 2015.

4th World Congress on Cell Science & Stem Cell Research, March 23-25, Chicago, USA.

Keystone Transcriptional and Epigenetic Influences on Stem Cell States (C9) Meeting, Steamboat Springs, CO, March 23-28, 2015.

Regenerative Medicine & Stem Cell 2015. Light the Hope of “Incurable” Diseases, Busan, Korea, March 23-25, 2015.

Frontiers in Stem Cells & Cancer, Heidelberg, Germany, March 29-31.

The Biology of Regenerative Medicines, Wellcome Trust, Hinxton, Cambridge, UK, April 22-24, 2015.

Stem Cell Summit 2015, Boston, MA, April 27-29, 2015

Regenerative Medicine Workshop at Hilton Head, Hilton Head Island, South Carolina, May 13-16, 2015.

World Stem Cells Regenerative Medicine Congress 2015, London, May 20-22, 2015.

Else Kröner-­Fresenius (EKF) Symposium on Adult Stem Cells in Aging, Diseases and Cancer, May 31-June 3, Erice/Sicily, Italy.

SelectBio Stem Cells in Drug Discovery, Cambridge, UK, June 2-3, 2015.

Stem cells: from basic research to bioprocessing, London, UK, June 9-11, 2015.

ISSCR 13th Annual Meeting, Stockholm, Sweden, June 24 –  27, 2015

The 2015 Tissue Engineering Congress, London, UK, September 8-10.

Cold Spring Harbor Stem Cell Biology Meeting, September 15-19, 2015, 

Stem Cell Epigenetics, Cell Symposia Meeting, Sitges, Spain, September 20-22.

Frontiers in Stem Cells and Regeneration. Woods Hole, MA September 27-October 3.

Stem Cell Meeting on the Mesa, La Jolla, CA October 7-9, 2015.

World Conference on Regenerative Medicine 2015, Leipzig, Germany, October 21-23, 2015