Crossing the Grad School Bridge of Self and Scientific Discovery

Since 2010, the CIRM Bridges Program has provided paid stem cell research internships to students at California colleges and universities that don’t have major stem cell research programs. In order to keep in touch with these interns, The Stem Cellar has an ongoing CIRM Scholars blog series, inviting alumni from our training programs to reflect on the importance of their internships, to update readers on their career path and to give career advice to the current interns.

The blog below, written by Mimi Krutein from the 2011 Bridges program at Cal State University San Marcos, is based on a presentation she gave in late July at the 2017 Annual CIRM Bridges Trainee Meeting in San Diego. 

Mimi Krutein

The science graduate school experience is not at all what I was expecting. I imagined it as a mentally stimulating flurry of discoveries and training; before I started I pictured a cross between Harry Potter and The Magic School Bus.  What I got, and what most graduate students get, is a vaguely escorted slog into a land of uncertainty and imposter syndrome, sprinkled with fleeting moments of clarity and excitement.  But don’t get me wrong; it is worth it.

My personal road to graduate school was quite unorthodox.  I entered California State University San Marcos (CSUSM) as a nursing major, because I had a genuine interest in medicine and was fascinated by the complexity of the human body.

 It also didn’t require calculus level math, so I was sold.
I generally enjoyed my courses but everything changed for me when I took microbiology.  It was my first introduction to basic science.  Disease mechanisms of microorganisms blew my mind, sparked my curiosity, and catalyzed a shift in focus that never readjusted.

It was then I decided to add a biology minor to feed the beast, but didn’t have the confidence to switch majors completely.  The pre-nursing program actually advised me not to add the minor; my grades at that point were good but not stellar, and they thought that the new load would be too difficult.  That summer I formally applied to the CSUSM nursing program and was rejected, missing the cutoff by one point.  Chalking it up to fate, I turned gracefully on my heels and belly flopped into a molecular biology major with open arms, calculus and all.

A few semesters passed and I desperately craved more lab time so I applied to 12 summer undergraduate research programs and was swiftly rejected due to lack of experience.  The only position I was offered was a 100-hour, unpaid internship at a tiny biotech composed of 5 people, where we utilized bioluminescent phytoplankton to monitor water toxicity.  Then I joined the only research lab at CSUSM with an opening, and under Dr. Betsy Read I studied the metabolic pathways of the model organism Emiliania huxleyi, also a phytoplankton.

As much as I loved the lab and industry training I was receiving, I wanted to integrate my fascination of human medicine with my passion for laboratory science.  Betsy pulled me into her office one day and asked the very obtuse question “what do you want to do in science?”  To her surprise –and slight disappointment I’m sure- I told her that I didn’t want to stay in phytoplankton, but rather explore medically relevant research, and study human disease.  Happily she lit up and frantically told me about the CIRM Bridges internship that would be perfect, the caveat being that applications were due that very day.  I received a 24-hour extension, and was later accepted for the 2011 program.

I was equal parts inspired and terrified
For my CIRM internship I joined Tobin Dickerson’s lab in the department of chemistry at The Scripps Research Institute.  I received excellent one-on-one training in a small lab studying highly infectious agents, primarily botulinum toxin.  Now, botulinum toxin has an extremely simple mechanism of action, however, it is also the most potent neurotoxin known to man.  Approximately 1 gram of aerosolized toxin can kill 1 million people; and the bacteria that produces it, Clostridium botulinum, is relatively easy to propagate, making it a potential bioterrorist agent.

iPSC-derived motor neurons. Image courtesey of Mimi Kreitin/The Scripps Research Institute

For this reason, The Department of Defense gave us a grant to pursue high-throughput screening of small molecule inhibitors that could block the effects of this toxin.  I assisted in the screening and follow up tests on individual inhibitors.  At the same time, I established a robust method for generating motor neurons from human embryonic and induced pluripotent stem cells.  This work provided us with a virtually endless pool of boltulinum-sensitive cells for the use of cellular studies with prospective inhibitors found in our initial screens.  Deriving the neurons from stem cells also eliminated the need for expensive and tiresome motor neuron harvests from animals.  The cells I produced in the lab presented as bonafide motor neurons because they produced an appropriate dose response to live toxin.

I finally felt like a real scientist
After my internship, I was formally hired by the lab as a part time technician while I finished my last year of classes as CSUSM.  My two years of work in the lab resulted in three publications, one of which was accepted for the cover of ACS Combinatorial Science.  More importantly though, the years I spent in the Dickerson lab provided room for me to grow into myself as a scientist, receive unparalleled training, and gain perspective on what it meant to be in the thick of academic research.

After many discussions with my peers and mentors, I decided graduate school, ideally a PhD track, was the next step for my scientific career.  I knew I loved research, but I wanted to learn how to think, how to approach unanswered questions in a productive manner.  I wanted to be trained by everyone who could provide me with knowledge.

I was just plain hungry.
And like most 20-somethings on the edge of graduation, my passion was mixed in equal parts with indecisiveness.  I really didn’t know what I wanted to study, but I knew I wanted to utilize my stem cell training, and I knew what made my mind light up; I was -and still am- fascinated by how diseases work on a cellular and molecular level.  So, after months of searching, digging, and crosschecking, I applied to a dozen translational research programs across the US.

And then the news arrived
While running late to a class, I got the acceptance email from my dream school; the University of Washington. After reading the subject line I was frozen with disbelief, I called my mom, forgot where I was going and took a stroll the other direction until I realized I had a test waiting for me.  It never occurred to me that I could actually do this for real.

My first day of grad school was one I will never forget.  After a lukewarm five minutes of awkwardly chatting with my new postdoc lab members, we go out to get coffee and I proceed to faceplant in the middle of a puddle-filled crosswalk directly in front of a truck.  I skinned my knee and sliced my hand open, but magically managed to keep my coffee upright.  Understandably, my newly acquired lab members didn’t let me touch anything of real importance for 2 weeks.  Even after being considered a ‘seasoned’ graduate student I still knock over racks of pipette tips or spill liters of E. coli cultures on my new jeans.  Such is the grad school life.  Part of me hopes once I earn those fancy three letters after my name, I’ll evolve to the perfect scientist, but I won’t bet on it.

To those of you considering graduate school
I’ll end with these parting thoughts. Obviously, I’m still not on the other end of this whole grad school thing, but I can tell you from the four years I’ve spent doing this so far, there has been no experience more rewarding and humbling than pursuing a PhD.  If you find yourself interested in taking the leap in a similar direction, know that if you choose this path, it’s a marathon, not a sprint so take care of yourself through the process.  Maintain a strong support system, both for your personal and professional well-being.  Foster relationships with your peers to gain strength in numbers and build mentorships with individuals you admire to perpetuate curiosity.  Choose your home lab thoughtfully; the Principal Investigator to Student dynamic is the cornerstone of the graduate school experience; you can’t be on different pages with the lab’s leader and expect to write the same story.

Imposter syndrome is the greatest barrier to your success
I spent 22 years wholeheartedly believing I couldn’t do the thing I’m currently doing, and I’ll tell you guys a secret, some days I still feel that way. But it’s vital to recognize that you are worthy of success and not defined by your failures.  Lastly, find humor where you can and stay hungry for opportunities that you believe are just outside of your reach. And stay hungry for knowledge, it’s one of few things that doesn’t expire.

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Don’t Be Afraid: High school stem cell researcher on inspiring girls to pursue STEM careers

As part of our CIRM scholar blog series, we’re featuring the research and career accomplishments of CIRM funded students.

Shannon Larsuel

Shannon Larsuel is a high school senior at Mayfield Senior School in Pasadena California. Last summer, she participated in Stanford’s CIRM SPARK high school internship program and did stem cell research in a lab that studies leukemia, a type of blood cancer. Shannon is passionate about helping people through research and medicine and wants to become a pediatric oncologist. She is also dedicated to inspiring young girls to pursue STEM (Science, Technology, Engineering, and Mathematics) careers through a group called the Stem Sisterhood.

I spoke with Shannon to learn more about her involvement in the Stem Sisterhood and her experience in the CIRM SPARK program. Her interview is below.


Q: What is the Stem Sisterhood and how did you get involved?

SL: The Stem Sisterhood is a blog. But for me, it’s more than a blog. It’s a collective of women and scientists that are working to inspire other young scientists who are girls to get involved in the STEM field. I think it’s a wonderful idea because girls are underrepresented in STEM fields, and I think that this needs to change.

I got involved in the Stem Sisterhood because my friend Bridget Garrity is the founder. This past summer when I was at Stanford, I saw that she was doing research at Caltech. I reconnected with her and we started talking about our summer experiences working in labs. Then she asked me if I wanted to be involved in the Stem Sisterhood and be one of the faces on her website. She took an archival photo of Albert Einstein with a group of other scientists that’s on display at Caltech and recreated it with a bunch of young women who were involved in the STEM field. So I said yes to being in the photo, and I’m also in the midst of writing a blog post about my experience at Stanford in the SPARK program.

Members of The Stem Sisterhood

Q: What does the Stem Sisterhood do?

SL: Members of the team go to elementary schools and girl scout troop events and speak about science and STEM to the young girls. The goal is to inspire them to become interested in science and to teach them about different aspects of science that maybe are not that well known.

The Stem Sisterhood is based in Los Angeles. The founder Bridget wants to expand the group, but so far, she has only done local events because she is a senior in high school. The Stem Sisterhood has an Instagram account in addition to their blog. The blog is really interesting and features interviews with women who are in science and STEM careers.

Q: How has the Stem Sisterhood impacted your life?

SL: It has inspired me to reach out to younger girls more about science. It’s something that I am passionate about, and I’d like to pursue a career in the medical field. This group has given me an outlet to share that passion with others and to hopefully change the face of the STEM world.

Q: How did you find out about the CIRM SPARK program?

SL: I knew I wanted to do a science program over the summer, but I wasn’t sure what type. I didn’t know if I wanted to do research or be in a hospital. I googled science programs for high school seniors, and I saw the one at Stanford University. It looked interesting and Stanford is obviously a great institution. Coming from LA, I was nervous that I wouldn’t be able to get in because the program had said it was mostly directed towards students living in the Bay Area. But I got in and I was thrilled. So that’s basically how I heard about it, because I googled and found it.

Q: What was your SPARK experience like?

SL: My program was incredible. I was a little bit nervous and scared going into it because I was the only high school student in my lab. As a high school junior going into senior year, I was worried about being the youngest, and I knew the least about the material that everyone in the lab was researching. But my fears were quickly put aside when I got to the lab. Everyone was kind and helpful, and they were always willing to answer my questions. Overall it was really amazing to have my first lab experience be at Stanford doing research that’s going to potentially change the world.

Shannon working in the lab at Stanford.

I was in a lab that was using stem cells to characterize a type of leukemia. The lab is hoping to study leukemia in vitro and in vivo and potentially create different treatments and cures from this research. It was so cool knowing that I was doing research that was potentially helping to save lives. I also learned how to work with stem cells which was really exciting. Stem cells are a new advancement in the science world, so being able to work with them was incredible to me. So many students will never have that opportunity, and being only 17 at the time, it was amazing that I was working with actual stem cells.

I also liked that the Stanford SPARK program allowed me to see other aspects of the medical world. We did outreach programs in the Stanford community and helped out at the blood drive where we recruited people for the bone marrow registry. I never really knew anything about the registry, but after learning about it, it really interested me. I actually signed up for it when I turned 18. We also met with patients and their families and heard their stories about how stem cell transplants changed their lives. That was so inspiring to me.

Going into the program, I was pretty sure I wanted to be a pediatric oncologist, but after the program, I knew for sure that’s what I wanted to do. I never thought about the research side of pediatric oncology, I only thought about the treatment of patients. So the SPARK program showed me what laboratory research is like, and now that’s something I want to incorporate into my career as a pediatric oncologist.

I learned so much in such a short time period. Through SPARK, I was also able to connect with so many incredible, inspired young people. The students in my program and I still have a group chat, and we text each other about college and what’s new with our lives. It’s nice knowing that there are so many great people out there who share my interests and who are going to change the world.

Stanford SPARK students.

Q: What was your favorite part of the SPARK program?

SL: Being in the lab every day was really incredible to me. It was my first research experience and I was in charge of a semi-independent project where I would do bacterial transformations on my own and run the gels. It was cool that I could do these experiments on my own. I also really loved the end of the summer poster session where all the students from the different SPARK programs came together to present their research. Being in the Stanford program, I only knew the Stanford students, but there were so many other awesome projects that the other SPARK students were doing. I really enjoyed being able to connect with those students as well and learn about their projects.

Q: Why do you want to pursue pediatric oncology?

SL: I’ve always been interested in the medical field but I’ve had a couple of experiences that really inspired me to become a doctor. My friend has a charity that raises money for Children’s Hospital Los Angeles. Every year, we deliver toys to the hospital. The first year I participated, we went to the hospital’s oncology unit and something about it stuck with me. There was one little boy who was getting his chemotherapy treatment. He was probably two years old and he really inspired to create more effective treatments for him and other children.

I also participated in the STEAM Inquiry program at my high school, where I spent two years reading tons of peer reviewed research on immunotherapy for pediatric cancer. Immunotherapy is something that really interests me. It makes sense that since cancer is usually caused by your body’s own mutations, we should be able to use the body’s immune system that normally regulates this to try and cure cancer. This program really inspired me to go into this field to learn more about how we can really tailor the immune system to fight cancer.

Q: What advice do you have for young girls interested in STEM.

SL: My advice is don’t be afraid. I think that sometimes girls are expected to be interested in less intellectual careers. This perception can strike fear into girls and make them think “I won’t be good enough. I’m not smart enough for this.” This kind of thinking is not good at all. So I would say don’t be afraid and be willing to put yourself out there. I know for me, sometimes it’s scary to try something and know you could fail. But that’s the best way to learn. Girls need to know that they are capable of doing anything and if they just try, they will be surprised with what they can do.

Life after SPARK: CIRM high school intern gets prestigious scholarship to Stanford

As part of our CIRM scholar blog series, we’re featuring the research and career accomplishments of CIRM funded students.

Ranya Odeh

Ranya Odeh

Meet Ranya Odeh. She is a senior at Sheldon high school in Elk Grove, California, and a 2016 CIRM SPARK intern. The SPARK program provides stem cell research internships to underprivileged high school students at leading research institutes in California.

This past summer, Ranya worked in Dr. Jan Nolta’s lab at UC Davis improving methods that turn mesenchymal stem cells into bone and fat cells. During her internship, Ranya did an excellent job of documenting her journey in the lab on Instagram and received a social media prize for her efforts.

Ranya is now a senior in high school and was recently accepted into Stanford University through the prestigious QuestBridge scholarship program. She credits the CIRM SPARK internship as one of the main reasons why she was awarded this scholarship, which will pay for all four years of her college.

I reached out to Ranya after I heard about her exciting news and asked her to share her story so that other high school students could learn from her experience and be inspired by her efforts.


How did you learn about the CIRM SPARK program?

At my high school, one of our assignments is to build a website for the Teen Biotech Challenge (TBC) program at UC Davis. I was a sophomore my first year in the program, and I didn’t feel passionate about my project and website. The year after, I saw that some of my friends had done the CIRM SPARK internship after they participated in the TBC program. They posted pictures about their internship on Instagram, and it looked like a really fun and interesting thing to do. So I decided to build another website (one that I was more excited about) in my junior year on synthetic biology. Then I entered my website in the TBC and got first prize in the Nanobiotechnology field. Because I was one of the winners, I got the SPARK internship.

What did you enjoy most about your SPARK experience?

For me, it was seeing that researchers aren’t just scientists in white lab coats. The Nolta lab (where I did my SPARK internship) had a lot of personality that I wasn’t really expecting. Working with stem cells was so cool but it was also nice to see at the same time that people in the lab would joke around and pull pranks on each other. It made me feel that if I wanted to have a future in research, which I do, it wouldn’t be doing all work all the time.

What was it like to do research for the first time?

Ranya taking care of her stem cells!

Ranya taking care of her stem cells!

The SPARK internship was my first introduction to research. During my first experiment, I remember I was changing media and I thought that I was throwing my cells away by mistake. So I freaked out, but then my mentor told me that I hadn’t and everything was ok. That was still a big deal and I learned a lesson to ask more questions and pay more attention to what I was doing.

Did the SPARK program help you when you applied to college?

Yes, I definitely feel like it did. I came into the internship wanting to be a pharmacist. But my research experience working with stem cells made me want to change my career path. Now I’m looking into a bioengineering degree, which has a research aspect to it and I’m excited for that. Having the SPARK internship on my college application definitely helped me out. I also got to have a letter of recommendation from Dr. Nolta, which I think played a big part as well.

Tell us about the scholarship you received!

I got the QuestBridge scholarship, which is a college match scholarship for low income, high achieving students. I found out about this program because my career counselor gave me a brochure. It’s actually a two-part scholarship. The first part was during my junior year of high school and that one didn’t involve a college acceptance. It was an award that included essay coaching and a conference that told you about the next step of the scholarship.

The second part during my senior year was called the national college match scholarship. It’s an application on its own that is basically like a college application. I submitted it and got selected as a finalist. After I was selected, they have partner colleges that offer full scholarships. You rank your choice of colleges and apply to them separately with a common application. If any of those colleges want to match you and agree to pay for all four years of your college, then you will get matched to your top choice. There’s a possibility that more than one college would want to match you, but you will only get matched with the one that you rank the highest. That was Stanford for me, and I am very happy about that.

Why did you pick Stanford as your top choice?

It’s the closest university to where I grew up that is very prestigious. It was also one of the only colleges I’ve visited. When I was walking around on campus, I felt I could see myself there as a student and with the Stanford community. Also, it will be really nice to be close to my family.

What do you do in your free time?

I don’t have a lot of free time because I’m in Academic Decathalon and I spend most of my time doing that. When I do have free time, I like to watch Netflix, blogs on YouTube, and I try to go to the gym [laughs].

Did you enjoy posting about your SPARK internship on Instagram?

I had a lot of fun posting pictures of me in the lab on Instagram. It was also nice during the summer to see other SPARK students in different programs talk about the same things. We shared jokes about micropipettes and culturing stem cells. It was really cool to see that you’re not the only one posting nerdy science pictures. I also felt a part of a larger community outside of the SPARK program. Even people at my school were seeing and commenting on what I was doing.

UC Davis CIRM SPARK program 2016

UC Davis CIRM SPARK program 2016

I also liked that I got feedback about what I was doing in the lab from other SPARK students. When I posted pictures during my internship, I talked about working with mesenchymal stem cells. Because we all post to the same #CIRMSPARKlab hashtag, I saw students from CalTech commenting that they worked with those stem cells too. That motivated me to work harder and accomplish more in my project. Instagram also helped me with my college application process. I saw that there were other students in the same position as me that were feeling stressed out. We also gave each other feedback on college essays and having advice about what I was doing really helped me out.

Do you think it’s important for students to be on social media?

Yes, I think it’s important with boundaries of course. There are probably some people who are on social media too often, and you should have a balance. But it’s nice to see what other students are doing to prepare for college and to let loose and catch up with your friends.

What advice would you give to younger high school students about pursuing science?

I feel like students can’t expect things to be brought to them. If they are interested in science, they need to take the initiative to find something that they are going to want to do. The CIRM internship was brought to my attention. But I have friends that were interested in medicine and they found their own internships and ways to learn more about what they wanted to do. So my advice is to take initiative and not be scared of rejection, because if you’re scared of rejection you’re not going to do anything.

To hear more about Ranya’s SPARK internship experience, read her blog “Here’s what you missed this summer on the show coats.” You can also follow her on Instagram and Twitter. For more information about the CIRM SPARK internship program, please visit the CIRM website.


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Science and Improv: Spotlight on CIRM Bridges Scholar Jill Tsai

As part of our CIRM scholar series, we’re featuring the research and career accomplishments of CIRM funded students.

What do science and improv have in common? The answer is not a whole lot. However, I recently met a talented student from our CIRM Bridges master’s program who one day is going to change this.

Jill Tsai

Jill Tsai, CIRM Bridges scholar

Meet Jill Tsai. She recently graduated from the CIRM Bridges program at the Scripps Research Institute in San Diego and is now starting a PhD program in cancer biology at the City of Hope in Duarte California.

Jill received her Bachelors from UC Merced general biology and went to Cal Poly Pomona for a Master’s program in cancer research. While at Cal Poly Pomona, she successfully applied for a CIRM Bridges internship that allowed her to finish her Master’s degree at Scripps in the lab of Dr. Lazzerini Denchi.

I met Jill at the 2016 Bridges Conference in July and was immediately impressed by her passion for science and communications. I was also intrigued by her interest in improv and how she balances her time between two very different passions. I’m thrilled that Jill agreed to an interview for the Stem Cellar as I think it’s valuable to read about scientists who are pursuing multiple passions not necessarily related to science.

Enjoy!

Q: What did you study during your Bridges internship?

JT: I was a research intern in the lab of Dr. Lazzerini Denchi. In his lab, we study telomeres, which are the pieces of DNA at the end of chromosomes that help protect them from being degraded. We’re specifically looking at proteins that help maintain telomere function in mouse stem cells. We do big protein pull downs to try to figure out what new and novel proteins are surrounding the mechanisms that maintain telomere function, and then we do functional assays to figure out what these proteins do.

Lazzerini Denchi’s lab focuses on basic research and how certain proteins affect telomere length and also the telomere deprotection response. One function of telomeres is that they suppress the double and single stranded DNA repair mechanism. If you don’t suppress those mechanisms, then the ends of those linear chromosomes look exactly like double stranded DNA breaks and repair proteins try to fix them by fusing those chromosomes together.

There are great pictures from Lazzerini Denchi’s first author publication showing chromosomes hooked end to end to end like long strings of spaghetti as a result of telomere deprotection. We are studying novel proteins that assist telomeres with the deprotection response and determining whether these proteins have some other kind of function as well.

Telomere deprotection results in chromosomes that are linked together (right) instead of separate (left). (Source Denchi et al. Nature)

Telomere deprotection results in chromosomes that are linked together (right) instead of separate (left). (Source Nature: Denchi et al., 2007)

Our larger focus in the lab is being able to understand cancer and specific telomere related genetic disorders that are associated with cancer.

Q: What was your CIRM Bridges experience like?

JT: CIRM was really amazing, and I credit it a lot for being able to start a PhD this fall. I’d been working in my lab at Cal Poly Pomona for five years, and my research unfortunately wasn’t working out. I was probably going to have to quit the program or take an out with an easier project. When I applied to CIRM, I was hoping to get the internship because if I didn’t get it, I was going to go down a completely different career path.

The CIRM internship was very valuable to me. It provided training through stem cell classes and lectures and allowed me to immerse myself in a real lab that had real equipment and personnel. The experience took my research knowledge to the next level and then some. And I knew for sure it had when I was at the poster session during the Bridges conference. I was walking around and asking students about their research, and I understood clearly the path of their research. I knew what questions were good to ask and what the graphs meant without having to take them home and dissect them. It was extremely satisfying to be able to understand other’s scientific research by just listening to them.

I am so excited to start my PhD in the fall. For the first time, I feel confident about my foundational biology and research skills. I also have a better understanding of myself and where I need to improve in comprehension and technique. I am ready to jump into grad school and improve as a scientist.

Q: What are your future career steps?

JT: I want to do something that involves teaching or being able to educate people. I’ve worked as a TA in my master’s program for a few years, and I really enjoy that experience of clarifying complex subjects for people. But to be honest, I also don’t know what I want to do right now so I’m keeping my options open.

Q: What’s your favorite thing about being scientist?

JT: Being a scientist forces you to never be complacent in what you understand. If I had never gotten my master’s, there would be this whole level of critical thinking that I wouldn’t have right now. Learning more is one of the biggest reasons why I want to get my PhD even if I don’t know exactly what I want to do yet.

I want to be able to think at a higher level because I think it’s valuable. And I see my Professor at Scripps: he has all these publications under his belt, but he’s always tinkering with things and he’s always learning new software and he’s always reading new papers. As a scientist, you can’t be stagnant in your learning, and I think because of that you’re always pushing yourself to your best potential.
Q: Do you have advice for future Bridges students?

JT: For anyone who is interested in doing a PhD, this is the world’s best preparatory program. After you start a PhD, you hit the ground running. If I were to give advice, I’d say to not be too hard on yourself. There’s going to be expectations put on you that you might not be ready for and you might not do the best job. But you should try your best and know it’s going to help you grow.

Usually people who go into PhD programs are people that have always done well in school. But it’s important to know that learning in grad school is very different than how we are taught to learn elsewhere. Every other time it’s just like show up, listen, take the test you’re done. A PhD relies on a little bit of luck, getting the right project, and doing everything meticulously.

Q: What are your hobbies?

JT: My favorite hobby is improv comedy. What I really like about improv is that it is so different from science and it helps me to relax after work.

Improv is performing comedic scenes on stage with a bunch of people without a script. Skills that it requires are not being stuck in your own head and really paying attention to what’s going on around you. You also need to take big risks and not worry so much about what the end result is going to be, which is very different from research. It’s a nice break to be able to make big giant mistakes and know that after that day it doesn’t matter.

As a researcher, it’s hard to make friends, and even if you have friends, it’s hard to find the time to hang out with them. I love improv because it’s a built in activity. All of my friends outside of work are in improv. We show up and we play make believe together on stage – it’s just a really nice atmosphere. In improv we teach a philosophy that everything you have is enough. Everything you come in with is enough. It’s really nice, because being an adult is hard and life is hard. So it’s a nice thing to hear.

Jill's Improv team.

Flyspace Improv team.

Q: Do you see yourself combining your passions for science and improve in the future?

JT: I do. I don’t know what I want to do yet as a career, but improv is such a big part of my identity that it will always play a role in my life. Improv is so important in communication and interpersonal connections. I believe everyone in science could benefit from it. Ideally, I will find a career that allows me to use both of these passions to help people.

CIRM Scholar Jessica Gluck on using stem cells to make biological pacemakers for the heart

As part of our CIRM scholar series, we feature the research accomplishments of students and postdocs that have received CIRM funding.

Jessica Gluck, CIRM Scholar

Jessica Gluck, CIRM Scholar

I’d like to introduce you to one of our CIRM Scholars, Jessica Gluck. She’s currently a Postdoctoral Fellow at UC Davis working on human stem cell models of heart development. Jessica began her education in textiles and materials science at North Carolina State University, but that developed into a passion for biomedical engineering and stem cell research, which she pursued during her PhD at UC Los Angeles. During her graduate research, Jessica developed 3D bio-scaffolds that help human stem cells differentiate into functioning heart cells.

We asked Jessica to discuss her latest foray in the fields of stem cells and heart development.


Q: What are you currently working on in the lab?

JG: I work as a postdoc at UC Davis in the lab of Deborah Lieu. She’s working on developing pacemaking cardiomyocytes (heart cells) from human induced pluripotent stem cells (iPS cells). Pacemaking cells are the cells of the heart that are in charge of rhythm and synchronicity. Currently, we’re able to take iPS cells and get them to a cardiomyocyte state, but we want to further develop them into a pacemaking cell.

So ultimately, we’re trying to make a biological pacemaker. We can figure out how we can make a cell become the cell that tells your heart to beat, and there’s two things we can get out of that. First, if we understand how we get these beating cells, the ones that are telling the other heart cells to beat, we might be able to understand how different heart diseases progress, and we might be able to come up with a new way to prevent or treat that disease. Second, if we understand how we’re getting these pacemaking cells, we could hopefully bioengineer a biological pacemaker so you wouldn’t necessarily need an electronic pacemaker. With a biological one, a patient wouldn’t have to go back to the doctor to have their battery replaced. And they wouldn’t have to have multiple follow up surgeries throughout their life.

Q: What models are you using to study these pacemaking cells?

JG: I’m looking at my project from two different directions. On one side, we’re using a pig model, and we’re isolating cells from the sinoatrial (SA) node, which is where the pacemaking cells actually reside in your heart. And there’s really not that many of these cells. You probably have about a billion cells in your heart, but there’s maybe 100,000 of these pacemaking cells that are actually controlling the uniform beating of the heart. So we’re looking at the native SA node in the pig heart to see if it’s structurally any different than ventrical or atrial heart tissue.

Diagram of the heart depicting the Sinoatrial Node. (Image from Texas Heart Institute.

Diagram of the heart depicting the Sinoatrial Node. (Image from Texas Heart Institute)

We’ve found that the SA node is definitely different. So we’re de-cellularizing that tissue (removing the cells but not the matrix, or support structure, that keeps them in place) thinking that we could use the native matrix as a scaffold to help guide these heart cells to become the pacemaking phenotype. On the other side, we’re taking dishes with a known elasticity and we’re coating them with different proteins to see if we can tease out if there’s something that an individual protein does or a certain stiffness that actually is part of the driving force of making a pacemaking cell. We’ve gotten some pretty good preliminary results. So hopefully the next phase will be seeing how functional the cells are after they’ve been on these de-cellularized matrices.

Q: Why does your lab work with pig models?

JG: Pig hearts are pretty close to the human heart – their anatomy is pretty similar. To give you context, a pig heart is slightly larger than the size of your two hands clasped together. But the SA node, when you isolate it out, is only a couple of millimeters squared. It’s a lot smaller than we originally thought, and if we had gone with a smaller animal model, we wouldn’t be able to tangibly study or manipulate the SA node area. Because we are at UC Davis, we have a Meat Lab on campus, and we are able to get the pig hearts from them.

Q: Have you run into any road blocks with your research?

JG: For anybody that’s working with cardiomyocytes, the biggest problem is getting stem cells to become mature cardiomyocytes. Some labs have shown that you can get cells to a more mature cardiomyocyte after it’s been in culture for almost 100 days, but that’s not exactly feasible or that helpful.

We’ve been able to isolate out a small population of cells that we’re pretty sure are pacemaking cells. Over the last year, we’ve realized that a lot of the information that we thought we knew about pacemaking cells isn’t necessarily specific to pacemaking cells. Many of the biological markers that people have published in the literature are present in pacemaking cells, but we realized that they are also present in other heart cells like atrial cells, just in a lower amount. So we haven’t really been able to pick one specific biomarker that we’ve been able to say, yes this is actually a pacemaking cell. Instead, we have a small percentage of cells that we’re able to study. But we’re trying to figure out if there’s a way that we could increase our yield, or if there’s something fundamentally different about the environment that would also increase the yield of these pacemaking cells. So we’ve had a lot of trouble shooting along the way.

Q: What was your experience like as a CIRM scholar?

JG: I became a CIRM scholar in the spring of 2014. It was through the UC Davis Stem Cell Training Program. The opportunity was very helpful for me because it was in my first year as a postdoc at Davis. I earned my PhD at UCLA, so I was dealing with being on a new campus, trying to figure out whose lab I could go to to borrow random things and where to find equipment that I needed to use. So it was helpful to be around a group of other people that were also doing stem cell projects. Even though a lot of us were focused on different areas, it was still helpful to talk to other people, especially if you get somebody’s perspective that isn’t necessarily in your field. They might come up with a random idea that you haven’t thought of before.

Over the course of the year, we had a journal club, which was always interesting to see what’s going on in the field. I also went to the annual International Society for Stem Cell Research meeting in Vancouver using CIRM funding. And as part of the program, we also worked with the CIRM Bridges program between UC Davis and Cal State Sacramento. There were Bridges master’s students that were there with us. It was interesting to hear their take on everything, and they were very enthusiastic. We have had two master’s students work in our lab. I think it was very beneficial to them because they got a lot of hands on training and both have gone on to jobs in the regenerative medicine field.

Q: What is the future of stem cell research?

JG: If you’re looking at heart disease and stem cell treatments, there’s been some interesting clinical trials that have come out that have some promising results. I think that for a couple of those studies, people might have jumped the gun a little getting the treatments into the clinic. There’s still a lot that people should study in the lab before we move on to clinical trials. But I do think that we will see something in the next 20 years where stem cell research is going to have a huge therapeutic benefit. The field is just moving so quickly, and I think it will be really interesting to see what advances are made.

For our research, I’ve always been fairly realistic, and unfortunately, I don’t think we will see this biological pacemaker any time soon. But I think that the research that we produce along the way will be very beneficial to the field and our work will hopefully improve the foundation of what is known about pacemaking cells. What I think is really interesting about our lab’s work, is that we are moving into a 3D culture environment. Cells behave very differently in the body as opposed to on a plastic petri dish. So I think it’s very encouraging that we are seeing a lot more labs moving towards a more physiologically relevant model.

Q: What are your future goals?

I’ve been lucky that I’ve been able to work with very well established professors and also brand new faculty. But I’ve seen how difficult the funding climate is – it’s very daunting. So I’m really not sure what will happen next, and I’m keeping my options open.

I’ve really enjoyed working with our undergraduate and graduate students. I’ve gotten involved with outreach programs in Sacramento that promote science to young kids. It’s something that I’ve really enjoyed, and it’s very interesting telling people that I work in stem cells. Middle school kids seem to think that stem cells are magic. It’s fun to explain the very basics of stem cells and to see the light bulb moment where they understand it. I’m hoping to end up in a career that is still within the stem cell field but more towards teaching or outreach programs.

Q: What is your favorite thing about being a scientist?

JG: The thing I really like is having a puzzle that you’re trying to figure out the answer to. It’s great because every time you answer one question, that answer is going to lead you to at least three or four more new questions. I think that that’s really interesting especially trying to figure out how all the puzzle pieces fit together, and I’ve really enjoyed getting to work with people in very different fields. My parents think its funny because they said even as a little kid, I hated not knowing the answers to questions – and still do! They were completely understanding as to why I stayed in school as long as I did.

You can learn more about Jessica’s research by following her on Twitter: @JessicaGluckPhD

CIRM Scholar Spotlight: Berkeley’s Maroof Adil on stem cell transplants for Parkinson’s disease

Maroof Adil, CIRM Scholar

Maroof Adil, CIRM Scholar

Stem cell therapy has a lot of potential for Parkinson’s patients and the scientists that study it. One of our very own CIRM scholars, Maroof Adil, is making it his mission to develop stem cell based therapies to treat brain degenerating diseases like Parkinson’s.

Maroof got his undergraduate degrees from MIT in both Chemical Engineering and Biology, and a PhD in Chemical Engineering from the University of Minnesota. As a graduate student, he dived into the world of cancer research and explored ways of delivering cancer-killing genes specifically to cancer cells in the body while leaving healthy tissues in the body unharmed.

While he enjoyed his time spent on cancer research, he realized his main interest was to apply his skills in chemical engineering and materials science to understand biological problems. This brought him to his current position as a postdoc at UC Berkeley in the Schaffer lab.

Maroof is doing some pretty cutting edge research to develop 3D biomaterials that will vastly improve the transplantation and survival of stem cell derived neurons (nerve cells) in the brain. Check out our exclusive interview with this talented scientist below!


Q: What are you working on and why?

MA: I have always been excited about finding engineering solutions to medically relevant problems. I decided to do a postdoc at UC Berkeley in David Schaffer’s lab because I wanted to combine chemical and materials engineering skills from my graduate research with stem cell technologies to solve biological problems. One of the exciting parts of Dave’s lab, and a reason why I joined, is that he is working on translational stem cell-based regenerative therapies for central nervous system diseases such as Parkinson’s and Huntington’s.

My current research is motivated by the need to find better therapies for these neurodegenerative diseases. While stem cell-based regenerative medicine is an up-and-coming field, there are still a lot of challenges that need to be addressed before stem cells can be successfully used in the clinic. There are three main challenges that are most relevant to my research. First, we need to improve the efficiency of stem cell differentiation, i.e. how well we can convert these stem cells to the mature, functional neurons that we need to treat neurodegenerative diseases. Second, after implanting these cells into the body, we need to increase their survival efficiency. This is because one of the main issues with stem cell-based transplants right now is that after implantation, most of these cells die. Given these first two challenges, we need to generate a lot of cells in order to effectively treat degenerative diseases. The third challenge is to make good quality, functional, transplantable cells in a large-scale fashion.

So given my chemical and materials engineering background, I wanted to see if we could use biologically inspired materials (biomaterials) to address some of these issues with stem cell differentiation and transplantation. In brief, we are developing functionalized biomaterials, differentiating stem cells within these biomaterials into neurons, characterizing the quality of these neurons, and testing the function of these stem cell-derived neurons in animal models of disease.

A major focus of our lab is to develop 3D biomaterials to increase the efficiency of large-scale production of clinical-grade stem cells [and the mature cells that are derived from them]. Our preliminary results suggest that we can get higher numbers of better quality neurons when we differentiate and grow them in 3D biomaterials compared to when they are traditionally grown on a flat, 2D tissue culture surface. Presently, I’m trying to verify that our 3D method works in the lab. If it does, this technology could help us save a lot of time and resources in generating the type of cells we need for effective cell replacement therapies.

Stem cells growing as clusters in 3D[1]Neurons generated in 3D platforms 1[1]

Stem cell derived neurons grown in 3D cultures (left) and generated on 3D biomaterials (right). Images courtesy of Maroof Adil.

Q: Your research sounds fascinating but complicated. How are you doing it?

MA: It’s certainly a multidisciplinary project, and constantly requires us to draw ideas from diverse fields including polymer chemistry, developmental biology and chemical engineering. I am very grateful to be part of a resourceful lab, to my mentors, and to have amazing, motivated people working with me. UC Berkeley provides a highly collaborative work environment. So for some of the follow-up work that further characterizes the quality of these stem cells and their mature cell derivatives, we are collaborating with other labs at UC Berkeley and at UCSF.

Q: Are you interested in applying this work to other brain diseases?

MA: Certainly. Although we are primarily working on generating stem cell-derived dopaminergic neurons, which are the major cell type that die in Parkinson’s patients, I’m also interested in applying similar biomaterials to derive other types of neurons, for instance medium spiny neurons for Huntington’s disease.

The advantage of some of the materials we are working with is their modular nature. That is, we can tune their properties so that they are useful for other applications.

Q: In your opinion what is the future of stem cells in your field? Will they bring cures?

MA: I am very hopeful given what I’m seeing right now in the scientific literature, and in clinical trials for stem cell-based therapies in general. Right now, there are several trials that are testing the benefit and safety of stem cell-based transplants in different diseases. However, right now there are no clinical trials applying stem cell-derived neurons to treat brain diseases. But I think there’s certainly a lot of promise. There are challenges that we need to address in this field, and some of these I outlined earlier. Researchers are working on finding solutions to these problems, and I think that if we find them, the chances of successfully finding cures will be higher.

Q: Tell us about your experience as a CIRM Scholar.

MA: I started as a CIRM scholar in 2014. It was really great to have a source of funding that lined up with what I was interested in, which was doing translational work in regenerative medicine.

I first began working with stem cells when I started my postdoc career, but I didn’t really have a background in this area. So being new to the stem cell field, I felt that CIRM provided the support structure that I needed. And I’m not just referring to funding. CIRM brings scientists with different scientific backgrounds together in one place, where we can learn from one another, and initiate fruitful collaborations. Being a CIRM scholar makes me feel like I’m part of a bigger community, with other scientists conducting very different, but related stem cell research.

Also, I am a big fan of the CIRM blog. I am able to learn about patients and about other researcher’s backgrounds. It helps you realize that patients and researchers are part of the same field. And I like that concept of bringing the field closer: patients towards researchers and researchers towards patients. I think that is useful to boost motivation for researchers, and to give patients a better idea of what we do.

Through CIRM, we’ve had a chance to go out into the local community and present some of our research. For example, the past two years I’ve talked to local high school students during Stem Cell Awareness Week, and that was a really great experience.  I’ve presented to other professionals before, but never to those as young as high school students.  To me, it was quite exciting to realize that these kids are very much interested in the type of work we are doing, and to feel like I was able to influence them to potentially pursue science as a career.

Q: What are your career goals?

MA: I definitely want to stay in science and solve medically relevant problems. It could be nice to be faculty at a research university and in a position to pursue my own independent ideas at the interface of biomaterials and stem cell based therapies. An industry position working towards regenerative medicine or other biologically relevant applications is also an exciting possibility. At this point, being in science is my priority.

Q: What’s your favorite thing about being a scientist?

MA: The excitement you get when your experiments work out, and the joy of making new discoveries. I also like the thrill of designing experiments that may advance the field, and the feeling that what you’re doing day-to-day is contributing to a body of knowledge that others may find useful. I find it especially rewarding to be a scientist in the medical field, working on translational projects closely related to finding cures for diseases.

CIRM Scholar Helen Fong on Stem Cells and Brain Disease

Helen Fong, CIRM Scholar and Research Scientist at the Gladstone Institutes

Helen Fong, CIRM Scholar and Research Scientist at the Gladstone Institutes

Meet another one of our talented CIRM Scholars, Helen Fong. She is currently a Research Scientist at the Gladstone Institutes and did her graduate work at the University of California, Irvine. Her passions include stem cells, disease modeling, and playing with differentiation protocols – the processes that tell stem cells to mature into specific tissues. As a CIRM Scholar, part of our educational training programs, Helen published four articles where she was listed as the first author. Her most recent one was a stellar study published in Stem Cell Reports using induced pluripotent stem cells (iPSCs) to model and understand a nerve cell-destroying brain disease called frontotemporal dementia.

We interviewed Helen to learn more about her work in stem cell research.


Q: What was your graduate school research on?

HF: I did my graduate work in the lab of Dr. Peter Donovan, who is a prominent germ cell and stem cell scientist, and was newly recruited to UCI when I began my studies. I was his first graduate student from UCI. Dr. Donovan’s research was focused on understanding the regulation of early human development using embryonic stem cells (ESCs) and how to improve human pluripotent stem cell culture. He was also interested in understanding the biological mechanisms that keep stem cells pluripotent (the ability to become all the other cell types in the body) and the genetic factors that are important for maintaining pluripotency. My graduate research was on understanding the basic biology of human ESCs. Specifically, I studied the role of the gene Sox2 in maintaining stem cell pluripotency and self renewal in human ESCs.

Q: What about your postdoctoral research?

HF: After my PhD, I decided to continue to work with stem cells because I knew that the field would continue to grow. There was still so much to be learned about these unique cells. I also genuinely enjoyed working with stem cells and couldn’t imagine not seeing them every day. I realized that I had a solid understanding of the basic biology of ESCs, but I wanted to use stem cells to study human disease. This ability is one of the huge selling points of working with human induced pluripotent stem cells (iPSCs) [which are created by reprogramming adult cells back to a pluripotent state]. The Gladstone Institutes was an excellent place to continue my training and to begin using iPSCs to understand neurological disease. I joined Dr. Yadong Huang’s lab in 2011 and am currently using human iPSCs to study brain degenerative diseases including frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), and Alzheimer’s disease (AD).

My recent publication in Stem Cell Reports used human iPSCs from a patient with FTD as a model to understand the mechanisms behind this condition. This patient carried a rare genetic mutation in the MAPT gene called TAU-A152T. Several studies have reported a number of patients with this specific mutation that could put them at risk for developing FTD, PSP, and AD. However, it wasn’t clear what this mutation was doing to cause these disorders.

One of the ways you can study neurodegenerative diseases is using stem cells derived from patients harboring the disease causing mutations. We obtained human iPSCs made from the skin cells of a patient with FTD and this TAU mutation. I then used zinc finger nuclease (ZFN) genome editing technology to genetically correct the mutation back to the wild type (normal) sequence to see if removing this mutation in the patient iPSCs would generate healthier neurons (nerve cells) that don’t have symptoms of FTD. I was able to study the disease-causing effects of the TAU mutation by comparing healthy neurons I made from the corrected (normal) iPSC line to diseased neurons made from the TAU mutant iPSC line.

Neurons generated from FTD patient iPSCs. (Image courtesy of Helen Fong)

Neurons generated from FTD patient iPSCs. (Image courtesy of Helen Fong)

The neurons that I differentiated from the iPSCs carrying the TAU mutation showed an increase in TAU protein fragmentation [meaning the protein gets degraded and isn’t present in its normal form], an abnormal characteristic that can be associated with FTD and AD. We didn’t see this phenomenon in the neurons from the corrected (normal) human iPSCs, indicating that removal of this TAU mutation could improve the symptoms of these diseases. These results were exciting because we now had a culprit for what could be causing disease in these patients with this mutation. There is still much to be learned about the mechanisms of this mutation and the iPSCs have been an invaluable resource.

Q: What was your experience like as a CIRM scholar?

HF: CIRM has funded me for almost all of my stem cell training and research. I got my first CIRM training grant as a graduate student at UCI in 2006 and was funded for three years as a postdoc at the Gladstone. So I have CIRM to thank for all of my training.

When I first started out as a CIRM scholar, I believe I was part of one of their earlier pre-doctoral training grant programs. As the program expanded, I got to meet many of the other trainees at CIRM research conferences and interact with prominent stem cell scientists in the area. This was an incredible experience because I was exposed to stem cell research outside of my own institute, and I was able to meet all the big players in the field!

CIRM has also been very generous and provided me a travel allowance to attend any scientific conference of my choice. Over the years, I’ve gone to a lot of conferences nationally and internationally including ISSCR (International Society for Stem Cell Research), Keystone symposia, and the Society for Neuroscience (SfN). I have given scientific talks both at Keystone and SfN, and they proved to be excellent exposure for my work as well as a good place to get feedback. Another one of my favorite perks was the ability to purchase reagents for my own work at my own discretion, which gave me some freedom in dictating which direction I wanted my project to go. If I wanted to study a particular protein and needed a specific antibody to do that, I was able to get it with my CIRM funding.

Q: What’s next for your career?

HF: Currently, I am hoping to wrap up the project I am working on in the lab right now and generate a publication. I plan to continue to work on stem cells in the next step of my career and to work on challenging and cutting-edge projects. I feel fortunate for all the training and resources that I’ve received that got me to where I am today, and I hope to pass on many of my skills and knowledge to budding, young scientists.

Q: What is your favorite thing about being a scientist?

HF: I really enjoy the fact that I have so much control over the fate of my stem cells. They have the ability to turn into almost any cell type, and we’ve developed so many protocols to guide them into the exact cell type we want. They don’t always behave, but I think figuring out the personality of each and every cell line is part of the fun.


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CIRM scholar Ke Wei talks heart regeneration

Ke Wei

Ke Wei

“How do you mend a broken heart?” was the topic of one of our recent Stem Cellar blogs highlighting a stellar CIRM-funded publication on the regenerative abilities of the protein FSTL1 following heart injury. One of the master-minds behind this study is co-first author Ke Wei. Ke is a postdoc in Dr. Mark Mercola’s lab at the Sanford Burnham Prebys Medical Discovery Institute located in balmy southern California. He also happens to be one of our prized CIRM scholars.

KeWeipatch

Cross sections of a healthy (control) or injured mouse heart. Injured hearts treated with patches containing FSTL1 show the most recovery of healthy heart tissue (red). Image adapted from Wei et al. 2015)

Upon hearing of Ke’s important and exciting accomplishments in the field of regenerative medicine for heart disease, we called him up to learn more about his scientific accomplishments and aspirations.

Q: Tell us about your research background and how you got into this field?

KW: I went to UCLA for my graduate school PhD, and I studied under Dr. Fabian Chen focusing on heart development. At that time, I mainly worked on very early heart development and other tissues like smooth muscle cells. For my graduate thesis work, I found that particular genes were important for smooth muscle development.

So I was trained as a heart developmental biologist, but after my PhD, I came to the Burnham Institute and I joined two labs: Dr. Mark Mercola and Dr. Pilar Ruiz-Lozano. They co-mentored me for the first couple of years of my postdoc. Mark is interested in using stem cells and high throughput screens to identify pharmaceutical compounds for inducing heart regeneration and treating heart diseases. Pilar is interested in the epicardium, the outer layer of the heart, which is known to play important roles during heart development. When I joined their labs, they had combined forces to study how the epicardium affects heart development and heart diseases.

In their labs, I used my developmental biologist background to combine in vitro stem cells based screening studies (Mark) and in vivo mouse embryonic heart development studies (Pilar) to dissect the function of the epicardium on heart development and disease.

Q: Tell us about your experience as a CIRM scholar and what you were able to accomplish.

KW: My two years of CIRM fellowship were separated but my focus was the same for both CIRM-funded periods: to understand the effect of the epicardium on heart development and diseases.

In my first project in 2008, we tried to generate an in vitro model of mouse epicardial cells and used those cells to study their influence on cardiac differentiation using both in vitro and in vivo experiments. We ran into a lot of technical difficulties, so at that time, we decided to switch to using existing in vitro epicardial cell lines, and using those to study their influence on cardiomyocytes (heart muscle cells).

In my second year of CIRM funding in 2011, we identified the genes and proteins that can promote immature cardiomyocytes to proliferate, and put them in vivo and it worked. So the success of our publication all started from my second year of CIRM-fellowship.

Q: What benefits did you experience as a CIRM scholar?

KW: I’ve really enjoyed being a CIRM scholar and took advantage of the resources they provided me over the years. One of the benefits I enjoyed the most was attending the CIRM annual meetings and retreats. I was able to talk with a lot of scientists with different backgrounds, and that really expanded my horizons.

As you can see from our paper in Nature, it’s definitely not only a developmental biologist paper. It’s actually very clinical and collaborative, and it was done by many different groups working together. By going to CIRM conferences and meeting all the other CIRM fellows, I got a lot of new ideas, and those ideas encouraged me to collaborate with more scientists. These events really encouraged me to look beyond the thoughts of a developmental biologist.

Our paper is co-authored by me and Vahid Serpooshan from Stanford. We co-first authored this paper, and my work mainly involved the in vitro studies that identified the regenerative proteins and their function in heart injury. Vahid’s approach was more bioengineering focused. He produced the FSTL1 patch, put it in the rodent heart, and conducted all the other in vivo studies. It was a perfect collaboration to push this project for publication in a high level journal like Nature.

Q: What is the big picture of your research and your future goals?

KW: I plan to stay in academia. The key thing about heart diseases is that heart regeneration is very limited. Using our approach, we found one particular protein that’s important to the regenerative process, and in reality, its concentration is very low in the heart when it’s infarcted (injured). I think we have set up a pretty good system to test all possible therapeutic means in the lab, including proteins from the epicardium, small molecules, microRNAs and other compounds to activate cardiomyocyte proliferation. I plan to focus on understanding the mechanisms for why cardiomyocytes stop proliferating in the adult heart, and what new approaches we can pursue to promote their expansion and regenerative abilities. The FSTL1 story is the start of this, and I will try to find new factors that can promote heart regeneration.

Q: Will your work involve human stem cell models?

KW: To make this study clinically relevant, we included the swine models. We are definitely testing FSTL1 in human cells right now. Currently we can produce a huge amount of the human cardiomyocytes. They seem to be at a different stage than rodent cells so we are optimizing the system to perform screens for human cell proliferation. When that system is set up, then anything that comes out of the screen will be much more relevant to clinical studies in humans.

Q: What is your favorite thing about being a scientist?

Knowing that the information I acquire through experiments is new to mankind, and that my actions expand the horizon of combined human knowledge, even just for a tiny bit, is a huge satisfaction to me as a scientist.

CIRM Scholar Spotlight: Matt Donne on Lung Stem Cells

CIRM has funded a number of educational and research training programs over the past ten years to give younger students and graduate/postdoc scholars the opportunity to explore stem cell science.

Two of the main programs we support are the Bridges and the CIRM Scholars Training Program. These programs fund future scientists from an undergraduate to postdoctoral level with a goal of creating “training programs that will significantly enhance the technical skills, knowledge, and experience of a diverse cohort of… trainees in the development of stem cell based therapies.”

The Stem Cellar team was interested to hear from Bridges and CIRM scholars themselves about their experience with these programs, how their careers have benefited from CIRM funding, and what research accomplishments they have under their belt. We were able to track some of these scholars down, and will be publishing a series of interview-style blogs featuring them over the next few months.

Matt Donne

Matt Donne

We start off with a Matt Donne, a PhD student at the University of California, San Francisco (UCSF) in the Developmental and Stem Cell Biology graduate program. Matt is a talented scientist and has a pretty cool story about his research training path. I sat down with Matt to ask him a few questions.


Q: Tell us how you got into a Stem Cell graduate program at UCSF.

MD: I was fortunate to have Dr. Carmen Domingo from San Francisco State support my application into the CIRM Bridges Program. I’d been working for Dr. Susan Fisher at UCSF for a couple of years and realized that I wanted to get a PhD and go to UCSF. I thought the best way to do that was improve my GPA and get a masters degree in stem cell biology. I applied to the CIRM program at SF State, and was accepted.

The Bridges Program has been a great feeder platform to get students more science experience exposure than they would have otherwise received, and prepares them well to move on to competitive graduate schools.

After receiving my Masters degree, I was admitted into the first year of the Developmental and Stem Cell Biology program at UCSF. When the opportunity to apply for a training grant from CIRM came about between my first and second year of at UCSF, I knew I had to give it a chance and apply. With the help of my mentor, Dr. Jason Rock, I wrote a solid proposal and was awarded the fellowship.

While at SF State, Carmen was extremely supportive and always available for her students. Since then, many of us still keep in touch and more have joined the UCSF graduate school community.

Q: Can you describe your graduate research?

MD: The field of regenerative medicine is searching for ways to allow us to repair injuries similar to how the Marvel Comic Wolverine can repair his wounds in the movies. One interesting fact which has been known for several decades, but has not been able to be investigated more deeply until now, is the innate ability for the adult lung to regrow lost lung tissue without any sort of intervention. My thesis focuses on defining the molecular mechanisms and stem cell niches that allow for this normal, healthy adult lung tissue growth. The working hypothesis is if we can understand what makes a cell undergo healthy tissue proliferation and differentiation, we could stimulate this response to cure individuals who suffer from diseases such as chronic obstructive pulmonary disease (COPD). Similarly, if we understand how a cell decides to respond in a diseased way, we could stop or revert the disease process from occurring.

One of the models we use in our lab is a “pneumosphere” culture. We essentially grow alveoli, which are the site of gas exchange in the lung, in a dish to attempt to understand how specific alveolar stem cells signal and interact with one another. This information will teach us how these cells behave so we can in turn either promote a healthy response to injury or, potentially, stop the progression of unhealthy cell responses. The technique of growing alveoli in a dish allows us to cut down on the “noise” and focus on major cellular pathways, which we can then more selectively apply to our mouse model systems.

Pneumospheres. (Photo by Matt Donne)

Pneumospheres or “lung cells in a dish”. (Photo by Matt Donne)

Lung cells.

Lung pneumospheres under a microscope. (Photo by Matt Donne)

We are now in the process of submitting a paper demonstrating some of the molecular players that are involved in this regenerative lung response. Hopefully the reviewers will think our paper is as awesome we as believe it to be.

Q: How has being a CIRM scholar benefited your graduate research career?

MD: Starting in my second year at UCSF, I was awarded the CIRM fellowship. I think it helped the lab to have the majority of my stipend covered through the CIRM fellowship, and personally I was very excited about the $5,000 discretionary budget. These monies allowed me to go to conferences every year for the past three years, and also have helped to support the costs of my experiments.

The first conference I attended was a Gordon Conference in Italy on Developmental Biology. There I was able to learn more about the field and also make friends with many professors, students, and postdocs from around the world. Last year, I went to my first lung-specific conference, and attended again this year. That has been one of the highlights of my PhD career. While there, one is able to speak and interact with professors whose names are seen in many textbooks and published papers. I never thought I would be able to so casually interact with them and develop relationships. Since then, I have been able to work on small collaborations with professors from across the US.

It was great that I could go to these conferences and establish important relationships with professors without being a major financial burden to my Professor. Plus, it has been hugely beneficial for my career as I now have professors whom I can reach out to as I look towards my future as a scientist.

Q: What other benefits did the CIRM scholars program provide you?

MD: Dr. Susan Fisher has been in charge of the CIRM program at UCSF. She organized lunch-time research talks that involved both academic as well as non-academic leaders in the field. I enjoyed the extra exposure to new fields of stem cell biology as well as the ability to learn more about the start-up and non-academic world. There are not many programs that offer this type of experience, and I felt fortunate to be a part of it. Also, the free lunches on occasion were a nice perk for a grad student living in San Francisco!

I attended the CIRM organized conferences whenever they happened. It’s always great presenting at or attending poster sessions at these events, seeing familiar faces and meeting new people. I took full advantage of the learning and networking that CIRM allowed me to do. The CIRM elevator pitch competition was really cool too. I didn’t win, came in third, but I enjoyed the challenge of trying to break down my thesis project into a digestible one-minute pitch.

Q: Where do you see the field of lung biology and regenerative medicine heading?

MD: My take away from the research conferences I have attended with the help of CIRM-funding is that we are in a very exciting time for lung stem cell research. The field overall is still young, but there are many labs across the world now working on a “lung mapping project” to better define stem cell populations in the lung. I see this research in the future translating in to regenerative therapies by which diseased cells/tissue will be targeted to actually stop the disease progression, and in turn possibly repair and regenerate healthy new tissue. This research has wide reaching implications as it has the potential to help everyone from a premature baby more quickly develop mature healthy lungs, to adults suffering from COPD brought on by environmental factors, such as air pollution. As many scientists are often quoted, “This is a very exciting time for our field.”

Q: What are your future plans?

MD: I expect to graduate in about a year’s time. In the future, I want to pursue a career focusing on the social impact of science. I aspire to be someone like UCSF’s former chancellor Dr. Susan Desmond-Hellmand. It’s really cool to go from someone who was the president of product development at Genentech, to chancellor at UCSF, to now president of the Bill and Melinda Gates Foundation. Bringing science to impact society in that way is what I hope to do with my future.


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