Related Disease
Cardiomyopathies, Cardiovascular Diseases
Anatomical Systems and Sites
Cardiovascular System, General Cell Biology, Heart
Research Models
Computational Modeling, Drosophila, Human
Techniques and Technologies
Bioinformatics, Cell Biology, Confocal Microscopy, Fluorescence Microscopy, Genetics, In vivo Modeling, Live Cell Imaging, Live Imaging, Microscopy and Imaging, Molecular Biology, RNA Interference (RNAi), Systems Biology, Transgenic Organisms
After a successful teaching career at the University of Michigan I have had the privilege to “reboot” my research career at Sanford Burnham Prebys where I have had the opportunity to develop novel methodologies to understand cardiomyopathy. I have also had the opportunity to work with NASA scientists to do experiments on the International Space Station.
Education
Postdoctoral Fellow, Stanford University, Palo Alto, CA, Neurochemistry Postdoctoral Fellow, University of Texas Medical School, Houston, TX, Neuroscience NIMH PhD, Wesleyan University, Middletown, CT, Neuroscience NIMH B.A., Lehigh University, Bethlehem, PA, Biology
Prestigious Runding Awards or Major Collaborative Grants
2015-2020: NIH R01 HL132241-01A1 – Using Drosophila genetics to identify molecular links between ion channel dysfunction and pathological cardiac remodeling. (PI) 2013-2018 NASA NRA #NNH12ZTT001N – The effects of microgravity on cardiac function, structure and gene expression using the Drosophila model. (Co-I)
Honor and Awards
2014: Space Florida International Space Station Research Competition Winner – Co-investigator – One of three Basic Research proposals selected for launch aboard SpaceX3 – Mission completed, live flies returned on May 18,2014 2001: Excellence in Teaching Award, University of Michigan 1997: Excellence in Teaching Award, University of Michigan 1986-1988: National Institute of Mental Health Fellowship 1983-1985: National Institute of Mental Health Fellowship 1981: Sigma Xi Research Award 1980 MBL Scholarship, Neural Systems and Behavior Course 1971-1975: National Merit Scholarship, Lehigh University
Board Appointments
2018-present: Board member American Society for Gravitational and Space Research
Anatomical Systems and Sites
Cardiovascular System, Heart
Research Models
Drosophila, Larval Zebrafish Heart, Zebrafish
Techniques and Technologies
Biophysiology, Cellular and Molecular Imaging, Fluorescence Microscopy, Gene Silencing, Genetics, In vivo Modeling, Ion Channels, Live Imaging, Microarrays, Microscopy and Imaging, Molecular Genetics, RNA Interference (RNAi), Semi-automated Optical Heartbeat Analysis (SOHA), Systems Biology, Transgenic Organisms
The Ocorr Lab is investigating the cellular and molecular basis of adult heart function and cardiomyopathies using the genetic model system Drosophila.
We use functional, electrophysiological, biochemical and immunohistochemical techniques that allow us to examine the roles of genes and gene products in cardiac channelopathies and stress-related cardiomyopathies.
Our lab pioneered the development of a novel methodology (Semi-automatic Optical Heartbeat Analysis, SOHA) that permits the quantification of heartbeat parameters in model systems with small hearts.
Using this system we have identified several ion channels in the fly heart that play prominent roles in repolarization of the human heart and cause arrhythmia in both the fly and in humans when mutated. We also have developed a number of other disease models including a diabetic-like cardiomyopathy induced by high sugar diet and hypoxia-induced cardiomyopathy.
Recently we have begun collaborations with NASA (by winning a Space Florida International Space Station Research Competition). We are using the fly to uncover the molecular/cellular basis for cardiac and muscle atrophy in astronauts exposed to extended periods of microgravity despite extensive exercise regimes aboard the ISS. Our flies were launched aboard SpaceX 3 for a month-long exposure to micro-gravity.
Karen Ocorr’s Research Report
My lab is working to understand the cellular and molecular basis of heart disease. One project is focused on the genetic basis of Atrial Fibrillation. This project is a collaborative one with the lab of Alexandre Colas. We are combining two model systems, the fly in my lab and human induced cardiomyocytes in his lab, to identify AFib genes that have been implicated from patient studies. Another project focuses on the role of metabolism in cardiomyopathies. This is because obesity and metabolic syndrome are linked to an increased risk of heart disease. We are studying the role of a key metabolic signaling molecule in hypertrophic cardiomyopathy. A separate effort is focused on the role of gravity in heart function. These studies will provide important information for future habitants of colonies on the moon and Mars. But they are also relevant to patients who are bedridden and to patients with muscle wasting (sarcopenia).
After receiving his early training in clinical chemistry/biochemistry at the University of Buenos Aires, Argentina, Dr. Millán first joined the La Jolla Cancer Research Foundation (LJCRF) in 1977, the predecessor of Sanford Burnham Prebys, as a trainee in clinical enzymology. He completed his PhD studies in Medical Biochemistry at the University of Umeå, Sweden and after post-doctoral stints in Copenhagen and LJCRF he was appointed to the faculty at SBP in 1986. He served as Professor of Medical Genetics in the Department of Medical Biosciences at his alma mater, Umeå University, Sweden, from 1995-2000. He was appointed Sanford Investigator at the Sanford Children’s Health Research Center at Sanford Burnham Prebys in 2008.
Honors and Recognition
2018: ASBMR Lawrence G. Raisz Award for Pre-clinical Research. 2001: Gold Medal of the Royal Academy of Medicine and Surgery, Murcia, Spain 1992: Honorary title of AcadémicoCorresponsal at the Royal Academy of Medicine and Surgery, Murcia, Spain.
Related Disease
Arthritis, Bone Mineralization Disorders, Cardiovascular Diseases, Colorectal Cancer, Crohn’s Disease (Colitis), Heart Disease, Inherited Disorders, Metabolic Syndrome, Peripheral Vascular Disease, Testicular Cancer
Phenomena or Processes
Cardiovascular Biology, Disease Therapies, Extracellular Matrix, Protein Structure-Function Relationships
Anatomical Systems and Sites
Cardiovascular System, Musculoskeletal System, Vasculature
Research Models
Mouse
The Millán laboratory works on understanding the mechanisms that control normal skeletal and dental mineralization and elucidating the pathophysiological abnormalities that lead to heritable soft bones conditions such as Hypophosphatasia (HPP) and to soft-tissue calcification, including vascular calcification, that is a hallmark in patients affected by a variety of rare genetic diseases as well as in chronic kidney disease. Dr. Millán’s research has already contributed to the implementation of a novel therapy for HPP, a genetic disease caused by deficiency in tissue-nonspecific alkaline phosphatase (TNAP) function, that leads to accumulation in the extracellular space of inorganic pyrophosphate (PPi), a potent inhibitor of mineralization. HPP is characterized by defective mineralization of bones (rickets or osteomalacia), and teeth that display a lack of acellular cementum, hypomineralized dentin and enamel, and periodontal defects. Dr. Millán’s team has demonstrated the effectiveness of enzyme replacement therapy using mineral-targeted recombinant TNAP (asfotase alfa) to prevent the skeletal and dental defects in the TNAP knockout mouse model of infantile HPP. This therapy was approved in 2015 for the treatment of patients with pediatric-onset HPP.
Current efforts, in collaboration with Professor Miyake’s group in Japan (https://www.nms-gt.org/en/members), focus on developing gene therapy as an alternative approach to treat HPP. Dr. Millán’s group has also identified key pathophysiological changes that lead to calcification of the arteries in animal models of generalized arterial calcification of infancy, pseudoxanthoma elasticum and related genetic diseases as well as in animal models of chronic kidney disease. His group, in collaboration with scientists at the Conrad Prebys Center for Chemical Genomics at Sanford Burnham Prebys, has developed proprietary compounds able to ameliorate the soft-tissue calcification in these conditions and clinical trials are now underway using these first-in-class small molecule inhibitors.
