Leading with Excellence 2011 Annual Report by Diabetes Research Institute Foundation

annual report 2011 >

The Diabetes Research Institute has made quantum leaps in the lab and these ground-breaking discoveries are here and now. By applying next-generation thinking, bridging research expertise across the globe and turning revolutionary ideas into actions, the DRI is Leading with Excellence toward a cure for diabetes.

Solely focused on one goal: a cure.

1 [2011 annual report]

About the Diabetes Research Institute

Mission and Goals

Message from the Scientific Director

Research Review

Patient Education Services

Faculty and Staff Listing

About the Diabetes Research Institute Foundation

Message from the Chairman and President

Financial Statement

To our Donors

The Heritage Society

National Board of Directors

Honorary and Regional Boards

DRI Foundation Staff

The DRI continues to be a strong voice for translational research, ensuring that promising findings in the lab are applied to patients in the fastest, safest and most efficient way possible. In contrast to the historically competitive world of medical research, the DRI is a unifier and a collaborator, bringing together scientists and centers to accelerate progress. Its multidisciplinary teams include researchers, engineers and clinicians, as well as a host of international partners, all working together to cure those now living with diabetes. Through this collaborative, fast-track approach, the DRI is able to advance the newest biomedical technologies that have a real potential to deliver a cure for diabetes, like tissue engineering, nanotechnology, immunemodulation, biomaterials, cellular reprogramming, and regenerative medicine, among others. This integration of technology and medicine, along with its singular focus on a cure, is what makes the DRI unique and distinguishes its research efforts from all others.

Pioneering New Therapies to Restore Insulin Production The Institute is an innovator in several research areas, however its principal focus is the biological replacement of natural insulin function to restore blood sugar control. DRI scientists have already shown that insulin independence can be achieved through cell replacement strategies. Expert teams continue to make strides in the two over-arching research issues necessary for curing this disease: Retraining the immune system – preventing the rejection of donor tissue and reversing the autoimmune attack which caused the onset of diabetes. 2. Increasing the supply of insulin-producing cells – identifying, developing and/or regenerating a limitless supply of cells to sense blood glucose levels and produce insulin.

International Recognition For more than 35 consecutive years, DRI scientists have been awarded competitive federal and state grants in the field of diabetes. The resulting discoveries have been published extensively in peer-reviewed journals and many of the DRI’s innovations are in current use at diabetes centers worldwide. As leaders in their respective fields, the Institute’s faculty serves on numerous national and international committees and provides leadership on many scientific review panels and associations.

about

the Diabetes Research Institute

The Hub of a Global Research Alliance The DRI has an impressive track record of scientific collaboration and its most far-reaching initiative to date is the Diabetes Research Institute Federation. Researchers from more than 20 medical centers from all corners of the world have agreed to form a one-of-a-kind alliance. This international network of collaborators share knowledge, pool expertise in specific research areas, and apply a diverse set of skills to the eradication of diabetes. The DRI leads this expanding effort with an underlying belief that the best way to make transformative discoveries – in the shortest amount of time – is to work together toward a cure.

The Diabetes Research Institute leads the world in cure-focused research. As the largest and most comprehensive research center dedicated to curing diabetes, the DRI is aggressively working to shrink the timeline toward the discovery of a biological cure for this disease. Since its inception, the DRI has made significant contributions to the field of diabetes, pioneering many of the techniques used in diabetes centers around the world. Having already shown that diabetes can be reversed through islet transplantation, the DRI is building upon these promising outcomes by bridging cell-based therapies with emerging technologies. The DRI also collaborates with other leading researchers worldwide to develop and test new approaches to restore natural insulin production.

The Best Work, The Best People, The Shortest Path The Institute’s open-door philosophy provides opportunities for scientists and biomedical companies around the world to develop and quickly test their most promising findings. Much of this work begins in the DRI’s Stern Fast Track Center for Testing, where investigators can access all three phases of research – basic (in the lab), pre-clinical (study models), and clinical (patient studies) – at the Institute and through its collaborating centers. This translational approach enables researchers to take potential new therapies begun in the lab and further develop these techniques to benefit those with diabetes. [diabetes research institute foundation] 2

[2011 annual report]

The Strength of Private Funding While competitive research grants are the mainstay of worldclass research institutes, the Diabetes Research Institute Foundation provides the DRI with critical seed funding to gather data that is often a prerequisite for larger grants. This funding stream is at the heart of DRI’s ability to innovate and make quantum leaps in the race for a cure. Supported by private philanthropy, the DRI Foundation also fills the gaps in many stages of the research process for which there is little federal funding, or for areas in which federal funding falls short of actual need. Driven by its core mission, the DRI Foundation’s support also ensures the body of work conducted at the DRI remains cure-focused and will ultimately benefit those with diabetes. A Community Resource The DRI is a designated Center of Excellence at the University of Miami Miller School of Medicine, providing informative education and training programs for many types of health care professionals and industry representatives. For patients with diabetes and their families, the DRI’s Kosow Diabetes Treatment Center offers the highest standards of health care delivery, ongoing management and education support, and numerous clinical research possibilities. The Best Hope for a Cure The Diabetes Research Institute was created for one reason – to cure diabetes – which is and will continue to be its singular focus until that goal is reached. With an aggressive approach to curing those living with diabetes, along with its unique spirit of collaboration and notable accomplishments, the DRI is leading the international effort to eradicate this disease. For the millions of people affected by diabetes, the DRI is 5 the best hope for a cure.

mission and goals

Goals • To foster a dynamic multidisciplinary research team comprised of basic and clinical scientists that conduct innovative diabetes research. • To facilitate the translation of new research findings into novel therapies for patients with diabetes as quickly as possible.

The Mission of the Diabetes Research Institute: To develop and rapidly apply the most promising research to treat and cure those now living with diabetes.

• To improve clinical care and enhance the quality of life for all patients with diabetes through professional training and education programs. • To expand collaborative alliances with other leading centers of research, thus creating a global intellectual environment, which streamlines research efforts worldwide and furthers our mission to cure diabetes. • To establish corporate, philanthropic and academic partnerships to share in the costs of research and development, thus accelerating the testing of new approaches and developments to cure diabetes.

[diabetes research institute foundation] 4

[2011 annual report]

Increasingly, we at the DRI find ourselves reaching out to like-minded scientists across the globe who are eager to share a curious finding with us, to senior investigators who want to partner with us in a fasttracked project, and to newly-formed teams abroad who seek and would benefit from our expertise in transplantation. The end game is the same for all of us in this field, the cure of a formidable disease that affects us all. What’s different today, however, is that limited resources are becoming even more scarce as typical sources of funding, like NIH grants, become more rare and difficult to secure for type 1 diabetes cure-focused research for example. The pace of communication is also much quicker, as findings in one lab can have immediate impact on work being carried out in another country, and no longer need to wait for publication in a paper journal.

message from the

scientific director

I’m very pleased to introduce to you this brief summary of the work underway at the Diabetes Research Institute, the country’s leading center for cure-focused research in diabetes. As technology makes our world smaller and more linked, we as scientists also see this global interconnectivity apply to the world of biomedical research.

• We reaffirm on a daily basis our open door philosophy of sharing with colleagues instead of competing with them, because that way it is the patient with diabetes that ultimately wins. In short, we at the DRI make our position as ‘the best hope for a cure’ a reality – as no other research center I know of does.

Please look through this compendium of work, and continue to support the work we do, together with our global partners. I believe it is only through collaboration and partnership that we can unlock the cure to diabetes in the shortest, most efficient way possible.

This brave new world we live in has made global outreach and collaborative research that much more vital to progress in the field of diabetes. Thus, we at the DRI have moved quickly to adapt and make the changes work for us.

Warmest regards,

With the worldwide network of centers comprising the DRI Federation, we have altered the way we do business, and have revised our model of translational research so that experimental agility and harmonization is at the forefront of all our work:

Camillo Ricordi, M.D.

• We have committed to leverage every dollar of support we receive and make it the most intelligently spent dollar possible. This means we conduct clinical trials with partners that have more streamlined regulatory processes, so that trials are conducted more expeditiously and results achieved with shorter timelines.

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

• We actively seek partners who bring unique talents to the table, regardless of where their base institutions may reside. Thus, our collaborators on a given project can be from the West Coast, the Pacific Rim, and the Netherlands – each contributing simultaneously to answer a critical question that is perhaps unanswerable unless we all work together.

[diabetes research institute foundation] 6

7 [2011 annual report]

[

research

Mesenchymal stem cells (MSCs), which are found in many tissues of the body, have a number of beneficial properties. Co-transplanting MSCs with islets can help prolong their survival and function.

review

THE CHALLENGE OF THE IMMUNE SYSTEM – THE CELLS OF OUR OWN BODY MAY HOLD THE KEY In type 1 diabetes, the immune system poses significant challenges. First you have the autoimmune attack that caused the initial onset of diabetes. This occurs when the body’s own immune system mistakenly destroys its insulin-producing beta cells in the pancreas. Halting the autoimmune attack on these cells and restoring natural insulin production continues to be an area of intense focus at the Diabetes Research Institute and several strategies are underway to address this issue.

[

At the Diabetes Research Institute, our vision is a world without diabetes. That’s why our singular focus is on a cure, so we can put an end to this disease once and for all. This has always been and will continue to be our sole mission until we reach this goal for millions of children and adults living with diabetes worldwide. Since our inception, the DRI has been at the forefront of cure-focused research, pioneering new therapies to restore insulin production. Working with a shared intensity to find a cure, our scientists have made quantum leaps in the lab. These ground-breaking discoveries are here and now, propelled by a far-reaching vision and extraordinary advances in technology. By applying next-generation thinking, bridging research expertise across the globe and turning revolutionary ideas into actions, the DRI is Leading with Excellence toward a cure for diabetes.

[diabetes research institute foundation]

Our scientists have been working on ways to give patients new insulin-producing cells through a procedure known as islet cell transplantation, which has shown great promise in ongoing clinical trials. DRI researchers have already shown that transplanting donor islet cells into patients with diabetes can restore natural insulin production. Some of our study patients have been insulin-free for more than a decade. Yet again, the immune system is at play because the body’s natural response is to reject these “foreign” cells. To prevent the destruction of the donor islets, transplant recipients must take powerful immunosuppressive (anti-rejection) drugs for life. These drugs often cause unwanted side effects, including damage to the islets themselves. They also shut down the patient’s entire immune system, leaving him/her susceptible to other viruses and infections. So, reversing diabetes requires a twopronged strategy: to halt autoimmunity and to prevent rejection of newly-transplanted cells. In both cases, the body must be re-educated to tolerate insulin-producing cells. The DRI is studying a number of ways to achieve tolerance and safely block the immune attack with a particular focus on using

[2011 annual report]

cells in the body that offer natural defenses. This past year, our researchers have pursued a number of promising strategies and were recognized for their ground-breaking discoveries in peer-reviewed scientific journals and by the National Institutes of Health.

Advancing Transplant Immunology with Mesenchymal Stem Cells (MSCs) Mesenchymal stem cells (MSCs) are found throughout the body and are considered “adult” stem cells because they are already committed to become tissues such as cartilage, bone and fat, among others. Several years ago, the DRI’s Dr. Norma Sue Kenyon, Martin Kleiman professor of surgery, medicine, microbiology and immunology and biomedical engineering and DRI senior scientist, also discovered that MSCs obtained from the bone marrow have other unique properties that enhance transplant acceptance, including the ability to limit inflammation, stimulate blood vessel growth (increase vascularization), prevent rejection and promote long-term function of islets.

[

Dr. Norma Kenyon and her team are testing a population of adult stem cells to enhance transplant acceptance and promote long-term function.

[

TBA

[

Dr. Antonello Pileggi and his team conduct the first steps in the translational research process by testing new strategies for immunomodulation, novel devices and materials, alternative sites for transplantation, and stem cell technologies among many other areas.

Observing Cell Attack Through the Eye in Real Time

In a study that was published in the journal Diabetes, Dr. Kenyon, together with collaborator Dr. Amelia Bartholomew from the University of Illinois/Chicago, demonstrated that when MSCs were transplanted alongside islets into the liver, recipients had double the function or more as compared to the recipients of islets alone. Furthermore, when the team observed a rejection episode, they administered additional MSCs, which resulted not only in reversed rejection but in enhanced function of the transplanted insulin-producing cells.

In this next series of studies, the collaborative team will seek to identify the optimal source of mesenchymal stem cells to enhance engraftment â&#x20AC;&#x201C; whether these cells should come from the recipient or from a different person. Thereafter, they will seek to 1) verify that MSCs can consistently reverse rejection and, if so, then develop an MSC-based antirejection therapy; 2) to identify and characterize the factors required for the optimal type of MSCs, since all of these cells are not identical; and finally 3) to complete islet and kidney pilot studies for inclusion in FDA Investigation New Drug (IND) submissions.

Furthering MSC Studies with a Major National Institutes of Health Grant

Targeting Inflammation with Antioxidants

The data from these preliminary MSC studies, which were funded by the Diabetes Research Institute Foundation, were so significant that Drs. Kenyon and Bartholomew and their collaborators were awarded a nearly $10 million five-year, multi-center grant from the National Institutes of Health to further their work with mesenchymal stem cells in the cellular and kidney transplant settings.

For years we've been reading about the benefits of antioxidants in helping to ward off the effects of free radicals that can damage cells and contribute to heart disease, cancer and other conditions. Now, DRI researchers have found that antioxidants, like MSCs, can help to prevent the inflammatory reaction often associated with transplanted islets. Ongoing studies conducted by the team led by Dr. Antonello Pileggi, director of the Preclinical Cell Processing and Translational Models Program at the DRI, demonstrated that antioxidants can be used to

[diabetes research institute foundation] 10

maximize the long-term acceptance of transplanted islets and the establishment of immune tolerance. The studies demonstrate the critical role of targeting inflammation pathways at the time of islet transplantation to enhance islet engraftment and long-term function.

Learning from Cancer DRI scientists are taking a page from new findings in cancer research and testing how naturally-occurring cells may be used to protect transplanted insulinproducing cells. Cancerous tumors are capable of escaping the immune system by surrounding themselves with a subset of bone marrow cells called myeloid-derived suppressor cells (MDSCs). These naturally-occurring cells play a major role in shielding the tumor from an immune attack by inducing a tolerogenic response, meaning the body does not recognize them as foreign or as a dangerous threat.

11 [2011 annual report]

A 2011 DRI study showed that the anterior chamber of the eye provides researchers with a unique platform to gain insights into the mechanisms involved in the cellular progression of autoimmunity. The research builds on our groundbreaking work with the "living window" â&#x20AC;&#x201C; a revolutionary technique that allows scientists to view, in real time through the cornea of a mouse, how transplanted insulinproducing cells function when they are inside a living organism. While researchers set out to use the living window to study islet cell biology and to monitor transplanted tissue, the technology is now allowing them to study the destruction of islet cells due to the bodyâ&#x20AC;&#x2122;s autoimmune attack. DRI scientists were among a group of collaborators that published the results of the pioneering study in the Proceedings of the National Academy of Science (PNAS) in 2011.

[

Dr. Luca Inverardi and his team (left) are testing the use of the recipient's own immune cells to prevent transplant rejection. Using drugs that are already approved for clinical use, they are expanding the population of these cells to suppress the immune response against the donor islets.

[

Drs. Alberto Pugliese (above), Thomas Malek and Allison Bayer are investigating a population of our body's own cells, called Regulatory T cells, that play a key role in autoimmune diseases, like type 1 diabetes.

Dr. Alice Tomei (right) is investigating the role of a protein found in cancerous tumors for its effect on evading immune system attack.

DRI researchers want to use these myeloid-derived suppressor cells for the better – to protect transplanted islets – and have found increasing evidence that MDSCs could represent an important tool for the treatment of autoimmune diseases and to prevent transplant rejection. In 2011, the DRI’s immunobiology team, led by Dr. Luca Inverardi, research professor of medicine, microbiology and immunology and deputy director of translational research, was able to mobilize and harvest large numbers of MDSCs from bone marrow and expand them in great quantities using a cocktail of drugs that is already FDA-approved for other medical uses. This provides researchers the opportunity to quickly translate this therapy into clinical trials if the use of MDSCs to protect islets continues to show promise. In another important advancement, the team showed that MDSCs can also be harvested from cord blood, which our researchers are already using to address the cell supply issue. The ability to utilize cord blood, which is in plentiful supply, as immune-regulatory cells represents an efficient and exciting new research pathway. The important role that MDSCs may play in modulating the immune system was also demonstrated in a separate study involving the use of another FDA-approved drug called Filgrastim (G-CSF).

In the study, Filgrastim, which is used to stimulate the growth of white blood cells, induced the growth of MDSCs and promoted longer islet transplant survival. The researchers will now further investigate its potential to improve islet transplantation outcomes. In related research, the DRI's Dr. Alice Tomei, research assistant professor of surgery and cell transplantation, and her team studied additional characteristics of cancerous tumors, and specifically, the role of a protein called CCL21 in evading immune system attack. Similar to MDSCs, CCL21 production has been shown to induce local immunosuppression by suppressing the activation of the killer T cells. The preliminary findings indicate that CCL21 may show promise in diabetes research by recruiting MDSCs to the site of CCL21-expressing grafts. The goal is to exploit the way tumor cells successfully evade immune recognition, which may be a safer alternative than the current immunosuppressive drugs used to promote islet survival after a transplant. Results of these DRI studies related to the use of myeloid-derived suppressor cells to achieve immune tolerance were presented at the Joint International Congress of the Cell Transplant Society – International Xenotransplantation Association in Miami Beach last October.

[diabetes research institute foundation] 12

Restoring Immune Balance with T-Regs DRI researchers have also focused their attention on another type of immune system cell called Regulatory T-cells or T-regs. This subset of immune cells actively prevents the immune system from reacting against the body’s own tissues and cells. They work with other protective factors to ensure that infections and foreign invaders are destroyed, but that “self” is not. It is a delicate balance. A loss of T-regs can cause several autoimmune diseases, including type 1 diabetes. Researchers believe that correcting this imbalance by replacing T-reg cells may be beneficial for promoting the acceptance of transplanted islet cells without the use of strong, immunosuppressive drugs and, potentially, for reversing autoimmunity. At the DRI, researchers have been developing methods to expand T-regs in culture in order to obtain a sufficient supply for testing. Having developed a reliable supply of these cells this past year, they will begin testing T-reg therapy in patients with type 1 diabetes going forward.

[2011 annual report]

In related studies, the research team is also investigating a natural substance known as IL-2 that is released by a type of white blood cell in the immune system. IL-2 is required for T-reg function and survival, as well as other immune cell types. Researchers have shown that administering low doses of IL-2 reverses type 1 diabetes in experimental models by improving T-reg function. Therefore, IL-2 itself could be seen as a potential drug for controlling autoimmunity. IL-2 is already being used in clinical trials, but at much higher doses for cancer therapy. Armed with this information and bolstered by a grant from the Peacock Foundation, Inc., Drs. Alberto Pugliese, professor of medicine, immunology and microbiology and head of the DRI's Immunogenetics Program, and Thomas Malek, professor and vice-chair of microbiology and immunology, and their teams have launched a new research initiative that focuses on identifying novel T-reg/IL-2 therapies in patients with type 1 diabetes. The goal is to identify ways that IL-2 can selectively promote and/or restore immune system function and halt the autoimmune attack by positively affecting T-reg function. Other projects using IL-2 have also been initiated under the direction of Dr. Allison Bayer, research assistant professor of microbiology and immunology.

DRI Research Featured on Covers of Three Prestigious Journals

THE CELL SUPPLY CHALLENGE – CREATING MORE INSULINPRODUCING CELLS

[

In the summer of 2011, our work was featured on the covers of three of the world’s most prestigious scientific journals. The cover stories are a testament to the DRI's research excellence that has been recognized by the scientific community.

Dr. Juan DominguezBendala and his team are focusing on developing a safe and unlimited supply of insulin-producing cells to treat the millions living with diabetes.

In addition to addressing the issues related to the immune system, another major challenge we face is the short supply of insulin-producing tissue for transplant. At the DRI, researchers are pursuing several strategies to create an unlimited supply of insulin-producing cells and/or to regenerate the islets that have been destroyed by the immune system. To create a new supply of cells, we have focused our attention on stem cell research, a field in which many promising developments have been made. In fact, there is no other discipline in the history of medicine that has been advancing as fast as stem cell research. At the DRI, which was the first center to bring embryonic stem cell research technology to the University of Miami, we continue to make steady progress. In 2011, our researchers reported on a number of significant developments with both embryonic and adult stem cells.

Improving Safety in Stem Cell Research

Testing Adult Stem Cells

Embryonic stem cells are considered the gold standard of all stem cells. They proliferate at a remarkable rate and have the potential to develop into any cell type within the body. These beneficial characteristics, however, also pose significant risks. When left unchecked, even a single, wildly-dividing embryonic stem cell can cause tumors to form. We are working to eliminate that risk by developing safer, more efficient protocols for the use of these cells.

Our scientists are investigating a variety of adult stem cell sources to induce their differentiation into beta cells. Of particular interest are stem cells obtained from cord blood, which are plentiful and pose no ethical barriers. DRI researchers have identified and isolated a unique population of these cord blood cells, known as mesenchymal stem cells (MSCs). As mentioned before, a mesenchymal stem cell is a type of cell that can become cartilage, bone, fat, blood vessels and other cell types. In this section on cell supply, we report on how our researchers are focusing on coaxing them to behave similar to beta cells. This past year, the team, including Drs. Luca Inverardi and Juan Dominguez-Bendala, has been successful in consistently harvesting these precursor cells, or stem cells, from the cord blood, expanding them and pushing them down a path to sense glucose and secrete insulin. These promising findings were reported in the journal Cell Transplantation. The next step will be to expand them in numbers that are sufficient for clinical translation and to ensure that these newly-derived beta cells are able to safely function like normal beta cells. DRI researchers are also looking at other possible adult stem cell sources that may be turned into insulin-producing cells, including the extra-hepatic biliary tree (in the liver), which is a

Led by Dr. Juan Dominguez-Bendala, director of stem cell development for translational research, our stem cell development team is genetically engineering embryonic stem cells so that they contain "suicide genes" that will kill cells that keep dividing or don't produce insulin—a kind of double-fail-safe mechanism. Over the past year, the team has been focusing on building this very complex sequence of genes containing these instructions and is now ready to begin in vitro work leading to pre-clinical testing.

[diabetes research institute foundation] 14

[

Combining molecular biology techniques with stem cell development, Drs. Ricardo Pastori (above) and Juan Dominguez-Bendala are testing a new molecule to transform the non insulin-producing cells of the pancreas into beta cells.

relatively new development, and adipose (fat) cells. In preliminary studies conducted with our collaborators in Milan, Italy, a portion of adiposederived cells were transformed into insulin-producing cells. Among the many possible sources, the team will identify the most promising option for adult stem cell focus and ongoing study.

Transforming Other Cell Types into Insulin-Producing Cells Another avenue we’re pursuing to alleviate the shortage of insulin-producing cells is a process called transdifferentiation. Rather than educating a stem cell from its earliest stages of development, transdifferentiation – or cell reprogramming – can potentially offer a “short cut” by enabling a more mature cell type to be transformed directly into a beta cell. To accomplish this, our stem cell development and molecular biology teams have been focusing on the acinar tissue of the pancreas. This “exocrine” or nonislet tissue produces digestive enzymes to process food and makes up almost 98 percent of the organ. It is typically discarded after an islet isolation procedure. Since the DRI is a leading islet isolation facility, we have a plentiful supply of acinar tissue.

[2011 annual report]

In Cell Metabolism: Using in-depth imaging techniques, DRI scientists observed the unique pattern of nerves (innervation) within a human islet, adding another key element to the understanding of Islet cell anatomy. These findings will contribute to developing the optimal environment for Islet replacement and stem cell development strategies. In Nature Medicine: DRI researchers discovered that a molecule, acetylcholine, essential for the support of beta cell health and insulin production is, surprisingly, secreted by alpha cells within the islets. It was long believed that this molecule was expressed by nerves but there was no such evidence in this study. These findings pave the way for strategies to target alpha cells to improve beta cell health and function. In Science Translational Medicine: The use of rituximab, an immunosuppressive drug developed for the cure of cancer and of transplant organ rejection, may be utilized to prevent the leakage of protein in the urine that characterizes the early stages of kidney disease.

This past fall, DRI researchers conducted preliminary experiments on the transdifferentiation of human acinar tissue resulting in a detectable increase in insulin production from these newly-reprogrammed cells. Previously, the teams had been testing a number of different proteins to try to reprogram these cells. In this latest study, led by Drs. Juan DomínguezBendala and Ricardo Pastori, research associate professor of medicine, immunology and microbiology and director of the DRI's molecular biology laboratory, and published in Public Library of Science One, the team used a slightly modified protein known as TAT-MafA. This particular protein was chosen because previous studies showed its potential at enhancing beta cell development. When delivered into the embryos of experimental models, the protein caused a faster maturation of beta cells. The pancreas of the study models also had twice as much insulin as the untreated control models, their islets were bigger, better formed, and, overall, exhibited traits of better functioning islets.

ENGINEERING NEW SITES AND NEW SOLUTIONS

[ Since MafA is an essential molecule to drive the process of transdifferentiation, this study represents a significant step toward reprogramming acinar tissue into insulin-producing cells for transplantation. One other approach to induce the process of stem cell transformation is to instruct cells to make their own proteins. We're using synthetic versions of molecules called "messenger RNAs" to relay the developmental signals necessary for that process. While this approach has been theoretically feasible for years, recently-discovered technologies make it practical. Results of a preliminary study conducted in 2011 are promising. By using synthetic messenger RNAs, more cells are receiving the developmental signals compared to previous approaches. Our scientists are now testing the order, timing and duration of the signals to achieve maximum efficiency.

Exploring the Natural Re-growth of Insulin-Producing Cells One other strategy to address the issue of supply is to induce islet regeneration – the natural re-growth of insulin-producing cells. We're exploring this strategy in partnership with

The Institute is in collaboration with DRI Federation partner Dr. Antonio Cuesta-Muñoz in Malaga, Spain, to study enzyme mutations that result in the formation of super islets, which are larger and produce significantly more insulin than normal islets.

DRI Federation partner, Dr. Antonio Cuesta-Muñoz, of the Carlos Haya Hospital in Málaga, Spain, a leading worldwide expert in glucokinase (GK), a molecule that is considered the “glucose sensor” of the beta cell. This enzyme instructs the beta cell to secrete more or less insulin according to the concentration of sugar sensed in the blood. Inactivating mutations of the enzyme cause diabetes, whereas activating mutations result in the opposite effect, i.e., hypoglycemia. One of the patients examined by Dr. Cuesta was a girl with one of the latter GK mutations. She experienced extreme and continuous hypoglycemia requiring the surgical removal of approximately 98 percent of her pancreas to stop the dangerous low blood sugars. Amazingly, several years after this drastic operation, the patient leads a normal life with just around 20,000 islets (as opposed to the normal 1 million). Biopsies of her “superislets” reveal that her beta cells are not only larger and more active than typical beta cells, but also replicate safely. These findings, published in the New England Journal of Medicine, provide us with a potential strategy to induce the natural re-growth of insulin-producing cells. In 2011, we began a partnership with Dr. Cuesta to further explore these findings as part of the Diabetes Research Institute Federation, a global alliance of research centers focused on curing diabetes. [diabetes research institute foundation] 16

[

Dr. Cherie Stabler and her team are developing and testing bio-compatible platforms to more closely mimic the native pancreas to restore natural insulin production.

In type 1 diabetes, as compared to other conditions, researchers have discovered a cell-based therapy that “works” – islet transplantation. The DRI and its collaborators worldwide have already demonstrated that islet transplantation has restored natural insulin production in patients involved in ongoing clinical trials. Study patients have achieved insulin-independence, experienced normalized blood sugar levels and have been freed from frightening hypoglycemic episodes after receiving infusions of the donor cells. This exquisite biological replacement approach has enabled some study participants to achieve insulin independence for more than a decade while others have maintained insulin function and improved blood sugar control without hypoglycemia for years.

While these study results are most encouraging, several challenges must be overcome before we can offer this therapy to millions of children and adults with diabetes. In addition to the aforementioned issues of immune tolerance and cell supply, researchers are investigating an optimal site within the body to house the transplanted cells – another key element towards discovering a universal cure. Although the liver has traditionally been the site of implantation, we’ve discovered that it is likely not the most ideal site for the transplanted cells. It is problematic for a variety of reasons. Upon infusion through the portal vein, a major vein that leads to the liver, islets are confronted with a variety of factors that cause inflammation which damages a large percentage of the fragile cells. Inflammation causes a stronger response by the immune system to “attack the problem,” much like what occurs when you get a splinter in your finger. Furthermore, when infused, the islets tend to clump together, preventing oxygen from reaching all the cells. Finally, the liver metabolizes the immunosuppressive drugs used to prevent rejection, which exposes the transplanted cells to the highest levels of these powerful drugs. But an alternative transplant site must do more than

[2011 annual report]

just serve as a new home for the insulin-producing cells. Prior to their destruction by the immune system, islets are very happy inside the pancreas, where they are surrounded by supporting tissue and other pancreatic cells. Additionally, there they receive an abundance of critical oxygen and other blood nutrients that are required to perform all the functions necessary to normalize blood sugar levels – both the highs and the lows. Considering the many needs of islets, the alternative site must provide the appropriate physical support for housing the new insulin-producing cells, an ability to deliver essential oxygen and nutrients, and finally, a means of protecting the cells from immune attack. Here’s where tissue engineering comes in. At the DRI, researchers are creating bio-engineered transplant sites that can provide the physical support necessary to house the islets – but that is just one piece of the puzzle. Our ultimate goal is to develop a “mini organ” that can mimic the native pancreas and be enhanced with oxygen, nutrients, nerves and blood vessel growth factors and other agents to protect the cells and promote their long-term survival.

The effort is being led by the DRI’s tissue engineering team, which is working together with the Institute’s many other research teams to bridge the areas necessary to attack each challenge. The DRI’s unique multidisciplinary structure, together with its worldwide network of collaborators through the DRI Federation, is what makes a project of this magnitude and significance possible. Over the last year, the DRI has taken a number of steps toward the realization of a “mini organ,” testing various bio-engineered devices together with immune agents and other enhancements.

Biohybrid Scaffolds – the framework for the “mini organ” Dr. Cherie Stabler, assistant professor of biomedical engineering and surgery and director of tissue engineering, and her team have developed a bioengineered scaffold to serve as the platform for building a “mini organ.” These scaffolds, developed at the DRI, provide a three-dimensional framework to house and protect insulin-producing cells. Like the spacing in the native pancreas, the scaffolds help to prevent islets from clumping together, allowing oxygen and other nutrients to efficiently reach each cell. In 2011, the team saw promising results using the scaffolds in pre-clinical

models, achieving insulin independence for extended periods of time. Also last year, we explored using scaffolds to deliver beneficial cells or agents to further increase the viability of transplanted islets. One strategy involved incorporating an oxygen-generating compound into the scaffolds. As mentioned above, oxygen is vital to islet health; while insulin-producing islets make up only one to two percent of the entire pancreas where they reside, they use almost 25 percent of the oxygen that flows through the organ. In one pre-clinical study, an oxygen-binding compound incorporated into a scaffold did improve the viability of islets and glycemic control in recipients. A second strategy involves co-transplanting into the scaffolds insulin-producing cells and mesenchymal stem cells (MSCs), which have shown the ability to minimize inflammation that enhances acceptance and prolongs the health and function of transplanted insulin-producing cells. These studies are currently underway in pre-clinical models.

Moving Toward Clinical Trials DRI researchers began pre-clinical testing of the spongelike scaffolds to implant insulin-producing islets in sites other than the liver. The plan is to optimize the scaffolds and conduct clinical pilot studies. During different phases of this project, DRI scientists will test the long-term viability of the materials [diabetes research institute foundation] 18

and the effects of co-transplanting “helper” cells alongside the islets into the scaffolds. These approaches include oxygen-binding compounds and other agents, the potential of low-dose local drug delivery and mesenchymal stem cells (MSCs) as described above.

Improving Encapsulation by "Shrink-Wrapping" Cells Further means to shield islets from immune attack may be achieved by encapsulating the cells in protective coatings. DRI researchers are developing and testing a number of ways to coat transplanted insulinproducing cells. In one method, our scientists devised a means to "shrink-wrap" cells with a protective layer that literally conforms to the size and shape of each cell. The conformal coating makes it easier for nutrients and oxygen to reach the cell, and for insulin to be released without the delay typical of previous encapsulation methods. The results of the conformal coating study, led by Drs. Alice Tomei and Chris Fraker, research assistant professor of surgery and cell transplantation, were reported at 2011 Cell Transplant Society-International Xenotransplantation Association combined conference. The team is currently testing materials to identify the optimal coating.

[2011 annual report]

[

Improving upon traditional encapsulation materials and techniques, Drs. Alice Tomei (top left) and Chris Fraker (seated) are developing methods to wrap islet cells with a coating that conforms to their individual sizes and shapes while providing critical oxygen.

[

Kellie Rodriguez, M.S.N., C.D.E., C.P.T., (left) director of patient education at the Diabetes Research Institute, and her team provide diabetes education and training to patients and their families.

Patient Education Services

[

The DRI's Dr. Rodolfo Alejandro, professor of medicine and director of clinical cell transplantation (seated, center) and the clinical cell transplant team.

Collaboration, innovation, integration and evaluation continues to be the driving force of the Diabetes Education, Nutrition and Exercise Service at the DRI’s Eleanor and Joseph Kosow Diabetes Treatment Center. The past 18 months has seen exciting expansion and coordination of education services, especially in the areas of nutrition and exercise, to meet the growing health and lifestyle needs of our diverse patient population. We continue to strive for excellence and optimal quality of patient education services, as evidenced by our certification as an American Diabetes Association’s Education Recognized Program (ADAERP). We are proud of our accomplishments over the past 18 months but we possess a greater excitement about our plans for further service expansion over the next 18 months. Looking back:

Clinical Study Update A clinical study shows that exenatide, a medication approved for the treatment of type 2 diabetes, had a positive impact on the survival of transplanted islets. In the study, transplant recipients were treated with exenatide over four years. According to DRI researchers, the use of exenetide prolongs islet function in islet transplant recipients although in many cases, the side effects made it difficult to tolerate the drug. In another study, the DRI’s Dr. Rodolfo Alejandro and the clinical cell transplant team together with collaborators Dr. Bernhard Hering and his team at the University of Minnesota have shown that long-term insulin independence can be achieved in islet transplant patients who receive potent immunosuppression during the pre-transplant phase. The patients who received the new immunosuppressive regimen were twice as likely to remain insulin free for more than five years as compared to patients receiving the previously-tested drug levels. Insulin independence rates in the recipients approach those seen in pancreas transplants. The results of the study, which were published in the Journal of Transplantation, suggest that this drug regimen may benefit long-term outcomes through improved engraftment of a greater number of islets – less islets die off during initial implantation – and minimized recurrent autoimmunity.

TrialNet Update: Results Released for Two Drug Studies Designed to Slow Progression of Type 1 Diabetes

[

Dr. Jay Skyler, TrialNet national chairman

The results of two diabetes drug studies, including one that shows promise for stopping the immune system’s attack on insulin-producing cells in people newly diagnosed with type 1 diabetes, were presented at the American Diabetes Association’s Scientific Sessions in San Diego. They were simultaneously published online in the British medical journal The Lancet. The studies were 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 DiabetesTrialNet.org.

[diabetes research institute foundation] 20

• Increase in referral sources, now reaching 70 internal DRI and external community referrers. Implementation of the University’s electronic medical record, UChart, has facilitated timely electronic referrals, coordination of education appointments and enhanced awareness and communication of education services provided to our patient population. • Further development of our Patient Education Service Electronic Data Management System (EDMS) has provided the ability to capture and now retrieve automated reports regarding essential demographic, clinical, education outcomes, department productivity and billings of all patients now attending our Service. With over 6,000 visits captured, the EDMS is an essential tool in both review of existing services and establishing direction of internal processes and future provision of services. An abstract on the EDMS will be published in the 2012 American Diabetes Association National Conference. A key objective now is to make the EDMS available to other Diabetes Education Services. • Patient Education Service team expansion has enabled the development of new programs and services, especially in the essential area of nutrition and exercise. Patients now have access to comprehensive nutrition classes in English and 21

[2011 annual report]

Spanish, as well as group exercise classes at the University’s state-of-the-art Wellness Center (Gymnasium). In addition to our 14 monthly education classes, we continue to conduct four times annually, our pinnacle five-day intensive insulin management program, Mastering Your Diabetes (MYD). Translated and implemented in Italy (Milan and Palermo) in 2010, MYD now has plans underway for webinar based components to provide greater access to this unique diabetes self-management program. • Increased collaboration with the DRIF has augmented both disease and Service awareness through newspaper, web, journal, seminar presentation and television opportunities. Looking forward, the Patient Education Service has plans to develop and implement: • A multi-disciplinary Transition Program, to assist children and parents in transition from pediatric to adult based diabetes management and care • A multi-disciplinary weight management program • A Type 1 diabetes Elite Athlete Program, in collaboration with our endocrinologists and the University’s Department of Exercise Physiology (upon employment of an exercise physiologist) • On-site and on-line general and specialized diabetes training programs for health care professionals involved in the care of people living with diabetes. This will also include collaboratives with dietetic, nursing and medical training programs to provide clinical rotations through the Education Service. • Enhancement of the Education section of the DRI website to provide interactive education opportunities The Patient Education Service and its team members, while proud of our past achievements, are excited about the direction we are taking to further enhance the Service we are providing to our referrers and people living with diabetes, to both optimize healthcare delivery and health outcomes.

Faculty Dr. Camillo Ricordi

Dr. Luca Inverardi

Dr. Robin Nemery

Stacy Joy Goodman Professor of Surgery Distinguished Professor of Medicine Director, Diabetes Research Institute and Cell Transplant Center

Research Professor of Medicine, Microbiology and Immunology Director, Immunobiology of Islet Transplantation Deputy Director for Translational Research

Adjunct Professor of Pediatrics Division Head of Pediatric Endocrinology at Joe DiMaggio Children’s Hospital

Dr. Rodolfo Alejandro Professor of Medicine Director, Clinical Cell Transplant Center (CCTP) Associate Director of Clinical Research Associate Director, Cell Transplant Center

Dr. Allison Bayer Research Assistant Professor of Microbiology and Immunology

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. Livio Luzi 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 in Sweden

Dr. Dora Berman-Weinberg

Adjunct Professor of Physiology Director, Amino Acid and Stable Isotopes Laboratory, Nutrition and Metabolism Program University of Milan, San Raffaele Scientific Institute, Milan, Italy

Dr. Thomas Malek Professor and Vice-Chair of Microbiology and Immunology

Research Associate Professor of Surgery

Dr. Jennifer Marks Dr. Peter Buchwald Assistant Professor Department of Molecular and Cellular Pharmacology Director, Drug Discovery Program and Fast Track Program

Dr. Juan Dominguez-Bendala Research Associate Professor of Surgery Director, Stem Cell Development for Translational Research

Dr. Luigi Meneghini

Dr. Alessia Fornoni

Associate Professor of Clinical Medicine Director, Eleanor and Joseph Kosow Diabetes Treatment Center

Dr. Chris Fraker Research Assistant Professor of Surgery and Cell Transplantation

Dr. Jeffrey Hubbell Adjunct Professor of Biomedical Engineering Director, Integrative Biosciences Institute Institute for Chemical Sciences and Engineering at Ecole Polytechnique Fédérale de Lausanne, Switzerland

and staff listing

[diabetes research institute foundation] 22

Dr. Armando Mendez Research Associate Professor of Medicine Division of Endocrinology, Diabetes and Metabolism

Assistant Professor of Clinical Medicine, Division of Nephrology and Hypertension

faculty

Professor of Medicine Division of Endocrinology, Diabetes and Metabolism

[2011 annual report]

Dr. Ricardo Pastori 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, Immunology and Microbiology 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, DRI Chairman, NIDDK Type 1 Diabetes TrialNet Study Group

Dr. Cherie Stabler Assistant Professor of Biomedical Engineering Director, Tissue Engineering Laboratory

Dr. Alice Tomei Research Assistant Professor of Surgery and Cell Transplantation

Dr. Andreas Tzakis Dr. Daniel H. Mintz Scientific Director Emeritus Professor of Medicine

Dr. Bresta Miranda-Palma Assistant Professor of Medicine Division of Endocrinology, Diabetes, and Metabolism

Professor and Director, Miami Transplant Institute Director of Microsurgery Core Facility in the Cell Transplant Center Chief of the Division of Liver and Gastrointestinal (GI) Surgery

Administrative Dr. Mitra Zehtab, Chief Operating Officer and Deputy Director Margie Collado, Chief Financial Officer Angie Arzani, Manager, Finance Sabrina Boulazreg, Sr. Manager, Business Operations Edmundo Caldera, Accounting Assistant Dora Cardenal, Manager, Accounting Ligia Delgado, Accounting Assistant Marc Friedenthal, Buyer Mabel Luis, Executive Assistant Grace Perez, Sr. Buyer Juan Perez-Scholz, Manager, Sponsored Programs Ilvis Torres, Administrative Assistant

Medical Development Gary Kleiman, Sr. Development Director, Major Gifts Aimee Siegel-Harris, Manager, Donor Relations

Bio-Informatics Roopesh Sadashiva-Reddy, Database Administrator

Clinical Chemistry Lab Dr. Armando Mendez, Research Associate Professor Dr. Ronald B. Goldberg, Professor of Medicine Elsa Cribeiro, Sr. Research Assistant Rosa Hernandez, Sr. Research Lab Tech Dr. Erica Leonardi, Research Scholar Espy Perez, Supervisor, Medical Technology

Clinical Cell Transplant Program (CCTP) Dr. Rodolfo Alejandro, Professor and Director Dr. Livio Luzi, Adjunct Professor of Surgery Dr. Eduardo Peixoto, Post Doctoral Associate Alina Cuervo, Sr. Medical Biller Eva Herrada, Manager, Researchr

Clinical Research Center Dr. Luigi Meneghini, Associate Professor of Clinical Dr. Claudia Ardila, Post-Doctoral Associate Ada Konwai, Sr. Research Assistant Burlett Masters, Research Support Specialist Jose Carlos Amezcua Martinez, Research Scholar

Diabetes Prevention Program (Type 2) Dr. Ronald B. Goldberg, Professor of Medicine Jeanette Gonzalez-Calles, Research Associate Juliet Ojito, Nurse Specialist, Research Lissett Oropesa, Senior Research Associate Wanda Ramirez, Secretary Bertha Veciana, Medical Assistant

Drug Discovery Program

Immunobiology of Islet Transplantation

Pre-Clinical Research

Dr. Peter Buchwald, Director Dr. Sirlene Cechin, Sr. Research Associate

Dr. Luca Inverardi, Director Dr. Paolo Serafini, Research Assistant Professor Dr. Kamalaveni Prabakar, Scientist Dr. Alessia Zoso, Scientist Kevin Johnson, Sr. Research Associate Rejane Lamazres, Research Associate Dr. Roberto Codella, Research Scholar Dr. Giacomo Lanzoni, Research Scholar

Dr. Norma Sue Kenyon, Director Dr. Dora Berman-Weinberg, Research Associate Professor Waldo Diaz, Manager, Research Laboratory Dr. Dongmei Han, Scientist Dr. Ana Hernandez, Associate Scientist Tamara Levine, Sr. Manager Business Operations Ena Poumian-Ruiz, Supervisor, Research Laboratory James Geary, Veterinary Tech Alexander Rabassa, Research Associate Reiner Rodriguez-Lopez, Veterinary Technician Melissa Willman, Sr. Manager, Research Laboratory

Eleanor and Joseph Kosow Diabetes Treatment Center Faculty Dr. Ronald B. Goldberg, Professor of Medicine Dr. Jennifer Marks, Professor of Clinical Dr. Luigi Meneghini, Professor of Clinical Medicine Dr. Daniel H. Mintz, Professor of Medicine Dr. Bresta Miranda-Palma, Assistant Professor of Medicine Dr. Jay S. Skyler, Professor of Medicine, Pediatrics and Psychology Dr. Maria del Pilar Solano, Assistant Professor of Clinical Medicine Health Care Professionals Andrea Allouche, Dietitian Alejandra Cordovez, Dietitian Kellie Rodriguez, Manager, Nursing Aleida Saenz, Nurse Educator Dr. Rogelio Suarez, Clinical Research Coordinator Allison Wick, Advanced Registered Nurse Practitioner Clinic Administration Dina Bardales, Sr. Patient Access Representative Arleen Barreiros, Sr. Administrative Assistant Starlette Canamero, Sr. Administrative Assistant Odalys Cano, Patient Access Representative Iliana Gonzalez, Patient Access Representative Eveling Gonzalez-Paniagua, Patient Access Representative Rubin Michel, Patient Access Representative Hariamnys Suarez, Administrative Assistant

Immunogenetics Program Dr. Alberto Pugliese, Director Dr. Isaac Snowhite, Associate Scientist Dr. Francesco Vendrame, Scientist Gloria Allende, Sr. Research Associate

Islet Physiology Dr. Per-Olof Berggren, Director Dr. Midhat Abdulreda, Post Doctoral Scholar Dr. Alberto Fachado, Sr. Research Associate Dr. Rayner Rodriguez-Diaz, Research Associate Dr. Joana Almaca, Research Scholar

Microbiology and Immune Tolerance Dr. Tom Malek, Director Dr. Allison Bayer, Assistant Professor Cecilia Cabello, Research Associate

Molecular Biology Dr. Ricardo Pastori, Director Dr. Dagmar Klein, Scientist

Stem Cell Development for Translational Research Dr. Juan Dominguez-Bendala, Director Silvia Alvarez, Manager, Research Laboratory Dr. Nancy Vargas, Research Associate Simona Maciotta, Research Scholar Carmen Rodriguez, Research Scholar

Biomedical & Tissue Engineering Dr. Cherie Stabler, Director Dr. Jeffrey Hubbell, Research Professor Dr. Kerim Gattas-Asfura, Associate Scientist Jaime Giraldo, Research Associate Dr. Hernan Rengifo, Post Doctoral Associate Dr. Alice Tomei, Research Assistant Professor Dr. Chris Fraker, Research Assistant Professor Elda-Margarita Duran, Research Associate Vita Manzoli, Sr. Research Associate Chiara Villa, Research Scholar

Diabetes TrialNet

Flow Cytometry Lab Dr. Oliver Umland, Assistant Scientist

Nephrology

Human Cell Processing (cGMP) Facility

Dr. Alessia Fornoni, Assistant Professor of Clinical Dr. Johanna Guzman, Post Doctoral Associate Dr. Dony Maiguel, Sr. Research Associate Dr. Rodrigo Villarreal, Post Doctoral Associate Dr. Yoo Tae Hyun, Research Scholar

Aisha Khan, Director, Laboratory Services Dr. Elina Linetsky, Director, Quality Assurance Xiumin Xu, Director, China-US, Collaborative Human Cell Transplant Program

Dr. Alejandro Alvarez-Garcia, Associate Scientist Carmen Castillo, Research Laboratory Technician Dr. Omaima Malik, Associate Scientist Kevin Peterson, Research Associate Tammy Suwunrut, Sr. Administrative Assistant Dr. Joel Szust, Scientist Dr. Xiao Jing Wang, Associate Scientist

Image Analysis Facility Dr. George McNamara, Scientist

[diabetes research institute foundation] 24

Pre-Clinical Cell Processing and Translational Models Dr. Antonello Pileggi, Director Dr. Damaris Molano, Scientist and Core Director Dr. Carmen Fotino, Post Doctoral Associate Maite Lopez-Cabezas, Research Associate Adriana Lopez-Ospina, Research Assistant Yelena Gadea, Sr. Veterinary Technician Irayme Labrada, Research Assistant Alejandro Tamayo-Garcia, Research Assistant Elsie Zahr, Sr. Research Associate Carlo Rosati, Research Scholar

[2011 annual report]

Dr. Jay Skyler, National Chairman Dr. Norma Sue Kenyon, Associate Chair for Immunology Dr. Jennifer Marks, Principal Investigator â&#x20AC;&#x201C;TrialNet Clinical Center Dr. Alberto Pugliese, Co-Investigator, Clinical Center Lisa Rafkin-Mervis, Study Co-Chairman Ray Arce, Registered Nurse Dr. Carlos Blaschke, Clinical Research Coordinator Della Matheson, Trial Coordinator Elizabeth Machado, Administrative Assistant Irene B. Santiago, Sr. Administrative Assistant

The Diabetes Research Institute Foundation (DRIF) is the organization of choice for those who are serious, passionate and committed to curing diabetes. Its 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 those living with diabetes. The Diabetes Research Institute has become the world leader it is today through the substantial funding provided by the Foundation. Supported by private philanthropy, the DRIF ensures the jumpstarting of new ideas and the continuation of innovative research projects that remain cure-focused and will ultimately benefit those with diabetes. The DRIF’s history of commitment dates back to 1971 when it was founded by a small group of parents of children with diabetes who were dedicated to finding a cure. Driven by a shared mission, they banded together to support a promising research program at the University of Miami solely aimed at curing those living with diabetes. In an unprecedented partnership that spans more than two decades and continues today, the AFL-CIO’s Building and Construction Trades Department (BCTD) joined with the Foundation’s leadership to help fulfill its mission to cure diabetes. The DRIF’s largest contributor, the BCTD committed to funding – and building – the Diabetes Research Institute facility. The unions have raised tens of millions of dollars for the DRI and today, under the banner of Project Type Zero, thousands of union members undertake fundraising projects nationwide to provide ongoing support.

MISSION: To provide the Diabetes Research Institute with the funding necessary to cure diabetes now.

The DRI Foundation is recognized as one of the world’s most respected diabetes organizations. Garnering the attention of influential people who are personally affected by diabetes, the Foundation has grown into an international coalition of business leaders, celebrities, scientists, clinicians, families and

about

the Diabetes Research Institute Foundation

[diabetes research institute foundation] 26

[2011 annual report]

other concerned individuals who have elevated the importance of cure-focused research and provided meaningful support for the DRI’s multidisciplinary research program. This funding is provided through individual and corporate donations, special events, sponsorships, cause marketing relationships and planned giving, which allows donors to provide a gift in the form of a will, trust or other deferred giving vehicle. In an effort to increase awareness about the latest advances toward a cure, the Foundation conducts a wide variety of activities both online and offline, hosts research updates and workshops for people with diabetes and their families, and produces numerous printed publications and e-communications to make this information accessible to people nationally and internationally. A 501(c)(3) not-for-profit corporation, the DRI Foundation has thousands of supporters in the United States and worldwide, and, in addition to its headquarters in Florida, operates regional development offices in New York, Long Island and Washington, D.C. The Diabetes Research Institute Foundation was created for one reason – to cure diabetes – which is and will continue to be its singular focus until that goal is reached. For the millions of individuals and families affected by diabetes, the Diabetes Research Institute Foundation is the best hope for a cure.

message from the

chairman and president

After launching our Reason to Believe campaign last fall, there was an outpouring of emotion from the diabetes community. Notes of gratitude were emailed to us and posted on our social media pages from around the world. Parents wrote about their children. Those with diabetes expressed hope for themselves.

The R2B campaign reaffirmed our tireless dedication to a cure-focused mission, shined the spotlight on this singular goal and instilled renewed hope that we will get the job done. In one of our videos, DRI researchers asserted their own reasons to believe, enumerating a string of research accomplishments in support of that notion, many of which are outlined in the Research Review section of this report. You can also hear about this progress directly from our scientists by viewing the Diabetes 2.0 research update online at DiabetesResearch.org/Diabetes2_0. The DRI has made quantum leap over time and much was accomplished this past year. From investigating ways to eliminate the need for powerful anti-rejection drugs by using the body’s own cells, to identifying new sources of stem cells to increase supply, to building a bio-engineered framework for a “mini organ,” and to developing a novel, conformal coating to protect islet cells, the DRI is Leading with Excellence toward a cure for the millions of children and adults living with diabetes. Progress on this scale is only possible with a true institutional commitment to putting an end to this disease. DRI Scientific Director Dr. Camillo Ricordi, together with the three newly-appointed deputy directors – Drs. Luca Inverardi, Jay Skyler and Mitra Zehtab –are steering the Institute on an efficient and productive path, bridging expertise in numerous disciplines and approaching the cure from many angles. Contributing to this work were the Institute’s numerous collaborative partners within the worldwide Diabetes Research Institute Federation. These global alliances have grown increasingly important as our scientists seek more resourceful ways to stretch scarce research dollars and navigate a complex web of economic, financial and regulatory barriers.

Many of these strategic alliances reach across the globe, while others are practically in the DRI’s back yard, like our partnership with Hackensack University Medical Center (HUMC). The two world-class centers were brought together through the passionate commitment of the Inserra family, who created the The Lindsey Diabetes Research Foundation at Hackensack University Medical Center to support this combined research effort.

Harold G. Doran

Robert A. Pearlman

Chairman

President and Chief Executive Officer

Overall, these larger gifts have not rebounded at adequate levels. Indeed, there are positive signs of improvement in many industries, but the continued uncertainty in the global economic environment has affected many in the nonprofit sector, the DRI Foundation included. In response, we have continued to streamline the Foundation’s operations and implemented additional cost-saving initiatives.

Also this year, another long-time donor, Shirley Harris, reconfirmed her commitment to the DRI with an extraordinary legacy gift of $3 million to ensure that research toward a cure will continue beyond her lifetime. In honor of her generosity, we dedicated the Shirley Harris Administrative Pavilion during a special ceremony and installed a permanent tribute in the DRI lobby.

Despite these challenges, our main priority remains providing our scientists with the funds they need to continue their research and maintain the scientific program at its highest standard. To bolster a steady stream of revenue, we are embarking upon a number of exciting initiatives, one of which is our participation in the University of Miami’s new $1.6 billion campaign, Momentum2: The Breakthrough Campaign for the University of Miami. The DRI Foundation has made the lead gift to this campaign, pledging $100 million for the DRI, a Center of Excellence at UM’s Miller School of Medicine. A gift of this magnitude presents a tremendous opportunity to fund the research at an unprecedented level and finally put an end to this disease.

Major grants received from foundations serve as an important source of funding. We are grateful to the Children with Diabetes Foundation, the Foundation for Diabetes Research, the Fred and Mabel R. Parks Foundation, and the Peacock Foundation, among many others, that have supported countless research projects.

While major gifts are most critical, income from events throughout our regions and the dedicated volunteers who make those events happen are invaluable. This past year, hundreds attended our three family events – Carnival for a Cure in New York City or Kids Party for a Cure in Long Island and South Florida – putting smiles on faces while supporting the work toward a cure.

Significant contributions like these are the lifeblood of this organization and sustain the Institute’s scientific program. While we are grateful for this support, we are still facing harsh fundraising challenges.

Our perennial galas, like the Empire Ball, Crystal Ball, and Love and Hope Ball, together with engaging dinners like D.R.E.a.M.S. in the city and Stand Up for a Cure, golf tournaments and many more events throughout the year, brought the DRI message to a growing circle of people and raised much-needed funds for research.

The Inserra family is one of our most substantial contributors and their support of the DRI goes well beyond the DRI-HUMC alliance, which is just one example of their generous involvement over the years.

[diabetes research institute foundation] 28

29 [2011 annual report]

Continuing their decades-long commitment, the men and women of the AFL-CIO’s Building and Construction Trades Department have stepped to the plate to support the DRI, despite suffering hard times themselves. The ongoing Project Type Zero fundraising effort raises significant funds each year through its two hallmark events, DAD’s Day (Dollars Against Diabetes) and the Labor of Love Golf Tournament, and numerous other fundraising activities. Additionally, our corporate partners initiated a variety of programs on our behalf. In an ongoing alliance, Walgreens in Florida is raising awareness and funds for the DRI through statewide walkathons and other retail-based promotions, employee contests and creative fundraising initiatives. In the diabetes arena, Animas and LifeScan continue to sponsor many of our marketing efforts that reach patients and their families alike. PumpWear, Inc., has also named the DRI as a beneficiary of its “Wall of Change” fundraising effort, which encourages kids to use spare change and photos to tell their diabetes story. We are grateful for the passionate commitment on everyone’s part to help us reach our ultimate goal. As we continue to work feverishly toward a cure for this disease, we are counting on you, our valued donors, to lend your support and take part in our mission. We cannot do it without you and we thank you for your ongoing generosity and involvement.

Harold G. Doran

Robert A. Pearlman

Chairman

President and Chief Executive Officer

Diabetes Research Institute Foundation Statement of Activities for the Year ended June 30, 2011 Support and Revenue Contributions Reimbursement Contracts Special Events, net of expenses Investment Income

$5,648,214 299,559 3,883,796 1,428,126

Total Support and Revenue

11,259,695

financial

Expenses and Fund Balances

statement

Program Services Research provided to the Diabetes Research Institute Community Education

7,242,583 621,032

Total Program Services

7,863,615 Through the support of private philanthropy, the Diabetes Research Institute Foundation has funded six chairs totaling over $10 million:

Support Services

“I saw something a few months back on the DRI website that just blew me away…’We are dedicated to putting ourselves out of business by finding a cure for Diabetes. At that very moment, I realized the DRI really and truly cared about families and kids like mine...the people I have met from the DRI have literally changed my life… I know in my heart I am in the right place and supporting the right people...It’s an overwhelming feeling of passion, on both the DRI's part and on mine.” - Dawn Lidwell

Administration and General Fundraising

831,605 1,914,143

Total Support Services

2,745,748

Change in Net Assets

650,332

Net Assets, Beginning of Year Net Assets, End of Year

The J. Enloe and Eugenia J. Dodson Chair in Diabetes Research, Stacy Joy Goodman Chair in Diabetes Research, Mary Lou Held Chair for Diabetes Research, Martin Kleiman Endowed Investigatorship, Daniel H. Mintz Visiting Professorship, and the Ricordi Family Chair in Transplant Immunobiology.

27,620,713 $28,271,045

Fundraising Percentage Fundraising Expense as a Percentage of Support and Revenue

17%

Diabetes Research Institute Statement of Activities Support and Revenue Diabetes Research Institute Foundation $7,242,583 National Institutes of Health Grants 5,179,190 Juvenile Diabetes Foundation International Grants 2,382,543 University of Miami 1,049,280 Kosow Center 906,682 Corporate Grants 759,089 State of Florida Education Grant 402,946 American Diabetes Association Grants 234,718 Total Support

$18,157,031

Expenditures Research Grants Research & Clinical Support Total Expenditures

[diabetes research institute foundation] 30

[2011 annual report]

$16,847,403 1,309,628 $18,157,031

40% 29% 13% 6% 5% 4% 2% 1% 100%

to our

donors Building and Construction Trades/AFL-CIO J. Enloe and Eugenia J. Dodson* Raymond and Russell Johnson* Sylvia and Rowland Schaefer

United Brotherhood of Carpenters & Joiners of America United Union of Roofers, Waterproofers and Allied Workers Cliff Viner Jill Viner

Chairman’s Council - $5,000,000+

Governors’ Society - $500,000 +

Polly and Baron de Hirsch Meyer* Leon J. Simkins

Jeanne and Virgil Christopher* Rose Cohen* Tom Curtis Kelly and Harold Doran E.R.A.S.E. Diabetes Florida Jaycees Florence Frank* Future Leadership Foundation, Inc. Douglas D. Gallagher Susan Gallagher Paola and Piero Ludovico Gandini Richard L. Gelb Family Martin Granowitz Louise K. and Robert T. Held, Sr.* Lola and Donald Jacobson Carole and Barry Kaye Blanche E. Kroloff* Isabel and Sam* May Amy and Alan Meltzer Million Dollar Hole in One Ted & Brenda Novak and Family Penny and Robert A. Pearlman Phil Peterson Key West Poker Run, LLC Risa and Jeff Pulver Redfern Foundation Miriam and James J. Sensale The Family of Samantha Max Stern Ferne and Daniel Toccin ULLICO Management Company Walgreens Bruce and Roberta Waller

Visionaries - $10,000,000+

Leadership Council - $1,000,000+

To our donors with our deepest gratitude… We wish to gratefully acknowledge all of our donors whose continued support has allowed DRI scientists to pioneer new therapies aimed at restoring insulin production, maintain their focus on curing diabetes and Lead with Excellence toward this singular goal. Our DRI family continues to grow and many new donors have joined us over this past year. We sincerely appreciate every single gift we receive, no matter the size. We would like to take this opportunity to recognize and thank our highest contributors, whose unwavering dedication and unparalleled generosity has truly helped accelerate progress toward a cure for diabetes. The individuals, families, corporations and foundations listed on the following pages have been the backbone of this organization since our inception almost four decades ago. Their names appear in the corresponding giving levels as of December 31, 2011. Again, we wish to deeply thank all of our donors the world over for your continued support of the Diabetes Research Institute and Foundation. [diabetes research institute foundation] 32

Anonymous Michele Bowman and Joseph Underwood Caesars Entertainment Trudy and Paul Cejas Diabetes Foundation of Florida Randy Dorfman The Esformes Family, Annie and Nate Esformes Foundation for Diabetes Research Stacy Joy Goodman Memorial Foundation Shirley D. Harris Inserra Family Foundation International Association of Bridge, Structural and Ornamental and Reinforcing Iron Workers International Association of Heat & Frost Insulators and Asbestos Workers International Brotherhood of Boilermakers, Iron Ship Builders, Blacksmiths, Forgers & Helpers International Brotherhood of Electrical Workers International Brotherhood of Teamsters International Union of Bricklayers & Allied Craftworkers International Union of Elevator Constructors International Union of Operating Engineers International Union of Painters and Allied Trades Richard H. Kline* Eleanor C. and Joseph* Kosow Laborers’ International Union of North America Alfred P. LaRose* The Molly and Lindsey Diabetes Research Foundation Operative Plasterers’ & Cement Masons’ International Association of the U.S. & Canada The Jack Parker Corporation Peacock Foundation, Inc. Ricardo Puente William and Deborah Rand Valerie and Camillo Ricordi Sheet Metal Workers International Association Dr. Denise R. and Thomas D. Stern United Association of Journeymen & Apprentices of the Plumbing & Pipe Fitting, Sprinkler Fitting Industry of the U.S. & Canada

[2011 annual report]

Distinguished Humanitarians $250,000+ Elizabeth M. and Robert W. Bradley* Jane and Bill Burt* Henry E. Caballero* Ivette and Juan Calles Pearl Coulter* Diabetes Research & Wellness Foundation Lloyd and Helen Dilworth Foundation Betty and Lowell* Dunn Joan and William J. Fishlinger Florida Power & Light Employees Jeanine Forman-Ham Paula N. Freund* Dr. and Mrs. Phillip T. George and Family Linda and Barry Gibb Nancy and Lawrence E. Glick Mary and Jay N. Goldberg Jill and Allen Greenwald Fran and Mel Harris Barbara Herzberg and Family The Holtz Family IBM Foundation and Employees

Louis Kaczmarek* Isolde Kaskel* The Martin Kleiman Family Connie and Harvey Krueger Ladyzinski Family Foundation Tova Leidesdorf Sandy and Sidney Levy Lions Club International Eleanor Lowe* Francine Lowe Micki* and Joseph Mele Charlotte and Eugene Milgram The Mostyn Foundation Ethel*and Marvin Oltchick Fred and Mabel R. Parks Foundation Cristina and Ramon Poo Barbara C. and John F. Popp* The Seaver Institute Shanken Family Foundation Shapiro-Silverberg Foundation Holly and David Sherr Muriel and Sherman Simon Philanthropic Fund Richard H. Simons Charitable Trust Sandy and Paul Steinberg Burton S. and Barbara F. Stern Symonds Family Van Pelt Foundation Ethel J. Vilm* Washington CLUB Rita and Stan Weinstein Westreich Foundation The Wilfork Family Sally Zak* Sonja Zuckerman

Grand Founders - $100,000+ Lisette and Norman* Ackerberg Joseph Alexander Foundation , Inc. Alliance Building Services Barbara and Philip Altheim American Building Maintenance Co. Arison Family Aurora Foods, Inc. Bankers Life & Casualty Co. Autis H. Barker* The Bastin Family Alan Bauer* Diane and Bernard Beber Margaret and Raymond Berner Buddy Blair* Nancy and Jerry Blair Belle and Albert* Blanton Martha and Tom Blash* Florence Averill Blocker* The Family of Dr. Adam H. Bloom Boehringer Mannheim Corp. Delores S. and William K. Brehm Sylvia Bruce* Marty B. Bruder Valetta Arlene Byrn* Carnival Cruise Lines Cynthia D. Carr Roberta O. and Harvey R. Chaplin Children with Diabetes Foundation The Cohen Family Charitable Foundation

Collins Building Services, Inc. Brian and Cheryl Coughlin Cushman & Wakefield, Inc. Tom Daly Dotty and George* Dâ&#x20AC;&#x2122;Amato Reva Dauer* Lucille S. Dell* The DeMatteis Family Foundation Lisa and David Desmond Jodi and Bob Dickinson Edna M. Donahue* Robert E. Dooley The Doscas Family Foundation The Durst Organization Cindi and Paul Elias CB Richard Ellis Cindy Epstein The Charles Evans Foundation Raymond Falkenstein* Elizabeth and Max Feldberg Fund Eric Feiler* Fidelity National Title Insurance Company First Quality Maintenance LTD. Randy and Mark Fisher Derry and Steven Fishman Valerie and Marc Fishman Tina Santi Flaherty Michael J. and Katherine E. Franco Foundation Fraternal Order of Eagles Marvin Ross Friedman Joan Galison Sherrie Garfield in Memory of Joseph Garfield* The Genatt Family Gibb Family Foundation Glen Cove Police Benevolent Association Esther and Marc S. Goodman Jane and Jerrold F. Goodman Alvin Grabow* Barbara Grace* Linda and Glenn Greenberg Maurice R. and Corinne P. Greenberg Grossjung Foundation Elizabeth A. Guon* Elizabeth and Gary Hall, Jr. Harvard Maintenance, Inc. Arthur H. Hertz The Hatz Family Kirsten and Steven Heinemann John W. Henry Sam Herzberg Judith and Lawrence Howard JAD Corp. of America Lynne and C. Shelton James Johnson and Johnson Family of Companies Paul Tudor Jones The Rose and Burton Kahn Family Foundation The Max and Yetta Karasik Family Foundation Henry A. Keller, Jr. Joan Keller Norman and Sue Kenyon Barbara and Martin P. Klein Tammy and Steven Klein Priscilla & Ira Kleinberg Foundation Sylvia Kwasha* Lucrezia and Vito LaForgia Oscar and Vivian Simkins Lasko Barbi and Warren Lazarow Robert Mace Anna Machado* Beverly and Mel Marks Julia and Gilbert Merrill Foundation Miami Beach Chapter/NCCH Miccosukee Tribe of Indians of Florida

Dottie and Julie Miller Matthew Miller Family Jeffrey Modell Foundation Ted Moudis Associates, Inc. Mutual of America The Norjana Charitable Foundation Sheila and William Natbony Novo Nordisk Pharmaceuticals Olstein Family Foundation for Brooke Goldfarb Onesource Facility Services, Inc. In memory of my wife, Laurie R. Parham, Ted Parham* Jane Parker and Francis Cosentino Louise and Allan Pashcow Feli and Gerd Petrik Carolyn Pflugk in Memory of Peter Pflugk Platinum Maintenance Service Corp. The Puntillo Family Steven Posner* and Kathryn Chesler Quality Building Services Corp. Red Apple Group John Reisman Judith A. and Paul B. Reisman The Retirement Research Foundation Margaret H. Reynolds* Jed Ringel Marie and Charles Rizzo C.H. Robinson Company Worldwide, Inc. Marion A. Roletti Foundation Ruth and Albert Rosenberg* Kelly and Charles Royal Madelyn Rubin Mark R. Rubin Charles Sakele* Olga and Carlos Saladrigas Leslie and Ricardo Salmon Sandoz Research Institute Wells K. Schuppner* Ruth and Samuel Schwartz* Inge and Maurice Schweizer* Barbara F. Scott Jacci S. and Floyd E. Seskin Shell Key West Challenge The Morton F. Silver Family Freda F. Silvers* Kathy Simkins Barbara and Sheldon Singer S L Green Management LLC Sandra Smith Louise B. Soehner* Jana and Steven Sonberg South Florida District Optimists International Spear, Leeds & Kellogg Sportsmen for Charity The Starr Foundation Gerald J. Steinberg* Frank Strick Foundation Marilyn and Gary Studley Suburban League Jack Taylor Family Foundation Anna and Leonard Thun Tiffany & Co. Together Against Diabetes Transel Elevator and Electric, Inc. Turner Construction Company, Anaheim, CA Turner Construction Company, New York, NY Lois and Joseph Umbach William T. Voigt* Laura Weinsoff* Barton G. Weiss Dorothy and Jack Weiss James Wenck, Jr.*

Lois and Richard Werner Helene Westreich* Dr. Jack Widrich Foundation Marion and Robert S. Wilson Susan Winberg and Kenneth Shewer Cynthia and Philip Wolman Ann Zorn* Barbara and Martin E. Zweig

Founders - $50,000 + Dr. and Mrs. Vincent J. Abbatiello Abbott Diabetes Care ACC Construction Corporation Adco Electrical Corporation Ahmuty, Demers & McManus AIG Carl J. Althoff* The Jeffrey A. Altman Foundation Ambassador Construction Co., Inc. American Airlines American Fruit & Produce Corp. Americana Manhasset Barbara Annis Aragon, LLC ATCO Properties & Management, Inc. Lillian Baker* The Bakery, Confectionary, Tobacco Workers and Grain Millers International Union Victor Ballard* George W. Bauer Family Foundation Marlene and David Berg Biogen, Inc. Blank Family Foundation, Inc. Esther Blattner* The Mary Farrell and Stuart Bloomberg Family Carol Nudelman Blumberg and Morton Blumberg Boca Group East LLC The Linda and Douglas Boyd Family C. Allen Brice Philip Brice Rita and Samuel* Brodie BrookBridge Consulting Services, Inc. Robert D. Buckler Bvlgari Camp NYDA Junior Division, Inc. Mary and Stephen Carner The Carrion Family Carrousel Centennial Elevator Industries, Inc. Chase Manhattan Bank Deborah Chodrow Tracy and James Ciocia Citigroup Beatrice Clancy Carole and H. L. Clark Terry Cook* Dr. Stephen B. Colvin* and Mrs. Helane Brachfeld-Colvin ConEdison Solutions, Inc. Murray Cornblum Coscan Waterways Carolyn and John Couts In Memory of Pat Covelli Arlyn and Stephen Cypen Damon Biotech Gertrude Davenport* Kathleen and Charles Delle Donne Delta Air Lines Gail and Charles DelVecchio Kim and Jordan Dickstein

[diabetes research institute foundation] 34

Gillian and Elliot* Dinnerstein Charles Domina Gary Dubin Maxine Dubin Durnan Group, Inc. Lola and Gus Efthimiou Eli Lilly & Co F.J. Sciame Construction Co., Inc. Chris and Kevin Fee Iris and David Feldman The Milton and Sally Feldman Foundation Doris Felner* Claudia M. Ferero Firequench, Inc. Mary Beth and Bruce Fishbein Shirley Fletcher* Fluor Constructors International, Inc. Fondazione Italiana Diabete Onlus Kathi and Scott Forbes The Foundation for Transplant Research Patricia Frankel Edith* and Sol Freedman Jack & Pauline Freeman Foundation Christine M. Frick* Joel S. Friedman and Victoria Agron Milton I. Friedman* John Gallin & Son, Inc. Gladys and Martin Gelb Fred Geller Electrical, Inc. Genovese Drug Stores/Eckerd Corporation Herbert and Elaine Gimelstob Becky and Braxton Glasgow Gloria* and Stanley Goldman Moises T. Grayson Amy, Scott, Jonathan & Lexi Greenwald Danielle and Troy Gregory Grubb & Ellis Guardian Service Industries, Inc. Jim L. and Betty L. Guy Edgar and Frieda Hamm Trust Kenneth Harple Nicki and J. Ira Harris Sigrid Haukland* Health Foundation of South Florida Hector Family Foundation Lady Monica Heftler Heisman Trophy Trust Roberta and Lawrence Helfant H. Kurtz Henley* HILTON WORLDWIDE Gertrude Hirsch Iacocca Foundation IESI Corporation Insulin-Free World Foundation JDP Mechanical, Inc. Kenny Johnson Mollie Kalman* Reuben Kaplan* Amy Katz Eleanor and Herbert* Katz Helene and Stanley Kellert* Kelly Press, Inc. Patricia and James Kennedy Stanley M. Kossoff Helene and Marc Kovens Burt Kozloff Janie and Ron Kupferman Lane Office Kenneth A. Lattman Foundation, Inc. Maximilian Lavine* Lehman Brothers Lehr Construction Corp. Fran and Robert Leichtung Meryl R. Lieberman

[2011 annual report]

Thomas J Lipton, Inc. Ann and James Long Long Island Board of Realtors Dr. & Mrs. John Lovecchio Lowenstein Sandler PC The Luebs Family William Macklowe Company Joan and Martin Maddaloni J.T. Magen & Company Inc. Magnus and Petherick Family Medimmune Linda and Thomas Meyer Milrose Consultants, Inc. Mitzi and Sol Center June Moran In Memory of M. Irene Stafford Marie G. Morandi MOSAIC M-T-M Printing Co., Inc. Mystic Pointe Neiman Marcus Neocrin Company Morton Neufeld Foundation New York City Transit Authority Judy and J. P. Newell, III Newmark & Company Real Estate, Inc. Kathryn A. Nicolosi The Nieweg Foundation NMAPC, Inc. Calvin & Flavia Oak Foundation The Oringer Family Foundation Otis Elevator Lisa and James Pappas Perlmart Pershing Square Capital Management, L.P. The Picard Family Ruth and Nathan* Plaks Plaza Construction Corporation Louise and Faustino Poo Porsche Ethel C. Posnick The Produce Connection Quality Fire Protection Consultants, Inc. Raymond C. and Diane F. Radigan In memory of my husband John, Lillian Redlich Maria and Eric Reeps Gertrude Reis* Remco Maintenance Corporation Myrna and Norman Ricken Blanca I. Rodriguez Helen L. Rossi* Iris and Gene Rothstein Adrienne R. and Arnold J. Rubin Florence and Arnold Rubin* Gloria and Dr. Larry Ruchman Roberta Sands Irela and Jose Saumat ScheinMedia Schindler Elevator Corporation Schnellbacher-Sendon Group, LLC Richard Schoninger and The Schoninger Fund Bruce and Mary Jo Schumin The Segel Company, Inc. Mildred and Julius Ser Tom Shanks Sanjiv Sharma and Nadine Allen Sherwood Medical Industries Iris and Milton Shlansky Thomas Silver Lenore Toby-Simmons and Dr. Bernard* J. Simmons The Simon Foundation Rose Sipocz*

Alan Smurfit Claudine Smurfit Iolanda M. Sobol Donald Soffer Frosene Sonderling* Southern Wine & Spirits of South Florida Abbe and Eric Spar Marilla M. Spear* Joan Spector Stanford Financial Group Debbie and Lou Steiner Structure Tone Inc. Brett and Daniel Sundheim To The Point Rick, Margarita and Steven Tonkinson The Torch Foundation Triangle Services, Inc. ThyssenKrupp Elevator Corporation Unity Electric Co., Inc. Vanguard Construction & Development Co., Inc. VITAZEST Water - Triple A Products, LLC Vivotech Vornado Realty Trust Wendy Waller The Reverend Ann Walling Rina and Jerrold Weinbrom Anne Weinstock* Laurie and Lawrence Wells Leslie Westreich Rhoda and Donald White Dan Whitney a.k.a. Larry the Cable Guy The Paula and Tom Wilson Family Sheila Wohl Josephine Wolf* Wollowick Family Foundation Donna and George Zoley - The GEO Group Zwicker Electric Co., Inc.

Benefactors - $25,000+ ABM Janitorial-Northwest A.F. Best Securities, Inc. A/R Environetics Group, Inc. Abbey Foundation Jayne and Leonard Abess/ City National Bank of Florida Alice and Arthur Adams* Sari and Michael Addicott Adelhardt Construction Corporation Arthur and Shelley Adler Advanced Electronic Solutions, Inc. Annette and Lee Aerenson AFL-CIO Housing Investment Trust/AFL-CIO Building Investment Trust Armando Alejandre Jr. Memorial Foundation Carmen Alexander-Printup* and Michael C. Alexander Allergan Medical Optics Amalgamated Transit Union American Healthcorp., Inc. American Home Products Corp. American International Group Animas Corporation A-One-A Produce & Dairy Architectural Tile Restoration, LLC Helen M. Aren* Peggy and Joseph Armaly The Artzt Family ASM Mechanical Systems Ruby Bacardi Sallie* and David Balogh Lydia and Paul Balzano

George W. Bauer Family Foundation Bay Area Produce Bear, Stearns & Co., Inc David A. Beckerman Foundation Marie Belanger Suzanne and Marc Bell Arvilla and Leo* Berger Ruth and Philip Berman Betagene Incorporated Donald Bezahler Suzanne Bezahler Jennifer and Robert C. Bills Biscayne Greyhound Track Blavin & Company, Inc. Bloomberg Ted Bodin* Michele and Peter Bongiorno BOSTON PROPERTIES The Boult Family Foundation Bovis Lend Lease, Inc. Bravo Brands Inc. Barbara and Louis Brindisi Bristol-Myers Squibb Company Romero Britto Dorothy and Michael Brumer Buchwald Jewelers Cheryl and David Bunzel Marilyn Cahn Kate Callahan and Peter Benjamin Canyon Ranch Health Resort Cartier, Inc. Sophia and William J. Casey Foundation CBRE Real Estate Services, Inc. Lee and Sidney Charnin Chase Enterprises Elizabeth Cheval Edwin S. Chua and Lori Dolce Cilco, Inc. Citrix Systems Karen B. Cohen Mr. and Mrs. Michael Cohen Ralph Cohen* Ruth E. Cohen* Vivian Cohen* Comet Electric Mabel B. Conklin Gertrude and Jack* Cooper Miller Cooper Lorraine and Sidney Cooperman Cathie and Robert Cornacchia Cornblum Family Corporate Interiors Contracting, Inc. Crossland Mechanical, Inc. Cure Diabetes Now Ron Darling Foundation, Inc. Jane and Lawrence David Merle M. DeLancey DeLancey Printing Delicious Brands, Inc. Ann and Norman Didriksen Diehard Exterminating, Inc. S. Di Giacomo & Son, Inc. Distillery Wine and Allied Workers RCDolner LLC Amy and William Donner Debbie and John Drury Dudley Foundation Mildred Edelstein* Edmar Cleaning Corporation Sheila Elias Susan and Gerard Elicks

Gail E. Ellis and Sandy J. Fox Empire Office, Inc. Erectra Construction Corp. ESS & VEE Acoustical Contractors, Inc. Eurohypo AG Rosa and Francis Feeney Mr. and Mrs. Keith Fell Marilyn Fellman Wilma Fetchko* Fine Art and Craft Co., Ltd. Pamela and Barry Fingerhut Lillian Fiolic* Fisher Brothers Management Co. FIT USA Foundation Florida Association of Furniture Manufacturers Florida District Kiwanis Florida Mushroom, Inc. Forest County Potawatomi Foundation Fried, Frank, Harris, Shriver & Jacobson In Loving Memory of Fred Friedland Friends United for Diabetes Research Doree and Malcolm Fromberg Thomas E. Frueh* G.L. Homes of Florida Corporation Anne Gache Mira and Murray* Gaines Gardiner & Theobald Inc. Gina and Peter Gardner Gensler Friends of Robert A. Georgine* Suzanne and Thomas* Gerard Niety and Gary Gerson Arnold Gertner Bunchy Gertner Judy and Robert Giaquinto Susan and Arthur Gillin Dalia and Saul Glottmann Marion and Donald Golden Carolyn and Marc Goldfarb Debora and David Goldfarb M. Robert Goldman & Company Goldman Sachs and Company Bella and Lester* Goldstein Lorraine Goldweber* Jennifer and Ian Goodman Nettie Gratkowski* Ellen and Irving Grauer Sylvia Gray George Green Sharon Gustafson and Barry Florescue Susan and Alan Habacht Amy and James Haber Foundation Norma and Herbert Hackmeyer* Patrick and Mary Hall Joseph and Sally Handleman Foundation Trust Daniel J. Hannon Hanover Moving & Storage Co., Inc. Deana and Stephen Hanson The Headlands Foundation Health Net, Inc. Ellen and Barry Heimlich Christopher and Joie Hein Mr. and Mrs. Robert T. Held, Jr. Mary K. Heller* Marilyn and Carl Hellman Janet and Barrett Hess Madeline and Herbert Hillsberg Louis Hirschfield The Hirshleifers

HLW International LLP Hochberg Family Foundation Lee S. Hochwald* The Homan Foundation Home Savings Bank of Florida Hotel Employees and Restaurant Employees International Union Shirley M. Hotto Household Credit Card Services Edith and Robert Hudson Hunter Roberts Construction Group LLC Peter Huri Hyatt Hotels Corporation ICAP Services North America LLC Insignia/ESG, Inc. International Association of Fire Fighters Intracoastal Abstract Co., Inc. ItaĂş USA Securities, Inc. Myra and Allen Jacobson JC & F Services, Inc. The Joachim Family Jones Lang Lasalle Americas Max D. Josephson* Juvenile Diabetes Research Foundation International K & R Industries Kaback Enterprises, Inc. Charlotte and Louis* Kaitz Howard Kane Mr. and Mrs. Michael A. Karsh Marsha and Arthur Katon Charles Kaufman Enterprises Joan and Myron Kaufman Beth and Sy Kirshner Klear Electrical Corp. Merrick R. Kleeman Harry Klein* Sheila and Arthur Kline Knight Electrical Services, Corporation Gary Koenig, in Memory of Walter D. Koenig Debra and Jerry Kramer Harry Kramer Memorial Fund Alvia Kreher* Bertha Kubler L & K Partners, Inc. Nancy and Richard Ladd LandAmerica Laurie and William* Landau Brian and Jill Landow Laro Service Systems, Inc. Lazard Freres & Co., LLC Carole and Marvin Leichtung Jan and Arthur* Leichtung M.K. LeLash Foundation Ellen and Joseph Leondis Joan and John Leondis Evelyn C. Levine* Pat and Mac Levitt Lodi Markets, LLC JoAnn B. Long* The Lostritto Family Alice Mace Margot Madans Mailboxes, Etc. Jack N. Mandel* Diane and Paul Manning PS Marcato Elevator Co., Inc. Marino Gerazounis & Jaffe Associates, Inc. Jodee and Steve Martin Martini, Iosue & Akpov Lisa and Richard Mattaway

[diabetes research institute foundation] 36

Linda and Bill McDonald, Jr. MC Energy Inc. Scott McDonald and Tiffany Schauer McGann Family The McLaughlin Company MDB Development Corp. Shelly, Ira and Matthew Meister Lois and Marvin L. Meitus Mercedes Benz of Palm Beach Joseph Messana Metropolitan Steel Industries, Inc. The Milch Family Foundation Dawn Mintz Memorial Fund Marge K. and Dr. Daniel H. Mintz Martha Mishcon Monster Worldwide, Inc. Monterey Fund, Inc. Leland and Jeannine Morris Edward Moss Robert Moss The Mufson Partnership, Inc. Stephen and Sandy Muss H. Herbert Myers Memorial Foundation National Association of Letter Carriers National Distributing Company National Music Publishers Association, Inc. Dr. Robin Nemery and Barry Hauser Eleanor & Roy Nester Family Foundation Sheldon Neuman* New York Community Bank Foundation New York Elevator Company, Inc. Ann and Jack Norman Northland Cranberries, Inc. Novocell, Inc. Sandra Nowicki In Memory of Gordon D. Oppenheimer Rosalie and Stephen Pandol Parents for the Cure Natalie and Michael* Pelavin Perry Ellis International Inc. David J. Peterson Doreen and Andrew Peykar Ruth Pfeffer Doris and Murray Plopper* Simon Portnoy Victor Posner* Hildine and Jerry Potashnick Premier Restoration Technologies, LTD. Prudential Financial Quality First Produce, Inc. Norma and Luis Quintero Honorable and Mrs. C. Raymond Radigan Rafa Machinery and Engineering Real Estate Media Rosalind and Daniel Richter Marsha and Barry Ringelheim Heather and Charles A. Ritter Robert Stigwood Organization Joan and Gerald Robins Deborah and Scott Robins Loree Rodkin Rooms To Go Childrens Fund IMA Helen and James Rosburg Harry & Bessye Rosenberg Charitable Trust Seymour Rosenberg Blanche I. Rosenblatt Jill and Robert Rosenhaus Mr. and Mrs. Maurice A. Ross Maritere and Jorge Rosso The Rothstein Family Ruth Rubenstein*

[2011 annual report]

Alice and Seymour Rubin * S.I.U. of North America Sager Development/Subway Saks Fifth Avenue Salomon Smith Barney Faryl and Jonathan Sandler Gerald P. Schein Jill Schildkraut-Katz Kathie Schlesinger Pamula and James Schlesinger Sue Schonfeld Patricia and Leonard Schupak Dr. Berthold* and Ardis Schwarz Donna and Marvin Schwartz Beatrice & Samuel A. Seaver Foundation Michele and Norman* Seiden Samantha Shanken Baker and Michael Baker Barbara and Norman Shapiro Louis K. Sher Beverlee Shere Dana and Andrew Shore Show Management Concession Inc. Sheila and Joseph Shulevitz The Silva Family, in Memory of Barbara Katz Casey and Matt Singer Samuel Singer* Dolly and Mitchell Sirgany Skadden, Arps, Slate, Meagher & Flom LLP SK Children's Charities Jay Skyler and Mercedes Bach The Slater Family Bernadette and Owen Smith Edward W. Smith Jr. Foundation Linda and Frank Smith Standard Drywall, Inc. Starvin Marvin Jewelry Inc. Steelcase Inc. Rhoda Stern Strauss Paper Company, Inc. Edith and Martin B. Stein Stuart Dean Co., Inc. Sugarman Family Partners in Memory of Fred Krutel*

Cindy and Michael Sweeney The Swisher Family Syska Hennessy Group, Inc. The Taub Family and Palm Bay International Team FootWorks Temco Service Industries, Inc. Tennessee Valley Authority Tishman Construction Corporation of New York Top Tomato Company In Memory of Joseph and Irene Tow TPG Planning & Design, LLC Tropical Shipping U.S. Trust Bank of America Private Wealth Management Union Bank The Union Central Life Insurance Company United Food & Commercial Workers International Union United States Sugar Corp. Vornado Realty Trust W5 Group, LLC Judy and Bruce Waldman Thomas J. and Holly C. Weger Carole and Marcus Weinstein Susan Blash Weiss and Gary Weiss Wells Fargo Foothill Winn-Dixie Stores, Inc. Marcia and Leon* Winograd Laurence G. Wolf Marsha and Fred Wolinsky Yates Restoration Group Ltd. In Memory of Lucian Zadrozny Deborah and Jeffrey Zane Althea Brandner Zansler* Mary Zuk* *deceased

national

the heritage

board of directors

society

> The Heritage Society of the Diabetes Research Institute Foundation was created to recognize individuals who have generously provided for our cure-focused research through their will, life insurance, charitable remainder trust and gift annuities, or other deferred giving vehicle. Their selfless legacy ensures that critical funding for the Diabetes Research Institute will continue into the future. Over the years, planned giving programs have allowed many donors to make substantial gifts to the DRI in ways that have complemented their personal financial objectives. Heritage Society members have chosen to create an enduring legacy and perpetuate their philanthropic goals to benefit countless children and adults affected by diabetes. The following list includes our Heritage Society members through December 31, 2011.

Cheryl Arnold and Don Van Pernis Nancy Barr Bisco E. Diane Beber Thomas and Martha Blash* Michele Bowman and Joseph Underwood Annemarie and Lester Brockmann Marty B. Bruder Jane D. Burt* Henry Caballero* Ivette and Juan Elias Calles Jeanette Carmel* Tom Curtis Aldo Del Re* Cindi and Paul Elias Eric Feiler* Carole D. Franklin Sherrie and Joseph* Garfield Stanley J. Garfinkel Dr. and Mrs. Phillip T. George Elizabeth A. Guon* Richard Alan Knowles Gurwitz Jim L. and Betty L. Guy J. Jean Hacker* Kenneth G. Harple Shirley Harris Frances Harrow Larry Hassenbein Barbara M. Haynes

Don and Diane Holmes Shirley M. Hotto Jill and Thomas Karlya Carole and Barry Kaye Dr. Norman and Sue Kenyon Richard H. Kline* Lorrie Ann Knowles Eleanor Kosow Rose B. Kramer Rebecca Krawitz* Sara Kupchik* Marc D. Levine* Margot Madans Muriel B. Mele* Jill and Gary Miller Howard C. Neumann Kim and Beverly Newlin Eleanor J. and Laurence S. Newman* Ethel* and Marvin Oltchick David Papier In memory of Laurie R. Parham Ruth Plaks Betty Pinto* Barbara C. Popp* Hildine and Jerome Potashnick Lori Chadick Randell James and Dr. Wendy Rapaport Lillian Redlich

Gertrude Reis* Margaret H. Reynolds* Jo-Ann Rifkind Susan and Neil D. Rosenberg Beatrice and William* Sahm Charles Sakele* Arline B. Schaeffer Kimberly Schlom Maurice and Inge Schweizer* Seskin Family Foundation Barbara and Sheldon Singer Emilia M. Stark Gale Goldstein Tucker Ilene and David Vinikoor Simon H. and Sandra F. Waugaman Esther Weingarden* Laura Weinsoff* Lori and Lary Weintraub Susan Blash Weiss and Gary Weiss Julius Werbner* Adele Wilson* Sally D. Zak* Dr. Sheldon and Elaine Zane Morris Zell Don Zipern Ann Zorn*

Chairman Harold G. Doran, Jr.

Secretary Barry C. Hauser

Immediate Past Chairman Thomas D. Stern

Directors Mark H. Ayers* Diane Beber Marlene Berg Ronald Maurice Darling, Jr. Piero Gandini Esther Goodman Marc S. Goodman Arthur Hertz Bonnie Inserra Glenn Kleiman Eleanor Kosow

Vice Chairmen William J. Rand, M.D. Charles Rizzo President and CEO Robert A. Pearlman Treasurer William J. Fishlinger

*deceased

[diabetes research institute foundation] 38

[2011 annual report]

Sandra Levy Sheila F. Natbony, D.O. Allan L. Pashcow Ramon Poo Risa Pulver Ricardo Salmon Kenneth A. Shewer Kathy Simkins Sheldon L. Singer Steven Sonberg Jill Viner Bruce Waller Sonja Zuckerman *deceased

honorary and regional boards

Florida Board of Directors

Northeast Board of Directors

Long Island Board of Directors

Chairman

Chairwoman

Chairman

William J. Rand, M.D.*

Risa Pulver*

Allan L. Pashcow*

Directors

Executive Committee

Sari Addicott Bernard Beber, M.D. Diane Beber* Crystal Blaylock Sanchez Sabrina R. Ferris Bruce Fishbein Joel S. Friedman Rene W. Guim Barry Hauser* Javier Holtz Norman Kenyon, M.D. Vito La Forgia Sandra Levy* Carol Nudelman, Ph.D. Ramon Poo* Cristina Poo Deborah Rand Michelle Robinson Madelyn Rubin Rosa Schechter James Sensale Jacci Seskin Don Strock Richard P. Tonkinson Stephen Wagman Rita Weinstein Sonja Zuckerman*

Samantha Shanken Baker Diane L. Cohen Peter L. DiCapua Kim Dickstein Jenna Dorn Marc S. Goldfarb Esther Goodman* Marc S. Goodman* Bonnie Inserra* Lindsey Inserra Alan Kava Meryl Lieberman Ricardo Salmon* David Sherr Kenneth A. Shewer* Thomas P. Silver Thomas D. Stern*

William J. Fishlinger* Barbara Hatz John Luebs Hon. C. Raymond Radigan Charles Rizzo*

* also member of the National Board of Directors

Directors Debra Carrion John Carrion Douglas R. Donaldson Iris Feldman Joan Fishlinger Jon Hatz Frances Luebs Louise Pashcow Marie Rizzo Miriam Shiff Bruce A. Siegel Steven Silva Bruce Waller* Roberta Waller Delia DeRiggi-Whitton

Honorary Board of Directors Lynne and Martin Baron Bernard Beber, M.D. Barbara and H. Tod Berman Juan Elias Calles Paul Cejas John Drury Annie and Nathan Esformes Linda and Jay Finkelstein Bernard Fogel, M.D.

Edward T. Foote, II Jeanine Forman Ham Samuel J. Fox Lisa and Mark M. Freedman C. Thomas Gallagher Douglas Gallagher Gladys and Martin Gelb Linda and Barry Gibb Dwina and Robin Gibb Yvonne Gibb Lawrence E. Glick Jay N. Goldberg Bella Goldstein Jane and Jerrold Goodman Senator Bob Graham Shirley Harris Lawrence Howard, M.D. Mary Lou and Robert T. Held, Jr. Fana and Abel Holtz Lola and Donald Jacobson Martin P. Klein Stanley M. Kossoff Harvey M. Krueger Robert Leichtung Sidney Levy Charlotte and Eugene Milgram Martha Mishcon Marge Kleiman Mintz Stephen Muss Judy and John P. Newell, III Edward James Olmos Michelle Robinson Blanche Rosenblatt Rowland Schaefer Donna Shalala Serena and Leon J. Simkins Oscar Sotolongo Ferne and Daniel Toccin Dottie and Jack S. Weiss Lenny Wolfe

National Office

Northeast Region

Administrative Assistant

Robert A. Pearlman President and Chief Executive Officer

Mary Revie Administrative Assistant

Deborah L. Chodrow

Mylinda Auguste

Chief Operating Officer

Data Entry Clerk

Jeffrey Young

Marisol McKay

Chief Financial Officer

Data Entry Clerk

Tom Karlya

Sarah Mehan

Vice President

Receptionist

Jill Shapiro Miller

Eddy Garcia

Vice President of Gift Planning

Courier

Bernadette Toomey Northeast Regional Director

Jill Salter Development Coordinator

Amy Epstein

Lori Weintraub, APR Vice President of Marketing & Communications

Director of Special Events

Tricia Pellizzi Administrative Assistant

Long Island Region Anthony E. Childs Long Island Regional Director

Florida Region Lily Scarlett Sheryl Sulkin

Lauren Schreier

Director of Special Events

Director of Marketing & Communications

Brian Huether

Director of Special Events

Melinda Ginsberg Special Events Coordinator

Associate Director of Special Events

Margaret Cassani

Barbara Singer Director of Special Projects

Nicole Otto Assistant Director of Special Events

Administrative Assistant/ Receptionist

Natasha Norris Communications and Social Media Manager

Meris Thomas Special Events Coordinator

Stacy Zolotin Gift Planning Manager

Karen Paraboo Administration and Database Coordinator

Laurie Cummings Communications Assistant

[diabetes research institute foundation] 40

Aurora Nunez

[2011 annual report]

dri

foundation staff

Regional Offices

200 South Park Road

Long Island

Suite 100

410 Jericho Turnpike

Hollywood, FL 33021

Suite 201

Telephone 954.964.4040

Jericho, NY 11753

Toll-free 1.800.321.3437

Telephone 516.822.1700

Fax 954.964.7036

Fax 516.822.3570

Northeast 381 Park Avenue South Suite 1118 New York, NY 10016 DiabetesResearch.org

DiabetesResearch.org

Telephone 212.888.2217 Fax 212.888.2219

National Office