annual report 2013 >
ONE GOAL: A CURE To restore natural insulin production and normalize blood sugar levels without imposing other risks.
Highlights of the Year
2
Financial Summary
30
Message from the Director
4
Making Progress Possible
32
Research Review
6
The Heritage Society
36
The Diabetes Education and Nutrition Service at the DRI
Boards of Directors
38
24 DRI Foundation Staff
40
Faculty and Staff
25
DRIF Chairman's Message
28
Highlights of the Year
Advancing Research to Patients
At the Diabetes Research Institute, scientists are urgently pursuing the most promising research findings that show true potential to benefit people living with diabetes. Nothing exemplifies that commitment more than moving exciting discoveries out of the laboratory and into clinical trials, which help move cutting-edge therapies ahead. This past year DRI scientists, together with their global collaborators, took several steps to advance cell replacement initiatives, pioneering a host of new possibilities for those with T1D. The FDA Phase III “registration” trial of islet transplantation by the NIH Clinical Islet Transplantation Consortium (CIT) was just completed. DRI Director Dr. Camillo Ricordi presented the results of this unprecedented multicenter clinical trial at the International Cell Therapy Society (ICTS) congress in Paris, France, on April 25, 2014. While islet transplantation is already approved at other DRI Federation locations, including Canada, England and Switzerland, the DRI is confident that this trial will lead to approval and eventual reimbursement of islet transplantation for the most severe forms of type 1 diabetes in the United States, as well. This could represent the first time that a biologically active cell product is approved in the U.S. by the FDA. The BLA (biologic license application) is currently in preparation, together with extensive manufacturing and clinical FDA reports by the NIH CIT Consortium Team. The comprehensive islet cell product manufacturing master batch record has been published and is available worldwide for “open access” download at http://www.cellr4.org/article/891. In this multicenter trial, as in most current trials of islet transplantation, the islets are transplanted into the liver of patients with the most severe forms of type 1 diabetes. However, this transplant site is not ideal for taking the next step on the path to a biological cure by moving away from generalized treatment with anti-rejection drugs, toward local immunomodulation and immunoprotection of the transplanted insulin-producing cells. In this direction, DRI scientists have been investigating other sites within the body that can serve as a better home for islet cells while eventually allowing for successful biologic replacement of insulin-producing cells without systemic immunosuppression of the recipients. In addition, this novel site to house the DRI BioHub mini organ would provide the insulinproducing cells with the spacing, support, oxygen and nutrients they need to survive and thrive long term, while allowing for strategies for prevention of recurrence of autoimmunity and/or immune rejection without the need for chronic administration of anti-rejection drugs. One area of focus is the omentum, an apron-like lining inside the abdomen. DRI scientists have been testing the omentum as a possible location for a DRI BioHub. Encouraging preliminary data has shown that islets in the omentum can
3 [2013 annual report]
engraft and improve blood glucose control. This exciting research is now moving into clinical trials. The Food and Drug Administration (FDA) has approved the DRI’s submission to initiate a pilot clinical study to test islets transplanted into one of the platforms considered for a DRI BioHub – a “biodegradable scaffold.” The pilot trial, which is expected to be underway in 2014, will compare the omentum to the liver as an optimal home for islets. The DRI also plans to test other BioHub platforms, including a “silicone scaffold.” Researchers are in late-stage discussions with the FDA and awaiting approval for that pilot clinical trial, which will also utilize the omentum as a transplant site. The DRI is also planning for clinical trials in the two additional key strategic areas: tolerance induction and cell supply. In the area of tolerance induction, the DRI is looking toward a pilot trial using tolerance-inducing cells to re-educate the immune system and restore self-tolerance to eliminate autoimmunity. This strategy, when successful, will also allow for transplantation of insulin-producing cells without antirejection drugs. Alternatively, it will allow for regeneration of insulin-producing cells from patients’ own tissues, such as the native pancreas or skin cells obtained from a minimallyinvasive biopsy. In the area of cell supply, the DRI was selected as one of the sites for future clinical trials involving transplantation of stem cell-derived insulin-producing cells.
We look forward to sharing exciting progress as the DRI’s research continues to advance.
Message from the Director
I am proud to share this report, highlighting the ongoing work at the Diabetes Research Institute and our efforts both here and abroad. This next year will be a pivotal one for cure-focused research, with several efforts coming to fruition across many areas and with significant impact in the field as a whole and for patients with T1D.
[diabetes research institute foundation] 4
Among these is the completion of an important Phase III clinical trial, sponsored by the Clinical Islet Transplantation Consortium (CIT), a multi-year, multi-center undertaking supported by two NIH institutes – the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Institute of Allergy and Infectious Diseases (NIAID). The next steps will require centers in the United States to band together and successfully complete a biological license application so that islet transplantation can be offered on a more widespread basis in our country. This cell replacement therapy is already available to patients in other countries, such as Switzerland and Canada, where it is an approved and reimbursable procedure through one’s health insurance. This regulatory hurdle, while not insurmountable, is important to the public’s understanding for the need of a worldwide collaboration – a strategy that the DRI continues to employ in structuring its long term research plans. The complexity of the U.S. regulatory system and the time/cost it takes to bring cellular therapies to the bedside can often move ahead much faster and more efficiently in other countries. At the DRI, we capitalize on the opportunity to more swiftly translate promising findings to patients through our network of global collaborators and international partners. You’ll read about some of the exciting results of these initiatives in the pages to follow.
DRI scientists have been investigating an optimal site within the human body that can host a BioHub, a location that would allow us to move toward a delivery system that will avoid the need for long-term use of anti-rejection drugs. To that end, a new site within the abdomen will be tested this year in a Phase I/II pilot trial, as part of the BioHub Initiative, pending final regulatory approvals. This first trial will test the use of a “biodegradable scaffold” to ensure the targeted site of implant is a suitable place for long-term islet survival. Also, the DRI is planning to test another BioHub platform in the coming year. We are in discussions with the FDA and are awaiting approval for that pilot trial to begin testing a “silicone scaffold” implanted in the omentum. Other clinical trials are in our research pipeline and will be conducted with our collaborators. The DRI has been selected as a testing site for several pending patient studies.
Please join the Diabetes Research Institute and its Foundation and be part of the team that will shape the future, making it one free of diabetes in our lifetime.
Warmest regards,
Today, the DRI is gearing up for critically important clinical trials that will take place in 2014. Among these, is the BioHub Initiative. About a year ago, the DRI announced the BioHub Initiative, a multidisciplinary effort to design, develop and test a bioengineered “mini organ” that mimics the environment of one’s own pancreas. This groundbreaking platform would house insulin-producing cells (islets) capable of sensing blood sugar and releasing insulin as needed, in real time, and represents a major step forward in cell replacement strategies. As opposed to infusing islets into the liver, a BioHub allows researchers to select a dedicated location for the mini-organ. This provides the ability to monitor the site and cells, incorporate other cell types that would facilitate engraftment, slow or prevent rejection, and allow for its retrieval if needed.
5
[2013 annual report]
Camillo Ricordi, M.D. Stacy Joy Goodman Professor of Surgery Distinguished Professor of Medicine Professor of Biomedical Engineering, Microbiology & Immunology Director, Diabetes Research Institute and Cell Transplant Center University of Miami
Research Review
[
Cases of diabetes have been documented for several thousand years, though the term wasn’t coined until the first century. For almost 2,000 years since then, the only treatment option for patients was starvation until the discovery of insulin in 1922. Insulin has indeed saved the lives of millions of people with this disease. Over the last century, advancements in new treatments, aided by the remarkable developments in computer technology, have helped patients better manage daily blood glucose (sugar) control. While it is a life-saving breakthrough, insulin is not a cure and insulin treatment still cannot fully prevent the chronic complications associated with diabetes. Additionally, intensive insulin treatment has led to an increased risk of severe hypoglycemia (dangerously low blood sugar levels).
[diabetes [diabetes research research institute institute foundation] foundation]6 6
Despite patients’ best attempts, diabetes management remains a challenging, daily balancing act that requires constant vigilance and attention. In other words, there are no breaks because technology cannot ideally mimic the exquisite, biological function of a healthy pancreas. Why? Pancreatic islet cells, which make up only one to two percent of the organ, have a built-in glucose sensor, produce their own insulin, secrete the precise amount needed in a perfectly-timed release, and produce counterregulatory hormones, such as glucagon, keeping blood sugar levels in a normal range for an entire lifetime – until these cells are destroyed by the immune system in those with type 1 diabetes. For decades, scientists across the globe have investigated methods to give back to patients the ability to make their own insulin. This has been the intense focus of the Diabetes Research Institute and Foundation, where the goal is to restore natural insulin production and normalize blood sugar levels without imposing other risks.
7
[2013 annual report]
Years of research advancements in cell replacement therapies have yielded promising results. The DRI and its collaborators worldwide already have demonstrated that natural insulin production can be restored through islet transplantation. Patients involved in clinical trials have achieved insulin-independence after receiving infusions of these cells; some study patients are living without the need for insulin injections for more than a decade. Those receiving islet transplants not only have had normalized blood sugar levels, they have also been freed from frightening hypoglycemic episodes and have experienced a much higher quality of life. Yet for all the benefits of islet transplantation, this therapy has been limited to only the most severe cases of diabetes due to several remaining challenges. Through decades of experience in clinical islet transplantation, DRI researchers are armed with critical insights for overcoming these hurdles and Reaching the Biological Cure.
Reaching the Biological Cure The DRI BioHub – A Unique Solution The Institute’s approach to restore natural insulin production is to develop a DRI BioHub, an integrated mini organ that mimics the native pancreas, containing the critical insulin-producing cells that naturally control blood sugar levels. But the BioHub goes beyond traditional islet transplantation and is uniquely different from the various approaches underway at other research centers. The BioHub attempts to replicate the cells’ ideal environment, where healthy islets thrive prior to their destruction by the immune system. Inside the pancreas,
the insulin-producing cells have sufficient oxygen, adequate space and all the nutrients needed to perform their demanding job of normalizing blood sugar levels. With a BioHub, scientists can manipulate and enhance the transplant site, add vital components, like oxygengenerating materials, “helper” cells or other agents to promote the cells’ long term function. Additionally, a BioHub platform can be used to house not just islets, but any insulin-producing cell type that scientists may create.
R Re-educating e-educating the Immune System System Reversing Reversing the autoimmune attack attack on the islet cells that that caused of diabetes. the onset of
Co-delivery Co-delivery o off “helper” ccells ells C ertain cells in the body Certain tha thatt ha have properties ve beneficial pr operties can be added to help promote promote survival. long-term islet sur vival.
Bioactive Bioac tive Surfaces Surfac a es A gents can be linked linked to the Agents material surface surface to either promote promote a material healthy microenvironment microenvironment or healthy responses. inhibit immune responses.
Localized Localized Drug Delivery Delivery Local deliv ery o Local delivery off low-dose low-dose drugs dir ectly in directly into to the site can rreduce educe inflamma inflammation protect tion and pr otect the islets fr om an immune a ttack. from attack.
[diabetes research institute foundation] 8
Encapsula Encapsulation tion Protective thatt cconform onfform to the Pr otective barriers tha e and shape o size off each islet and individual siz free off nutrien nutrients, ee flow o ts, glucose allow the fr glucose screening eening out harmful and insulin while scr immune system cells.
Vascular V asc ascular Infiltr Infiltration ation FFactors actors can be added to promote promote blood vvessel essel growth growth to supply critical o xygen and nutrients. nutrients. oxygen
Struc Structural tural Housing Three-dimensional Three-dimensional structure structure provides pr ovides spacing and a physical physical site that that can be monitored monitored and modified, and retrieved, retrieved, if necessary. necessary.
Oxygen Oxygen Delivery Delivery Oxygen-generating materials materials Oxygen-generating serve as a bridge until until new blood serve vessels grow. grow. vessels
9
[2013 annual report]
THE DRI’S TEAMS OF RESEARCHERS ARE COMBINING THEIR MULTIDISCIPLINARY EXPERTISE TO ADDRESS THREE MAJOR CHALLENGES THAT THE BIOHUB PLATFORM OVERCOMES: AREA 1: The Site – developing an optimal environment within the body to house and protect insulin-producing cells.
AREA 2: Sustainability – retraining the immune system to prevent the rejection of donor tissue and reversing the autoimmune attack which caused the onset of diabetes. AREA 3: Supply – identifying, developing and/or regenerating a limitless supply of cells to sense blood glucose levels and produce insulin.
Over the last year, DRI scientists have made significant progress in each of these areas toward the development of the DRI BioHub.
AREA 1
THE SITE
In traditional islet cell transplantation, the donor cells are infused into the patient’s liver. The liver has been the site of choice due to its many advantages: it is easily accessible; cells can be implanted without invasive surgery; and it’s rich in blood vessels, which can supply the cells with oxygen and nutrients.
While this approach has shown that islet replacement can work, there are concerns that only a portion of the islets may survive post-transplant. That’s because when islets are infused into the liver, the site becomes inflamed, the cells tend to clump together due to the lack of appropriate spacing, and blood flow and oxygen are reduced. Also, the cells are continuously exposed to harmful medications and other toxins that are processed in the liver.
[
For years, scientists have been transplanting islet cells into the liver, but that site may not be an ideal home for the cells. The focus is now on the omentum, an apron-like lining inside the abdomen.
To overcome this challenge, the DRI is exploring alternative implant sites and is now focused on the omentum, the inside lining of the abdomen. The omentum plays an important role in protecting the internal organs from infections, bleeding, trauma and inflammation. Implanting islets into the omentum is appealing because the site is rich with blood vessels throughout its large surface area. Also, it can be easily accessed surgically.
[diabetes research institute foundation] 10
Preliminary data has been very encouraging in demonstrating that islets in the omentum can fully engraft and improve blood glucose control in experimental and pre-clinical models.
While pursuing FDA approval, the DRI is speaking with its DRI Federation collaborators outside of the United States to assess the ability to begin initial clinical testing in their centers so that the pilot studies are not delayed.
DRI scientists are focused on two approaches using the omentum as an alternative transplant site. In the past year, significant progress has been made with each as the work moves toward pilot clinical trials.
BIODEGRADABLE SCAFFOLD In addition to using silicone scaffolds, DRI researchers are developing and testing a biodegradable scaffold to serve as a BioHub platform.
SILICONE SCAFFOLD The DRI’s tissue engineering team, led by Dr. Cherie Stabler, has created a sponge-like scaffold to serve as a physical platform for housing the transplanted islet cells. These scaffolds are comprised of only 10 percent silicone. The rest is open space, creating tiny pores that can house thousands of insulin-producing cells of many shapes and sizes. While the islet-loaded scaffold has shown safety and the ability to achieve insulin independence in pre-clinical study models, DRI researchers have been confronted with several regulatory hurdles. When the IND (Investigational New Drug/Device) application was submitted, the FDA classified the silicone scaffold platform as a combination of both a new “Biological” and new “Device” application, and required further pre-clinical studies before approving pilot clinical trials.
[ 11
[2013 annual report]
This approach uses the patient’s own plasma, the liquid part of the blood that does not contain any cells, together with thrombin, a commonly-used, clinical-grade enzyme. When combined, they create a gel-like substance that sticks to the omentum and holds the islets in place. Researchers will then fold over part of the omentum to create a protective pouch around the biodegradable scaffold mixture. Over time, the body will absorb the gel, leaving the islets intact, while new blood vessels are formed to support their survival and function. The biodegradable scaffold will allow researchers to add vital components to optimize islet acceptance and promote their long-term survival and function, such as oxygen promoters, helper cells, local drug delivery and cells encapsulated with protective coatings.
Dr. Cherie Stabler, director of tissue engineering, and her team developed a silicone scaffold, one of the platforms being tested for a DRI BioHub.
AREA 2
SUSTAINABILITY
The body’s immune system serves as a protector from harmful bacteria and viruses in the environment. This is why people rarely become ill with infections despite the fact that they probably encounter infectious agents every day. Like built-in “radar,” the immune system continually scans the body, discriminating what is “self” and what is “foreign” and needs to be eliminated.
Yet the immune system is not perfect, and despite many mechanisms of control and regulation, mistakes can occur. Such mistakes can result in autoimmune diseases; like “friendly fire,” the immune system mistakenly destroys its own tissues or cells. This is the case with type 1 diabetes (T1D) in which the insulinproducing cells within the pancreas are mistakenly targeted and destroyed. The DRI already has shown that natural insulin production can be restored by transplanting insulin-producing islet cells into patients with type 1 diabetes. Many transplant recipients have been able to stop taking insulin injections; some for more than 10 years. But challenges remain, among them keeping the transplanted islets healthy and functioning. That’s because the recipient’s immune system sees the cells as “foreign” and wants to destroy them. To prevent the body from rejecting the cells, patients must take powerful anti-rejection drugs. They’re called immunosuppressants because they suppress the immune system. But these powerful drugs, which the recipient must take long-term, suppress a patient’s entire immune system, leaving him or her exposed to illnesses. The drugs also can cause serious side effects and can even damage the transplanted cells. That’s why islet transplantation has been limited to only the most severe cases, including people who are unaware when their blood sugar levels drop dangerously low (a condition called hypoglycemic unawareness).
The DRI is committed to making this therapy available to all who can benefit. DRI scientists are focusing a great deal of attention, and resources, on protecting islets and establishing immune tolerance by educating the immune system so it “tolerates” the transplanted insulin-producing cells without the need for long-term immunosuppressants. With the DRI BioHub, the Institute is pursuing several promising strategies to sustain the long-term health and function of the insulin-producing cells by preventing their destruction by the immune system.
USING BONE MARROW-DERIVED CELLS TO ACHIEVE TOLERANCE Scientists have shown that transplanting bone marrow from a donor to a recipient can help re-educate the recipient’s immune system. If a peaceful co-existence of the two immune systems can be maintained, then the recipient will recognize any transplanted organs, tissues or cells from the same bone marrow donor as “self” and no chronic immunosuppression will be needed. The mixture of these two immune systems is known as chimerism. In the past, scientists were reluctant to use this approach. That’s because they had to give recipients harsh preconditioning treatments prior to the bone marrow transplant. For example, in cases of blood disease, the patient undergoes radiation to destroy the diseased cells and to make space for the new, healthy bone marrow cells. Researchers could not justify this risky pre-conditioning regimen in patients with type 1 diabetes who are otherwise healthy. But now, improved technology and advances in the laboratory have led to innovative clinical trials using bone marrow aimed at establishing immune tolerance to transplanted organs.
[diabetes research institute foundation] 12
DRI Director Dr. Camillo Ricordi and the University of Louisville’s Dr. Suzanne Ildstad were among the first to show that establishing stable chimerism resulted in tolerance to transplanted pancreatic insulin-producing islet cells – preventing immune destruction.
inflammation that is characteristic of autoimmunity. The DRI’s goal is to determine what causes this imbalance and dysregulation in the innate immune system and to restore the natural balance between those NK cells that initiate an immune response, and those that prevent it.
Utilizing a new process with a specialized population of bone marrow cells, Dr. Ildstad and her team performed bone marrow transplants using the new protocol in kidney transplant patients. Over 20 patients have been treated with this novel protocol that was successful in establishing high levels of chimerism, allowing patients to discontinue the use of anti-rejection drugs, now for over five years.
NK cells are especially important because they’re involved so early in immune response. By focusing on NK cells, researchers are trying to stop the autoimmune process “upstream.” They believe that upstream imbalances in the NK cell population, particularly in the regulatory subpopulation, likely lead to the "downstream" destruction of “self” tissue in autoimmunity. Additionally, they feel that by fixing the “upstream” problems, the downstream effect might be the correction of the dysregulated late immune response and inflammation of autoimmunity.
The DRI is collaborating with Dr. Ildstad and her colleagues to adapt this approach for the reversal of type 1 diabetes. The new processing technology, developed by Dr. Ildstad, has shown great potential to eliminate the need for anti-rejection drugs in organ transplant recipients.
RESTORING IMMUNE SYSTEM BALANCE When the immune system works properly, it performs a delicate balancing act. On one side: cells that are poised to attack. On the other: cells that prevent an attack. When all goes according to plan, the first group will attack “foreign” invaders such as viruses. But the second group will prevent the first from attacking “self” – a person’s own organs and tissues.
Drs. Luca Inverardi, Allison Bayer and Chris Fraker are investigating the role of regulatory NK cells in the onset of autoimmunity, using type 1 diabetes as the model system. Current studies at the DRI are providing important signaling data involved in increasing the numbers of functional regulatory NK cells. Additional studies will focus on identifying NK cells during disease progression, how to utilize these cells as a cellular therapy in the context of islet transplantation and their role in cell replacement therapies.
In autoimmune diseases such as type 1 diabetes, the immune system loses that balance and cells are able to harm the body. DRI researchers are focused on restoring that balance and are currently pursuing two strategies.
NATURAL KILLER CELLS – THE FIRST LINE OF DEFENSE When something foreign enters the body, “innate immunity” is the first line of defense. The immune system initiates a cascade of events that ultimately eliminates the invader. The first responders are called “Natural Killer” or “NK” cells. As the name suggests, they are the attackers of the innate immune system. As in downstream immune responders, the NK cells have both an “attacking” arm and a “regulatory” arm to keep the immune response from getting out of control. Research shows that in people with autoimmune diseases, such as type 1 diabetes, NK cells are dysfunctional and are fewer in number, causing dysregulated immune responses and the shift to the late immune responses and unchecked
13
[2013 annual report]
[
Drs. Chris Fraker and Allison Bayer are investigating the role of a special population of immune cells that play a key role in autoimmunity.
BOOSTING THE NUMBER OF REGULATORY T CELLS The effector (attacker) cells involved in the downstream immune response, mentioned above, identify what is “foreign” and then destroy the invaders. But in autoimmune diseases, effector cells target a patient’s own tissues and cells. In type 1 diabetes, they attack the insulin-producing cells in the pancreas. Another group of immune cells is supposed to control effector cells and prevent autoimmunity. These protective cells are known as Regulatory T cells, or T-regs. In many autoimmune diseases, T-regs appear to be impaired. If researchers are able to boost their numbers and improve their function, then they may help them control effector cells and avoid autoimmunity. Over the past several years, DRI researchers have been studying the role of IL-2 (interleukin 2), a natural substance and a growth factor released by certain types of immune cells. IL-2 plays a critical role in the function of both effector cells and T-regs. High dose IL-2 has been used in cancer patients as a way to stimulate the effector cells to eliminate the cancer. The DRI’s Dr. Thomas Malek’s landmark studies in experimental mice showed that IL-2 also plays a key role in maintaining proper T-reg function – preventing autoimmunity. This past year, Drs. Alberto Pugliese and Malek showed that human T-regs are highly sensitive to IL-2 and respond to much lower doses compared to effector and memory immune cells, which need much higher levels of IL-2 to initiate a response. Other researchers also showed that low-dose IL-2 improved T-reg function and was able to reverse autoimmune diabetes in experimental models. These important findings point to the use of IL-2 itself, at low dose, as a potential therapy for the control of
autoimmunity. By using low doses of IL-2, researchers hope to selectively boost the levels and function of T-regs without activating effector cells. In doing so, enhanced T-reg function should control autoimmunity with a therapy that stimulates the natural regulatory properties of the immune system, as opposed to the conventional anti-rejection drug therapy and their associated harsh side effects. Low dose IL-2 recently has been tested in clinical trials of two immune-mediated diseases, showing safety and improved T-reg function, as well as improvements of clinical symptoms. Drs. Pugliese and Malek have been working with Dr. David Klatzmann at the Université Pierre et Marie Curie in Paris. He recently completed a pilot clinical trial in patients with type 1 diabetes. The study tested safety and compared various low doses of IL-2 to begin to determine the optimal dose and the potential effects on diabetes and T-reg function. The researchers are encouraged by the preliminary results and enthusiastic about the potential of low dose IL-2 therapy to stimulate regulation and restore the immune system’s balance in type 1 diabetes. The use of a natural substance should be much safer than conventional anti-rejection drug therapy and their associated harsh side effects. Success will enable researchers to intervene and prevent diabetes in individuals at the time of diagnosis, while they still have some functioning insulin-producing cells, and pre-empt the onset of diabetes in those who are known to be at high risk for developing the disease. This therapy may also be applicable to patients undergoing an islet transplant (or any other insulin-producing cell replacement therapies under development), as a means of ensuring that the autoimmune disease
[
In an effort to restore immune system balance, Drs. Alberto Pugliese (left) and Thomas Malek have shown that the use of low doses of IL-2 is effective in increasing the number of Regulatory T cells, which play a critical role in autoimmune diseases, like T1D.
[diabetes research institute foundation] 14
that caused type 1 diabetes in the first place doesn’t attack the new cells. Dr. George Burke, a University of Miami transplant surgeon, and Dr. Pugliese have identified pancreas transplant recipients, who, over time, had a recurrence of autoimmunity. The insulin-producing cells in the transplanted pancreas are targeted for destruction which, again, results in type 1 diabetes. The researchers plan to test low dose IL-2 in these patients to see if this approach can stop the process and save the cells.
LEARNING FROM CANCER Scientists have been studying how some tumors have evolved in such a manner that they can escape from the immune system so that they’re not eliminated. That’s why tumors are able to grow and spread. The DRI is studying how tumors actually block the immune system from targeting and destroying them – and trying to turn that into a positive for type 1 diabetes. Can something be learned from cancer – and protect islet cells from attack, too? Malignant tumors can produce certain molecules, “chemokines,” that help them escape destruction. These molecules help suppress the immune system by recruiting a population of immune cells called myeloid-derived suppressor cells (MDSCs) to the tumor. The MDSCs block the immune system’s attack on the tumor cells. Researchers want to use this same protective mechanism to stop an immune response to the body’s own insulinproducing islet cells (autoimmunity) or to newly transplanted islets. The ultimate goal is to establish permanent acceptance of the insulin-producing cells without the need for anti-rejection drugs. Currently available agents have been used to trigger the production
[ 15
Dr. Alice Tomei and her team are investigating ways that tumors evade attack by the immune system and applying those findings to protect insulin-producing cells.
[2013 annual report]
of MDSCs. DRI scientists believe that similar results may be achieved by giving the recipient a short course of these chemokines at the time of islet transplantation. In experimental models, Dr. Luca Inverardi, DRI’s deputy director, and his immunology team, have achieved encouraging results suggesting that giving chemokines to recipients at the time of an islet transplant prolongs the survival of the tissue. During the past year, the researchers have also gained a greater understanding of why MDSCs have the ability to suppress the immune system’s recognition and reaction to unwanted cells. They have been studying MDSCs taken from the umbilical cord blood of healthy babies and learned that MDSCs are capable of producing Regulatory T Cells (T-regs), which are critical in maintaining the immune system’s balance. They have also observed that the increase in T-reg cells was dependent on the production of a key molecule (IDO). IDO activates the process that leads to immune tolerance during pregnancy, which is why pregnant women are able to accept a fetus instead of rejecting it, even though the unborn child’s immune system is different than the mother’s. The researchers have found MDSCs offer other potential benefits. As they began in-depth studies of the cells’ characteristics, they discovered that these cells express unique markers that also classify them as fibrocytes. Fibrocytes play a key role in promoting wound healing. The team believes that this novel discovery will have a positive impact on the use of these MDSC/fibrocytes for both their powerful immunosuppressive properties as well as their ability to repair injured tissue. The DRI's Biomedical and Immune Engineering team is exploring another approach to protect transplanted pancreatic islets without the need for any anti-rejection therapy. The focus: the molecule CCL21.
[ Dr. Alice Tomei, the DRI’s co-director of bioengineering, has shown that tumors release the molecule CCL21, which plays a central role in protecting them from immune attack. More recently, Dr. Tomei has applied those findings to cell transplantation in experimental models. She and her team engineered cells to express CCL21 within the transplanted tissue. They also engineered proteins to deliver CCL21 within a local transplant environment, such as a DRI BioHub. By delivering the molecule locally, many recipients accepted the cells – without systemic anti-rejection drugs. Also, in preliminary studies, the team showed that the production of CCL21 in islets creates a lymph node-like environment, removing unwanted cells that can promote an autoimmune response. Ongoing studies are looking at the mechanism by which these structures prevent the development of autoimmune diabetes in experimental models. Preliminary evidence points to the involvement of certain stromal cells within these structures. Stromal cells are the connective tissue cells of any organ. The interaction between stromal cells and tumor cells is known to play a major role in cancer growth and progression. Based on the initial findings, the team will conduct additional studies to further characterize these cells and the role they can play in preventing the development of autoimmunity, as well as the recurrence of autoimmunity after islet transplantation.
CONTROLLING INFLAMMATION As part of the multi-pronged approach to protect insulin-producing cells from immune attack, researchers are also aiming to quell the danger signals that cause
Dr. Antonello Pileggi and his team are investigating methods to reduce harmful inflammation that threatens the survival of transplanted islet cells in the critical, early phase post-transplant
inflammation and are harmful to islet cells. When someone gets a splinter in their finger, the immune system senses something foreign, and potentially dangerous, and reacts immediately. A series of highly-regulated, complex responses kick into gear – and the skin around the finger becomes inflamed. This process also occurs when transplanting islet cells. The immune system reacts to the biological “insult,” triggering inflammation that can damage the transplanted cells and prompt further immune attacks. Controlling inflammation is a major research priority and the focus of numerous studies aimed at protecting transplanted islets, as well as the onset or recurrence of autoimmune diabetes. DRI researchers are currently pursuing two different approaches. The DRI’s Dr. Antonello Pileggi and his team are working with a molecule that appears to be a critical player in activating inflammation: extracellular adenosine tri-phosphate (eATP). ATP serves as a source of energy within each cell. In pancreatic beta cells, the release of low amounts of ATP is part of a sophisticated check-andbalance mechanism that regulates optimal cell function. But when cells are stressed – by a biological insult or other unfavorable conditions (such as a transplant and autoimmunity development) – they release large amounts of ATP into the local environment (that is eATP). The team is assessing whether the release of high levels of ATP stimulates an immune response that, in turn, contributes to the destruction of the cells themselves. Initial studies in experimental models of islet, heart and lung transplantation demonstrated that, by blocking the function of eATP, they were able to reduce the activation of pro-inflammatory immune cells and, in turn, prolong the survival of transplanted tissues.
[diabetes research institute foundation] 16
[
Dr. Peter Buchwald is testing agents that prevent inflammation, as well as low-dose anti-rejection drugs that may be used locally within a DRI BioHub to prevent an immune attack on the transplanted cells.
The studies also revealed a remarkable synergy when combined with immune-modulating agents. The findings were the result of an international collaborative initiative with Professor Fabio Grassi at the Institute for Research in Biomedicine, Bellinzona, Switzerland, and Dr. Paolo Fiorina at Children’s Hospitals, Harvard University in Cambridge, MA. Their research led to the publication of three seminal manuscripts that appeared in the peer-reviewed, scientific journals, Diabetes (islet transplantation), Circulation (heart transplantation), and American Journal of Respiratory Cell and Molecular Biology (lung transplantation), respectively, as well as a recent review manuscript describing the working hypothesis published in the American Journal of Transplantation. The data has been presented at recent professional scientific meetings. Having demonstrated the beneficial effects of the systemic modulation of eATP signaling in transplantation models, the current efforts are concentrating on the role of eATP on islet immunogenicity and in the development of T1D. Dr. Pileggi’s group is further pursuing this important research to better understand the role and mechanisms associated with the eATP pathway in islet immunity (innate immunity, rejection and autoimmunity), as well as identifying other potential targets involved in this process. The ultimate goal is to characterize the presence of specific signaling molecules and test methods to modulate the immune response and restore immune regulation in T1D, and protect islet transplants in the local microenvironment. This approach could result in synergy with cell-based immunotherapies aimed at protecting islet cells at the time of autoimmune diabetes onset as well as in a DRI BioHub.
17
[2013 annual report]
In another approach, researchers are looking at a part of the immune system – the TGF-ß molecule – that is supposed to control inflammation. However, scientists have learned that in certain diseases, a protein, Smad7, interferes with the TGF-ß pathway. The result: Smad7 promotes immune cell signaling and immune responses. The DRI is testing agents that block Smad7. This would allow TGF-ß to function properly and help regulate inflammation. Scientists already have identified a therapeutic agent that targets Smad7 and are using this agent in clinical trials to treat inflammatory bowel disease (IBD), with encouraging early results. In addition to preventing the inflammatory and immune response associated with islet transplantation, there is also the intriguing possibility of preventing or even reversing diabetes in new-onset patients. At the DRI, Dr. Peter Buchwald, director of drug discovery, and his colleagues have conducted preliminary studies showing that, by inhibiting/blocking Smad7 at the time of diabetes onset, diabetes went into remission. More than half of the treated models experienced normal blood glucose levels and adequate insulin secretion – even long-term after discontinuation of the treatment. These results are particularly encouraging, raising the possibility of reducing inflammation and controlling the immune attack to the ongoing destruction of the insulinproducing cells in new-onset patients. This could also be beneficial to islet transplant recipients. Ongoing studies are aimed at assessing the timing and dosing requirements needed for efficacy as well as assessing the mechanism of action. The researchers are also conducting larger-scale experiments needed to evaluate the potential of translating these encouraging results into novel type 1 diabetes clinical trials.
[ The DRI is also investigating the use of certain types of cells in the body that can hamper inflammation, promote tissue repair and enhance blood vessel growth. Mesenchymal stem cells, or MSCs, can become a variety of cell types, including bone, cartilage and fat. They also have several properties that can help improve the success of islet transplantation. DRI immunologists, along with colleagues on the tissue engineering team, have shown that by co-transplanting insulin-producing cells with MSCs, they were able to promote blood vessel growth and tissue repair. Dr. Norma S. Kenyon, who heads the MSC research project, conducted pre-clinical studies using this combination of cells within a silicone scaffold, one of the platforms being tested for a DRI BioHub. This BioHub platform was placed within an omental pouch, which was created by folding a piece of the apronlike tissue covering the abdomen. This approach has resulted in enhanced acceptance and extended viability of transplanted insulin-producing cells. With the support of a multi-center NIH grant, Dr. Kenyon and her colleagues are now conducting research to identify the specific characteristics of the most effective MSC populations for islet transplantation and their incorporation into a DRI BioHub. Once an effective MSC product is defined and demonstrated to be optimal for intrahepatic (within the liver) islet transplantation, the same cells will be utilized in future tissue engineering experiments.
Dr. Norma Kenyon and her team conducted pre-clinical studies testing the co-transplantation of islets and mesenchymal stem cells (MSCs) within a DRI BioHub platform.
CELL ENCAPSULATION: PROTECTIVE BARRIERS FOR ISLETS What if islet cells could be physically shielded from attack by immune system cells by encapsulating the cells in a protective skin, or barrier? For more than 40 years, the encapsulation of islet cells has been researched as a potential therapy for type 1 diabetes. However, there has been limited success in translating this approach to patients due to a number of issues, including the size of the capsules themselves, the materials used to coat the cells and the inability to provide the encapsulated islets with enough oxygen to keep them healthy and functioning long term. The DRI has been pursuing several strategies aimed at overcoming these challenges and has made significant progress over the last year. The bioengineering team has invented and optimized several new technologies to individually coat the islets in ultra-thin layers that camouflage them from the recipient’s immune system. By minimizing the space surrounding the islet cell, not only can they enhance the oxygen and nutrient delivery to the cells, but also have the ability to transplant the cells within a DRI BioHub. The DRI’s Dr. Cherie Stabler and her team have invented a technology that generated nanoscale (less than microscopically thin) coatings onto islets. This is achieved by “dipping” the cells in polymers to create individual layers. Nanoscale, or layer-by-layer, encapsulation is a technique that has been used for decades in the electronics, optics and sensor industries.
[diabetes research institute foundation] 18
This encapsulation methodology provides significant control over the properties of the layers, resulting in a coating that is 500-fold smaller than conventional microcapsules. The team’s recently published study in the journal Advanced Healthcare Materials is the first to show that layer-by-layer nanoscale coating can prevent rejection of transplanted islets in rodents, resulting in long-term function. This is a major step forward in nanoscale encapsulation research. These layered coatings also provide a platform for attaching immunomodulatory agents to the surface of the cells that can help fight off an immune attack. Dr. Alice Tomei and her team are developing another encapsulation strategy, the conformal coating process, that “shrink wraps” each islet cell with the coating material as it passes through a special microfluidic system. As with a person’s own skin, which has small pores that provide protection and allow oxygen to enter, cell coatings must be designed in much the same way. The pores need to screen out destructive immune system cells but allow oxygen, glucose (blood sugar) and insulin to easily pass through. Over the last two years, the team has demonstrated long-term immunoprotection of transplanted islets encapsulated with conformal coatings in rodent models of diabetes. In these studies, diabetes was reversed in less than two weeks and the coatings were able to protect transplanted islets from rejection while maintaining normal blood sugar levels in the experimental models. The islets continued to function long term without the use of any anti-rejection drugs. The team is currently reproducing these results in a larger cohort of experimental models, in larger pre-clinical models, and in clinically relevant sites. DRI scientists are also tackling another major factor that inhibits islet engraftment – the lack of adequate oxygen in the immediate post-transplant period. After islets are transplanted into a patient, it takes several weeks for new blood vessels to form, which transport the critical oxygen and nutrients these cells demand. Closing this oxygen gap is a top priority for healthy islet function. Several approaches are underway to address this issue. First, the use of specific growth factors released in a controlled manner, which have been successful in speeding blood vessel development (as early as seven days after transplant) and improving post-transplant islet function and reducing islet loss. Alternatively, in a unique approach to oxygen delivery, DRI researchers are focusing on incorporating oxygen directly within each capsule by mimicking a process that occurs in nature every day – photosynthesis. Plants convert sunlight and water into its components, one of which is oxygen. Dr. Chris Fraker has developed a
19
[2013 annual report]
>
An Eye on Immune Tolerance DRI scientists have been working to determine if the successful achievement of immune tolerance through the anterior chamber of the eye will allow for survival of transplanted islets without immunosuppression. Following their cover-featured publication in the peerreviewed journal Diabetologia, which reported on the use of the anterior chamber of the eye as a transplantation site in pre-clinical models to treat type 1 diabetes, Drs. Per-Olof Berggren, Midhat Abdulreda, Norma Kenyon, and Dora Berman-Weinberg developed a collaboration with researchers from Seoul National University in Korea to further investigate this approach and help establish it as a clinical transplantation site. Studies have been ongoing concurrently in Seoul and at the DRI in Miami. These studies explore the feasibility of intraocular islet transplantation in pre-clinical models of type 1 diabetes.
similar process in the lab using naturally-occurring metals (minerals) that can, under the proper conditions, generate oxygen spontaneously from water. A side benefit to this approach is that these metals can also scavenge free radicals and other damaging particles by converting those into oxygen in addition to other harmless components. He and his team are making microscopic particles (nanoparticles) out of the metals and incorporating them into the polymers used to encapsulate the cells, giving them a type of built-in oxygen provider. The nanoparticles can be used together with any type of biomaterials used for the coatings, as well as being incorporated within a BioHub platform, to increase oxygen levels and improve transplant outcomes.
LOCAL DRUG DELIVERY The development of a DRI BioHub provides the ability to incorporate anti-inflammatory and anti-rejection drugs within the bioengineered device. Local drug delivery is commonly used in a variety of treatments requiring antiinflammatory steroid delivery and hormone therapy. DRI researchers are testing similar approaches to those in use for these conditions, such as thin rods and drugeluting polymers for the long-term, sustained release of therapeutic agents as a means of protecting transplanted islets within the local environment. This could allow for the use of much smaller local doses and avoid or minimize the systemic side effects of current therapies. The DRI’s bioengineering team, in conjunction with Dr. Peter Buchwald, head of DRI's drug discovery program, is using a unique embedding and coating process to deliver sustained-released drugs that are known to minimize this initial immune inflammatory response. This past year, the team tested several combinations of drugs to determine the best results. The local delivery of low-dose anti-inflammatory and/or anti-rejection drugs at the transplant site offers the opportunity to minimize or maybe even eliminate the current, systemic drugs that pose so many unwanted side-effects.
TARGETING CELLS IN VIVO Researchers continue to develop new and significantly more precise methods to deliver desired molecules and other agents to targeted cells within the body or in a DRI BioHub. New advances in imaging and nanotechnology are allowing scientists to test a special class of molecules which are, essentially, the chemical equivalent of antibodies.
Known as aptamers, these tiny strands are able to hone in and bind to specific targets on the cell surface. Aptamers are an attractive alternative to previous drug delivery techniques due to their small size and relatively low production cost. Aptamers also have the advantage of being highly specific, meaning they can bind to targeted cell markers without eliciting a foreign tissue (immune) response. The DRI team, including Drs. Luca Inverardi, Paolo Serafini, Alessia Zoso, and Giacomo Lanzoni, have selectively screened for aptamers unique to islets and beta cells for the rodent model. The team is now focused on adapting the same methods to create an aptamer library specific to human islets and beta cells. The team is also using this novel technology to "tag" living insulin-producing cells within the native pancreas or in a DRI BioHub by attaching fluorescent markers to the aptamers. After binding to the targeted islet/beta cell, sophisticated scanners will be able to pick up the fluorescently-labeled islets, providing valuable information as to the quantity of living islets/beta cells and their location. The team is also adapting this technology for its use with clinical instruments, such as Magnetic Resonance Imaging (MRI), that is routinely used in the clinic. This will also allow for the delivery of anti-inflammatory and/or anti-rejection agents directly to the desired cells instead of shutting down the entire system with systemic immunosuppression. Since the discovery of aptamers in the early 1990s, great efforts have been made to make them clinically relevant for diseases like cancer, HIV, and macular degeneration. In the last two decades, many aptamers have been clinically developed and FDA approved. In 2004, aptamer-based therapy was approved for the treatment of age-related macular degeneration and several other aptamers are currently being evaluated in clinical trials.
[
Drs. Alessia Zoso and Paolo Serafini are part of the team that is testing a special class of molecules, called aptamers, that bind to insulin-producing beta cells. The aptamers enable researchers to attach markers directly to the cells in order to track and image the living cells in the body.
[diabetes research institute foundation] 20
Area 3
Supply
Currently, islets used for transplantation come from the pancreases of deceased donors. With organ donation in the United States at critically low levels – about 1,700 pancreases were available last year – there is clearly not enough supply to treat the millions of children and adults living with diabetes.
The DRI is pursuing several strategies to develop a reliable supply of insulinproducing cells. Identifying the right stem cells – those with the potential to become islet cells – is a key step for the design of cell replacement, regenerative and reprogramming strategies.
At the DRI, researchers are using certain populations of stem cells, as well as reprogramming other cells of the body that have an entirely different function to becoming insulin-producing cells.
THE BILIARY TREE: A NOVEL SOURCE OF INSULIN-PRODUCING CELLS An area that has sparked great interest is the discovery of stem cells in the "biliary tree" – a network of drainage ducts that connect the liver and pancreas to the intestine. DRI scientists are interested in these cells because they are pancreatic "precursor" cells – that is, they already have started down the path to become pancreatic cells. This could make it easier for scientists to produce a more efficient maturation and a higher yield of islet cells. The DRI’s Drs. Luca Inverardi, Giacomo Lanzoni and Juan Dominguez-Bendala are collaborating with Dr. Lola Reid from the University of North Carolina, a recognized expert in liver development and regeneration, who discovered these peculiar stem cells. In the past year, they showed that stem cells within the biliary tree can transform into both liver and pancreatic cells, including insulin-producing islet cells. They obtained the pancreatic precursor cells from the biliary tree. The researchers then cultured these cells with a mixture of growth factors and components found in the natural islet environment. These molecular signals instruct the cells to mature into islets. The process resulted in structures that looked like islets and contained both insulin- and glucagon-producing cells.
21
[2013 annual report]
These islet structures released insulin and C-peptide (a component of natural insulin production) in response to glucose challenges. The researchers demonstrated that transplanting these structures into diabetic mice dramatically improved blood sugar control. The group has identified an extended network of stem cell pockets that branch out from the more naïve stem cells in the biliary tree to more and more mature cells in the pancreas and liver. These findings suggest that the development of the pancreas does not come to an end in adulthood and may continue as a life-long process that can regenerate the stressed organ, islet cells included. The investigators are scaling up these findings and testing regenerative strategies based on biliary tree stem cells for type 1 diabetes. As a result of this collaboration between Miami and Chapel Hill, several research papers have been published in prestigious journals, and others are in press. A paper titled “Biliary Tree Stem Cells, Precursors to Pancreatic Committed Progenitors: Evidence for Possible Life-long Pancreatic Organogenesis” appeared in the journal Stem Cells, along with a review on “Clinical programs of stem cell therapies for liver and pancreas.” Ongoing studies are aimed at establishing proof of concept that these cells can be used to reverse diabetes in pre-clinical models. The team is also assessing optimal implantation sites as well as strategies to aid in “transforming” or differentiating these pancreatic precursors by mimicking the critical components of their native environment combined with newly discovered islet-specific growth factors.
REPROGRAMMING THE NON-ISLET TISSUE OF THE PANCREAS INTO INSULIN-PRODUCING CELLS Rather than educating a stem cell from its earliest stages of development – pushing it down the long path to become an islet-type cell – transdifferentiation can potentially offer a short cut. In this approach, scientists take a more mature cell type and “reprogram” it, transforming it directly into an insulin-producing cell.
To accomplish this, the DRI has been focusing on the part of the pancreas that does not produce insulin: the nonendocrine pancreatic tissue, or NEPT. NEPT makes up almost 98 percent of the organ. It helps process food by producing digestive enzymes. NEPT typically is discarded after an islet isolation procedure. Since the DRI is a leading islet isolation facility, it has a plentiful supply of NEPT. One of the interesting features of NEPT is its high plasticity – its ability to turn into other cell types or tissues. At the DRI, Drs. Juan-Dominguez-Bendala, Ricardo Pastori and Luca Inverardi are developing and testing new methods to reprogram human NEPT into insulin-producing cells. The team is assessing whether this tissue can be transformed and used as a source for cell transplantation. During the past year, the researchers discovered that, once placed in culture, these cells tend to lose their identity within days, progressively becoming a cell type called “mesenchymal” that is virtually useless for reprogramming purposes. This “degradation” process is known as Epithelial to Mesenchymal Transition (EMT). The team took the novel approach of adding a currently available agent to the culture – and successfully blocked EMT. This led to robust reprogramming and an extraordinary yield of NEPT into insulin-secreting cells. The ability to chemically block EMT allowed for the generation of cells that secrete insulin in response to glucose with total insulin levels comparable to those of native islets. Importantly, preliminary experiments showed that reprogramming is also possible using frozen NEPTs. This could be important for clinical islet transplantation because, down the line, it might allow for a second infusion of insulin-producing cells from the same donor.
The DRI is now focused on optimizing the culture conditions to induce reprogramming into insulinproducing cells and subsequently transplanting these cells in experimental models. They will also optimize conditions for reprogramming of previously frozen NEPTs. Additional research will focus on identifying subsets of cells within the NEPT that may be more prone to islet cell reprogramming.
CONVERTING SKIN FIBROBLAST CELLS INTO BETA CELLS When a stem cell is undifferentiated or uncommitted – before it “decides” to become a certain kind of cell – its DNA is “loose.” It’s able to develop into many cell types. This ability is known as “pluripotency.” As a cell develops and commits to a specific function, its DNA “hardens.” But scientists are now able to “loosen” the DNA of an adult, committed cell. And that cell can regain some degree of pluripotency. This “loose” state does not last long, but long enough for scientists to push the cell down a new path to become a different kind of cell. DRI collaborators at the University of Milan, Italy, led by Dr. Tiziana Brevini, recently developed a method to convert skin “fibroblast” cells into insulin-producing beta cells. Fibroblasts are found throughout the human body. These cells are known as pancreatic epigenetic converted cells (EpiCC). They show many characteristics of mature beta cells and also include other key endocrine cells of healthy islets. As reported in the May, 2013 Proceedings of the National Academy of Science (PNAS), studies have demonstrated that the EpiCC are able to secrete C-peptide in response to glucose and maintain this ability for more than 100 days.
[
Drs. Juan Dominguez-Bendala (standing, left), Luca Inverardi and Ricardo Pastori (seated) are developing and testing methods to reprogram the nonendocrine tissue of the pancreas to increase the supply of insulin-producing cells.
[diabetes research institute foundation] 22
When injected into diabetic mice, EpiCC, which were developed from human skin cells, quickly restored normal blood glucose levels. All mice were able to maintain these levels for 133 days, at which time the EpiCC were removed. Subsequently, a rapid increase of blood sugar was observed along with an equally rapid loss of detectable human insulin, which was previously present. Preliminary results indicate that EpiCC may be converted into insulin-expressing cells. The researchers will continue to characterize the converted fibroblasts, following the method developed in the Brevini lab, to evaluate insulin production and other characteristics of pancreatic endocrine cells. The DRI is pursuing the potential of using EpiCC as an alternative source because such cells could provide a near limitless supply of insulin-producing cells in response to changing levels of glucose. In addition, the converted skin cells obtained from the patient would not be seen as “foreign” and therefore would not be rejected, which occurs with transplanted cells from another donor.
The research projects that comprise the DRI BioHub receive critical philanthropic support from the Diabetes Research Institute Foundation. Funding for the DRI BioHub is also provided by other sources including the ADA, JDRF, The Leona M. and Harry B. Helmsley Charitable Trust, National Institutes of Health (NIH), NIH Small Business Innovation Research, Ri.MED Foundation, University of Miami, and additional public and corporate partners.
TRIALNET UPDATE
[
Dr. Jay Skyler, DRI deputy director, serves as study chairman for the NIH-sponsored TrialNet, an international network conducting clinical trials to prevent, delay and reverse type 1 diabetes.
TrialNet has conducted several studies aimed at slowing the immune system’s attack on insulin-producing cells in people newly diagnosed with type 1 diabetes. Two of the studies that TrialNet has conducted, and a third organized by the Immune Tolerance Network with TrialNet participation, have identified drugs with promise of benefit. Currently, TrialNet is focused on altering the immune system attack in order to delay or prevent type 1 diabetes in relatives found to be at risk for the disease. Three prevention studies are ongoing – using oral insulin, the
23
[2013 annual report]
immune co-stimulation blocking drug abatacept, and a monoclonal antibody targeting activation of the immune system. In addition, TrialNet is poised to launch additional studies in people newly diagnosed with type 1 diabetes. The studies are conducted by the National Institutes of Health’s international network of researchers, Type 1 Diabetes TrialNet Study Group, which is housed at the DRI, under the direction of Dr. Jay Skyler, TrialNet national chairman. To learn more about TrialNet, visit www.DiabetesTrialNet.org.
THE DIABETES EDUCATION AND NUTRITION SERVICE AT THE DRI The Diabetes Education and Nutrition Service at the DRI’s Eleanor and Joseph Kosow Diabetes Treatment Center continues to use collaboration, innovation, integration and evaluation as the driving forces behind its patient initiatives.
The past year has represented one of transition – education team members leaving for new professional opportunities and new education team members coming to the DRI to experience the incredible educational offerings that comes from working with highly-skilled providers and researchers. New leadership is already in place with the directorship being shared by two past DRI diabetes educators, Lisa E. Rafkin, MS, RD, LD, CDE, CCRC, research assistant professor of medicine, and Della Matheson, RN, CDE, both of whom have worked for many years at the DRI in the area of clinical research, and on the DRI diabetes management team under the guidance of Dr. Jay Skyler some 20 years ago. They will be joined by several newly hired specialists, including dietitians and certified diabetes educators, so that they will be able to meet the increasing demand for patient education and medical nutrition therapy at the DRI. The program remains certified as an American Diabetes Association’s Education Recognized Program, which enables collection of revenues for education and nutrition services. Under Dr. Skyler’ s supervision, the new team will continue to strive for excellence and continued improvement in overall patient services. Looking back over the past 12 months: • More and more patients are being referred to the DRI’s unique education program, and these patients come from the DRI Clinic, University departments, including Pediatric Endocrinology, and a growing number of community providers. The recent closure of three large, community-based diabetes education programs over the past two years has made the services provided by the DRI even more crucial for patients and their families. • With over 8,000 visits captured, the DRI’s use of an innovative data management system has enabled optimization of existing services and targeted improvements of internal processes and future provision of services. • The DRI team continues to be involved in professional and community outreach initiatives, including but not limited to: – UM campus and community health services, including expansion sites throughout South Florida
– Diabetes Research Institute Foundation – PEP (Parents Empowering Parents) Squad and ‘Top Tips’ articles – Seminole Media Productions
• The DRI Diabetes Education and Nutrition Service also coordinated more than a dozen clinical experience training programs during the past year, up-skilling industry representatives on the medical and education standards for diabetes care. Over 800 representatives attended, with outstanding program satisfaction ratings across all programs offered. With an eye toward the future, the DRI Diabetes Education and Nutrition Service is updating its very successful educational curriculum to continue the current class schedule (e.g., Healthy Me, Diabetes Made Simple, Pump Training and the highly acclaimed Mastering Your Diabetes program), and is adding several innovative components in the near future:
– Florida International University Dietetic Student Internship Program
• A DRI online, interactive diabetes education program, tailored for health care professionals involved in the care of people living with diabetes.
– Local professional presentations by the American Diabetes Association, Health Choice Network, National Podiatry Association and the University of Miam iGrand rounds
• A multi-disciplinary Transition Program, to assist children and parents in transition from pediatric to adult-based diabetes management and care
– Professional Association Positions (NCBDE, AADE, GMADE)
• A Diabetes Prevention Recognition Program (based on CDC and AADE program standards) [diabetes research institute foundation] 24
DIABETES RESEARCH INSTITUTE FACULTY AND STAFF Faculty Dr. Camillo Ricordi
Dr. Jeffrey Hubbell
Stacy Joy Goodman Professor of Surgery Division of Cell Transplantation Distinguished Professor of Medicine Director, Diabetes Research Institute and Cell Transplant Center
Adjunct Professor of Surgery Director, Integrative Biosciences Institute Institute for Chemical Sciences and Engineering at Ecole Polytechnique FĂŠdĂŠrale de Lausanne, Switzerland
Dr. Midhat H. Abdulreda
Dr. Luca Inverardi
Assistant Professor of Surgery Division of Cell Transplantation
Research Professor of Medicine, Microbiology and Immunology Director, Immunobiology of Islet Transplantation Deputy Director for Translational Research
Dr. Rodolfo Alejandro Professor of Medicine Director, Clinical Cell Transplant Center Associate Director of Clinical Research Associate Director, Cell Transplant Center
Dr. Allison Bayer Research Assistant Professor of Microbiology and Immunology
Dr. Per-Olof Berggren Mary Lou Held Visiting Scientist Adjunct Professor of Surgery Head of Cell Biology and Signal Transduction Professor and Head, Experimental Endocrinology at the Karolinksa Institute, Sweden
Dr. Dora Berman-Weinberg Research Associate Professor of Surgery
Dr. Peter Buchwald Associate Professor of Molecular and Cellular Pharmacology Director, Drug Discovery Program
Dr. Juan Dominguez-Bendala
Dr. Norma S. Kenyon Martin Kleiman Professor of Surgery, Medicine, Microbiology and Immunology, and Biomedical Engineering Director, Wallace H. Coulter Center For Translational Research Chief Innovation Officer, University of Miami
Dr. Jennifer Marks Professor of Medicine Division of Endocrinology, Diabetes and Metabolism
Dr. Armando Mendez Research Associate Professor of Medicine Division of Endocrinology, Diabetes and Metabolism Director, Advanced Technology Platforms
Dr. Daniel H. Mintz Scientific Director Emeritus Professor Emeritus of Medicine
Dr. Bresta Miranda-Palma
Research Associate Professor of Surgery Director, Stem Cell Development for Translational Research
Assistant Professor of Medicine Interim Director, Eleanor and Joseph Kosow Diabetes Treatment Center Division of Endocrinology, Diabetes, and Metabolism
Dr. Chris Fraker
Dr. Ricardo Pastori
Research Assistant Professor of Surgery Division of Cell Transplantation
25 [2013 annual report]
Research Professor of Medicine, Immunology and Microbiology Director, Molecular Biology Laboratory
Dr. Maria del Pilar Solano Assistant Professor of Medicine
Dr. Antonello Pileggi Research Associate Professor of Surgery Director, Pre-Clinical Cell Processing and Translational Models
Dr. Alberto Pugliese Research Professor of Medicine, Microbiology and Immunology Director, Immunogenetics Program
Dr. Jay Skyler Professor of Medicine, Pediatrics and Psychology Division of Endocrinology, Diabetes and Metabolism Deputy Director for Clinical Research and Academic Programs, Diabetes Research Institute Chairman, NIDDK Type 1 Diabetes TrialNet Study Group
Dr. Cherie Stabler Associate Professor of Biomedical Engineering, Surgery Director, Tissue Engineering Laboratory
Dr. Alice Tomei Research Assistant Professor of Surgery Division of Cell Transplantation
DIABETES RESEARCH INSTITUTE FACULTY AND STAFF Administrative
Clinical Chemistry Lab
Drug Discovery Program (DPP)
Dr. Mitra Zehtab,
Dr. Armando Mendez,
Dr. Peter Buchwald, Associate Professor
Chief Operating Officer and Deputy Director
Research Associate Professor of Medicine, Director
Mabel Luis, Executive Assistant Dora Cardenal, Director, Accounting Sabrina Boulazreg, Sr. Manager, Business Operations
Angie Arzani, Sr. Manager, Finance Juan Perez-Scholz, Manager, Sponsored Programs
Dr. Ronald B. Goldberg, Dr. Marcos Levy-Bercowski, Voluntary Assistant Professor of Surgery
Dr. Monia Cecati, Research Scholar Esperanza Perez, Supervisor, Medical Technologists
Rosa Hernandez, Research Associate 1 Elsa Cribeiro, Sr. Research Assistant Zackary Barnes, Sr. Research Assistant
Medical Development
Clinical Cell Transplant Program (CCTP)
Sr. Development Director, Major Gifts
Dr. Rodolfo Alejandro,
Aimee Siegel-Harris,
Professor of Medicine, Director
Manager, Donor Relations
Bioengineering
Dr. Sirlene Cechin, Assistant Scientist Dr. Jinshui Chen, Post-Doctoral Associate Omar Lopez-Ocejo, Research Associate 1 Yun Song, Student Research Assistant
Professor of Medicine
Ligia Delgado, Sr. Accounting Assistant Grace Perez, Sr. Buyer Marc Friedenthal, Buyer Ilvis Torres, Administrative Assistant
Gary Kleiman,
of Molecular and Cellular Pharmacology, Director
Eleanor and Joseph Kosow Diabetes Treatment Center Faculty Dr. Ronald B. Goldberg, Professor of Medicine
Dr. Jennifer Marks, Professor of Medicine Dr. Daniel H. Mintz, Professor Emeritus
Dr. Eduardo Peixoto, Assistant Scientist Ana Alvarez Gil, ARNP Alina Cuervo, Sr. Medical Biller
Dr. Chris Fraker,
of Medicine
Dr. Bresta Miranda-Palma, Assistant Professor of Clinical of Medicine, Interim Director
Dr. Maria del Pilar Solano,
Research Assistant Professor of Surgery
Clinical Research Center
Assistant Professor of Clinical of Medicine
Dr. Alice Tomei,
Dr. Bresta Miranda-Palma,
Research Assistant Professor of Surgery
Assistant Professor of Medicine, Director
Vita Manzoli, Sr. Research Associate 1 Mejdi Najjar,
Burlett Masters,
Dr. Jay Sosenko, Professor of Medicine Dr. Jay S. Skyler,
Research Assistant Professor 1
Research Support Specialist
Professor of Medicine, Pediatrics and Psychology
Ada Konwai, Sr. Research Assistant
Dr. Lisa Rafkin-Mervis,
Chiara Villa, Non-Enrolled Fellow
Research Assistant Professor of Medicine
Bio-Informatics
Diabetes Prevention Program (Type 2)
Roopesh Sadashiva-Reddy,
Dr. Ronald B. Goldberg,
Database Administrator
Professor of Medicine, Director
Juliet Ojito, Nurse Specialist, Research Jeanette Gonzalez-Calles, Research Associate
Maria Valbuena, Research Associate 1 Bertha Veciana, Medical Assistant Wanda Ramirez, Secretary
Health Care Professionals Lory Gonzalez, Nurse Educator Gwen Enfield, Clinical Dietitian Amy Kimberlain, Dietitian
Clinical Administration Dina Bardales, Supervisor, Patient Access
Arleen Barreiros, Project Coordinator Starlette Canamero, Sr. Administrative Assistant
[diabetes research institute foundation] 26
Flow Cytometry Lab
Microbiology and Immune Tolerance Alexander Rabassa,
Dr. Oliver Umland, Assistant Scientist
Dr. Tom Malek, Professor of Microbiology
Histology
Dr. Allison Bayer, Assistant Professor of
and Immunology
Kevin Johnson, Sr. Research Associate 3
Microbiology and Immunology
Dr. Allison Bayer, Assistant Professor Human Cell Processing (cGMP) Facility Cecilia Cabello, Research Associate 3 Shane Mackey, Research Associate 1 Dr. Luca Inverardi, Research Professor of Medicine, Facility Director
Dr. Elina Linetsky, Director, Interim Director Laboratory Services
Dr. Joel Szust, Scientist Dr. Alejandro Alvarez-Garcia, Associate Scientist
Dr. Xiao Jing Wang, Associate Scientist Dr. Greta Minonzio, Research Scholar Dr. Muyesser Sayki, Research Scholar Carmen Castillo,
Molecular Biology Dr. Ricardo Pastori, Research Professor of Medicine, Director
Dr. Camillo Ricordi, Stacy Joy Goodman Professor of Surgery, Director
Xiumin Xu, Director, DRI-China, Collaborative Human Cell Transplant Programy
Image Analysis Facility
Marta Garcia Contreras, Sr. Research
Associate Associate 1
Immunobiology of Islet Transplantation
Pre-Clinical Cell Processing and Translational Models
Dr. Luca Inverardi, Research Professor of
Dr. Antonello Pileggi, Research Professor
Dr. Alessia Zoso, Scientist Dr. Giacomo Lanzoni, Assistant Scientist Dr. Sophie Borot, Research Scholar Matteo Battarra, Research Scholar
Immunogenetics Program Dr. Alberto Pugliese, Research Professor of Medicine, Director
Dr. Francesco Vendrame, Scientist Dr. Isaac Snowhite, Research Scholar Gloria Allende, Sr. Research Associate
of Surgery, Director
Dr. Ruth Damaris Molano, Scientist and Core Director
Dr. Carmen Fotino, Assistant Scientist Dr. Ulissi Ulisse, Research Scholar Alejandro Tamayo-Garcia, Research Associate 1
Yelena Gadea, Sr. Veterinary Technician Adriana Lopez-Ospina, Research Assistant
Pre-Clinical Research Dr. Norma Sue Kenyon, Martin Kleiman Professor of Surgery, Director
Islet Physiology
Dr. Dora Berman-Weinberg,
Dr. Per-Olof Berggren, Adjunct Professor
Research Associate Professor
of Surgery, Director
Dr. Midhat Abdulreda, Assistant Professor of Surgery
Dr. Joana Almaca, Research Scholar Alexander Shishido, Research Associate 1
Dr. Dongmei Han, Scientist Dr. Ana Hernandez, Associate Scientist Waldo Diaz, Sr. Manager, Research Laboratory
Melissa Willman, Sr. Manager, Research Support
27 [2013 annual report]
Veterinary Technician
Stem Cell Development for Translational Research Dr. Juan Dominguez-Bendala, Research Associate Professor of Surgery, Director
Dr. Sara Garcia Serrano, Research Scholar Silvia Alvarez, Manager, Research Laboratory
Tissue Engineering Fast Track
Dr. Fanuel Messaggio, Post-Doctoral
Medicine, Director
James Geary, Sr. Veterinary Tech Reiner Rodriguez-Lopez,
Dr. Dagmar Klein, Scientist
Research Laboratory Technician
Dr. Marcia Boulina, Assistant Scientist
Sr. Research Associate 3
Dr. Cherie Stabler, Associate Professor of Biomedical Engineering, Director
Dr. Jeffrey Hubbell, Adjunct Professor of Surgery
Dr. Kerim Gattas-Asfura, Associate Scientist Joshua Gardner, Sr. Research Associate 1 Irayme Labrada-Miravet, Research Assistant Maria Coronel, Student Research Assistant Anthony Frei, Student Research Assistant Jaime Giraldo, Student Research Assistant Kaiyuan Jiang, Student Research Assistant Mike Valdes, Student Research Assistant Ethan Yang, Student Research Assistant
Diabetes TrialNet Dr. Jay Skyler, National Chairman Dr. Norma Sue Kenyon, Associate Chair for Immunology
Dr. Jennifer Marks, Principal Investigator –TrialNet Clinical Center
Dr. Alberto Pugliese, Co-Investigator, Clinical Center
Dr. Gerit Holger-Schernthaner, Voluntary Assistant Professor of Surgery
Dr. Lisa Rafkin-Mervis, Study Co-Chairman Dr. Luz Arazo, Clinical Research Coordinator Dr. Carlos Blaschke, Clinical Research Coordinator
Della Matheson, Trial Coordinator Natalia Sanders, Research Associate 1 Irene B. Santiago, Sr. Administrative Assistant Elizabeth Machado, Administrative Assistant
DRIF Chairman's Message
Those who are involved with the Diabetes Research Institute Foundation, like my wife, Kelly, and I, want nothing more than to find a cure for their loved ones, themselves, and millions of others who have diabetes. Despite the many advances that have been made in managing diabetes, none of us is content to just live with this disease. Certainly, people with T1D have benefited from advances in management and treatment, but our focus is on a cure so we can render all of that moot. The DRI’s cure-driven mission exemplifies why an ever-growing circle of passionate and committed people have chosen to invest their support – in both time and money – here. More than a decade ago, when I first learned about the DRI, it marked the first time that I really felt there was a strategy in place for Reaching the Biological Cure. In the years since, while we have seen wonderful progress toward that goal, we continue to feel an urgent need to cross the finish line for our son, Will, and for every other family affected by diabetes.
[diabetes research institute foundation] 28
This past year, the unveiling of the DRI BioHub, coupled with the Institute’s plans to initiate Phase I/II clinical trials in 2014, has further cemented my belief that we are on our way to ending diabetes once and for all. Subsequent to the BioHub roll-out, the DRI Foundation received a number of significant contributions from donors who recognize the inherent promise of this ground-breaking initiative – and, also, are acutely aware of the tremendous investment in research that is needed to bring the BioHub to fruition. While we have witnessed a successful year in terms of our fundraising – one in which we were able to direct a greater level of funding to our scientists – these gifts represent a mere fraction of the resources necessary to get this job done. The overwhelming need for research funding is palpable and serves as the driving force behind all of our activities. Having streamlined our operating expenses over the past several years, we were in a strong position to move forward and maximize the revenue we transferred to the DRI for BioHub programs. In turn, that support helped to deliver these research advancements. We allocated the DRIF’s funding, which came from generous people like you, to a number of projects within the major scientific areas that comprise the DRI BioHub: the Site, Sustainability, and Supply. As summarized in the Research Review section of this report, our DRI scientists have made progress in these areas across the board, and have demonstrated encouraging results that are moving into the next phases of testing. Undeniably, the most exciting news centers on the DRI’s plan to begin pilot clinical trials in 2014. Demonstrating their commitment to bringing the most promising findings from the lab to patients with type 1 diabetes, DRI scientists will test whether an alternative site in the body – the omentum – is a more ideal home for transplanted islet cells than the liver. In this trial, the islet cells will be implanted within a “biodegradable scaffold,” one of the platforms originally considered for a DRI BioHub. Plans are also underway to utilize the omentum as a site for a second BioHub platform, a “bioengineered scaffold,” once approval is obtained from the regulatory bodies. As you read in Dr. Ricordi’s message, the research process is not without its hurdles, and unforeseen delays certainly extend the timeline for moving our work forward. What we cannot and should not accept, however, is for the lack of adequate funding to be an additional impediment to progress. As those of us who are affected by this devastating disease well know, tomorrow is not soon enough to find a cure.
29 [2013 annual report]
Thankfully, numerous individuals, families, businesses, and foundations have played a huge role in bolstering our efforts to further the research this past year. None of this work would have been possible without the extraordinary contributions from those who have made supporting cure-focused research their top priority. Many of these donors are pictured on the following pages. On behalf of the entire organization, I want to extend our deepest gratitude to them and countless others for their generosity and tireless efforts. While this past year has been one of significant advances, it was also a year of transition as we welcomed new leadership at the Diabetes Research Institute Foundation with the appointment of Joshua Rednik as president and CEO. Josh, who brings with him almost two decades of experience in fundraising organizations, will help guide the Foundation into an exciting era for those living with this disease. I, together with my board colleagues, have the highest confidence in his ability to lead with distinction and integrity. A new governance structure for the Northeast Region was adopted and new co-chairs were appointed. The members of the new Northeast Region Executive Committee and Board are a strong contingent of new and veteran leaders, each of whom has a personal stake in fulfilling our mission. This group of individuals joins our National and Florida Region leadership in ensuring the highest standards of fiscal oversight, accountability, and donor stewardship.
As we head into the next year with excitement and optimism, we hope we can count on your continued support to make our progress possible. Thank you again for your generosity and friendship.
Sincerely,
Harold G. Doran, Jr. Chairman
Financial Summary
Research Funding is Critical The Diabetes Research Institute Foundation provides the DRI with critical seed funding to gather data that is often a prerequisite for larger grants. The mission – to provide the Diabetes Research Institute with the funding necessary to cure diabetes now – is a testament to the belief that tomorrow is not soon enough to cure this disease. The DRIF's funding stream is at the heart of DRI’s ability to innovate and make significant strides toward a cure. In addition to receiving the DRIF's support, DRI scientists have been awarded competitive grants from numerous funding entities for almost 40 consecutive years.
[diabetes research institute foundation] 30
Diabetes Research Institute Foundation Statement of Activities for the Year ended June 30, 2013 Support and Revenue Contributions Reimbursement Contracts Special Events, net of expenses Investment Income
$7,144,705 184,950 4,332,230 1,006,302
Total Support and Revenue
12,668,187
Expenses and Fund Balances Program Services Research provided to the Diabetes Research Institute Community Education
7,031,358 804,661
Total Program Services
7,836,019
Support Services Administration and General Fundraising
1,610,401 1,765,139
Total Support Services
3,375,540
Change in Net Assets
1,456,628
Net Assets, Beginning of Year
24,850,703
Net Assets, End of Year
$26,307,331
Through the support of private philanthropy, the Diabetes Research Institute Foundation has funded six chairs totaling almost $13 million. The J. Enloe and Eugenia J. Dodson Chair in Diabetes Research
Fundraising Percentage Fundraising Expense as a Percentage of Support and Revenue
Stacy Joy Goodman Chair in Diabetes Research Mary Lou Held Chair for Diabetes Research
14%
Martin Kleiman Endowed Investigatorship Daniel H. Mintz Visiting Professorship Ricordi Family Chair in Transplant Immunobiology.
Diabetes Research Institute Statement of Activities Support and Revenue Diabetes Research Institute Foundation National Institute of Health JDRF Grants* Kosow Center University of Miami Corporate Grants American Diabetes Association/ American Heart Association Grants State of Florida Education Grant Total Support
$7,031,358 6,455,822 2,104,852 1,094,725 491,940 405,718
40% 36% 12% 6% 3% 2%
51,566 34,708
.5% .5%
$17,670,689
100%
Expenditures Research Grants Research & Clinical Support
$15,862,809 1,129,433
Total Expenditures
$16,992,242
31 [2013 annual report]
*includes support from The Leona M. and Harry B. Helmsley Charitable Trust
Making Progress Possible
To Our Generous Donors and Volunteers... The Diabetes Research Institute and Foundation wishes to gratefully acknowledge all of our donors and volunteers who are enabling us to make great strides toward a biological cure for diabetes. Your generous contributions and tireless efforts make the DRI's progress possible. Thank you to every individual, family, foundation and business, many of whom are pictured on the following pages, that have given generously over the last year and throughout the years. We would not have been able to come this far without you.
[diabetes research institute foundation] 32
“Your support means the world to the millions of families like mine who have been affected by diabetes. Over the years, these funds have helped the scientists get closer to finding a cure.” – Renee Aronin (center)
“In total, the Dad's Day program has raised over $40 million, which has enabled the DRI to make exciting advances toward finding a cure for this disease that afflicts so many Americans.” – Sean McGarvey, president, North America's Building Trades Unions (right).
>
33 [2013 annual report]
>
“Walgreens is honored to support the work of the Diabetes Research Institute. We are very grateful to our customers and associates who have been exceptional in supporting the DRI Walk For Diabetes & Family Fun Day, as well as supporting our in-store fundraising program."
>
– Roy Ripak, Walgreens market vice president (left)
pic 37
“My family and I, are led by my parents, Rowland and Sylvia Schaefer, became involved with the DRI because we believe the cure for diabetes is within reach and that it will be found by these scientists." – Roberta Waller (second from left)
[diabetes research institute foundation] 34
>
“Our children are our inspiration, and we need to find a cure for everyone living with diabetes as quickly as possible.” – Bonnie Inserra (second from left)
“We had the opportunity to tour the Diabetes Research Institute and we saw what they do first hand...When we talk about finding a cure, they are the ones who are in the lab every single day really making it happen.” – Ray Allen (second from left)
>
35 [2013 annual report]
>
pic 51
The Heritage Society
“I knew that I wanted to support research for a cure...It’s really a miracle what they’re doing at the Diabetes Research Institute…My advisor was looking out for my best interest and assured me that this was the thing to do. I’m happy that I could establish this gift.” - Frances Harrow
[diabetes research institute foundation] 36
“This will help me rest in peace knowing that I’ve left behind a legacy. I also hope to set an example for my daughter so that she is charity-oriented when she is my age.”
“I am thankful for the life
I have lived and truly believe that each of us can make a difference by giving back.” – Shirley Harris
“Now is the time when we can and must give back and help people.”
– Norman Shapiro
“Of all the diabetes
organizations, I chose the Diabetes Research Institute because most of the funds go toward what the gift is intended for – a cure.” – Mark Hariton
– Cindi Elias
The Heritage Society of the Diabetes Research Institute Foundation was created to recognize individuals who have generously made provisions in their wills, through life insurance, charitable remainder trusts and gift annuities, or other deferred giving vehicles to ensure that critical funding for the Diabetes Research Institute continues into the future. Over the years, planned giving programs have enabled many donors to make substantial gifts to the DRI in ways that have complemented their individual financial objectives. Heritage Society members have chosen to create their own personal legacies and perpetuate their philanthropic goals for all those affected by diabetes. We are exceptionally grateful to all of our Heritage Society donors who demonstrate the passion and vision to advance a cure beyond their lifetime.
37 [2013 annual report]
NATIONAL BOARD OF DIRECTORS
Chairman Harold G. Doran, Jr.
President and CEO Joshua W. Rednik
Immediate Past Chairman Thomas D. Stern
Directors Diane Beber Marlene Berg Ronald Maurice Darling, Jr. John C. Doscas Piero Gandini Esther E. Goodman Marc S. Goodman Arthur Hertz Glenn Kleiman Eleanor Kosow Sandra Levy Sean McGarvey
Vice Chairmen William J. Rand, M.D. Charles Rizzo Treasurer William J. Fishlinger Secretary Bonnie Inserra
Shelia F. Natbony, D.O. Allan L. Pashcow Ramon Poo Ricardo Salmon David Sherr Kenneth A. Shewer Kathy Simkins Sheldon L. Singer Jill Viner Bruce Waller Sonja Zuckerman
The organization of choice for those who are serious, passionate and committed to curing diabetes.
[diabetes research institute foundation] 38
REGIONAL BOARDS OF DIRECTORS Florida Region
Northeast Region
Chairman William J. Rand, M.D.*
Co-chairs Marc S. Goldfarb Bruce A. Siegel
Directors Sari Addicott Bernard Beber, M.D. Diane Beber* Crystal Blaylock Sanchez Sabrina R. Ferris Bruce Fishbein Joel S. Friedman Rene W. Guim Shirley Harris Javier Holtz Norman Kenyon, M.D. Vito La Forgia Sandra Levy* Ramon Poo* Cristina Poo Deborah Rand
*Also member of National Board of Directors
39
[2013 annual report]
Michelle Robinson Rosa Schechter James Sensale Jacci Seskin Don Strock Richard P. Tonkinson Stephen Wagman Rita Weinstein Sonja Zuckerman*
Executive Committee William J. Fishlinger* Marc S. Goodman* Barbara Hatz Bonnie Inserra* Directors Greg Besner John Carrion Diane Cohen Delia DeRiggi-Whitton Peter L. DiCapua Kim Dickstein Douglas R. Donaldson Iris Feldman Joan Fishlinger Lindsey Inserra-Hughes John Luebs Louise Pashcow Hon. C. Raymond Radigan Marie Rizzo Ricardo Salmon* Samantha Shanken Baker
Meryl Lieberman Allan L. Pashcow* Charles Rizzo*
Thomas P. Silver Bruce Waller* Roberta Waller Wendy Waller
DRI FOUNDATION STAFF Joshua W. Rednik
Laurie Cummings
President and Chief Executive Officer
Communications Assistant
Deborah L. Chodrow
Aurora Nunez
Chief Operating Officer
Administrative Assistant
Jeffrey Young
Oneida Osuna
Chief Financial Officer
Accounting Assistant
Tom Karlya
Mary Revie
Vice President
Administrative Assistant
Director of Special Events, Jericho Office
Jill Shapiro Miller
Mylinda Auguste
Jill Salter
Vice President of Gift Planning
Data Entry Clerk
Development Manager
Lori Weintraub, APR
Marisol McKay
Melinda Megale
Northeast Region Anthony E. Childs Director
Amy Epstein
Vice President of Marketing and Communications
Lauren Schreier
Director of Special Events, Manhattan Office
Lily Scarlett
Date Entry Clerk
Special Events Coordinator
Eddy Garcia
Tricia Pellizzi
Courier
Special Events Coordinator
Director of Marketing and Communications
Barbara Singer Director of Special Projects
Florida Region Sheryl Sulkin Director of Special Events
Karen Paraboo Administration and Database Coordinator
Nicole Otto
Joelle Parra
Dena Kawecki
Communications and Social Media Coordinator
Melissa Pe単a Development Coordinator
Associate Director of Special Events
Special Events Manager
Sarah Mehan Special Events Coordinator
[diabetes research institute foundation] 40
National Office Florida Region
Northeast Region
200 South Park Road
410 Jericho Turnpike
Suite 100
Suite 201
Hollywood, FL 33021
Jericho, NY 11753
Jericho Office
Telephone 954.964.4040
Telephone 516.822.1700
Toll-free 1.800.321.3437
Fax 516.822.3570
Fax 954.964.7036
Manhattan Office 381 Park Avenue South Suite 1118 New York, NY 10016 Telephone 212.888.2217
Designed by Franz Franc Design Group
Fax 212.888.2219
DiabetesResearch.org
44
[2013 annual report]