DRC & Research News

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UCSF DC Bhushan Hebrok

Halting Diabetes: UCSF Researchers Publish Study

UCSF DC Bhushan HebrokWritten by Kathleen Jay on June 23, 2015, via Diabetes Center at UCSF. Click here to read original article.

This week, novel findings by UCSF researchers Anil Bhushan, PhD, and Matthias Hebrok, PhD, for developing therapeutic strategies to combat diabetes were published in the Journal of Clinical Investigation.

The study, entitled “DNA methylation directs functional maturation of pancreatic beta cells,” analyzes how pancreatic beta cells become fully functional after birth.

“Pancreatic beta cells respond to glucose increases after a meal by secreting insulin. On the other end of the spectrum, the cells react to fasting conditions by preventing insulin production,” said Bhushan, a professor at the Diabetes Center at UCSF. “These cells only acquire the ability to secrete insulin in response to changing glucose levels post-natally, indicating that epigenetic mechanisms direct beta cell maturation after birth.”

External or environmental processes can affect how genes are expressed through a process known as epigenetics. If the DNA code for genes are the words in a book, epigenetics are like bookmarks that direct how and if the words are read. External factors can lead to epigenetic alterations, with molecular changes such as DNA methylation,that affect gene expression, without altering the underlying DNA sequence. Thus, epigenetic modifications provide an additional layer of control of how genes are expressed and impact whether a gene is turned “on” (expressed) or “off” (inhibited).

“Our results highlight a novel epigenetic mechanism that governs how beta cells functionally mature during neonatal life and provide new insights into impaired beta cell function in diabetes,” Bhushan said.

To develop these findings, Sangeeta Dhawan, PhD (now an independent scientist at UCLA) in the Bhushan team worked collaboratively with the Hebrok lab, which performed human beta cell analysis for this study.

“Because diseases, such as diabetes, are characterized by beta cell dysfunction which may involve epigenetic changes, we are trying to counteract these modifications with therapeutic, epigenetic treatments,” Bhushan said. “Unlike DNA sequence mutations, epigenetic changes – by nature – appear to be reversible.”

“With Anil’s arrival to UCSF this year, we have elevated beta cell work to new heights,” Hebrok, the director of the Diabetes Center at UCSF said. “This type of research will be highly useful in predicting diseases, such as type 1 diabetes, as well as improving the overall effectiveness of therapeutics to both reduce beta cell destruction and to promote beta cell regeneration.”

For more information, visit http://diabetes.ucsf.edu.


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Diabetes Research Connection

Crowdfunding Platform Created To Fund Type 1 Diabetes Research

DRC Logo for NewsWritten by Api Podder on June 24, 2015, via GoodCrowd.info. Click here to read original article.

One out of every hundred Americans has type 1 diabetes. Millions of children and adults struggle with this autoimmune disease. Despite these numbers, funding has decreased for research to prevent, cure, and better manage the disease. Of the funding available, 97% goes to established scientists with conventional projects. Scientists starting out in diabetes research, also known as early-career scientists, have a difficult time finding money to support their innovative ideas.

Considering Albert Einstein developed the general theory of relativity at the age of 26, Frederick Sanger determined the structure of insulin at age 34, and Francis Crick and James Watson discovered the structure of the DNA molecule at age 37 – just imagine our world today if these scientists had not received funding for their research?

DRC created a platform connecting donors directly with early-career scientists throughout the country, enabling them to perform research designed to prevent and cure type 1 diabetes, minimize its complications, and improve the quality of life for those living with the disease.

Early-career scientists from across the country submit their projects and a panel of more than 80 of the leading diabetes experts review it for innovation, feasibility, value, and achievability. As established scientists, DRC’s panel of experts donate their time and expertise to encourage the next generation of diabetes investigators to push the envelope.

The time from application to funding can be as little as 12 weeks, compared to over a year for many research grants, and 100% of research funds go directly to the scientists in 2015. To ensure transparency, each researcher provides updates on their project, posting final outcomes on DRC’s website.

Dr. Todd Brusko from the University of Florida successfully funded his project through DRC. He received $50,000 to begin working on his project titled, “Can we engineer a patient’s immune cells to stop the autoimmune attack that causes type 1 diabetes?”

“The Brusko lab is incredibly grateful for the donation received to drive this exciting research project forward. Conducting research on this scale is a team effort,” says Brusko.

The Diabetes Research Connection was established in 2012 by five tireless proponents of diabetes research. Dr. Alberto Hayek, emeritus professor from the University of California and Scientific Director at Scripps/Whittier Diabetes Institute in San Diego; Doctors Nigel Calcutt and Charles King, diabetes research scientists affiliated with the University of California, David Winkler, an attorney, entrepreneur and venture philanthropist who was diagnosed with type 1 diabetes at the age of six, and Amy Adams, a writer and business owner whose son has lived with type 1 diabetes for most of his life.

“As someone who has lived with type 1 diabetes for more than 50 years, and who has other family members and friends who have diabetes, I know firsthand how this disease impacts a person’s life and the lives of those around them,” says Winkler.

Alberto Hayek, M.D., co-founder and president of The Diabetes Research Connection and world-renowned diabetes expert believes that the lack of funding for early, discovery-stage projects is one of the biggest problems in research. “With DRC, we are giving scientists the resources to test and validate research that departs from conventional thinking, because the opportunity to pursue new paths is when and where breakthroughs occur,” says Hayek.

For more information on the remarkable work being done at the Diabetes Research Connection, please visit the website at:www.drcsite.wpengine.com, or connect with them on Twitter @DiabetesRsrch or Facebook.com/ DiabetesResearchConnection.

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Insulin Patch

The Smart Insulin Patch: Replace Injections For Diabetic Patients?

Insulin PatchWritten by Brady Dennis on June 22, 2015, via Washington Post. Click here to read original article.

Researchers in North Carolina are developing a “smart” insulin patch that can automatically detect and manage blood sugar levels, an effort they hope might one day make painful, persistent insulin injections obsolete for millions of people with diabetes.

The patch is a thin square no larger than a penny. Its surface is covered in scores of “microneedles,” each about the size of an eyelash, which store both insulin and a glucose-sensing enzyme that can recognize increases in blood sugar. When that happens, the tiny needles can deliver the needed dose of insulin quickly and painlessly.

Researchers from a joint project at the University of North Carolina and North Carolina State University have tested the smart insulin patch only in mice so far. But the patch showed the ability to lower blood glucose levels in mice with Type 1 diabetes for up to nine hours, according to a study published Monday in the Proceedings of the National Academy of Sciences.

“This is way cool technology,” said John Buse, a co-author of the paper and director of the UNC Diabetes Care Center. “It’s very, very exciting, but very preliminary. It will take years to work out whether this actually will work well in humans. But if it did, it would be amazing.”

Diabetes affects nearly 350 million people worldwide, according to the World Health Organization, and that number is expected to continue to climb. Nearly 30 million Americans suffer from the disease, according to the Centers for Disease Control and Prevention.

Managing blood sugar levels for many people with diabetes is a constant chore, marked by finger pricks, insulin shots and monitoring of the diet. Even then, keeping glucose levels in check is an imprecise science with serious consequences if a patient receives too much or too little of the hormone. In particular, patients with rarer Type 1 diabetes, in which the body doesn’t produce the insulin needed to convert sugars and other food into useful energy, have to maintain a consistent watch on blood sugar levels. But even patients with Type 2 diabetes can find it hard to give themselves the proper dose of insulin.

“The hard thing is to take care of diabetes day after day after day,” Buse said. “It’s somewhere in between a hassle and straight up pain in the butt.”

Advances in technology have helped make the task easier over time. Researchers have tried to cut back on the potential for human error by developing “closed-loop” systems that connect devices that monitor blood sugar and administer insulin. But even those products require regular attention; they have mechanical sensors and pumps that can malfunction and needle-tipped catheters that must be replaced.

The idea behind the “smart” insulin patch, is to eliminate some of those headaches while emulating the body’s natural insulin generators, known as beta cells, which sense increases in blood sugar and trigger a release of insulin. When the patch is placed on the skin, researchers said, the microneedles painlessly pierce the surface and tap into the blood flowing through the capillaries.

In early tests, the researchers found that diabetic mice given injections of insulin saw their blood sugar levels normalize but then climb back into hyperglycemic range relatively quickly. Mice that received the insulin patch, however, saw glucose levels come under control in a half hour and stay that way for several hours.

In addition, researchers said they discovered that they could fine tune the patch to alter blood sugar levels within a certain desired range. That offers hope that the patch might one day be tailored to each patient. They also hope to develop a patch that eventually could work several days at a time for human patients.

“The whole system can be personalized to account for a diabetic’s weight and sensitivity to insulin,” Zhen Gu, a professor in the Joint UNC/NC State Department of Biomedical Engineering, said in a statement about the study. “So we could make the smart patch even smarter.”

Monday’s study was funded in part by awards from the North Carolina Translational and Clinical Sciences Institute and the American Diabetes Association.

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immune organoid

First Working Synthetic Immune Organ With Controllable Antibodies

First Working Synthetic Immune Organ With Controllable Antibodies
When exposed to a foreign agent, such as an immunogenic protein, B cells in lymphoid organs (such as the spleen) undergo germinal center (immune defense) reactions. The image on the left is an normal immunized mouse spleen with activated B cells (brown) that produce antibodies. At right, top: a scanning electron micrograph of synthetic porous synthetic immune organoids that enable rapid proliferation and activation of B cells into antibody-producing cells. At right, bottom: primary B cell viability and distribution is visible 24 hours following encapsulation of B cells from the mouse lymphoid organ into the synthetic organoids. (credit: Singh Lab)

Click here to read the original article published on Kurzweil.

Cornell University engineers have created a functional, synthetic immune organoid (a lab-grown ball of cells with some of the features of a normal organ) that produces antibodies. The engineered organ has implications for everything from rapid production of immune therapies to new frontiers in cancer or infectious disease research.

The first-of-its-kind immune organoid was created in the lab of Ankur Singh, assistant professor of mechanical and aerospace engineering, who applies engineering principles to the study and manipulation of the human immune system.

Simulating the body’s immune response

The synthetic organ is bio-inspired by secondary immune organs like the lymph node or spleen. It is made from a hydrogel (a soft, nanocomposite gelatin-like biomaterial), reinforced with silicate nanoparticles to keep the structure from melting at body temperature.

This biomaterial is also seeded with B cells. It mimics the body’s normal anatomical microenvironment of lymphoid tissue, which produces lymphocytes and antibodies in the lymph nodes, thymus, tonsils, and spleen.

Like a real organ, the organoid converts B cells — which make antibodies that respond to infectious invaders — into germinal centers, which are clusters of B cells that activate, mature and mutate their antibody genes when the body is under attack. (Germinal centers are a sign of infection and are not present in healthy immune organs.)

The engineers have demonstrated how they can control this immune response in the organ and tune how quickly the B cells proliferate, get activated and change their antibody types. According to their paper, their 3-D organ outperforms existing 2-D lab cultures and can produce activated B cells up to 100 times faster.

A new tool for studying immune functions

Silicate nanoparticles
Silicate nanoparticles (SiNP) are used for ionic crosslinking of gelatin to form stable hydrogel at body temperature (credit: Alberto Purwada et al./Biomaterials)

According to Singh, the organoid could lead to increased understanding of B cell functions, an area of study that typically relies on animal models to observe how the cells develop and mature, and could also be used to study specific infections and how the body produces antibodies to fight those infections — from Ebola to HIV.

“You can use our system to force the production of immunotherapeutics at much faster rates,” he said. Such a system also could be used to test toxic chemicals and environmental factors that contribute to infections or organ malfunctions.

The process of B cells becoming germinal centers is not well understood, and in fact, when the body makes mistakes in the genetic rearrangement related to this process, blood cancer can result.

“In the long run, we anticipate that the ability to drive immune reaction ex vivo [outside the body] at controllable rates grants us the ability to reproduce immunological events with tunable parameters for better mechanistic understanding of B cell development and generation of B cell tumors, as well as screening and translation of new classes of drugs,” Singh said.

The work was published online June 3 in Biomaterials and will appear later in print.

Abstract of Ex vivo Engineered Immune Organoids for Controlled Germinal Center Reactions

Ex vivo engineered three-dimensional organotypic cultures have enabled the real-time study and control of biological functioning of mammalian tissues. Organs of broad interest where its architectural, cellular, and molecular complexity has prevented progress in ex vivo engineering are the secondary immune organs. Ex vivo immune organs can enable mechanistic understanding of the immune system and more importantly, accelerate the translation of immunotherapies as well as a deeper understanding of the mechanisms that lead to their malignant transformation into a variety of B and T cell malignancies. However, till date, no modular ex vivo immune organ has been developed with an ability to control the rate of immune reaction through tunable design parameter. Here we describe a B cell follicle organoid made of nanocomposite biomaterials, which recapitulates the anatomical microenvironment of a lymphoid tissue that provides the basis to induce an accelerated germinal center (GC) reaction by continuously providing extracellular matrix (ECM) and cell-cell signals to naïve B cells. Compared to existing co-cultures, immune organoids provide a control over primary B cell proliferation with ∼100-fold higher and rapid differentiation to the GC phenotype with robust antibody class switching.

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diabetes gauge

Gene Sheds Light on Development of Type 1 Diabetes, Autoimmune Disease

Diabetes GaugeWritten by Catharine Paddock PhD on May 13, 2015. Original article via MNT.

Type 1 diabetes and multiple sclerosis are types of autoimmune disease – where the immune system attacks the body’s own tissue. Autoimmunity is a complex process, and scientists do not fully understand how it begins. Now, a new study finds an important clue in a gene called Clec16a that appears to control how immune system T cells are primed to attack targets.

When the study team, including Stephan Kissler, assistant professor of medicine at Harvard Medical School, Boston, MA, turned the gene off in mice genetically engineered to developdiabetes, the vast majority of the animals did not develop the disease.


The researchers believe the discovery brings closer the day when we will be able to prevent diabetes.

They report their findings in the journal Immunity.

Prof. Kissler, an immunology investigator at Harvard’s Joslin Diabetes Center, says they think the reason Clec16a is associated with so many different types of autoimmune disease is because it plays a key role in a process at the heart of the immune system. He explains:

“It’s nothing that’s specific for type 1 diabetes, it’s nothing that’s specific to multiple sclerosis. The way T cells are selected is something that’s common to all these diseases.”

Clec16a is involved in the development of type 1 diabetes through autophagy

Autophagy is a process that goes on in all cells. Literally it means “eat oneself,” and is the process through which cells digest their own waste proteins and put the recycled material on their cell surfaces – like putting out the trash.

Autophagy can be activated for different reasons. For instance, if there is a shortage of nutrients or if cells are infected with a virus.

However, epithelial cells in the thymus – a specialized immune system organ that resides behind the breastbone and above the heart – use autophagy in a different way. They use it to show T cells which proteins belong in the body and which should be eliminated.

The researchers showed that the Clec16a gene is involved in the development of type 1 diabetes through the process of autophagy.

Prof. Kissler explains:

“By changing autophagy in TECs [thymic epithelial cells] you change T cell selection, and by changing T cell selection you change the risk of autoimmune disease.”

Switching Clec16a off in diabetes-prone mice significantly reduced risk of disease

For their study, he and his colleagues turned the gene off in 40 mice engineered to develop type 1 diabetes. Only 2 mice developed diabetes compared to 60% in another group of similar mice that were left to develop naturally.

While the team could see that switching off Clec16a made a big difference, they could not see which organ was involved or how the effect came about.

Through a series of transplant experiments, they found that the gene regulates T cell education indirectly in the thymus.

The team has achieved similar results with other genes before, but nothing as dramatic as with Clec16a, says Prof. Kissler.

In a further investigation, the team found that Clec16a is also involved in of human cell autophagy.

They now plan to find out if Clec16a affects T cell education in the human thymus. Prof. Kissler concludes:

“All we know for now is the gene has an effect on human autophagy. Is the same true in human thymus? How does that compare to what we’ve described in the mouse?”

Discovering that Clec16a plays the same role in the human thymus as in the mouse, would be a big step toward solving the mystery of how a complicated diseases like type 1 diabetes, multiple sclerosis and other autoimmune disorders develop.

Earlier this year, Medical News Today learned of another study that found women with multiple sclerosis may have a lower intake of anti-inflammatory and antioxidant nutrients, such as folate, vitamin E and magnesium. However, the researchers could not say if this is a cause or an effect of the disease.

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See our approved research projects and campaigns.

Role of the integrated stress response in type 1 diabetes pathogenesis
In individuals with type 1 diabetes (T1D), the insulin-producing beta cells are spontaneously destroyed by their own immune system. The trigger that provokes the immune system to destroy the beta cells is unknown. However, accumulating evidence suggest that signals are perhaps first sent out by the stressed beta cells that eventually attracts the immune cells. Stressed cells adapt different stress mitigation systems as an adaptive response. However, when these adaptive responses go awry, it results in cell death. One of the stress response mechanisms, namely the integrated stress response (ISR) is activated under a variety of stressful stimuli to promote cell survival. However, when ISR is chronically activated, it can be damaging to the cells and can lead to cell death. The role of the ISR in the context of T1D is unknown. Therefore, in this DRC funded study, we propose to study the ISR in the beta cells to determine its role in propagating T1D.
Wearable Skin Fluorescence Imaging Patch for the Detection of Blood Glucose Level on an Engineered Skin Platform
A Potential Second Cure for T1D by Re-Educating the Patient’s Immune System
L Ferreira
Validating the Hypothesis to Cure T1D by Eliminating the Rejection of Cells From Another Person by Farming Beta Cells From a Patient’s Own Stem Cells
Han Zhu
Taming a Particularly Lethal Category of Cells May Reduce/Eliminate the Onset of T1D
JRDwyer 2022 Lab 1
Can the Inhibition of One Specific Body Gene Prevent Type 1 Diabetes?
Is Cholesterol Exacerbating T1D by Reducing the Functionality and Regeneration Ability of Residual Beta Cells?
Regeneration Ability of Residual Beta Cells
A Call to Question… Is T1D Caused by Dysfunctionality of Two Pancreatic Cells (β and α)?
Xin Tong
Novel therapy initiative with potential path to preventing T1D by targeting TWO components of T1D development (autoimmune response and beta-cell survival)
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