Stories that caught our eye: smelling weight gain, colon cancer & diet and diabetes & broken bones

How smelling your food could cause weight gain (Karen Ring).
Here’s the headline that caught my eye this week: “Smelling your food first can make you fat…”

It’s a bizarre statement, but the claim is backed by scientific research coming from a new study in Cell Metabolism by researchers at the University of California Berkeley. The team found that obese mice who smelled their food before eating it were more likely to gain weight compared to obese mice that couldn’t smell their food.

Their experiments revealed a connection between the olfactory system, which is responsible for our sense of smell, and how the mice metabolize food into energy. Obese mice that lost their ability to smell actually lost weight on a high-fat diet, burned more fat, and became more sensitive to the hormone insulin. Insulin regulates how much glucose, or sugar, is in the blood by facilitating the absorption of glucose by fat, liver and muscle cells. In obese individuals, insulin resistance can occur where their cells are no longer sensitive to the hormone and therefore can’t regulate how much glucose is in the blood.

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Both mice in this picture were fed the same high-fat diet. The only difference: the lower mouse’s sense of smell was temporarily blocked. Image: UC Berkeley

For obese mice that could smell their food, the same high fat diet given to the “no-smellers” resulted in massive weight gain in the “smellers” because their metabolism was impaired. Even more interesting is the fact that other types of smells unrelated to food, such as the scent of other mice, influenced weight gain in the “smellers”.

The authors concluded that the centers in our brain that are responsible for smell (the olfactory system) and metabolism (the hypothalamus) are connected and that manipulating smell could be a future strategy to influence how the brain controls the balance of energy during food consumption.

In an interview with Tech Times, senior author on the study, Dr. Andrew Dillin, explained how their research could potentially lead to a new strategy to promote weight loss,

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Andrew Dillin. Image: HHMI

“Sensory systems play a role in metabolism. Weight gain isn’t purely a measure of the calories taken in; it’s also related to how those calories are perceived. If we can validate this in humans, perhaps we can actually make a drug that doesn’t interfere with smell but still blocks that metabolic circuitry. That would be amazing.”

A link between colorectal cancer and a Western diet identified
Weight gain isn’t the only concern of a eating a high-fat diet. It’s thought that 80% of colorectal cases are associated with a high-fat, Western diet. The basis for this connection hasn’t been well understood. But this week, researchers at the Cleveland Clinic report in Stem Cell Reports that they’ve pinpointed a protein signaling network within cancer stem cells as a possible source of the link.

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Cancer stem cells have properties that resemble embryonic stem cells and are thought to be the source of a cancer’s unlimited growth and spread. A cancer stem cell maintains its properties by exploiting various cell signaling processes that when functioning abnormally can lead to inappropriate cell division and tumor growth. In this study, the team focused on one cell signaling process carried out by a protein called STAT3, known to promote tumor growth in a mouse model of colon cancer. When the team blocked STAT3 activity, high fat diet-induced cancer stem cell growth subsided.

In a press release, Dr. Matthew Kalady, a colorectal surgeon at the Cleveland Clinic and an author on this study, explained how this new insight can open new therapeutic avenues:

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Matthew Kalady. Image: Cleveland Clinic

“We have known the influence of diet on colorectal cancer. However, these new findings are the first to show the connection between high-fat intake and colon cancer via a specific molecular pathway. We can now build upon this knowledge to develop new treatments aimed at blocking this pathway and reducing the negative impact of a high-fat diet on colon cancer risk.”

 

 

Scientists connect dots between diabetes and broken bones.
Type 2 diabetes carries a whole host of long-term complications including heart disease, nerve damage, kidney dysfunction and even an increased risk for bone fractures. The connection between diabetes and fragile bones has not been well understood. But this week, researchers at New York University of Dentistry, Stanford University and China’s Dalian Medical University published a report, funded in part by CIRM, in this week’s Nature Communications showing a biochemical basis for this connection. The new insight may lead to treatment options to prevent fractures.

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Chemical structure of succinate.
Image: Wikimedia Commons.

Fundamentally, diabetes is a disease that causes hyperglycemia, or abnormally high levels of blood sugar. The team ran a systematic analysis of hyperglycemia’s effects on bone metabolism using bone marrow samples from diabetic and healthy mice. They found that the levels of succinate, a key molecule involved in energy production, are over 20 times higher in the diabetic mice. In turns out that succinate also acts as a stimulator of bone breakdown. Now, bone is continually in a process of turnover and, in a healthy state, the breakdown of old bone is balanced with the formation of new bone. So, it appears that the huge increase of succinate is tipping the balance of bone turnover. In fact, the team found that the porous, yet strong inner region of bone, called trabecular bone, was significantly reduced in the diabetic mice, making them more susceptible to fractures.

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The density of spongy bone, or trabecular bone, is reduced in type 2 diabetes.
Image: Wikimedia commons

Dr. Xin Li, the study’s lead scientist, explained the importance of these new insights for people living with type 2 diabetes in a press release:

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Xin Li.
Image: NYU Dentistry

“The results are important because diabetics have a significantly higher fracture risk and their healing process is always delayed. In our study, the hyperglycemic mice had increased bone resorption [the breakdown and absorption of old bone], which outpaced the formation of new bone. This has implications for bone protection, as well as for the treatment of diabetes-associated collateral bone damage.”

 

Stem Cell Stories that Caught our Eye: finding the perfect match, imaging stem cells and understanding gene activity

Here are the stem cell stories that caught our eye this week. Enjoy!

LAPD officer in search of the perfect match.

LAPD Officer Matthew Medina with his wife, Angelee, and their daughters Sadie and Cassiah. (Family photo)

This week, the San Diego Union-Tribune featured a story that tugs at your heart strings about an LAPD officer in desperate need of a bone marrow transplant. Matthew Medina is a 40-year-old man who was diagnosed earlier this year with aplastic anemia, a rare disorder that prevents the bone marrow from producing enough blood cells and platelets. Patients with this disorder are prone to chronic fatigue and are at higher risk for infection and uncontrolled bleeding.

Matthew needs a bone marrow transplant to replace his diseased bone marrow with healthy marrow from a donor, but so far, he has yet to find a match. Part of the reason for this difficulty is the lack of diversity in the national bone marrow registry, which has over 25 million registered donors, the majority of which are white Americans of European decent. As a Filipino, Matthew has a 40% chance of finding a perfect match in the national registry compared to a 75% chance if he were white. An even more unsettling fact is that Filipinos make up less than 1% of donors on the national registry.

Matthew has a sister, but unfortunately, she wasn’t a match. For now, Matthew is being kept alive with blood transfusions at his home in Bellflower while he waits for good news. With the support of his family and friends, the hope is that he won’t have to wait for long. Already 1000 people in his local community have signed up to be bone marrow donors.

On a larger scale, organizations like A3M and Mixed Marrow are hoping to help patients like Matthew by increasing the diversity of the national bone marrow registry. A3M specifically recruits Asian donors while Mixed Match focuses on people with multi-ethnic backgrounds. Ayumi Nagata, a recruitment manager at A3M, said their main challenge is making healthy people realize the importance of being a bone marrow donor.

“They could be the cure for someone’s cancer or other disease and save their life. How often do we have that kind of opportunity?”

An algorithm that makes it easier to see stem cell development.

To understand how certain organs like the brain develop, scientists rely on advanced technologies that can track individual stem cells and monitor their fate as they mature into more specialized cells. Scientists can observe stem cell development with fluorescent proteins that light up when a stem cell expresses specific transcription factors that help decide the cell’s fate. Using a time-lapse microscope, these fluorescent stem cells can easily be identified and tracked throughout their lifetime.

But the pictures don’t always come out crystal clear. Just as a dirty camera lens makes for a dirty picture, images produced by time-lapse microscopy images can be plagued by shadows, artifacts and lighting inconsistencies, making it difficult to observe the orchestrated expression of transcription factors involved in a stem cell’s development.

This week in the journal Nature Communications, a team of scientists from Germany reported a solution that gives a clear view of stem cell development. The team developed a computer algorithm called BaSiC that acts like a filter and removes the background noise from time-lapse images of individual cells. Unlike previous algorithms, BaSiC requires fewer reference images to make its corrections.

The software BaSiC improves microscope images. (Credit: Tingying Peng / TUM/HMGU)

In coverage by Phys.org, author Dr. Tingying Peng explained the advantages of their algorithm,

“Contrary to other programs, BaSiC can correct changes in the background of time-lapse videos. This makes it a valuable tool for stem cell researchers who want to detect the appearance of specific transcription factors early on.”

The team proved that BaSiC is an effective image correcting tool by using it to study the development of hematopoietic or blood stem cells. They took time-lapse videos of blood stem cells over six days and observed that the stem cells chose between two developmental tracks that produced different types of mature blood cells. Using BaSiC, they found that blood stem cells that specialized into white blood cells expressed the transcription factor Pu.1 while the stem cells that specialized into red blood cells did not. Without the algorithm, they didn’t see this difference.

Senior author on the study, Dr. Nassir Navab, concluded by highlighting the importance of their technology and sharing his team’s vision for the future.

“Using BaSiC, we were able to make important decision factors visible that would otherwise have been drowned out by noise. The long-term goal of this research is to facilitate influencing the development of stem cells in a targeted manner, for example to cultivate new heart muscle cells for heat-attack patients. The novel possibilities for observation are bringing us a step closer to this goal.”

Silenced vs active genes: it’s like oil and water (Todd Dubicoff)

The DNA from just one of your cells would be an astounding six feet in length if stretched out end to end. To fit into a nucleus that is a mere 4/10,000th of an inch in diameter, DNA’s double helical structure is organized into intricate twists within twists with the help of proteins called histones.

Together the DNA and histones are called chromatin. And it turns out that chromatin isn’t just for stuffing all that genetic material into a tiny space. The amount of DNA folding also affects the regulation of genes. Areas of chromatin that are less densely packed are more accessible to DNA-binding proteins called transcription factors that activate gene activity. Other regions, called heterochromatin, are compacted which leads to silencing of genes because transcription factors are shut out.

But there’s a wrinkle in this story. More recently, scientists have shown that large proteins are able to wriggle their way into heterochromatin while smaller proteins cannot. So, there must be additional factors at play. This week, a CIRM-funded research project published in Nature provides a possible explanation.

Liquid-like fusion of heterochromatin protein 1a droplets is shown in the embryo of a fruit fly. (Credit: Amy Strom/Berkeley Lab)

Examining the nuclei of fruit fly embryos, a UC Berkeley research team report that various regions of heterochromatin coalesce into liquid droplets which physically separates them from regions where gene activity is high. This phenomenon, called phase-phase separation, is what causes oil droplets to fuse together when added to water. Lead author Dr. Amy Strom explained the novelty of this finding and its implications in a press release:

“We are excited about these findings because they explain a mystery that’s existed in the field for a decade. That is, if compaction [of chromatin] controls access to silenced [DNA] sequences, how are other large proteins still able to get in? Chromatin organization by phase separation means that proteins are targeted to one liquid or the other based not on size, but on other physical traits, like charge, flexibility, and interaction partners.”

Phase-phase separation can also affect other cell components, and problems with it have been linked to neurological disorders like dementia. In diseases like Alzheimer’s and Huntington’s, proteins aggregate causing them to become more solid than liquid over time. Strom is excited about how phase-phase separation insights could lead to novel therapeutic strategies:

“If we can better understand what causes aggregation, and how to keep things more liquid, we might have a chance to combat these types of disease.”

Trash talking and creating a stem cell community

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Imilce Rodriguez-Fernandez likes to talk trash. No, really, she does. In her case it’s cellular trash, the kind that builds up in our cells and has to be removed to ensure the cells don’t become sick.

Imilce was one of several stem cell researchers who took part in a couple of public events over the weekend, on either side of San Francisco Bay, that served to span both a geographical and generational divide and create a common sense of community.

The first event was at the Buck Institute for Research on Aging in Marin County, near San Francisco. It was titled “Stem Cell Celebration” and that’s pretty much what it was. It featured some extraordinary young scientists from the Buck talking about the work they are doing in uncovering some of the connections between aging and chronic diseases, and coming up with solutions to stop or even reverse some of those changes.

One of those scientists was Imilce. She explained that just as it is important for people to get rid of their trash so they can have a clean, healthy home, so it is important for our cells to do the same. Cells that fail to get rid of their protein trash become sick, unhealthy and ultimately stop working.

Imilce is exploring the cellular janitorial services our bodies have developed to deal with trash, and trying to find ways to enhance them so they are more effective, particularly as we age and those janitorial services aren’t as efficient as they were in our youth.

Unlocking the secrets of premature aging

Chris Wiley, another postdoctoral researcher at the Buck, showed that some medications that are used to treat HIV may be life-saving on one level, preventing the onset of full-blown AIDS, but that those benefits come with a cost, namely premature aging. Chris said the impact of aging doesn’t just affect one cell or one part of the body, but ripples out affecting other cells and other parts of the body. By studying the impact those medications have on our bodies he’s hoping to find ways to maintain the benefits of those drugs, but get rid of the downside.

Creating a Community

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Across the Bay, the U.C. Berkeley Student Society for Stem Cell Research held it’s 4th annual conference and the theme was “Culturing a Stem Cell Community.”

The list of speakers was a Who’s Who of CIRM-funded scientists from U.C. Davis’ Jan Nolta and Paul Knoepfler, to U.C. Irvine’s Henry Klassen and U.C. Berkeley’s David Schaffer. The talks ranged from progress in fighting blindness, to how advances in stem cell gene editing are cause for celebration, and concern.

What struck me most about both meetings was the age divide. At the Buck those presenting were young scientists, millennials; the audience was considerably older, baby boomers. At UC Berkeley it was the reverse; the presenters were experienced scientists of the baby boom generation, and the audience were keen young students representing the next generation of scientists.

Bridging the divide

But regardless of the age differences there was a shared sense of involvement, a feeling that regardless of which side of the audience we are on we all have something in common, we are all part of the stem cell community.

All communities have a story, something that helps bind them together and gives them a sense of common purpose. For the stem cell community there is not one single story, there are many. But while those stories all start from a different place, they end up with a common theme; inspiration, determination and hope.

 

Celebrating Stem Cell Awareness Day with SUPER CELLS!

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To all you stem cell lovers out there, today is your day! The second Wednesday of October is Stem Cell Awareness Day (SCAD), which brings together organizations and individuals that are working to ensure the general public realizes the benefits of stem cell research.

For patients in desperate need of treatments for diseases without cures, this is also a day to recognize their struggles and the scientific advances in the stem cell field that are bringing us closer to helping these patients.

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Induced pluripotent stem cells.

How are people celebrating SCAD?

This year, a number of institutes in California are hosting events in honor of Stem Cell Awareness Day. Members of the CIRM team will be speaking on Saturday about “The Power of Stem Cells” at the Buck Institute for Research on Aging in Novato (RSVP on Facebook) and at the Berkeley Student Society for Stem Cell Research Conference in Berkeley (RSVP on Eventbrite). There are also a few SCAD events going on this week in Southern California. You can learn more about these all events on our website.

You can also find out about other SCAD celebrations and events on social media by following the hashtag #StemCellAwarenessDay and #StemCellDay on Twitter.

Super Cells: The Power of Stem Cells

Super Cells exhibit at the Lawrence Hall of Science

Super Cells exhibit at the Lawrence Hall of Science

Today, the CIRM Stem Cellar is celebrating SCAD by sharing our recent visit to the Lawrence Hall of Science, which is currently hosting an exhibit called “Super Cells: The Power of Stem Cells”.

This is a REALLY COOL interactive exhibit that explains what stem cells are, what they do, and how we can harness their power to treat disease and injury. CIRM was one of the partners that helped create this exhibit, so we were especially excited to see it in person.

Super Cells has four “high-tech interactive zones and a comprehensive educational guide for school children ages 6-14”. You can read more details about the exhibit in this promotional handout. Based on my visit to the exhibit, I can easily say­­ that Super Cells will be interesting and informative to any age group.

The exhibit was unveiled on September 28th, and the Hall told us that they have already heard positive reviews from their visitors. We had the opportunity to talk further with Susan Gregory, the Deputy Director of the Hall, and Adam Frost, a marketing specialist, about the Super Cells exhibit. We asked them a few questions and will share their interview below followed by a few fun pictures we took of the exhibit.


Q: Why did the Lawrence Hall of Science decide to host the Super Cells exhibit?

The Lawrence Hall of Science has a history of bringing in exciting and engaging traveling exhibitions, and we were looking for something new to excite our visitors in the Fall season. When the opportunity presented itself to host Super Cells, we thought it would be a good fit for our audience. Additionally, the Hall is increasing its programming and exhibits in the fields of biology, chemistry and bioengineering.

Q: What aspects of the Super Cells exhibit do you think are valuable to younger kids?

We strive to make our exhibit experiences hands-on and interactive. The Hall believes that the best way for kids to learn science is for them to be active in their learning. Super Cells offers a variety of elements that speak to our philosophy of learning and make learning science more fun.

Q: How is exhibit similar or unique to other exhibits you’ve hosted previously?

 The Hall hosts and develops exhibits across a broad range of scientific, engineering, technology and mathematical topics. We are always looking for exhibits that address recent scientific advances, and also try to showcase cutting edge research.

Super Cells presents both basic cell biology and information about recent medical and scientific advances, so it fits. Also, as mentioned in our behind the scenes story about the exhibit install, in the past many of our traveling exhibits were very large experiences that tended to take up a lot of space on the museum floor. One thing that is great about Super Cells is that it packs a lot of information into a relatively small space, allowing us to keep a number of experiences and activities that our audience has come to love on the floor, instead of removing them to make room.

Q: Will there be any special events at the Hall featuring this exhibit?

On November 11, the Hall will host a fun day of activities centered around DNA and the exhibit. Younger visitors will make DNA bracelets based on the unique traits in their genome, while older kids will isolate their own DNA using a swab from inside their cheek. We are still finalizing the details of this event, but it will definitely happen.

Q:  Why do you think it’s important for younger students and the general public to learn about stem cells and stem cell research?

As UC Berkeley’s public science center, the Hall is committed to providing a window into cutting edge research and the latest scientific information. We think it’s really important for people and kids to learn about the skills and science behind current research so they can be prepared for a future of incredible scientific challenges and opportunities that we can’t foresee.


Super Cells will be open at the Lawrence Hall of Science until November 27th, so be sure to check it out before then. If you don’t live in California, don’t worry, Super Cells will be traveling around the U.S., Europe and Canada. You can find out where Super Cells is touring next on their website.

We hope you enjoy our photos of the Super Cells exhibit!

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Stem cell stories that caught our eye: healing diabetic ulcers, new spinal cord injury insights & an expanding CRISPR toolbox

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

Stem cells heal diabetic foot ulcers in pilot study
Foot ulcers are one of the many long-term complications that diabetics face. About 15 percent of patients develop these open sores which typically appear at the bottom of the foot. In a quarter of these cases, the ulcers lead to serious infection requiring amputation.

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Diabetic foot ulcers are open sores that don’t heal and in many cases leads to amputation. Image source: Izunpharma

But help may be on the horizon in the form of stem cells. Researchers at Mansoura University in Egypt recently presented results of a small study in which 10 patients with diabetic foot ulcers received standard care and another 10 patients received standard care plus injections of mesenchymal stem cells that had been collected from each patient’s own bone marrow. After just six weeks, the stem cell treated group showed a 50% reduction in the foot ulcers while the group with only standard care had a mere 7% reduction.

These superior results with the stem cells were observed even though the group receiving the stem cells had larger foot ulcers to begin with compared to the untreated patients. There are many examples of mesenchymal stem cells’ healing power which make them an extremely popular cell source for hundreds of on-going clinical trials. Mesenchymal stem cells are known to reduce inflammation and increase blood vessel formation, two properties that may be at work to give diabetic foot ulcers the chance to get better.

Medscape Medical News reported on these results which were presented at the 2016 annual meeting of the European Association for the Study of Diabetes (EASD) 2016 Annual Meeting

Suppressing nerve signals to help spinal cord injury victims
Losing the use of one’s limbs is a profound life-altering change for spinal cord injury victims. But their quality of life also suffers tremendously from the loss of bladder control and chronic pain sensations. So much so, victims often say that just improving these secondary symptoms would make a huge improvement in their lives.

While current stem cell-based clinical trials, like the CIRM-funded Asterias study, aim to reverse paralysis by restoring loss nerve signals, recent CIRM-funded animal data published in Cell Stem Cell from UC San Francisco suggest that nerve cells that naturally suppress nerve signals may be helpful for these other symptoms of spinal cord injury.

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Mature inhibitory neuron derived from human embryonic stem cells is shown after successfully migrated and integrated into the injured mouse spinal cord.
Photo by Jiadong Chen, UCSF

It turns out that the bladder control loss and chronic pain may be due to overactive nerve signals. So the lab of Arnold Kriegstein transplanted inhibitory nerve cells – derived from human embryonic stem cells – into mice with spinal cord injuries. The scientists observed that these human inhibitory nerve cells, or interneurons, successfully made working connections in the damaged mouse spinal cords. The rewiring introduced by these interneurons also led to reduced pain behaviors in the mice as well as improvements in bladder control.

 

 

In a Yahoo Finance interview, Kreigstein told reporters he’s eager to push forward with these intriguing results:

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Arnold Kriegstein, UCSF

“As a clinician, I’m very aware of the urgency that’s felt among patients who are often very desperate for treatment. As a result, we’re very interested in accelerating this work toward clinical trials as soon as possible, but there are many steps along the way. We have to demonstrate that this is safe, as well as replicating it in other animals. This involves scaling up the production of these human interneurons in a way that would be compatible with a clinical product.”

 

Expanding the CRISPR toolbox
If science had a fashion week, the relatively new gene editing technology called CRISPR/Cas9 would be sure to dominate the runway. You can think of CRISPR/Cas9 as a protein and RNA complex that acts as a molecular scissor which directly targets and cuts specific sequences of DNA in the human genome. Scientists are using CRISPR/Cas9 to develop innovative biomedical techniques such as removing disease-causing mutations in stem cells in hopes of developing potential treatments for patients suffering from diseases that have no cures.

What’s particularly interesting about the CRISPR/Cas9 system is that the Cas9 protein responsible for cutting DNA is part of a family of CRISPR associated proteins (Cas) that have similar but slightly different functions. Scientists are currently expanding the CRISPR toolbox by exploring the functions of other CRISPR associated proteins for gene editing applications.

A CIRM-funded team at UC Berkeley is particularly interested in a CRISPR protein called C2c2, which is different from Cas9 in that it targets and cuts RNA rather than DNA. Led by Berkeley professor Jennifer Doudna, the team discovered that the CRISPR/C2c2 complex has not just one, but two, distinct ways that it cuts RNA. Their findings were published this week in the journal Nature.

The first way involves creation: C2c2 helps make the guide RNAs that are used to find the RNA molecules that it wants to cut. The second way involves destruction: after the CRISPR/C2c2 complex finds it’s RNAs of choice, C2c2 can then cut and destroy the RNAs.

Doudna commented on the potential applications for this newly added CRISPR tool in a Berkeley News release:

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Jennifer Doudna: Photo courtesy of iPSCell.com

“This study expands our molecular understanding of C2c2 to guide RNA processing and provides the first application of this novel RNase. C2c2 is essentially a self-arming sentinel that attacks all RNAs upon detecting its target. This activity can be harnessed as an auto-amplifying detector that may be useful as a low-cost diagnostic.”

 

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.

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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.