CHORI’S Dr. Ronald Krauss Receives NIH Pharmacogenomics In Precision Medicine Grant Aimed At Improving Prediction Of Statin Response In Individual Patients
Oakland, CA (September 9, 2015) – Children’s Hospital Oakland Research Institute (CHORI) Senior Scientist Dr. Ronald Krauss has received a five-year, $13,184,000 grant from the National Institutes of Health (NIH) for precision medicine research in statin response. The grant, awarded September 7 from the NIH’s National Institute of General Medical Sciences (NIGMS), will enable Dr. Krauss and his colleagues to apply a multi-disciplinary approach to identify genetic determinants of the efficacy of statin drugs in reducing the risk of cardiovascular disease (CVD), as well as the risk for adverse effects of statins, specifically myopathy and type-2 diabetes.
To this end, Dr. Krauss and his team have created a Center for Pharmacogenomics in Precision Medicine with a research program that utilizes an innovative "systems" approach. This will incorporate complementary genomic, transcriptomic, and metabolomic tools, together with studies in cellular and animal models, and innovative informatics models. In carrying out this research program, Dr. Krauss will be working closely with Dr. Marisa Medina at CHORI, who leads one of the Center's three projects.
Through queries of electronic medical records, Dr. Medina and colleagues will recruit statin users from Kaiser Permanente of Northern California who have experienced adverse outcomes - namely, individuals for whom statins have not prevented a major adverse coronary event, such as a heart attack, as well as those who developed either myopathy or type-2 diabetes while on treatment. Using cell lines established from these individuals, as well as from matched controls, i.e. statin users who have not had an adverse outcome on treatment, they will identify genes and metabolites whose expression differs between cases and controls. Dr. Medina pioneered the approach of performing molecular profiling of patient-derived cells for pharmacogenomic discovery.
The Center also includes investigators from UCSF, UC Berkeley, UCLA, University of Washington, and Penn State. The team's ultimate goal is to enable use of the information derived from this program to identify new biomarkers that modulate the multiple actions of statins and that can be used to guide more effective use of this widely used class of drugs. “Our previous research has shown that investigation of molecular and cellular mechanisms influenced by statins can lead to identification of genetic variants that contribute to clinically important differences in response to statin treatment,” says Dr. Krauss. “This grant allows us to extend this approach to identify genetic variants and molecular mechanisms that influence statin-related myopathy and new-onset diabetes.”
Statins are among the most widely prescribed drugs in the western world, used to treat elevated cholesterol levels and reduce the risk of cardiovascular disease. While statins are highly effective and generally safe, adverse effects occur in a small proportion of users, which represents a large number of individuals due to statins' widespread use. In some individuals, statins adversely affect muscle, with symptoms ranging from mild pain to the breakdown of muscle tissue. Other statin users may be at increased risk for type-2 diabetes.
Dr. Krauss’s grant is one of three “P50” grants recently awarded by NIGMS to establish specialized research centers for pharmacogenomics in precision medicine. Dr. Krauss has been one of the principal investigators in the Pharmacogenomics Research Network (PGRN), a network of scientific groups focused on understanding how a person’s genes affect his or her response to medicines that has been supported since 2000 by the NIH.
“These grants allow the investigators to pursue a range of basic, clinical and translational research that will contribute to a fundamental understanding of how to use drugs safely and effectively, which is an important aspect of precision medicine." said NIGMS’ Rochelle M. Long, Ph.D., who directs the program.
About UCSF Benioff Children’s Hospital Oakland
UCSF Benioff Children’s Hospital Oakland (formerly Children’s Hospital & Research Center Oakland) is a premier, not-for-profit medical center for children in Northern California, and is the only hospital in the East Bay 100% devoted to pediatrics. UCSF Benioff Children’s Hospital Oakland affiliated with UCSF Benioff Children’s Hospital San Francisco on January 1, 2014. UCSF Benioff Children’s Hospital Oakland is a national leader in many pediatric specialties including cardiology, hematology/oncology, neonatology, neurosurgery, orthopedics, pulmonology, and sports medicine. The hospital is one of only five ACS Pediatric Level I Trauma Centers in the state, and has one of largest pediatric intensive care units in Northern California. UCSF Benioff Children’s Hospital Oakland has 190 licensed beds, over 500 physicians in 43 specialties, more than 2,600 employees, and a consolidated annual operating budget of more than $500 million. UCSF Benioff Children’s Hospital Oakland is also a leading teaching hospital with an outstanding pediatric residency program and a number of unique pediatric subspecialty fellowship programs.
UCSF Benioff Children’s Hospital Oakland’s research arm, Children’s Hospital Oakland Research Institute (CHORI), is internationally known for its basic and clinical research. CHORI is at the forefront of translating research into interventions for treating and preventing human diseases. CHORI has 250 members of its investigative staff, a budget of about $50 million, and is ranked among the nation’s top ten research centers for National Institutes of Health funding to children’s hospitals. For more information, go to www.childrenshospitaloakland.org and www.chori.org.
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To this end, Dr. Krauss and his team have created a Center for Pharmacogenomics in Precision Medicine with a research program that utilizes an innovative "systems" approach. This will incorporate complementary genomic, transcriptomic, and metabolomic tools, together with studies in cellular and animal models, and innovative informatics models. In carrying out this research program, Dr. Krauss will be working closely with Dr. Marisa Medina at CHORI, who leads one of the Center's three projects.
Through queries of electronic medical records, Dr. Medina and colleagues will recruit statin users from Kaiser Permanente of Northern California who have experienced adverse outcomes - namely, individuals for whom statins have not prevented a major adverse coronary event, such as a heart attack, as well as those who developed either myopathy or type-2 diabetes while on treatment. Using cell lines established from these individuals, as well as from matched controls, i.e. statin users who have not had an adverse outcome on treatment, they will identify genes and metabolites whose expression differs between cases and controls. Dr. Medina pioneered the approach of performing molecular profiling of patient-derived cells for pharmacogenomic discovery.
The Center also includes investigators from UCSF, UC Berkeley, UCLA, University of Washington, and Penn State. The team's ultimate goal is to enable use of the information derived from this program to identify new biomarkers that modulate the multiple actions of statins and that can be used to guide more effective use of this widely used class of drugs. “Our previous research has shown that investigation of molecular and cellular mechanisms influenced by statins can lead to identification of genetic variants that contribute to clinically important differences in response to statin treatment,” says Dr. Krauss. “This grant allows us to extend this approach to identify genetic variants and molecular mechanisms that influence statin-related myopathy and new-onset diabetes.”
Statins are among the most widely prescribed drugs in the western world, used to treat elevated cholesterol levels and reduce the risk of cardiovascular disease. While statins are highly effective and generally safe, adverse effects occur in a small proportion of users, which represents a large number of individuals due to statins' widespread use. In some individuals, statins adversely affect muscle, with symptoms ranging from mild pain to the breakdown of muscle tissue. Other statin users may be at increased risk for type-2 diabetes.
Dr. Krauss’s grant is one of three “P50” grants recently awarded by NIGMS to establish specialized research centers for pharmacogenomics in precision medicine. Dr. Krauss has been one of the principal investigators in the Pharmacogenomics Research Network (PGRN), a network of scientific groups focused on understanding how a person’s genes affect his or her response to medicines that has been supported since 2000 by the NIH.
“These grants allow the investigators to pursue a range of basic, clinical and translational research that will contribute to a fundamental understanding of how to use drugs safely and effectively, which is an important aspect of precision medicine." said NIGMS’ Rochelle M. Long, Ph.D., who directs the program.
About UCSF Benioff Children’s Hospital Oakland
UCSF Benioff Children’s Hospital Oakland (formerly Children’s Hospital & Research Center Oakland) is a premier, not-for-profit medical center for children in Northern California, and is the only hospital in the East Bay 100% devoted to pediatrics. UCSF Benioff Children’s Hospital Oakland affiliated with UCSF Benioff Children’s Hospital San Francisco on January 1, 2014. UCSF Benioff Children’s Hospital Oakland is a national leader in many pediatric specialties including cardiology, hematology/oncology, neonatology, neurosurgery, orthopedics, pulmonology, and sports medicine. The hospital is one of only five ACS Pediatric Level I Trauma Centers in the state, and has one of largest pediatric intensive care units in Northern California. UCSF Benioff Children’s Hospital Oakland has 190 licensed beds, over 500 physicians in 43 specialties, more than 2,600 employees, and a consolidated annual operating budget of more than $500 million. UCSF Benioff Children’s Hospital Oakland is also a leading teaching hospital with an outstanding pediatric residency program and a number of unique pediatric subspecialty fellowship programs.
UCSF Benioff Children’s Hospital Oakland’s research arm, Children’s Hospital Oakland Research Institute (CHORI), is internationally known for its basic and clinical research. CHORI is at the forefront of translating research into interventions for treating and preventing human diseases. CHORI has 250 members of its investigative staff, a budget of about $50 million, and is ranked among the nation’s top ten research centers for National Institutes of Health funding to children’s hospitals. For more information, go to www.childrenshospitaloakland.org and www.chori.org.
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