Daniel Kelly Archives - Sanford Burnham Prebys

Tag: Daniel Kelly

Institute News

Exciting diabetes and obesity research highlights from Medical City

AuthorDeborah Robison
Date

May 22, 2017

diabetes wordcloud

Center for Metabolic Origins of Disease

With more than one-third of adults in the U.S. considered obese, scientists are searching for new ways to treat obesity and associated health problems such as type 2 diabetes. Four researchers from Sanford Burnham Prebys Medical Discovery Institute (SBP) at Lake Nona have been invited to present new perspectives and insights at the American Diabetes Association’s 77th Scientific Sessions, to be held June 9-13, 2017, in San Diego. The conference is the world’s largest gathering of research experts and clinicians focused on diabetes research, prevention and care. The presentations will inform new treatment strategies for the nearly 30 million people diagnosed with diabetes.

Potential early therapeutic target for diabetes prevention
Obesity often leads to accumulation of fat in muscle and faulty machinery involved in taking up glucose from a meal to use it for energy, leading to type 2 diabetes. A recent advance from the laboratory of Daniel P. Kelly, MD, scientific director of SBP at Lake Nona, may lead to a way to stop this pre-diabetic state from advancing. Dr. Kelly will present findings on a recently discovered cellular glucose sensor in muscle that serves as a key connection between insulin resistance and accumulation of fat in muscle, which occurs in obesity-related diabetes. When the protein is inhibited in skeletal muscle cells, regulatory genes that influence glucose uptake and insulin signaling are enhanced. The team is now validating the pathway as a therapeutic target to prevent type 2 diabetes.

Fatty liver and type 2 diabetes
Peter Crawford, MD, PhD, director of SBP’s Cardiovascular Metabolism Program, is studying the root causes of nonalcoholic fatty liver disease (NAFLD), a condition that affects nearly 80 percent of people with type 2 diabetes. About 5 percent of NAFLD cases advance to liver cirrhosis – a disease characterized by scarring and fibrosis that could require liver transplant. Dr. Crawford is an expert on how the liver processes energy derived from food. At the ADA meeting, he will discuss how the interruption of normal fat metabolism can lead to enhanced scarring. Through ongoing research, he hopes to be able to specifically identify which diabetes patients are at risk of developing advanced liver disease and to develop therapies that protect against disease progression.

Brain nutrient sensors help maintain energy balance
Diabetes researcher Julio Ayala, PhD wants to understand how specialized regions in the brain control food intake, energy expenditure and body weight. His ADA presentation will focus on how nutrient-sensors that control the balance between energy-consuming and energy-producing processes in almost every cell in our bodies also play a very specific role in the brain. His research shows that hormones, such as glucagon-like peptide-1 (GLP-1) regulate the activities of these brain nutrient sensors to influence hunger, satiety and ultimately body weight. Defective sensors are implicated in obesity and could be a target for new therapeutic treatments.

Glucose Sensor in Macrophages
Insulin resistance is a key feature of type 2 diabetes. When present, the impairment prevents insulin from getting glucose into muscle where it’s used for energy, and instead causes blood sugars to become elevated. The events that drive the development and progression of insulin resistance are not known. Laszlo Nagy, MD, PhD, director of SBP’s Genomic Control of Metabolism Program, will present new research that suggests that the inflammatory process—and specifically a type of white blood cells called macrophages—are involved. He will present a novel hypothesis on the role of macrophages, defined in Greek as “big eaters”, and identify molecules involved in muscle growth and glucose metabolism. His research aims to reveal cellular interactions that could become new therapeutic targets to treat type 2 diabetes.

Institute News

Simulation matters at Lake Nona Research Day, from cells to big data

AuthorCommunications
Date

October 14, 2016

Peter Crawford at Lake Nona Research Symposium

Scientists, physicians and trainees recently gathered at the first Lake Nona Research Day to share the latest research and technologies that are contributing to innovations in health care.. The event brought together senior and junior practitioners from Medical City’s five institutions.

“As we planned the symposium, we decided to focus on the trainees, who then became the glue that brought everything together,” said Philip Wood, D.V.M., PhD, director of academic affairs at Sanford Burnham Prebys Medical Discovery Institute (SBP) at Lake Nona and chair of the Medical City Research Council. “Their enthusiasm to share their science is evident in the 120 research posters that highlight the research emerging from SBP, the University of Central Florida, the University of Florida, Nemours Children’s Hospital, and the Orlando VA Medical Center.” The symposium was presented by the Lake Nona Institute.

Disease modeling by high-tech simulation and data mining were themes of featured talks. Lawrence Lesko, PhD, professor, Center for Pharmacometrics at UF, described using biosimulation to project drug performance in virtual patients. “What we do is like a flight simulator—we evaluate drug impact before testing in patients, frequently focusing on drug-drug interactions,” said Lesko.   

Similarly, Daniel Kelly, MD, scientific director of SBP at Lake Nona, spoke about his lab’s work to study the changes in mitochondria function that are seen in heart failure patients and to simulate disease in a dish using human induced pluripotent stem cell-derived cardiomyocytes.  “We need to become mitochondrial doctors to treat heart failure,” said Kelly. “These models will help us discover therapeutic approaches tailored to the etiology of a subset of heart failure cases that could be given earlier than current treatments.”

Steven Kern, PhD, deputy director, Quantitative Sciences at the Bill and Melinda Gates Foundation, delivered the keynote on using data to decide how to invest $1 billion in precision public health projects on a global scale. “We build drug-disease models to determine how to prevent epidemics like malaria. In our Healthy Birth and Growth Project, we model real-world data to determine the right interventions, in the right dosage, to get the right response—to get children to the healthiest stage at 100 days of life,” explained Kern. 

David Odahowski, president and CEO of the Edyth Bush Charitable Foundation, which sponsored the symposium, concluded the program by observing that innovation often comes from the intersection of disciplines. “I think what we learned today is that collaboration is the true measure of success and that is especially true here in Medical City.”

Institute News

How energy starvation leads to heart failure

Authorjmoore
Date

February 25, 2016

Header image

Almost 6 million people in the US have failing hearts, which can arise following heart attacks, longstanding high blood pressure, defective heart valves or genetic disorders, among other causes. While management of heart failure (HF) is improving, only 50% of patients will survive five years after diagnosis. No current treatments directly treat the disease, particularly at early stages, so development of new preventive or therapeutic drugs could make an enormous difference for patients.  Continue reading “How energy starvation leads to heart failure”

Institute News

How mitochondria “grow up”

AuthorGuest Blogger
Date

December 4, 2015

Header image

Few cellular systems are more important than mitochondria. These organelles convert the body’s fuels into ATP, the biological energy packets that power many of the cell’s most important functions. Mitochondria are especially important in the heart and other muscles, which use a lot of energy.

Needless to say, impaired mitochondria could have a major impact on health, making them an intense area of study in the biomedical community. Daniel Kelly, M.D., scientific director at SBP’s Lake Nona campus, recently collaborated with investigators at Washington University to better understand how heart mitochondria are built after birth.

“During fetal development, the heart does not have huge energy requirements,” notes Dr. Kelly. “But after birth, it has to pump blood throughout the body—and that takes a tremendous amount of energy. To equip itself, the heart has a virtual explosion of mitochondrial biogenesis after birth.”

A few years ago, Dr. Kelly’s lab showed that a group of proteins called PGC-1 coactivators drive this mitochondrial population explosion. But in the new study, led by Washington University researcher Gerald Dorn, MD, and published in the journal Science, the team showed that it’s not enough to just add new mitochondria; heart cells must first remove older, fetal mitochondria, a process called mitophagy. Fetal mitochondria just aren’t well-suited for this new role.

“During the fetal period, heart mitochondria largely use glucose,” says Dr. Kelly. “But after birth they switch to multiple higher octane fuels, particularly fatty acids. You have to wipe out the fetal mitochondria and build new mitochondria that are capable of using fatty acids.”

In the study, the researchers suppressed mitophagy in mice shortly after birth by preventing a protein called Parkin from driving this important quality control function. They found that, without clearing old mitochondria, new ones were not produced, dramatically impacting heart size and function.

Dr. Kelly’s lab and Lake Nona’s metabolomics facility played a major role in the research, providing expertise on mitochondria and measuring the compounds produced by mitochondria to track their function. The adult metabolomics signature did not occur when mitophagy was prevented. This study provides great insights into mitochondrial adaptability and could illuminate better ways to treat adult disease conditions.

“Although it’s early days, this work has profound implications for diseases related to mitochondrial dysfunction, such as heart failure, diabetes, and neurological conditions,” says Dr. Kelly. “It’s possible that under stressful conditions, such as a heart attack or high blood pressure over long periods, the body calls on this quality sorting mechanism again to adapt. Future studies will address this question.”

This post was written by Josh Baxt, a freelance writer.

To read the paper click here

Institute News

Leading cardiometabolic researcher to join SBP

Authordrobison
Date

November 5, 2015

Header image

The cardiovascular researcher who pioneered visualizing the function of the human heart using the most powerful magnetic resonance available will soon join SBP’s Florida campus. E. Douglas Lewandowski, PhD, will become professor in the Cardiovascular Metabolism Program and director of Cardiovascular Translational Research starting December 2015. He is among the most preeminent investigators in the world who specialize in the metabolic basis of heart failure, including ischemic heart disease and diabetic cardiomyopathy.

“Doug Lewandowski’s pioneering work has unveiled new concepts and therapeutic strategies aimed at improving the treatment of heart failure, a worldwide health problem. He will continue this work at SBP, leading an innovative bench-to-clinic research program at SBP and the Florida Hospital Translational Research Institute for Metabolism and Diabetes (TRI-MD). His recruitment is transformational for our translational research efforts in the cardiovascular arena,” said Daniel P. Kelly, MD, Tavistock Distinguished Professor and scientific director, Center for Metabolic Origins of Disease at SBP Lake Nona.

Lewandowski’s contributions to understanding metabolic pathways and fuels that may protect against the high-morbidity, -mortality, and economic health burden of heart failure are recognized as among the most rigorous and field-advancing. He is renowned in the use of nuclear magnetic resonance (NMR) spectroscopy to visualize and measure metabolic activity in the intact beating heart in health and disease. His expertise in medical imaging techniques involves manipulation of metabolic activity in the ailing heart with pharmacological agents and targeted gene manipulation.

He will hold a joint appointment at Florida Hospital as senior principal investigator at the TRI-MD. He views the partnership between SBP’s basic research and the TRI’s clinical investigations as an attractive and effective research model that will accelerate the translation of the fundamental mechanisms of heart disease and therapeutic targets toward patient-based studies to identify new treatments, therapeutics, and cures.

“With Lake Nona’s emphasis and existing expertise in cardiometabolic disease, I feel that I can immediately contribute to team science approaches to elucidate fundamental mechanisms of heart and metabolic disease. My focus will be to translate findings in SBP’s laboratories to human studies of the metabolic basis of heart disease at the TRI,” said Lewandowski. “It is this partnership that I anticipate will be a game changer in the way I will be able to implement the translation of my laboratory investigations, and I find this very, very exciting.”

Prior to joining SBP, Lewandowski held the position of professor in the Department of Physiology and Biophysics, in the Department of Medicine, and director of the Program in Integrative Cardiac Metabolism at the University of Illinois at Chicago. Previously, Dr. Lewandowski spent a decade on the faculty at Harvard Medical School with hospital appointments at Massachusetts General Hospital in Boston, Mass.

Institute News

10 years of studying metabolism, nutrition, and human energy—what have we REALLY learned?

Authorsgammon
Date

August 17, 2015

Header image

Every day we read or hear something about a food that is bad for us, a fruit that will help us lose weight, or a supplement that will extend our lives beyond their natural endpoint. Unquestionably, every year a significant amount of money, research, and time is spent exploring the cause and prevention of obesity, diabetes, heart disease, and the myriad of other metabolic conditions that affect our health and well-being. But what do scientists think are the truly important things we have learned about our metabolism, diet, and exercise over the last decade?  And how is this leading to the next-generation of medicines to treat metabolic disorders? Continue reading “10 years of studying metabolism, nutrition, and human energy—what have we REALLY learned?”

Institute News

New collaboration strives to find novel treatment approaches for cardiovascular disease

Authorpbartosch
Date

May 28, 2015

Header image

Sanford-Burnham today announced it has signed a two-year partnership agreement with Takeda Pharmaceutical Company Ltd. of Japan to study the potential role of several gene regulatory proteins as targets for the treatment of heart failure. Based on research conducted in Sanford-Burnham laboratories, the collaborating scientists will screen and develop molecules that have the potential to improve the metabolism and function of the failing heart. Continue reading “New collaboration strives to find novel treatment approaches for cardiovascular disease”

Institute News

A signature for early-stage heart failure could improve diagnosis and prevent disease progression

AuthorGuest Blogger
Date

September 30, 2014

Header image

This is a post by our guest writer Janelle Weaver, PhD

Heart failure affects about five million people in the United States, and about half of these individuals die within five years of diagnosis. This condition occurs when the heart can’t pump enough blood to meet the body’s needs, and evidence suggests that abnormalities in energy metabolism play an important role. However, many past studies addressing the underlying molecular mechanisms have focused on severe, late-stage heart failure, potentially missing out on early events that could guide the development of treatment strategies for early disease stages. Continue reading “A signature for early-stage heart failure could improve diagnosis and prevent disease progression”

Institute News

A summer of learning and research

Authoradmin
Date

August 20, 2014

Header image

All around Central Florida, students are returning to school for the fall semester. At Sanford-Burnham in Lake Nona, we take a closer look at some of the lab experiences of our high-school interns who have spent part of their summer in our labs getting a taste for what it’s like to work in basic-science research.

Continue reading “A summer of learning and research”