Development of autoimmunity at an early age associated with more aggressive form of the disease in genetically susceptible children, a USF Health-led study suggests

TAMPA, Fla. (Oct. 21, 2021) — New findings from the international The Environmental Determinants of Diabetes in the Young (TEDDY) study add to the growing body of evidence indicating that type 1 diabetes is not a single disease. The presentation and, perhaps, cause of autoimmune diabetes differs among genetically high-risk children, the research suggests.

In a cohort study published July 22 in Diabetologia, lead author Jeffrey Krischer, PhD, director of the Health Informatics Institute at the USF Health Morsani College of Medicine, and TEDDY colleagues compared the characteristics of type 1 diabetes diagnosed in children before vs. after age 6.  The paper’s senior author was Beena Akolkar, PhD, of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

“Our results underscore the importance of taking into account the age at development of multiple autoantibodies when evaluating risk factors for progression to a diabetes diagnosis,” said lead author Dr. Krischer, a Distinguished University Health Professor and co-chair for the National Institutes of Health-funded TEDDY consortium. “When the changing picture of autoantibody presentation is considered, it appears type 1 diabetes at an early age is a more aggressive form of the disease.”

In type 1 diabetes, a misdirected immune response attacks and destroys insulin-producing beta cells in the healthy person’s pancreas – a process occurring over months or many years. Four autoantibodies directed against the pancreatic β-cells — glutamic acid decarboxylase autoantibody (GADA), insulin autoantibody (IA), insulinoma-associated-protein-2 autoantibody (IA2-2A), and zinc transporter 8 autoantibody (ZnT8A) – are thus far the most reliable biological indicators of early type 1 diabetes, before symptoms appear. Not all children who test positive for one or more autoantibodies progress to a diagnosis of type 1 diabetes, which requires lifelong administration of insulin to control blood sugar levels and reduce health complications.

Over the last decade, TEDDY researchers have learned more about how the order, timing and type of autoantibodies can help predict which genetically susceptible children are most likely to get type 1 diabetes as they age.

For this multisite study in the U.S. and Europe, the researchers analyzed data from 8,502 children, all at genetically high risk for developing autoimmunity and type 1 diabetes. The children were followed from birth to a median of 9 years. Over this period, 328 study participants (3.9%) progressed from a presymptomatic stage in which autoantibodies first appeared in their circulating blood (signaling initial autoimmunity) to the onset of symptomatic type 1 diabetes.

Study lead author Jeffrey Krischer, PhD, directs the USF Health Informatics Institute and is co-chair for the National Institutes of Health-funded TEDDY consortium.

Half of the 328 participants (2.0%) were diagnosed before age 6, while the other half (1.9%) developed diabetes between ages 6 and 12. The aim was to determine whether the younger group diagnosed with type 1 diabetes differed from the older group, which would suggest that a different form of type 1 diabetes emerges in children as they grow older.

Among the findings:

• As expected, TEDDY participants who progressed to diabetes between ages 6 and 12 were more likely to have first-appearing autoantibodies to the pancreatic enzyme glutamic acid decarboxylase (GAD autoantibodies), while first-appearing insulin autoantibodies (IA antibodies) were much more common in younger children developing the disease.
• The rate of progression to type 1 diabetes was slower if multiple (two or more) autoantibodies appeared after age 6 than if they were present before age 6.
• The significant association of country of origin with diabetes risk found in the younger group declined in the older group. Conversely, the link between certain genotypes and a higher likelihood of developing diabetes significantly increased in the older children.
• Among children 6 and older with multiple autoantibodies, family history did not appear to play a role in whether the child progressed to type 1 diabetes.

“Much of the observed differences in the relationship between genes and environmental exposures can be explained by the age at appearance of autoantibodies,” Dr. Krischer said. “That is important, because it means factors linked with diabetes risk need to be conditioned on age to be properly understood. There may be different environmental exposures occurring at different ages that trigger autoimmunity, or the same environmental trigger may act differently at different ages.”

The research was funded by grants from the NIDDK and several other NIH institutes, JDRF, and the Centers for Disease Control and Prevention (CDC); and supported in part by NIH/NCATS Clinical and Translational Science Awards.

The Environmental Determinants of Diabetes in the Young study is led by USF Health’s Jeffrey Krischer, who has built a worldwide epidemiological hub for T1D research at USF

TAMPA, Fla (July 11, 2021) — The National Institutes of Health (NIH) has awarded the University of South Florida total expected funds of $69.9 million over the next four years to continue the follow-up of study participants in The Environmental Determinants of Diabetes in The Young (TEDDY) consortium. TEDDY is the largest multicenter prospective study of young children with genetic susceptibility to type 1 diabetes (T1D).

The new grant from the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases will also support a second case control study, building upon earlier TEDDY analyses examining how genetic factors and environmental exposures such as infectious agents, diet, and psychosocial stress affect T1D development in high-risk children. The extended project will incorporate viral biomarkers to help explain how viruses may trigger or contribute to the disease process.

Jeffrey Krischer, PhD, is principal investigator of the TEDDY study

Distinguished University Health Professor Jeffrey Krischer, PhD, director of the Health Informatics Institute at the USF Health Morsani College of Medicine, is the principal investigator for TEDDY. He has overseen the NIH-supported data coordinating center for this consortium since its inception in 2004. The Health Informatics Institute employs advanced technologies such as proteomics, epigenetics, gene expression analyses, and metabolomics for TEDDY and other NIH initiatives. Under Dr. Krischer’s leadership, USF has built an internationally recognized hub for epidemiological research in T1D.

A 2019 Nature Medicine paper by Kendra Vehik, PhD, and colleagues at the USF Health Informatics Institute, reporting on unexpected connections between viruses and autoimmune-related diabetes, was recently highlighted by Nature as one of 24 milestones in diabetes research over the last 100 years (milestone No. 23).

Type 1 diabetes is an autoimmune disease in which the body’s immune system attacks the pancreatic β-cells making insulin – a process that occurs over months or many years. The presence of autoantibodies (immune proteins) in circulating blood indicates that the body has begun targeting its own tissues or organs.

TEDDY researchers at six clinical centers in the U.S. and Europe have been following 8,500 children from birth up to age 15, with the aim of identifying environmental factors that influence autoimmune destruction of β-cells. Beta cell autoimmunity ultimately leads to the onset of T1D, which requires life-long insulin injections to treat symptoms.

A 2019 published discovery stemming from TEDDY research showed unexpected connections between viruses, like the enteroviruses illustrated here, and autoimmune-related diabetes. The paper by USF Health’s Kendra Vehik and colleagues was recently highlighted as one of 24 Nature Milestones in Diabetes. | Credit: Kateryn Kon

“Our TEDDY study group has made great strides in understanding the different biological pathways by which a child may develop diabetes-related autoimmunity,” Dr. Krischer said. “We are grateful to the many patients and families who collaborate in our studies. Their resolve inspires us to accelerate our efforts to pinpoint the mechanisms of type 1 diabetes, with the goal of preventing, delaying or reversing this life-altering condition.”

The exact causes of TD1 are unknown. But TEDDY has more clearly defined combined risk factors that can help predict β-cell autoimmunity and T1D onset, including the rates of disease progression, and the distinct stages of type 1 diabetes development.

“Dr. Krischer and his team have provided valuable insights into the interplay between genetic and environmental factors underlying the complex disease process of autoimmune diabetes,” said Charles J. Lockwood, MD, senior vice president of USF Health and dean of the Morsani College of Medicine. “Their work, powered by a research platform supporting high-performance computing and big data, is rigorous and critically important for finding new treatments and preventive approaches.”

Children and adults with type 1 diabetes must monitor their dietary intake and exercise and take insulin injections, or use an insulin pump, daily to help control their blood sugar levels.

Key discoveries from TEDDY investigations over the last several years include:

• Maternal stress during pregnancy and child’s T1D genetic risk: Certain psychological stress during pregnancy (interpersonal and job-related life events) are differentially related to first-appearing autoantibodies –insulin autoantibodies (IAA) vs. glutamic acid decarboxylase autoantibodies (GADA). Excess T1D risk often depends upon specific interactions between the mother’s environmental stress and the child’s genes.

• Distinct autoantibody spreading and progression to disease: Detailed information about the order, timing and type of autoantibodies appearing after the first autoantibody can significantly improve prediction of which children are most likely to advance from initial autoimmunity to symptomatic T1D more rapidly.

• A possible infectious cause of diabetes: In young children at increased genetic risk for T1D, prolonged enterovirus infection plays a role in the development of autoimmunity that precedes T1D diagnosis.

• Human gut microbiome in early-onset T1D: For the first time, TEDDY extensively  characterized the developing gut microbiome (collection of bacteria, viruses and other microorganisms inhabiting the gastrointestinal tract) in relation to T1D. The work laid the foundation to identify gut microbes that may predict, protect against. or cause T1D risk or disease progression.

• Gene-environment interactions modify risk of diabetes-related autoimmunity: In TEDDY children up to age 6, T1D-related immunological changes were clearly dependent upon the interactions of genetic factors and environmental exposures that give rise to IAA or GADA as the first-appearing autoantibodies.

• Linking early supplemental probiotics with T1D autoimmunity: Early intake of probiotics, potentially helpful in maintaining the balance of gut microbes, may decrease the risk of autoimmunity in children at highest genetic risk for T1D. Further studies are needed before probiotic supplementation could be recommended.

***
The new grant is funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the NIH under Award Number U01DK128847.

Illustration of enteroviruses | Credit: Kateryn Kon

A 2019 Nature Medicine paper by Kendra Vehik, PhD, MPH, and colleagues at the USF Health Informatics Institute has been recognized as one of 24 key advances in diabetes research since insulin was discovered 100 years ago.

Highlighted this month as part of a Nature Milestones in Diabetes special issue, the 2019 research by Vehik et. al. provided intriguing evidence showing that, in young children with increased genetic risk for type 1 diabetes (T1D), prolonged enterovirus infection plays a role in the autoimmune destruction of insulin-producing beta cells. Beta cell autoimmunity ultimately leads to the onset of T1D, a serious chronic disease that requires life-long insulin injections to treat.

The USF Health-led work represented a major advance in understanding the links between the virome (all the viruses in the body) and T1D. Dr. Vehik (lead author) and USF Health coauthors Kristian Lynch, PhD, and Health Informatics Institute Director Jeffrey Krischer, PhD, were members of the research team that used sophisticated genomic sequencing technologies to delve deeper into a possible infectious cause for T1D.

Kendra Vehik, PhD, is a professor of epidemiology at the USF Health Informatics Institute.

The pivotal study was one of many that continue to be generated from The Environmental Determinants of Diabetes in the Young (TEDDY) consortium, the largest multicenter prospective study of young children with a genetic susceptibility to T1D. Dr. Krischer is the principal investigator overseeing the National Institutes of Health-supported TEDDY project, which aims to identify environmental factors, including diet, infections and psychological stress, that may trigger or protect against autoimmunity and T1D onset.

“Our next step includes pinpointing biological responses — changes in inflammatory markers, metabolites and proteins — that may explain how viral infections can influence or contribute to beta cell autoimmunity and the progression of T1D,” Dr. Vehik said. “We are honored to be counted among the researchers whose many years of cumulative work has greatly improved our understanding of the complexity of diabetes.”

To read more about the scientific achievement (Milestone in Diabetes No. 23), go to: https://www.nature.com/articles/d42859-021-00026-x

Dr. Jeffrey Krischer of the USF Health Informatics Institute oversees the new NIH-funded study

Tampa, FL (Sept. 30, 2020) – The USF Health Morsani College of Medicine’s Health Informatics Institute is coordinating a nationwide study funded by the National Institutes of Health (NIH) that seeks to discover the cause of several unusual forms of diabetes. For years, doctors and researchers have been stymied by cases of diabetes that differ from known types. Through research efforts at the University of South Florida (USF) and 19 other U.S. research institutions, the study aims to discover new forms of diabetes, understand what makes them different, and identify their causes.

The Rare and Atypical Diabetes Network, or RADIANT, plans to screen about 2,000 people with unknown or atypical forms of diabetes that do not fit the common features of type 1 and type 2 diabetes.

Dr. Jeffrey Kirscher, who leads the USF Health Informatics Institute, is study chair and director of the coordinating center for the new NIH-funded RADIANT study.  He also oversees TEDDY and TrialNet, both NIH-sponsored international clinical networks investigating the causes and outcomes of type 1 diabetes. | Photo by Allison Long, USF Health Communications

A person with atypical diabetes may be diagnosed and treated for type 1 or type 2 diabetes, but not have a history or signs consistent with their diagnosis. For example, they may be diagnosed and treated for type 2 diabetes but may not have any of the typical risk factors for this diagnosis, such as being overweight, having a family history of diabetes, or being diagnosed as an adult. Alternately, a person with atypical diabetes may respond differently than expected to the standard diabetes treatments.

“With help from participants and their families, we aim to develop a comprehensive description of the genetic and clinical characteristics of these rare forms of diabetes,” said RADIANT Study Chair and Coordinating Center Director Dr. Jeffrey Krischer, director of the USF Health Informatics Institute and a professor in the Morsani College of Medicine’s Department of Internal Medicine. “This information could help to establish new diagnostic criteria for diabetes, find new markers for screening, or identify drug targets for new therapies that could ultimately bring precision medicine to diabetes.”

RADIANT researchers will build a comprehensive resource of genetic, clinical, and descriptive data on previously unidentified forms of diabetes for the scientific and health care communities.

The study’s researchers will collect detailed health information using questionnaires, physical exams, genetic sequencing, blood samples, and other tests. People found to have unknown forms of diabetes may receive additional testing. Some participant family members may also be invited to take part in the study.

“It’s extremely frustrating for people with atypical diabetes when their diabetes seems so different and difficult to manage,” said the study’s project scientist, Dr. Christine Lee of NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). “Through RADIANT, we want to help patients and the broader health care community by finding and studying new types of diabetes to shed light on how and why diabetes can vary so greatly.”

USF is the study’s coordinating center, and the lead centers include Baylor College of Medicine in Houston and the University of Chicago. The Broad Institute in Cambridge, Massachusetts, and Baylor serve as the genomic sequencing centers for the project. University of Florida, Gainesville, provides the study’s laboratory services. Other participating centers are:

• Columbia University, New York City
• Duke University, Durham, North Carolina
• Geisinger Health System, Danville, Pennsylvania
• Indiana University, Indianapolis
• Massachusetts General Hospital, Boston
• NorthShore University Health System, Chicago
• Seattle Children’s Hospital
• SUNY Downstate Health Sciences University, Brooklyn
• University of Colorado, Denver
• University of Maryland, Baltimore
• University of Michigan, Ann Arbor
• University of North Carolina, Chapel Hill
• University of Washington, Seattle
• Vanderbilt University, Nashville, Tennessee
• Washington University in St. Louis

“The RADIANT study will further clarify diabetes as a disease that has many different forms, and for which diagnosis and management for some of those forms remain a challenge,” said NIDDK Director Dr. Griffin P. Rodgers. “The discoveries of the study should provide critical understanding of the spectrum of diabetes and improve lives of people with rare forms of diabetes and everyone who cares for them.”

The study opened recruitment on Sept. 30, 2020 for people with atypical diabetes or a form of diabetes that seems different from known types of diabetes. Visit for more information on the study and how to join.

Support for the study is provided through NIDDK grants U54DK118638 and U54DK118612.

Two USF Health Morsani College of Medicine research-focused institutes rank among the Top 10 Institutes and Centers within Florida’s State University System (SUS).  The ranking was derived from the SUS 2018 survey of its 536 university institutes and centers engaged in scientific research, education, community service and other scholarly activity supported by public and private funds.

The USF Health Informatics Institute (HII) was the No 1 institute with $69.6 million in total expenditures. HII is led by Distinguished University Professor Jeffrey Krischer, PhD, who ranks in the top 1 percent of all National Institutes of Health-funded principal investigators worldwide (Blue Ridge Institute for Medical Research, 2018). He has made USF an international hub for NIH epidemiological research initiatives in both type 1 diabetes and rare diseases.

The USF Health Heart Institute, directed by Samuel Wickline, MD, professor of cardiovascular sciences, attained the No. 7 spot, with $13.4 million in total expenditures. The Heart Institute, created with the support of state and county funding, brings together NIH-funded laboratory researchers and physician-scientists to pioneer new discoveries for heart attacks, stroke and other cardiovascular diseases.

Jeffrey Krischer, PhD, leads the USF Health Informatics Institute

Virtually every major university conducting type 1 diabetes research is linked to Dr. Krischer’s institute at USF Health. The HII team coordinates, analyzes and maintains data from several international NIH-sponsored clinical networks investigating the causes and outcomes of type 1 diabetes, including The Environmental Determinants of Diabetes in the Young (TEDDY), TrialNet, the Rare and Atypical Diabetes Network (RADIANT), and the Trial to Reduce IDDM in the Genetically at Risk (TRIGR). Members of the Institute also have funding from industry, the Patient-Centered Outcomes Research Institute (PCORI) and the NIH for studies in oncology, type 2 diabetes, molecular biology and “big data” (‘omics).

“The Health Informatics Institute has been able to design and implement an infrastructure to support high performance computing and big data and create a platform for scientific advances yet to come,” Dr. Krischer said.

Samuel Wickline, MD, is founding director of the USF Health Heart Institute.

The USF Health Heart Institute will be housed within the new Morsani College of Medicine building now in the final stages of construction in downtown Tampa. By bridging basic science and clinical translational research to create new therapies for heart disease, generating biomedical inventions leading to patents and licenses, and attracting biotech and pharmaceutical companies with its innovative work, the Heart Institute is expected to be a major driver of economic activity in the Tampa Bay region.

“USF has put forward a significant investment to pursue solutions to cardiovascular disease, the number one cause of death and health care expenditures worldwide,” said Dr. Wickline, a pioneer in harnessing nanotechnology to combat all types of inflammatory diseases. “It’s vital to the public good for universities to undertake applied translational research that achieves useful bench-to-bedside successes.”

A TEDDY progress report, led by USF’s Jeffrey Krischer, shows for the first time that combining genetic and environmental factors substantially increases prediction of future diabetes

TAMPA, Fla. (July 15, 2019) — With the help of children and their families worldwide, scientists continue to identify how genetic and environmental risk factors converge to trigger autoimmunity and progression to type 1 diabetes in some genetically-susceptible youngsters, but not others.

Since The Environmental Determinants of Diabetes in the Young (TEDDY) study began in 2004, this ongoing National Institutes of Health-sponsored consortium has published research examining type 1 diabetes risk factors, including genotypes, sex, family history, genetic variations, diet (including probiotics and types of infant formula), growth in early life, the microbiome, proteomics, metabolomics, age at autoantibody seroconversion, and first-appearing autoantibody. The 8,600 TEDDY-enrolled children across six centers in the U.S. and Europe are monitored for up to 15 years; those who began being followed as infants are currently ages nine to 14.

Now, in a progress report published June 2019 in Diabetes Care, lead author Jeffrey Krischer, PhD, at the USF Health Morsani College of Medicine, University of South Florida, and colleagues evaluate the ability of TEDDY-identified risk factors to predict islet autoimmunity and progression to type 1 diabetes. The researchers found that individually these statistically significant TEDDY risk factors contribute little in discriminating between children who will get the disease and those who will not. However, when combined in a well-designed, time-dependent statistical model, the factors substantially increased the power of predicting both islet autoimmunity and type 1 diabetes.

Dr. Krischer, an epidemiologist and professor in Morsani College of Medicine’s Department of Internal Medicine, leads coordination and analysis of the massive TEDDY data generated globally — from collection of samples (including blood, saliva, urine, toenails,  stool and even discarded primary teeth) and careful review of parent diaries on everything from doctor visits to over-the counter medications their children take.

“Earlier studies have identified independent risk factors for type 1 diabetes. But this paper, for the first time, describes a way to combine risk factors that shows their combined power to discriminate between those who will or will not develop autoimmunity and diabetes,” Dr. Krischer said. “It demonstrates how much each risk factor contributed to prediction. This has moved the field from having only a genetic-based risk assessment to one that includes gene-environment interactions.”

Jeffrey Krischer, PhD

Type 1 diabetes is an autoimmune disease in which the immune system destroys insulin-producing pancreatic cells – a process that occurs over months or many years.  The presence of autoantibodies (immune proteins) in circulating blood indicates that the body has started to target its own tissues or organs.

TEDDY previously published evidence of two subtypes of type 1 diabetes, each associated with distinct risk factors, which may prove pivotal for future preventive trials. Insulin autoantibodies (IAA) directly attack insulin and appear at an earlier age than glutamic acid decarboxylase antibodies (GADA), the autoantibodies that destroy the enzyme glutamic acid decarboxylase regulating insulin-making cells in pancreatic islets. Most with type 1 diabetes develop one of these autoantibodies first, and many eventually end up with both.

The recently published TEDDY study includes 7,777 children of the original TEDDY cohort, from birth to a median age of approximately 9, for development of islet autoantibodies and progression to type 1 diabetes. A graph plotting time-dependent true positive rates (sensitivity) against false positive rates (specificity) was used to estimate the individual and collective predictive ability of risk factors. Among the findings:

• Human leukocyte antigen (HLA) genotype contributed the most to prediction of IAA appearing first, after family history of type 1 diabetes.
• A child’s weight at age 1 was the best predictor of GADA as the first appearing autoantibodies.
• Age at onset of multiple autoantibodies was the strongest predictor of a child’s progression to type 1 diabetes.

TEDDY’s ultimate aim is to uncover the causes of type 1 diabetes and determine what risk factors might be altered to prevent or delay the condition, which requires life-long dependence on insulin therapy.

“TEDDY is uniquely poised to make this contribution as it adds environmental exposures, pathogens, and extensive genomics to the risk factors identified so far,” Dr. Krischer and his fellow authors conclude. “Going forward, this evaluation framework will serve as a summary tool to evaluate new risk factors as they are identified.”

Distinguished University Health Professor Jeffrey P. Krischer, PhD, an internationally leading researcher in autoimmune diseases, will be formally recognized as a new honorary doctor of medicine by the Lund University Faculty of Medicine on May 25, 2018, at Lund Cathedral in Sweden.

Jeffrey Krischer, PhD

Dr. Krischer, director of the Health Informatics Institute at the USF Health Morsani College of Medicine, is one of the world’s foremost experts in the mechanisms behind autoimmune diseases such as type 1 diabetes and celiac disease. He coordinates several major international, NIH-sponsored clinical networks investigating the causes and outcomes of type 1 diabetes, including TEDDY (The Environmental Determinants of Diabetes in the Young) and TrialNet, in which Lunden University and Skane University Hospitals are a central hub. Many key findings have emerged from these studies, including insight into the co-occurrence of type 1 diabetes and celiac disease autoimmunity, the effects of gluten consumption on the risk of celiac disease, and dietary recommendations on gluten for children in Sweden.

Dr. Krischer’s work has led to the recognition of two distinct patterns of autoimmunity in children at high genetic risk for diabetes that could lead to targeted prevention strategies. They give rise to autoantibodies that are age and genetically linked.

Dr. Krischer has collaborated with researchers at the Lund University Faculty of Medicine since 2002, contributing his expertise in the design and analysis of clinical studies, said Lund professor Ake Lernmark. “Not least, he acts as a mentor for several junior researchers in Lund who have had the opportunity to conduct research with him at his institute in Tampa.”

Three other leading researchers — neuroscientist Elena Catteneo, a professor at the University of Milan; astrophysicist Sandor J. Kovacs, a professor at Washington University, St. Louis; and cardiovascular expert John Chalmers, a professor at The George Institute for Global Health, Sydney, and the University of New South Wales – will be recognized as honorary doctors along with Dr. Krischer at the ceremony in May.

Lund University is one of Europe’s oldest, largest and most prestigious universities, consistently ranked among the world’s top 100 universities.

USF Health clinical and molecular geneticist Rebecca Sutphen, MD, has survived breast cancer and melanoma.

Genetic testing has been available since the mid-1990s to determine if a woman is likely to face one of her gender’s greatest fears: inherited breast and ovarian cancer. Yet, questions remain about whether common tests for the genes BRCA1 and BRCA2, which identify mutations that significantly increase a woman’s risk of breast and ovarian cancers, are reaching those who can most benefit and how the information learned from the testing is put to use.

USF Health medical and molecular geneticist Rebecca Sutphen, MD, a breast cancer and melanoma survivor, has broad expertise in genetic conditions affecting both adults and children. She has devoted much of her recent career working with Facing Our Risk of Cancer Empowered (FORCE), the leading national nonprofit advocacy organization for hereditary breast and ovarian cancer, to seek answers that will improve health outcomes of women at high risk for these cancers.

Dr. Sutphen’s research is guided in part by her own experiences as a patient, as well as Big Data’s emerging power to integrate electronic medical information and help build evidence about the effectiveness of clinical care. She emphasizes the need to ensure that patients help shape the investigative process.  In addition to her academic work, she is the chief medical officer of InformedDNA, a national genetic services organization.

The National Cancer Institute estimates only 3 percent of adults with cancer participate in clinical trials, with members of racial and ethnic minorities and low-income individuals particularly underrepresented.

“If research started with the questions that patients want answered, it seems likely there would be more participation in clinical studies, and it would be more obvious to patients how the research is relevant to them,” said Dr. Sutphen, professor of genetics at the USF Health Morsani College of Medicine’s Health Informatics Institute.

Cancer studies still largely focus on determining what treatments contribute to longer life, she said.

“Obviously survival is very important, but patients with cancer often have several options for treatment. What we learn from patients is that they also care about maintaining quality of life – things like the ability to get in their cars and continue to go to the grocery store, or to sleep at night… So, how can we better tailor the treatment options available to match each individual’s preferences?”

 Dr. Sutphen discusses the powerful potential of Big Data.

Dr. Sutphen works out of the Morsani College of Medicine’s Health Informatics Institute led by Jeffrey Krischer, PhD. She is pictured here with clinical research associate Beth Ann Clark, right.

USF helps lead way in BRCA testing and counseling

Dr. Sutphen, proficient in sign language, has a brother and sister who were both born deaf. She says her interest in genetics was sparked as a medical student when she accompanied her sister and her sister’s husband to Johns Hopkins medical genetics clinic for an evaluation of her 2-month-old nephew, also born deaf.

What the family learned about genetics and the probabilities of inheriting certain conditions was informative and fascinating, Dr. Sutphen said. “I saw genetics emerging as a new, growing area of science with the opportunity to impact the lives of people who really need information and can use it in a proactive way to make better decisions for themselves and their families.”

After earning an MD degree from Temple University School of Medicine, she completed a pediatrics residency at All Children’s Hospital in St. Petersburg and a fellowship in human genetics at USF. She is certified by the American Board of Medical Genetics in both clinical and molecular genetics.

In 1995 Dr. Sutphen joined the USF College of Medicine as a faculty member and shortly thereafter became the director of clinical genetics at All Children’s Hospital and at Moffitt Cancer Center.   As BRCA testing became commercially available, she helped USF establish one of the first programs in the state to offer clinical genetic testing and counseling for cancer.

For the first time, a test could identify if a person had inherited a defect in BRCA1 or BRCA2, and therefore tell who was at greater susceptibility for developing breast and ovarian cancer. Also, even if a woman with the inherited mutation never developed cancer herself, she would know she had a 50 percent chance of passing down the mutation, and increased risk, to any offspring.

But many more questions could not be answered. Was the risk the same for everyone who inherited a mutation? Was there a certain age the cancer would be likely to emerge? Could anything modify the risk? Will intensive screening (mammograms, MRIs, ultrasounds) catch a cancer early enough? Should a woman have her breasts or ovaries removed?

“While there was great excitement about the clinical availability of this new testing, there was a huge gap in what we could tell people about their own particular situation and what to do about it,” Dr. Sutphen said.

 Dr. Sutphen comments on engaging patients in the research process.

In the 1990s, Dr. Sutphen helped USF establish one of the first programs in the state to offer clinical genetic testing and counseling for hereditary breast and ovarian cancer.

Meeting begins enduring research collaboration, friendship

Dr. Sutphen began working with Distinguished University Health Professor Jeffrey Krischer, PhD, now director of the Health Informatics Institute, to develop NIH project proposals that would meaningfully address some of these unanswered questions. And in 2004, Dr. Sutphen invited Dr. Sue Friedman, founder and executive director of FORCE, to meet with the USF team to discuss how to best integrate “the patient voice and community” into the group’s hereditary cancer research.

After that initial meeting and learning about USF’s advanced health informatics capabilities, Dr. Friedman said, she quickly drafted a proposal to move her fledging nonprofit organization and family from South Florida to Tampa to work more closely with the USF team.

“When we first started looking at what a collaboration for hereditary breast and ovarian cancer research would look like, we included things like a yearly conference, a patient registry, research grants, writing a book. And, while there have been challenges along the way, in the last 12 years we’ve accomplished a lot of what we dreamed about and continue to build upon it,” Dr. Friedman said. “Aligning with USF has enhanced our organization’s ability to deliver meaningful research to the community, not just in terms of recruiting patients and reporting study results, but to actually help drive the research at every level.”

Along the way, Dr. Friedman, also a breast cancer survivor, and Dr. Sutphen became best friends as well research partners. “Rebecca has been visionary in recognizing the value of including health plan data in the research, and extraordinarily open to bringing in patients as equal stakeholders.”

Sue Friedman (left), founder and executive director of Facing Our Risk of Cancer Empowered, or FORCE, and USF’s Dr. Sutphen have worked together for the last 12 years. They have become friends who share a commitment to making patients equal stakeholders in driving hereditary cancer research.

 Inherited breast and ovarian cancer community’s influence on personalized medicine.

Research and advocacy join forces

Combining their complementary expertise in research and advocacy, USF Health and FORCE have attracted several highly competitive grants. Currently, Dr. Sutphen is the lead investigator for two national research awards focused on hereditary breast and ovarian cancer research.

• Impact of BRCA Testing on Newly Diagnosed U.S. Breast Cancer Patients. This landmark study, supported by a $2.8-million NIH RO1 award, is conducted in collaboration with the commercial health insurance plan Aetna. Researchers previously examined de-identified data on thousands of Aetna members across the country who received BRCA testing and surveyed them about factors associated with the use of this testing including genetic counseling services. Now, analyzing de-identified health claims information, Dr. Sutphen and colleagues will track the outcomes of consenting patients with increased risk for breast and ovarian cancer syndrome — including what types of health care professionals the women saw and how the positive genetic test results affected their decisions about managing cancer risk (including preventive treatment options), which patients subsequently were diagnosed with cancer and their medical treatment choices.

“To date,” Dr. Sutphen said, “there has been no similar study evaluating the health outcomes of a national sample of women undergoing BRCA testing in community settings.”

• Patient-Powered Research Networks, American BRCA Outcomes and Utilization of Testing Network (ABOUT Network). The project, totaling $2.4-million in support from the Patient Centered Outcomes Research Institute (PCORI) for Phases I and II, continues the work led by USF and FORCE to advance a national patient-centered research network of individuals with hereditary breast and ovarian cancer. The ABOUT Network was created to identify this patient community’s unmet needs, promote their governance in research and focus on the questions and outcomes that matter most to patients and their caregivers. USF’s ABOUT patient-powered research network is one of 20 nationwide participating in PCORI’s initiative to help individuals access their electronic health records data through existing patient portals and share it for research that could improve care for their conditions.

“We are establishing mechanisms to allow any patient in the U.S. who has hereditary breast and ovarian cancer to participate in studies relevant to them,” Dr. Sutphen said. “Harnessing the power of Big Data with guidance from patients enables a scale of research never before possible.”

Some early findings have begun to be disseminated. In a study published last year in JAMA Oncology, which attracted national media attention, Dr. Sutphen and co-authors found that most women who underwent BRCA testing did not receive genetic counseling by trained genetics professionals — and lack of physician recommendation was the most commonly reported reason. Yet, those who did get this clinical service before testing were more knowledgeable about BRCA and reported more understanding and satisfaction than women who did not.

This demonstrates gaps in services to be addressed, Dr. Sutphen said, because consultation with a trained genetics clinician is widely available (by phone or in person) and now covered as a preventive health service by most insurers with no out-of-pocket costs to patients.

 Dr. Sutphen talks about her breast cancer diagnosis.

Researcher confronts breast cancer as patient

Dr. Sutphen was diagnosed with breast cancer in 2008, following a routine mammogram. She was premenopausal and had no family history of cancer.   The radiologist who read her mammogram, a colleague, pulled her out of clinic at the Moffitt Lifetime Cancer Screening Center to alert her to the abnormality on her X-ray. The biopsy confirmed early-stage breast cancer.

“I was shocked,” she said. “I remember the part of the conversation ‘you have cancer,” seeing the doctor’s mouth moving and then not hearing any words after that.”

She called her best friend Sue Friedman, herself a breast cancer survivor, for support and after careful consideration of her treatment options decided to undergo a bilateral mastectomy with reconstruction.   The choice worked well for her, Dr. Sutphen said, but another friend with the same type of breast cancer chose lumpectomy instead.

“The first thing to look at is whether the likelihood for a recurrence of the cancer is the same if you have a lumpectomy or a mastectomy – and if the answer is yes, then beyond that it’s a matter of personal preference,” Dr. Sutphen said. “So, two people can make very different choices, but the right choice for each of them.”

In 2013, after having a “mole that looked different” on her arm checked out, Dr. Sutphen was diagnosed and treated for melanoma.

Her own experiences as a two-time cancer survivor have added perspective to her research, Dr. Sutphen said. “It really emphasized to me just what it’s like to be a patient, how difficult the decisions are to make, and how challenging your emotional state becomes.”

To make the often confusing and complex journey a little easier for patients and their families, Dr. Friedman and Dr. Sutphen collaborated with freelance writer Kathy Steligo on a book titled Confronting Hereditary Breast and Ovarian Cancer: Identify Your Risk, Understand Your Options, Change Your Destiny. They wanted to integrate into one book the latest evidence-based information to help women with cancer-susceptibility genes maximize their long-term survival and quality of life.

“The book was published in 2012, but it’s still 95 percent relevant today,” she said.

Dr. Sutphen with her daughter Serenity, 11.

Something you may not know about Dr. Sutphen

Dr. Sutphen was named one of the top 10 cancer medical geneticists in the United States in Newsweek’s “Top Cancer Doctors 2015” list. In 2012, she was selected by TEDMED to be the advocate leading its “Shaping the Future of Personalized Medicine” program, part of the Top 20 Great Challenges annual conference.

For many years she enjoyed the scenic adventure of flying paraplanes, or powered parachutes, ultralight aircraft with a motor, wheels and a parachute. But these days Dr. Sutphen prefers remaining on the ground to cheer on daughter Serenity, 11, a horseback rider who competes in barrel racing.

Photos by Eric Younghans, and audioclips by Sandra C. Roa, USF Health Communications

Jeffrey Krischer, PhD, Distinguished University Health Professor and director of the Health Informatics Institute at the University of South Florida Morsani College of Medicine, has been appointed Vice Chair of Research for the college’s Department of Internal Medicine.

In his new role within Internal Medicine, Dr. Krischer – who attracts record federal research dollars to USF – will work with leadership to recruit National Institutes of Health R01-funded researchers and mentor junior faculty with the goal of strengthening federal research funding in basic, translational and clinical sciences.

Jeffrey Krischer, PhD

Dr. Krischer has a longstanding commitment to diabetes research and to understanding the mechanisms of autoimmunity and disease progression.  His NIH-funded research in the latest Blue Ridge Institute for Medical Research report totals more than $64 million, making him the #1 highest funded principal investigator in the world.

Dr. Krischer oversees the Health Informatics Institute in the Morsani College of Medicine. The Institute coordinates, analyzes and maintains research data from several international, NIH-sponsored clinical networks investigating the causes and outcomes of type 1 diabetes, including The Environmental Determinants of Diabetes in the Young (TEDDY), Type 1 Diabetes TrialNet, and the Trial to Reduce IDDM in the Genetically at Risk (TRIGR). Members of the Institute have funding from industry, the Patient-Centered Outcomes Research Institute (PCORI) and the NIH for studies in oncology, type 2 diabetes, molecular biology and “big data” (‘omics).

He is also principal investigator for a major NIH data coordinating center that supports the Rare Diseases Clinical Research Network, which addresses the challenges of diagnosing and treating rare diseases. The Network includes more than 250 university medical centers worldwide.

Dr. Krischer holds a USF Endowed Chair in Diabetes Research and is director of the USF Diabetes Center. He is a professor and head of the Division of Epidemiology and Biostatistics, Department of Pediatrics, with joint appointments as a professor in the Department of Internal Medicine and in the Department of Neurology.

Dr. Krischer received a PhD in applied math from Harvard University. Before joining USF in 1993, he was professor and chief of the Division of Epidemiology and Biostatistics in the Department of Pediatrics at the University of Florida College of Medicine. For 10 years Dr. Krischer served as Associate Center Director and Chief Information Officer for Moffitt Cancer Center.