Stem cell summer: high school students document internships via social media, Part 2

Well, just like that, summer vacation is over. Most kids in California are back in school now and probably one of the first questions they’ll ask their friends is, “what did you do this summer?”. For 58 talented high school students, their answer will be, “I became a stem cell scientist.”

Best Instagram Post Award: Mia Grossman

Those students participated in a CIRM-funded internship called the Summer Program to Accelerate Regenerative medicine Knowledge, or SPARK for short, with seven programs throughout Northern and Southern California which include Caltech, Cedars-Sinai, City of Hope, Stanford, UC Davis, UCSF and the UCSF Benioff Children’s Hospital Oakland. Over the course of about 8 eight weeks, the interns gained hands-on training in stem cell research at some of the leading research institutes in California. Last week, they all met for the annual SPARK conference, this year at the UC Davis Betty Irene Moore School of Nursing, to present their research results and to hear from expert scientists and patient advocates.

As part of their curriculum, the students were asked to write a blog and to post Instagram photos (follow #cirmsparklab) to document their internship experiences. Several CIRM team member selected their favorite entries and presented awards to the winning interns at the end of the conference. We featured two of the winners in a blog from last week.

Our two winners featured today are Cedars-Sinai SPARK student, Mia Grossman – a senior at Beverly Hills High School – one of the Instagram Award winners (see her looping video above) and UC Davis SPARK student Anna Guzman – a junior at Sheldon High School – one of the Blog Award winners. Here’s her blog:

The Lab: A Place I Never Thought I’d Be
By Anna Guzman

AnnaGuzman

Anna Guzman

My CIRM SPARK journey started long before I ever stepped foot in the Institute for Regenerative Cures at UC Davis. Instead, my journey started two years earlier, when my older sister came home from the same internship with stories of passaged cells, images of completed western blots, and a spark in her eye when she described the place she had come to love. Barely 14 years old, I listened wide-eyed as my sister told us about the place she disappeared to each morning, stories of quirky professors, lovable mentors, and above all, the brilliant flame that everyone in her lab shared for learning. But even as she told her stories around the dinner table, I imagined this cold place where my charismatic, intelligent, and inquisitive sister was welcomed. I imagined the chilling concentration of dozens of geniuses bent over their work, of tissue culture rooms where every tiny movement was a potential disaster, and above all, of a labyrinth of brilliant discoveries and official sounding words with the door securely locked to 16 year old girls – girls who had no idea what they wanted to do with their life, who couldn’t confidently rattle words like “CRISPR,” “mesenchymal” and “hematopoietic” off their tongues. In short, this wasn’t a place for me.

But somehow I found myself applying for the CIRM SPARK internship. Seconds after I arrived for my first day at the place I was sure I would not belong, I realized how incorrect my initial assumption of the lab was. Instead of the intimidating and sophisticated environment filled with eye-rolling PhDs who scoffed at the naïve questions of a teenager, I found a room filled with some of the kindest, funniest, warmest people I had ever met. I soon found that the lab was a place of laughter and jokes across bays, a place of smiles in the hallways and mentors who tirelessly explained theory after theory until the intoxicating satisfaction of a lightbulb sparked on inside my head. The lab was a place where my wonderful mentor Julie Beegle patiently guided me through tissue culture, gently reminding me again and again how to avoid contamination and never sighing when I bubbled up the hemocytometer, miscalculated transduction rates, or asked question after question after question. Despite being full of incredibly brilliant scholars with prestigious degrees and publications, the lab was a place where I was never made to feel small or uneducated, never made to feel like there was something I couldn’t understand. So for me, the lab became a place where I could unashamedly fuel my need to understand everything, to ask hundreds of questions until the light bulbs sputtered on and a spark, the same spark that had glowed in the eyes of my sister years ago, burned brightly. The lab became a place where it was always okay to ask why.

At moments towards the middle of the internship, when my nerves had dissolved into a foundation of tentative confidence, and I had started to understand the words that tumbled out of my mouth, I’d be working in the biosafety cabinet or reading a protocol to my mentor and think, Wow. That’s Me. That’s me counting colonies and loading gels without the tell-tale nervous quiver of a beginner’s hand. That’s me explaining my project to another intern without an ambiguous question mark marring the end of the sentence. That’s me, pipetting and centrifuging and talking and understanding – doing all the things that I was certain that I would never be able to do. That’s the best thing that the CIRM SPARK internship has taught me. Being an intern in this wonderful place with these amazing people has taught me to be assured in my knowledge, unashamed in my pursuit of the answer, and confident in my belief that maybe I belong here. These feelings will stay with me as I navigate the next two years of high school and the beginning of the rest of my life. I have no doubt that I will feel unsure again, that I will question whether I belong and wonder if I am enough. But then I will remember how I felt here, confident, and unashamed, and assured in the place where I never thought I’d be.

It was not until the end of my internship, as I stood up to present a journal article to a collection of the very people who had once terrified me, that I realized the biggest thing I was wrong about two years ago. I was wrong when I assumed that this was a place where I would never belong. Instead, as I stood in front of this community of amazingly brilliant and kind people, my mouth forming words that I couldn’t have dreamed of understanding a month ago, I realized that this was precisely where I belonged. This was the place for me.

Stem cell summer: high school students document internships via social media, Part 1

My fellow CIRM team members and I just got back from two days in Sacramento where we attended one of our favorite annual events: the CIRM SPARK Student Conference. SPARK, which is short for Summer Program to Accelerate Regenerative medicine Knowledge, is a CIRM-funded education program that offers California High School students an invaluable opportunity to gain hands-on training in stem cell research at some of the leading research institutes in California.

This meeting represents the culmination of the students’ internships in the lab this summer and gives each student the chance to present their project results and to hear from stem cell research experts and patient advocates. Every summer, without fail, I’m blown away by how much the students accomplish in such a short period of time and by the poise and clarity with which they describe their work. This year was no exception.

Best Instagram Post Award: Skyler Wong

To document the students’ internship experiences, we include a social media curriculum to the program. Each student posts Instagram photos and writes a blog essay describing their time in the lab. Members of the CIRM team reviewed and judged the Instagram posts and blogs. It was a very difficult job selecting only three Instagrams out of over 400 (follow them at #cirmsparklab) that were posted over the past eight weeks. Equally hard was choosing three blogs from the 58 student essays which seem to get better in quality each year.

Over the next week or so, we’re going to feature the three Instagram posts and three blogs that were ultimately awarded. Our two winners featured today are UC Davis SPARK student, Skyler Wong, a rising senior at Sheldon High School was one of the Instagram Award winners (see his photo above) and Stanford SPARK student Angelina Quint, a rising senior at Redondo Union High School, was one of the Blog Award winners. Here’s her blog:

Best Blog Award:
My SPARK 2018 summer stem cell research internship experience
By Angelina Quint

Angelina2

Angelina Quint

Being from Los Angeles, I began the SIMR program as a foreigner to the Bay Area. As my first research experience, I was even more so a foreigner to a laboratory setting and the high-tech equipment that seemingly occupied every edge and surface of Stanford’s Lorry I. Lokey Stem Cell building. Upon first stepping foot into my lab at the beginning of the summer, an endless loop of questions ran through my brain as I ventured deeper into this new, unfamiliar realm of science. Although excited, I felt miniscule in the face of my surroundings—small compared to the complexity of work that laid before me. Nonetheless, I was ready to delve deep into the unknown, to explore this new world of discovery that I had unlocked.

Participating in the CIRM research program, I was given the extraordinary opportunity to pursue my quest for knowledge and understanding. With every individual I met and every research project that I learned about, I became more invigorated to investigate and discover answers to the questions that filled my mind. I was in awe of the energy in the atmosphere around me—one that buzzed with the drive and dedication to discover new avenues of thought and complexity. And as I learned more about stem cell biology, I only grew more and more fascinated by the phenomenon. Through various classes taught by experts in their fields on topics spanning from lab techniques to bone marrow transplants, I learned the seemingly limitless potential of stem cell research. With that, I couldn’t help but correlate this potential to my own research; anything seemed possible.

However, the journey proved to be painstakingly arduous. I soon discovered that a groundbreaking cure or scientific discovery would not come quickly nor easily. I faced roadblocks daily, whether it be in the form of failed gel experiments or the time pressures that came with counting colonies. But to each I learned, and to each I adapted and persevered. I spent countless hours reading papers and searching for online articles. My curiosity only grew deeper with every paper I read—as did my understanding. And after bombarding my incredibly patient mentors with an infinite number of questions and thoughts and ideas, I finally began to understand the scope and purpose of my research. I learned that the reward of research is not the prestige of discovering the next groundbreaking cure, but rather the knowledge that perseverance in the face of obstacles could one day transform peoples’ lives for the better.

As I look back on my journey, I am filled with gratitude for the lessons that I have learned and for the unforgettable memories that I have created. I am eternally grateful to my mentors, Yohei and Esmond, for their guidance and support along the way. Inevitably, the future of science is uncertain. But one thing is always guaranteed: the constant, unhindered exchange of knowledge, ideas, and discovery between colleagues passionate about making a positive difference in the lives of others. Like a stem cell, I now feel limitless in my ability to expand my horizons and contribute to something greater and beyond myself. Armed with the knowledge and experiences that I have gained through my research, I aspire to share with others in my hometown the beauty of scientific discovery, just as my mentors have shared with me. But most of all, I hope that through my continued research, I can persist in fighting for new ways to help people overcome the health-related challenges at the forefront of our society.

 

What makes an expert an expert?

When we launched our Facebook Live “Ask the Expert” series earlier this year we wanted to create an opportunity for people to hear from and question experts about specific diseases or disorders. The experts we turned to were medical ones, neurologists and neuroscientists in the case of the first two Facebook Live events, stroke and ALS.

Then we learned about a blog post on the ALS Advocacy website questioning our use of the word “expert”. The author, Cathy Collet, points out that doctors or scientists are far from the only experts about these conditions, that there are many people who, by necessity, have become experts on a lot of issues relating to ALS and any other disease.

Cathy Collet ALS

 

Here’s Cathy’s blog. After you read it please let us know what you think: should we come up with a different title for the series, if so what would you suggest?

 

 

 

“Over the years I’ve experienced many “Ask the Experts” sessions related to ALS.  It’s always a panel of neuroscientists who talk a lot about ALS research and then take a few questions.

The “Expert” crown defaults to them.  They speak from the dais.  We get to listen a lot and ask.  They are by default “The Experts” in the fight against ALS.

But wait, there are all kinds of people with superb and valuable knowledge related to ALS –

  • There are people who know a lot about insurance.
  • There are people who know a lot about communication technology.
  • There are people who know a lot about low-tech hacks.
  • There are people who know a lot about suction machines.
  • There are people who know a lot about breathing.
  • There are people who know a lot about the FDA.
  • There are people who know a lot about moving a person on and off a commode.
  • There are people who know a lot about taxes.
  • There are people who know a lot about drugs.
  • There are people who know a lot about data.
  • There are people who know a lot about choking.
  • There are people who know a lot about financing research.
  • There are people who know a lot about stem cells.
  • There are people who know a lot about feeding tubes and nutrition.
  • There are people who know a lot about what’s important in living with the beast ALS.
  • There are people who know a lot about primary care in ALS.
  • There are people who know a lot about constipation.

Our default implication for the word experts being neuroscientists is revealing. There are many people in the fight against ALS, including those living with it, who know a lot.  We still live in a hierarchy where people with ALS and caregivers are at the bottom.

Words matter.  “Expert” is not a royal title to be owned by anyone by default.

It’s time for simple changes to some traditions.  “Ask the Neuroscientists,” anyone?

 

By the way, our next Facebook Live “Ask the ?” feature is targeting Sickle Cell Disease. It will be from noon till 1pm on Tuesday August 28th. More details, and maybe even a new name, to follow.

 

ALS is in the spotlight in CIRM’s “Ask the Expert About ALS & Stem Cells” Facebook Live event

The Catch

San Francisco 49ers Dwight Clark makes his iconic “Catch” against the Dallas Cowboys

American Football great Dwight Clark was renowned for having the safest hands in the game when he played for the San Francisco 49ers. But in September 2015 he was diagnosed with ALS (also known as Lou Gehrig’s disease) after not being able to use those hands to open a package of sugar. Less than three years later he was dead.

Amyotrophic lateral sclerosis – ALS’ formal title – is a nasty disease that relentlessly destroys the nerve cells in the brain and spinal cord that control movement and breathing. It is always fatal. There are only two drugs approved for ALS and they don’t work for most people. There is no cure.

AskExpertsALSJUL2018

That’s why CIRM chose ALS to be the subject of its latest Facebook Live Ask the Expert event (click here for the event’s FaceBook Live page). There’s a real need for new approaches to help people battling this deadly condition. And CIRM is funding two clinical trials that hope to do just that.

This Ask the Expert event will feature Clive Svendsen, PhD, Director of Cedars-Sinai’s Board of Governors Regenerative Medicine Institute, and Robert Baloh, MD, PhD, Director of Neuromuscular Medicine at Cedars-Sinai. They’ll be joined by Ralph Kern, MD, Chief Operating Officer and Chief Medical Officer at  BrainStorm Cell Therapeutics. The panel will be completed by CIRM Senior Science Officer Lila Collins.

The four will discuss the clinical trials that CIRM is funding with Cedars-Sinai and BrainStorm, and look at other promising research taking place.

Ask the Experts About ALS and Stem Cells is an opportunity for everyone in the ALS community to hear about the very latest in stem cell research targeting this devastating disease,” Svendsen said. “There has recently been some progress in the search for new treatments, which has energized all of us looking for effective therapies—and one day, a cure.”

Because Facebook Live is an interactive event people will be able to post comments and ask questions of the experts.

Dr. Baloh says we are now at a crucial time in the search for new approaches to help people with ALS.

“Many researchers believe that stem cells and gene therapies hold great promise for finding effective treatments, and more trials are needed to explore that potential.”

Our Facebook Live event, “Ask the Experts About ALS and Stem Cells” is tomorrow – Tuesday, July 31st – from noon till 1pm PST. You can join us by logging on to Facebook and going to the FaceBook Live broadcast link at: https://bit.ly/2uYQ8wM

Also, make sure to “like” our FaceBook page before the event to receive a notification when we’ve gone live for this and future events.

We want to hear from you, so you will be able to post questions in real-time for the experts to answer or, you can email them directly to us beforehand at info@cirm.ca.gov

If you miss the event, not to worry. A recording of the session will be available in our FaceBook videos page shortly after the broadcast ends.

We look forward to seeing you there.

 

School’s Out! Stem cells are in! High school students start CIRM-funded summer research internships.

Robotic engineering, coding, video game design, filmmaking, soccer and swimming: these are just a few of the many activities that are vying for the attention of high school students once school lets out for the summer.

But a group of about 50 high schoolers in California have chosen a different path: they will be diving into the world of stem cell biology. Each student earned a spot in one of seven CIRM-funded SPARK Programs across California. That’s short for Summer Program to Accelerate Regenerative Medicine Knowledge (yes, technically it should be SPARMK but we like SPARK better).

The SPARK students will gain hands-on training in stem cell research at some of the leading research institutes in California by conducting a six-week research internship in a stem cell lab. Maybe I’m bias, as the Program Director at CIRM who oversees the SPARK programs, but I think they’ve made a great decision. Stem cell research is one of, if not the most exciting and cutting-edge fields of research science out there today.

The pace of progress is so rapid in the field that a large workforce over the next century is critical to sustain CIRM’s mission to accelerate stem cell treatments to patients with unmet medical needs. That’s why the Agency has invested over $4 million to support over 400 SPARK interns since 2012.

Yesterday, I had the pleasure to be in Sacramento to welcome the UC Davis SPARK interns on their first day of their program which is led by Gerhard Bauer, director of the Good Manufacturing Practice (GMP) laboratory at the UC Davis Institute for Regenerative Cures. The other programs, like the one at Cedars-Sinai in Los Angeles (see photo below), are also starting this week or next.

CedarSinaiSPARK2018

Because everything we do at CIRM is focused on the patient, the SPARK programs are required to include patient engagement as part of the students’ internships. Here are some Instagram posts from last year that highlight those patient-centered activities.

CedarSinaiSPARK2017Patients

And speaking of Instagram, we have also included a social media component to the program. We believe it’s critical for scientists to connect with the public about the important work they do. During the UC Davis orientation, Jan Nolta, PhD, the director of the Stem Cell Program at UC Davis School of Medicine, pointed out to the students that making the science accessible and understandable to the public, makes stem cell research less scary and, as a result, it’s more likely to gain public support.

So, as part of their curriculum, the interns will share a few Instagrams per week that capture their summer in the lab. You can follow their posts at #CIRMSPARKLab. In addition to communicating through photos, the students will describe their internship experiences by writing a blog. We’ll post the most outstanding blogs later this summer. In the meantime, you can read last summer’s winning blogs.

At the end of their program, the students get to show off their hard work by presenting their research at the SPARK annual conference which will be held this year at UC Davis. It’s going to be an exciting summer!

A Cowboys Fan’s Take on The Catch and Dwight Clark’s Passing Due to ALS

I grew up in Dallas in the 80’s. Needless to say, I was a diehard fan of the Dallas Cowboys National Football League (NFL) team and January 10, 1982 will forever be seared into my memory. Late in the fourth quarter, the Cowboys were leading the San Francisco 49ers 27-21 in the conference championship with the winner moving on to the Super Bowl. But then, with less than a minute remaining, The Catch happened. Dwight Clark of the 49ers sailed over the Cowboys’ Everson Walls to catch Joe Montana’s game-winning pass in the end zone. I was crushed and had a dark cloud over my head for many days afterward.

thecatch.gif

Dwight Clark sails over Everson Walls for The Catch

Though I’ve lived in the Bay Area for the past twenty years and become a 49ers fan, it’s still hard for me to watch video clips of The Catch which is arguably this region’s greatest moment in the history of professional sports. Over the years of listening to sports talk radio, I heard interviews with and about Dwight Clark and have come to realize what a terrific person he was. So, I may hate that play, but I certainly can’t hate the man. That’s why I was as heartbroken as everyone else around here with yesterday’s news that Clark had succumbed, at only 61 years of age, to his battle with amyotrophic lateral sclerosis (ALS) also known as Lou Gehrig’s disease, an incurable neurodegenerative disorder that is usually fatal within 2 to 5 years after diagnosis.

Not surprisingly, the ALS Association’s Golden West Chapter, which covers the entire West Coast, was contacted by every Bay Area TV station about Clark’s death. In her KTVU news segment, TV reporter Deborah Villalon explained what Clark meant to ALS patient advocates who often feel invisible:

“To the ALS community he is a hero for raising awareness in the very public way he faced the disease. Clark faced the terminal illness head-on, speaking publicly of his challenges, even appearing on the big screen at Levi’s Stadium last fall, to thank fans for their support.”

At CIRM, we are funding two clinical trials run by Cedars-Sinai and BrainStorm Cell Therapeutics testing stem cell-based treatments for ALS. In Clark’s memory and for everyone in the ALS community, we hope these trials one day lead to new treatment options for the 5,000 thousand newly diagnosed cases each year in the U.S.

Boosting immune system cells could offer a new approach to treating Lou Gehrig’s disease

ALS

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is one of those conditions that a lot of people know about but don’t know a lot about. If they are fortunate it will stay that way. ALS is a nasty neurodegenerative disease that attacks motor neurons, the cells in the brain and spinal cord that control muscle movement. As the disease progresses the individual loses their ability to walk, talk, eat, move and eventually to breathe. There are no effective treatments and no cure. But now research out of Texas is offering at least a glimmer of hope.

Dr. Stanley Appel, a neurologist at the Houston Methodist Neurological Institute noticed that many of the ALS patients he was treating had low levels of regulatory T cells, also known as Tregs. Tregs play a key role in our immune system, suppressing the action of molecules that cause inflammation and also helping prevent autoimmune disease.

In an article on Health News Digest Appel said:

Stanley Appel

Dr. Stanley Appel: Photo courtesy Australasian MND Symposium

“We found that many of our ALS patients not only had low levels of Tregs, but also that their Tregs were not functioning properly. We believed that improving the number and function of Tregs in these patients would affect how their disease progressed.”

And so that’s what he and his team did. They worked with M.D. Anderson Cancer Center’s Stem Cell Transplantation and Cellular Therapy program on a first-in-human clinical trial. They took blood from three people with different stages of ALS, separated the red and white blood cells, and returned the red blood cells to the patient. They then separated the Tregs from the white blood cells, increased their number in the lab, and then reinfused them into the patients, in a series of eight injections over the course of several months.

Their study, which appears in the journal Neurology,® Neuroimmunology & Neuroinflammation, found that the therapy appears to be safe without any serious side effects.

Jason Thonhoff, the lead author of the study, says the therapy also appeared to help slow the progression of the disease a little.

“A person has approximately 150 million Tregs circulating in their blood at any given time. Each dose of Tregs given to the patients in this study resulted in about a 30 to 40 percent increase over normal levels. Slowing of disease progression was observed during each round of four Treg infusions.”

Once the infusions stopped the disease progression resumed so clearly this is not a cure, but it does at least suggest that keeping Tregs at a healthy, high-functioning level may help slow down ALS.

CIRM is funding two clinical trials targeting ALS. One is a Phase 1 clinical trial with Clive Svendsen’s team at Cedars-Sinai Medical Center, the other is a Phase 3 project with Brainstorm Cell Therapeutics.

Meet the high school student who moonlights as a neuroscientist

As part of our CIRM scholar blog series, we’re featuring the research and career accomplishments of CIRM funded students. Today, you’ll read about one of our former SPARK high school students.


Emma Friedenberg and former CIRM SPARK Director Karen Ring at the 2017 SPARK Conference.

Emma Friedenberg is a high school senior at Campbell Hall in North Hollywood, California. She’s also an up-and-coming neuroscientist who has her sights set on unraveling the complexities of the brain and discovering cures for degenerative brain diseases. Emma spent the summer of 2017 studying Huntington’s disease in the lab of Dr. Virginia Mattis at the Cedars-Sinai Medical Center. Her internship was possible because of the CIRM SPARK high school educational program which gives California students the opportunity to do stem cell research for a summer.

Below is an interview with Emma about her SPARK experience and how the program is helping her pursue her passions for research and medicine.

Q: How did you learn about the CIRM SPARK program and why did you want to apply?

I’ve been a clinical volunteer at Cedars-Sinai Medical Center for two years in the Intensive Care Unit and the Neurology and Spine Unit. I was submitting my application to return as a volunteer when I explored Cedars-Sinai’s Outreach website page and found the CIRM SPARK program. I knew immediately it was a perfect fit. I plan on studying neuroscience in college with an intention of obtaining my medical degree and becoming a surgeon. The CIRM SPARK program at Cedars within the Board of Governor’s Regenerative Medicine Institute had an option to be involved specifically in the Brain Program. In Dr. Virginia Mattis’ lab, I studied translational stem cell therapies for neurodegenerative diseases, in particular Huntington’s Disease. As Cedars-Sinai calls it, a “bench to bedside” approach is an unparalleled and invaluable experience and huge advantage in science.

Q: What was your SPARK research project?

At Cedars-Sinai, I was mentored by Dr. Virginia Mattis in her stem cell lab. The Mattis Lab researches stem cell therapies for Huntington’s disease (HD), a neurodegenerative brain disease. HD is caused by a loss of neurons, specifically medium spiny neurons in the striatum of Huntington’s patients. We used induced pluripotent stem cells to model HD in a petri dish to study the development of the disease and to create medium spiny neurons that could one day be transplanted into Huntington’s patients to replace lost and damaged cells.

Medium spiny neurons made from Huntington’s disease patient induced pluripotent stem cells. (Image credit: Mattis Lab, Cedars Sinai)

My primary research in the Mattis Lab was experimenting on our cell line to find the most time and cost-effective procedure to produce large populations of medium spiny neurons, because current methods are expensive and largely inefficient. However, my internship was not limited to the laboratory. I spent a significant amount of time shadowing doctors in the ALS Clinic.

Q: What was your experience in the CIRM SPARK program like?

In one word, the CIRM SPARK program was incredible –a one of a kind opportunity. The sciences are my personal passion and the cornerstone of my academic pursuits. The CIRM SPARK program has bolstered my scientific knowledge and provided practical experience in a real-world laboratory environment. A career in medicine is a significant commitment, and I’m confident the CIRM SPARK program was a beneficial start to obtaining my goals.

Cedars-Sinai SPARK students celebrating the completion of their 2017 internships.

Q: What do you value most about your SPARK experience?

It was wonderful to be part of a program which understood collaboration and offered a plethora of learning opportunities outside of the wet lab. What I will keep with me is not only techniques of immunocytochemistry and microscopy, but also the advice and encouragement from accomplished scientists like Clive Svendsen and my mentor Virginia Mattis.

Q: What are your future goals?

I plan on studying neuroscience in college with an intention of obtaining my medical degree and becoming a surgeon.

Q: Who is your scientific idol and why?

I recently read Dr. Eric Kandel’s book, The Age of Insight: The Quest to Understand the Unconscious in Art, Mind, and Brain, from Vienna 1900 to the Present. Dr. Kandel is a neuroscientist and a Professor at Columbia University. He received the Nobel Prize for his work in memory storage using Aplysia, a type of sea slug. His book examines how the human brain responds to art. What I find so inspiring about his book is his interdisciplinary approach to science, a combination of neuroscience, psychoanalysis, biology, and art. The human brain is so complicated that it can be studied from numerous perspectives, from biology to chemistry to electrophysiology. It is not until we can begin to merge these understandings that we will begin to unlock the secrets of the brain. Dr. Kandel is not only a scientist, but an intellectual.

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

For centuries, the human brain was an anomaly, unexplainable by science. With 100 billion neurons and 100 trillion connections, the brain is the most complex network in the universe. How the brain functions as an information-processing organ and regulates emotion, behavior, and cognition as well as basic body functions like breathing remains a mystery. In recent years, there has been significant progress in brain research. Scientists are on the brink of major breakthroughs, but there is significant work to do particularly on neurological brain disorders. Being a scientist means living on the cutting-edge of human innovation. I enjoy being able to both ask and answer questions that will benefit humankind.


Related Links:

Stem Cell Roundup: The brain & obesity; iPSCs & sex chromosomes; modeling mental illness

Stem Cell Image of the Week:
Obesity-in-a-dish reveals mutations and abnormal function in nerve cells

cedars-sinai dayglo

Image shows two types of hypothalamic neurons (in magenta and cyan) that were derived from human induced pluripotent stem cells.
Credit: Cedars-Sinai Board of Governors Regenerative Medicine Institute

Our stem cell image of the week looks like the work of a pre-historic cave dweller who got their hands on some DayGlo paint. But, in fact, it’s a fluorescence microscopy image of stem cell-derived brain cells from the lab of Dhruv Sareen, PhD, at Cedars-Sinai Medical Center. Sareen’s team is investigating the role of the brain in obesity. Since the brain is a not readily accessible organ, the team reprogrammed skin and blood cell samples from severely obese and normal weight individuals into induced pluripotent stem cells (iPSCs). These iPSCs were then matured into nerve cells found in the hypothalamus, an area of the brain that regulates hunger and other functions.

A comparative analysis showed that the nerve cells derived from the obese individuals had several genetic mutations and had an abnormal response to hormones that play a role in telling our brains that we are hungry or full. The Cedars-Sinai team is excited to use this obesity-in-a-dish system to further explore the underlying cellular changes that lead to excessive weight gain. Ultimately, these studies may reveal ways to combat the ever-growing obesity epidemic, as Dr. Sareen states in a press release:

“We are paving the way for personalized medicine, in which drugs could be customized for obese patients with different genetic backgrounds and disease statuses.”

The study was published in Cell Stem Cell

Differences found in stem cells derived from male vs female.

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Microscope picture of a colony of iPS cells. Credit: Vincent Pasque

Scientists at UCLA and KU Leuven University in Belgium carried out a study to better understand the molecular mechanisms that control the process of reprogramming adult cells back into the embryonic stem cell-like state of induced pluripotent stem cells (iPSCs). Previous studies have shown that female vs male embryonic stem cells have different patterns of gene regulation. So, in the current study, male and female cells were analyzed side-by-side during the reprogramming process.  First author Victor Pasquale explained in a press release that the underlying differences stemmed from the sex chromosomes:

In a normal situation, one of the two X chromosomes in female cells is inactive. But when these cells are reprogrammed into iPS cells, the inactive X becomes active. So, the female iPS cells now have two active X chromosomes, while males have only one. Our results show that studying male and female cells separately is key to a better understanding of how iPS cells are made. And we really need to understand the process if we want to create better disease models and to help the millions of patients waiting for more effective treatments.”

The CIRM-funded study was published in Stem Cell Reports.

Using mini-brains and CRISPR to study genetic linkage of schizophrenia, depression and bipolar disorder.

If you haven’t already picked up on a common thread in this week’s stories, this last entry should make it apparent: iPSC cells are the go-to method to gain insight in the underlying mechanisms of a wide range of biology topics. In this case, researchers at Brigham and Women’s Hospital at Harvard Medical School were interested in understanding how mutations in a gene called DISC1 were linked to several mental illnesses including schizophrenia, bipolar disorder and severe depression. While much has been gleaned from animal models, there’s limited knowledge of how DISC1 affects the development of the human brain.

The team used human iPSCs to grow cerebral organoids, also called mini-brains, which are three-dimensional balls of cells that mimic particular parts of the brain’s anatomy. Using CRISPR-Cas9 gene-editing technology – another very popular research tool – the team introduced DISC1 mutations found in families suffering from these mental disorders.

Compared to cells with normal copies of the DISC1 gene, the mutant organoids showed abnormal structure and excessive cell signaling. When an inhibitor of that cell signaling was added to the growing mutant organoids, the irregular structures did not develop.

These studies using human cells provide an important system for gaining a better understanding of, and potentially treating, mental illnesses that victimize generations of families.

The study was published in Translation Psychiatry and picked up by Eureka Alert.

Straight to brain: A better approach to ALS cell therapies?

Getting the go ahead to begin a clinical trial by no means marks an end to a research team’s laboratory studies. A clinical trial is merely one experiment and is designed to answer a specific set of questions about a specific course of treatment. There will inevitably be more questions to pursue back in the lab in parallel with an ongoing clinical trial to potentially enhance the treatment.

That’s the scenario for Cedar-Sinai’s current CIRM-funded clinical trial testing a cell therapy for amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. Animal studies published this week in Stem Cells suggests that an additional route of therapy delivery may have potential and should also be considered.

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Microscopy image showing transplanted neural progenitor cells (green), the protein GDNF (red) and motor neurons (blue) together in brain tissue. Credit: Cedars-Sinai Board of Governors Regenerative Medicine Institute

ALS is an incurable disease that destroys motor neurons responsible for communicating muscle movement between the brain and the rest of the body via the spinal cord. ALS sufferers lose the use of their limbs and eventually the muscles that control breathing. They rarely live more than 3 to 5 years after diagnosis.

The CIRM-funded trial uses neural progenitor cells – which are similar to stem cells but can only specialize into different types of brain cells – that are genetically engineered to release a protein called GDNF that helps protect the motor neurons from destruction. These cells are being transplanted into the spinal cords of the clinical trial participants.

While earlier animal studies showed that the GDNF-producing progenitor cells can protect motor neurons in the spinal cord, the researchers also recognized that motor neurons within the brain are also involved in ALS. So, for the current study, the team tested the effects of implanting the GDNF-producing cells into the brains of rats with symptoms mimicking an inherited form of ALS.

The team first confirmed that the cells survived, specialized into the right type of brain cells and released GDNF into the brain. More importantly, they went on to show that the transplanted cells not only protected the motor neurons in the brain but also delayed the onset of the disease and extended the survival of the ALS rats.

These results suggest that future clinical trials should test transplantation of the cells into the brain in addition to the spinal cord. The team will first need to carry out more animal studies to determine the cell doses that would be most safe and effective. As first author Gretchen Thomsen, PhD, mentions in a press release, the eventual benefit to patients could be enormous:

Gretchen-Miller-photo

Gretchen Thomsen

“If we are able in the future to reproduce our research results in humans, we could improve both the quality and length of life for patients diagnosed with this devastating disease.”