- Introductory Remarks
- Ebashi Lecture
- Poster Flash
- Welcome Party
- Session 1
- Session 2
- Session 3
- Poster Session 1
- Session 4
- Session 5
- Poster Session 2
- Session 6
- Session 7
- Session 8
- Nishizuka Lecture
- GALA Dinner
- Session 9
- Session 10
- Award and Closing Remarks
Introductory Remarks [15:30 ～ 16:00]
Ebashi Lecture [16:00 ～ 17:00]
- Chikashi Toyoshima
- (The University of Tokyo)
- Chikashi Toyoshima is Professor and Director of the Center for Structural Biology of Challenging Proteins at the Institute of Molecular and Cellular Biosciences, the University of Tokyo. He received his PhD degree from the Physics Department at the University of Tokyo in 1983 under the supervision of Prof. Ebashi. He was a postdoctoral fellow at Stanford University and at the MRC Laboratory of Molecular Biology, Cambridge, UK, before he assumed a position as Associate Professor in the Department of Biological Sciences at the Tokyo Institute of Technology in 1990. In 1994 he accepted his current position at the University of Tokyo, Japan. In 2005 he was elected as Foreign Associate of the National Academy of Sciences of the United States of America, and in 2007 he was awarded the Hitchcock Professorship at the University of California, Berkeley, USA. He was also endowed with a Medal with Purple Ribbon from Japan in 2015, and the Gregori Aminoff Prize 2016 from the Royal Swedish Academy of Sciences. His research focuses on the structural biology of membrane-bound ion pumps, especially the calcium pump of sarcoplasmic reticulum, using X-ray crystallography.
Poster Flash [17:00 ～ 18:30]
Welcome Party [19:00 ～ 21:00]
Session 1: Intracellular Ca2+ Stores [8:30 ～ 10:25]
- Andrew Marks
- (Columbia University, USA)
- Andrew R. Marks, MD, was born February 22, 1955 in New York City. He received his undergraduate degree from Amherst College in 1976 where he was the first student in the history of the college to graduate with honors in two subjects (Biology and English), and his MD from Harvard Medical School in 1980. Following an internship and residency in internal medicine at the Massachusetts General Hospital (MGH), he was a post-doctoral fellow in molecular genetics at Harvard Medical School, and then a clinical cardiology fellow at the MGH. He is board certified in internal medicine and in cardiology. Dr. Marks is Chair and Professor of the Physiology and Cellular Biophysics Department at Columbia University. From 2002-2007 Dr. Marks was Editor-in-Chief of the Journal of Clinical Investigation. His honors include: ASCI (1995) AAP, the Institute of Medicine of the National Academies, American Academy of Arts and Sciences and the National Academy of Sciences. Doctor of Science Honoris Causa from Amherst College (2009), Docteur Honoris causa, del’Université de Montpellier (2016), the ASCI Stanley J. Korsmeyer Award (2010), the Pasarow Foundation Award for Cardiovascular Research (2011) and the Ellison Medical Foundation Senior Scholar in Aging Award (2011), Glorney-Raisbeck Award from NY Academy of Medicine (2016). In 2015 Dr. Marks was chosen to present the Ulf von Euler lecture at the Karolinska Institute. Dr. Marks’ identification of the mechanism of action of rapamycin’s inhibition of vascular smooth muscle proliferation and migration lead to the development of the first drug-eluting stent (coated with rapamycin) for treatment of coronary artery disease. This substantially reduced the incidence of instent restenosis. In 2014 Dr. Marks reported the high resolution structure of the mammalian type 1 ryanodine receptor/calcium release channel (required for excitation-contraction coupling in skeletal muscle) which he had cloned and work on since 1989. His work has contributed new understandings of fundamental mechanisms that control muscle contraction, lymphocyte activation, and cognitive function. He discovered that “leaky” intracellular calcium release channels (ryanodine receptors) contribute to heart failure, fatal cardiac arrhythmias, and impaired exercise capacity particularly in muscular dystrophy, post-traumatic stress disorder (PTSD) and Alzheimer’s Disease. Dr. Marks discovered a new class of small molecules (Rycals), developed in his laboratory, that target leaky ryanodine receptor channels and effectively treat cardiac arrhythmias, heart failure, muscular dystrophy and prevent stress induced cognitive dysfunction in pre-clinical studies. Rycals are now in Phase II clinical trials for the treatment of heart failure and cardiac arrhythmias, and entering clinical trials for the treatment of Duchenne Muscular Dystrophy.
- David Yule
- (University of Rochester, USA)
- David I. Yule. PhD. University of Liverpool, UK. (1990). Fellow, University of Michigan, USA (1990-1998) Professor of Pharmacology and Physiology, University of Rochester, USA (1998-present). Over the past 20 years, the focus of my research has been to gain a better understanding of how intracellular free Ca2+, a ubiquitous second messenger, can control a multitude of cellular processes with precise specificity and fidelity. In particular, my lab has investigated the mechanisms, which underlie Ca2+ signaling events and their downstream effectors necessary for proper exocrine function in pancreatic and salivary acinar cells. A particular focus of the laboratory is investigating the properties and regulation of Inositol 1,4,5-trisphosphate receptors, the primary Ca2+ release mechanisms in many cell types. This knowledge is important because it is increasing clear that dysregulation of normal signaling is a common occurrence in pathological states of many organ systems. Our primary approaches involve imaging techniques including multi-photon, confocal and TIRF microscopy complemented by single channel and whole-cell patch clamp electrophysiology. Throughout the past 15 years we have complemented this experimental work by using a computation and modeling systems biology based approach through a collaboration with Dr. James Sneyd at the University of Auckland, NZ.
- Sandip Patel
- (University College London, UK)
- Sandip Patel obtained his PhD under the supervision of Colin W. Taylor (Cambridge, 1995). He did post-doctoral work with Andrew P. Thomas (USA, 1996-1999) and Antony Galione (Oxford, 1999). Sandip started his own lab in 2000 in Oxford through a Wellcome Trust Career Development Fellowship which he re-located to its present location at University College London in 2001. He was promoted to Professor in 2011.
Sandip was Vice-chair of the Signalling Panel of the Biochemical Society (2009-2012) and currently a member of the Grants advisory panel of Parkinson’s UK (2016-). He is an Associate Editor of Messenger (2012-) and a member of the Editorial boards of Biology of the Cell (2003-2006), the Biochemical Journal (2004-2011) and Cell Calcium (2007-).
He was elected a Fellow of the Royal Society of Biology (FRSB) in 2013.
- Roberto Docampo
- (University of Georgia, USA)
- Prof. Roberto Docampo graduate work at the University of Buenos Aires (1976-1979) revealed the role of free radicals in the mechanism of action and toxicity of antiparasitic drugs. During his postdoc work at the NIH (1982-1986), Docampo discovered the first and only example of a biochemical reaction (pyruvate-ferredoxin oxidoreductase) in which two free radicals, a carbon-centered free radical derived from pyruvate and a thyil radical derived from CoA, combine to form a high-energy compound (acetyl-CoA). When a Visiting Professor at the Federal University of Rio de Janeiro (1986-1988), his lab found that Trypanosoma cruzi, the agent of Chagas disease, possesses a mitochondrial calcium uniporter of similar characteristics to those of the mammalian uniporter, a finding that was fundamental for the recent discovery of the gene encoding this uniporter in eukaryotes. When a Professor at the University of Illinois at Urbana-Champaign (1990-2004) his lab discovered and characterized the acidocalcisome, an acidic calcium store rich in polyphosphate that is the only organelle conserved from bacteria to mammalian cells. The finding of similar acidocalcisome-like organelles rich in polyphosphate in human platelets (dense granules) led to his lab discovery of the role of this polymer as a procoagulant and antifibrinolytic agent, and the further discovery of its role in inflammation and thrombosis. His lab also discovered the antiparasitic action of pyrophosphate analogs (bisphosphonates), some of which had curative effects on experimental trypanosomiasis. He moved to the University of Georgia in 2005, where he further characterized the composition and functions of acidocalcisomes, their presence in mast cells, human basophils, and insect eggs, and their interaction with other organelles, such as mitochondria and the contractile vacuole. His lab discovered a role of the contractile vacuole of T. cruzi in trafficking proteins to the plasma membrane and acidocalcisomes. His most recent work at UGA was the first successful development of the CRISPR/Cas9 technique for genome editing (gene knockout and gene tagging) of these parasites and the characterization of their calcium signaling pathways. He is the Editor-in-Chief of the Journal of Eukaryotic Microbiology, and member of the Editorial Boards of several journals. He is the principal investigator on three major research grants (R0ls) from the National Institutes of Health. For his scientific contributions, he was recognized as Fellow of the American Academy of Microbiology, and the American Association for the Advancement of Science, and as corresponding member of the Brazilian Academy of Sciences, and the Latin American Academy of Sciences. He was also recognized as Doctor Honoris Causa of the University of San Martin, Argentina
- Nagomi Kurebayashi
- (Jyuntendo University)
Coffee Break [10:25 ～ 10:45]
Session 2: Effectors of Ca2+ Signaling [10:45 ～ 12:30]
- Alexej Verkhratsky
- (University of Manchester, UK)
- Professor Alexei Verkhratsky, PhD, D.Sc, Member of Academia Europaea (2003), Member of the German National Academy of Sciences Leopoldina (2013), Member of Real Academia Nacional de Farmacia of Spain (2012), member of The Dana Alliance for Brain Initiatives (2012), was born in 1961 in Stanislaw, Galicia, Western Ukraine. Alexei graduated from Kiev Medical Institute in 1983, and received PhD (1986) and D.Sc. (1993) in Physiology from Bogomoletz Institute of Physiology also in Kiev. In the period between 1989 and 1995 he was visitor scientist in Heidelberg and Gottingen, and between 1995 and 1999 he was a Research Scientist at Max Delbrück Centre of Molecular Medicine in Berlin. He joined the Division of Neuroscience, School of Biological Sciences in Manchester in September 1999, became a Professor of Neurophysiology in 2002 and served as Head of the said Division from 2002 to 2004. From 2007 to 2010 he was appointed as a visitor professor/Head of Department of Cellular and Molecular Neurophysiology at the Institute of Experimental Medicine, Academy of Sciences of Check Republic. Alexei also serves as a Research Professor of the Ikerbasque (Basque Research Council) in Bilbao, where, from 2012, he acts as Adjunct Scientific Director of the Achucarro Basque Center for Neuroscience; from 2011 he is as a Honorary Visitor Professor at Kyushu University, Fukuoka, Japan. Alexei is the editor-in-chief of Cell Calcium, Receiving Editor of Cell Death & Disease and member of editorial boards of many journals including Pflugers Archiv European Journal of Physiology, Glia, Purinergic Signalling, ASN Neuro &c.
Alexei Verkhratsky is an internationally recognised scholar in the field of cellular neurophysiology. His research is concentrated on the mechanisms of inter- and intracellular signalling in the CNS, being especially focused on two main types of neural cells, on neurones and neuroglia. He made important contributions to understanding the chemical and electrical transmission in reciprocal neuronal-glial communications and on the role of intracellular Ca2+ signals in the integrative processes in the nervous system. Many of Alexei’s studies are dedicated to investigations of cellular mechanisms of neurodegeneration. A. Verkhratsky was the first to perform intracellular Ca2+ recordings in old neurones in isolation and in situ, which provided direct experimental support for “Ca2+ hypothesis of neuronal ageing”. In recent years he studies glial ageing and gliopathology in age-related brain diseases, including Alzheimer disease as well as in neuropsychiatric diseases. He authored a pioneering hypothesis of astroglial atrophy as a general mechanism of cognitive brain disorders including neurodegenerative and psychiatric diseases.
Scientometry: Prof Verkhratsky authored and edited 12 books and published ~ 400 papers and chapters. His papers were cited >17500 times, H-index 72 (ISI, 05/2017).
He was among 30 Most cited European neuroscientists in 2016
- Anne Bresnick
- (Albert Einstein College of Medicine, USA)
- Anne Bresnick, Ph.D., is Professor of Biochemistry and Director of the Belfer Institute for Advanced Biomedical Studies, which administers postdoctoral affairs at the Albert Einstein College of Medicine. An internationally recognized researcher in myosin biology and biochemistry, Dr. Bresnick directs a multidisciplinary research program focused on the regulation of myosin-II function by covalent modification and interactions with novel regulatory proteins. Dr. Bresnick is interested in how these regulatory mechanisms contribute to both physiological and pathological motility, and in leveraging this information for the development of therapeutics that target tumor invasion and metastasis. Work in the Bresnick laboratory is supported by several grants from the National Institutes of Health.
Dr. Bresnick earned her bachelor’s degree in biochemistry from the University of Maryland and her Ph.D. in biochemistry from Einstein. After completing postdoctoral training at Johns Hopkins School of Medicine in cell biology and biochemistry she joined the Einstein faculty.
- Jan Parys
- (KU Leuven, Belgium)
- Dr. Jan B. Parys completed his Ph.D. in Molecular Physiology at the KU Leuven (Belgium) in 1986. After a 3-years period in which he erected the Laboratory of Genetics at the U.S.T.H.B. in Algiers (Algeria), he moved to the group of Kevin P. Campbell at the Howard Hughes Medical Institute facility at the Dept. of Physiology and Biophysics, University of Iowa (USA). In 1992 he returned to Belgium where he became independent investigator of the National Fund for Scientific Research in 1996 and faculty member at the School of Medicine, KU Leuven in 1997. Since 2006 he is ordinary professor of Physiology and since 2013 he heads the Laboratory of Molecular and Cellular Signaling at the Dept. of Cellular and Molecular Medicine, KU Leuven.
His research always concerned the understanding of the mechanisms for Ca2+ homeostasis in general and the structure, function and regulation of the inositol 1,4,5-trisphosphate receptor (IP3R), a central player in the initiation and propagation of intracellular Ca2+ signals, in particular. More recently, he focused on the role of the IP3R in conjunction with other Ca2+-transporting proteins of the endoplasmic reticulum, the mitochondria and the lysosomes in cell survival and cell death, and especially in the processes of apoptosis and autophagy. He published over 250 research and review papers and book chapters on these topics.
From 2003 till 2012 he was Editor of Biology of the Cell and in 2013 he was Editor of “Calcium Techniques, a Laboratory Manual”, published by Cold Spring Harbor Laboratory Press. Currently he is Associate Editor of Frontiers in Oncology and is Guest Editor of special issues focusing on Ca2+ and cell death and autophagy for various journals. Since 2010 he is Secretary-General of the European Calcium Society (ECS), and was organizer or co-organizer of multiple international meetings (Leuven, Belgium, 2008; Aix-en-Provence, France, 2014; Valladolid, Spain, 2016) and workshops (Leuven, Belgium, 2013) of the ECS.
- Masayuki X Mori
- (Kyoto University)
- Janhawi Janhawi
- (Jawaharlal Nehru University)
Lunch [12:30 ～ 14:10]
Session 3: Ca2+ Signaling in Neurobiology (glia) [14:10 ～ 15:55]
- Axel Nimmerjahn
- (Salk Institute, USA)
- Axel Nimmerjahn received his Ph.D. in physics in the laboratories of Fritjof Helmchen and Bert Sakmann at the Max Planck Institute for Medical Research and the University of Heidelberg, Germany. Following postdoctoral training with Mark J. Schnitzer and Ben A. Barres in the Departments of Biology and Applied Physics at Stanford University, USA, he joined the Waitt Advanced Biophotonics Center at the Salk Institute for Biological Studies, USA, as an assistant professor. As of 2017, he is an associate professor at the same institution.
Dr. Nimmerjahn’s research focuses on elucidating the role of glial cells in protecting and maintaining mammalian central nervous system (CNS) function. To study glia he and his team have developed novel in vivo imaging, staining, molecular genetic, behavioral and computational methods. This has allowed them to provide the first study of microglia’s immune surveillance dynamics in the intact healthy and injured brain. They showed that microglial branch motility and convergence to sites of blood-brain barrier disruption depends on the TAM receptor tyrosine kinases Mer and Axl. They further demonstrated that TAM receptors play crucial roles in the removal of virus-transduced and newborn cells, and they identified mechanisms through which the viral innate immune response by microglia can be controlled. Through development of two- and miniaturized one-photon microscopes, and the discovery of sulforhodamine 101 as a glial marker, they provided the first study of astrocyte calcium excitation in the brain and spinal cord of behaving animals. This revealed that astrocytes exhibit distinct forms of neural activity-dependent and -independent calcium excitation. In particular, they showed that behavioral transitions in the brain and nociceptive signaling in the spinal cord can evoke millimeter-scale excitation in astrocyte networks, placing these cells in a position to initiate macroscopic changes in CNS dynamics.
Dr. Nimmerjahn’s work has been recognized by a variety of awards, including the Du Bois-Reymond Award of the German Physiologic Society, Otto Hahn Medal and Award of the Max Planck Society, a Rita Allen Foundation Scholar Award, and New Innovator and EUREKA Awards by the National Institutes of Health.
- Dmitri Rusakov
- (University College London, UK)
- Dmitri A. Rusakov is a professor and a Wellcome Trust principal fellow at the UCL Institute of Neurology, University College London, UK. Following his MSc in physics, he obtained his PhD in biophysics in Bogomoletz Institute of Physiology (Kiev, Ukraine) and received postdoctoral training at the Open University (Milton Keynes, UK) and at the National Institute for Medical Research, London. He has also received several personal fellowship awards from the Medical Research Council and the Wellcome Trust. The laboratory he heads focuses on the principles of synaptic organisation and use-dependent plasticity, and also on the mechanisms of astrocyte–neuron communication. Dmitri A. Rusakov’s homepage www.ucl.ac.uk/ion/synaptic-imaging.
- Schuichi Koizumi
- (University of Yamanashi, Japan)
Dept. Neuropharmacol., Interdisciplinary Grad. Sch. Med., Univ. Yamanashi,
1110 Shimokato, Chuo, Yamanashi 409-3898, JAPAN
Phone: +81-55-273-9503, Fax: +81-55-273-6739, Email: email@example.com
2007-present: Professor, Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi, Japan
1999-2006: Lab Chief, National Institute of Health Sciences, Tokyo, Japan (Glial sciences)
1996-1998: Posdoc, Univ Cambridge, Cambridge, UK. (Neurobiology, at Mike Berridge Lab)
1995: Researcher, National Institute of Health Sciences, Tokyo, Japan (Glial sciences)
1992-1995: Posdoc, Human Health Science Foundation (Molecular Biology)
1992: Ph.D., Kyushu Univ, Fukuoka, Japan. (Neuropharmacology)
1989: M.A., Kyushu Univ, Fukuoka, Japan. (Neuroscience)
1987: B.S., Kyushu Univ, Fukuoka, Japan. (Pharmacology)
1 Morizawa et al., Nat Commun, 8, 28 (2017).
2 Shinozaki et al., Cell Rep, 19, 1151-1164 (2017).
3 Miyamoto et al., Nat Commun, 7, 12450 (2016).
4 Kim et al., J. Clin. Invest, 126, 1983-1997 (2016)
5 Koizumi et al., Nature, 446, 1091-1095 (2007).
2009 Japan Academy Medal
2009 Japan Society for the Promotion Science Prize
2003 First Prize for Young Researchers of Japanese Society for Neurochemistry.
- Viktoria Szabolcsi
- (University of Fribourg)
- Hajime Hirase
Poster Session 1 [16:00 ～ 18:00]
Session 4: Ca2+ Signaling and Cancer [8:30 ～ 9:50]
- Gregory Monteith
- (University of Queensland, Australia)
- Greg Monteith is a Professor in the School of Pharmacy at the University of Queensland. He completed his Pharmacy degree and PhD at the University of Sydney. His research team seeks to identify and characterise novel therapeutic targets for the treatment of cancer. A particular focus of his research group is the identification of calcium channels and pumps that may be drug targets for breast cancer subtypes for which there are few effective therapies and the prognosis is still poor. His group’s work is published in leading scientific journals including Nature Reviews Cancer, Oncogene, Journal of Biology Chemistry and Trends in Pharmacological Sciences. His laboratory is currently supported by the National Health and Medical Research Council of Australia
- Thomas Simmen
- (University of Alberta, USA)
- My laboratory focuses on the characterization of connections between the endoplasmic reticulum (ER) and mitochondria and their role in disease. We are interested in understanding how mitochondria influence ER homeostasis and how ER stress triggers ER-mitochondria calcium exchange and eventually apoptosis. We examine why tumor cells often are defective for these signaling mechanisms, resulting in the excessive toxin production by tumor cells that would normally trigger apoptosis, but which fail to do so in a cancer setting. Additionally, we examine the significance of the MAM in neuroinflammation. Since its start-up in 2005, our laboratory has been awarded with an operating grant from the Canadian Institutes of Health Research (CIHR), 2 operating grants from the Canadian Cancer Society Research Institute (CCSRI) and the National Science and Engineering Research Council (NSERC) each, one Canadian Breast Cancer Foundation (CBCF) operating grant and one Cancer Research Society (CRS) grant, among others.
Scientific Work Experience
2011- Associate Professor, University of Alberta, Canada 2005-2011 Assistant Professor, University of Alberta, Canada 2001-2005 Post-doc funded by EMBO and the Swiss National Fund at the Vollum Institute in Portland/OR, USA (lab of Dr. Gary Thomas) 1999-2001 Post-doc funded by TELETHON Italy at the DIBIT/S. Raffaele Hospital in Milan/Italy (lab of Dr. Roberto Sitia) 1998-1999 Maître assistant remplaçant at the University of Lausanne in the group of Dr. Walter Hunziker 1994-1998 Studies for the Ph.D. in Biochemistry at Lausanne University (lab of Dr. W. Hunziker)
Current Research Projects
- Characterization of the function of the thioredoxin-related transmembrane proteins TMX and TMX4 as redox sensors of the endoplasmic reticulum and potential regulators of apoptosis onset; role of TMX and TMX4 in melanoma
- Characterization of the role of Rab32 for mitochondria morphology and apoptosis onset; role of Rab32 in breast cancer and melanoma; role of Rab32 in Multiple Sclerosis (with Dr. Fabrizio Giuliani, UofA, Edmonton)
- Hiroshi Tokumitsu
- (Okayama University)
- Walter Blum
Coffee Break [9:50 ～ 10:10]
Ca2+ Signaling in the Heart - Mechanisms and Disease [10:10 ～ 11:55]
- S. R. Wayne Chen
- (University of Calgary, Canada)
- Dr. S. R. Wayne Chen has made significant contributions to the understanding of the structure, function, regulation and role in disease of calcium release channels/ryanodine receptors (RyRs). His work on the luminal calcium activation of RyRs provides important insights into the cause of calcium-mediated cardiac arrhythmias and malignant hyperthermia, and how fundamental cellular calcium waves are generated. His work has been translated into a clinical trial and the development of novel anti-arrhythmic drugs.
- Walter J Chazin
- (Vanderbilt University, USA)
- Dr. Chazin received a B.Sc. in Chemistry from McGill University in 1975 and a Ph.D. in Chemistry from Concordia University in Montreal in 1983. He was a postdoctoral fellow in the lab of Kurt Wüthrich at the E.T.H. in Switzerland (2002 Nobel laureate in Chemistry). After 12 years on faculty in the Department of Molecular Biology at the Scripps Research Institute, he moved to Vanderbilt in 1999 where he holds the Chancellor’s Chair in Medicine as Professor in the Departments of Biochemistry and Chemistry, and serves as Director of the Center for Structural Biology and the Molecular Biophysics Training Program. He has mentored ~100 graduate students and postdocs and ~30 undergraduate students in his 29 years as an independent investigator. He has published over 200 peer reviewed papers and 50 book chapters and reviews, and serves on a number of advisory committees and editorial boards. His honors include American Cancer Society Junior Faculty and Faculty Research Awards, serving as a National Academy of Science (NAS) International Travel Fellow and NAS Teaching Fellow, Regents Visiting Professor at the University of Naples in Italy, and appointments as a Fellow of the American Association for the Advancement of Science and Fellow of the Biophysical Society. The Chazin laboratory is currently using an array of biochemical, biophysical and structural tools to interrogate the structure, dynamics and function of proteins and protein complexes involved in calcium signaling, innate immunity, and DNA replication, damage response and repair.
- Naomasa Makita
- (Nagasaki University, Japan)
Department of Molecular Physiology
Nagasaki University Graduate School of Biomedical Sciences
1-12-4 Sakamoto, Nagasaki, 852-8523, JAPAN
December 3, 1956
1977-1983: Hokkaido University School of Medicine, Japan
Degree: M. D.
1983- 1987: Hokkaido University Graduate School, Japan
Degree: Ph. D. (Dr. of Medical Science)
Postgraduate Training and Faculty Appointment
1984-1985: Residency (Internal Medicine)
Asahikawa Municipal Hospital, Asahikawa
1987-1990: Postdoctoral Fellow (Cardiovascular)
Hokkaido University School of Medicine
1990-1994: Postdoctoral Fellow (Nephrology)
Vanderbilt University School of Medicine
Nashville, TN, USA
1994-1996: Instructor in Medicine, Vanderbilt University,
Nashville, TN, USA
1999-2007: Assistant professor, Department of Cardiovascular Medicine,
Hokkaido University Graduate School of Medicine, Japan
2007-2008 Lecturer, Hokkaido University Hospital, Japan
2008-2009.4: Associate professor, Department of Cardiovascular Medicine,
Hokkaido University Graduate School of Medicine, Japan
2009.5-2012.3 Professor, Chair, Department of Visceral Physiology and Body Fluid
Nagasaki University Graduate School of Biomedical Sciences
2012.4-Present Professor, Chair, Department of Molecular Physiology.
Nagasaki University Graduate School of Biomedical Sciences
American Heart Association
Heart Rhythm Society
Japanese Circulation Society
The Japanese Heart Rhythm Society
The Physiological Society of Japan
License and Certification
Japanese Medical License 273790
- Stephan E Lehart
- (University of Medical Center Goettingen)
- Takanori Saeki
- (Nagoya City University)
Excursion: Uzushio Cruising Tour with box lunch [12:30 ～ 16:45]
Poster Session 2 [17:00 ～ 19:00]
Ca2+ Signaling in Neurobiology/Neuropathology [8:30 ～ 10:10]
- Ryohei Yasuda
- (Max Planck Florida, USA)
- Dr. Ryohei Yasuda was named Scientific Director of the Max Planck Florida Institute for Neuroscience in 2012 and heads the Neuronal Signal Transduction Lab. The focus of Dr. Yasuda’s lab is to elucidate some of the molecular mechanisms underlying synaptic plasticity and ultimately learning and memory.
Dr. Yasuda received his PhD in Physics in 1998 from Keio University Graduate School of Science and Technology in Yokohama, Japan. In his PhD studies, he demonstrated that the enzyme ATP synthase is a rotary motor made of single molecule and that its energy conversion efficiency is close to 100%. From 2000 to 2005, he was a post-doctoral fellow at the Cold Spring Harbor Laboratory where he built an imaging device to monitor protein interactions in living cells with high sensitivity and resolution. From 2005 to 2012, he was an assistant professor of the Neurobiology department at the Duke University Medical Center where he developed a number of techniques to visualize signaling activity in single synapses. From 2009 to 2012, Dr. Yasuda served as an Early Career Scientist at the Howard Hughes Medical Institute.
Dr. Yasuda has received a number of awards for his research accomplishments including the Career Award at the Scientific Interface from the Burroughs Wellcome Fund, the Alfred P. Sloan Fellowship, the New Investigator Award from the Alzheimer’s Association, Research Award for Innovative Neuroscience from the Society for Neuroscience, NIH Director's Pioneer Award from NIH, and Nakaakira Tsukahara Award from Japanese Neuroscience Society / Brain Science Foundation.
- Hilmar Bading
- (University of Heidelberg, Germany)
- Hilmar Bading studied medicine at Heidelberg University, Germany, did post-doctoral work at the Max-Planck-Institute for Molecular Genetics, Berlin, Germany, and at Harvard Medical School, Boston, USA. He was a group leader at the Medical Research Council (MRC) Laboratory of Molecular Biology, Cambridge, UK, and is currently Professor of Neurobiology, Head of the Department of Neurobiology, and Director of the Interdisciplinary Center for Neurosciences at Heidelberg University. He studies synapse-to-nucleus communication pathways that control genomic events critical for adaptive responses in the nervous system, in particular acquired neuroprotection and long-term memory. His work focuses on the role of nuclear calcium signaling in these processes and how the dialogue between synapses and the nucleus is disturbed by the stimulation of extrasynaptic NMDA receptors that initiates excitotoxicity (https://en.wikipedia.org/wiki/Hilmar_Bading).
- Ilya Bezprozvanny
- (University of Texas, USA)
- Ilya Bezprozvanny received M.Sci in Physics (1989) from the St Petersburg Polytechnical University and a Ph.D. in Cell Biology (1992) from the Institute of Cytology Russian Academy of Sciences (scientific advisors - Alex P. Naumov and Galina N. Mozhayeva). As a part of his training, Ilya worked with Barbara E. Ehrlich (1990-1994) at the University of Connecticut Health Center at Farmington, Connecticut and then with Richard W. Tsien (1994-1996) in the Department of Molecular and Cellular Physiology at Stanford University Medical Center, Stanford, California. In 1996, Ilya joined the faculty of the Physiology department in UT Southwestern Medical Center at Dallas. Since 2007 Ilya is a Professor in the Department of Physiology in UT Southwestern Medical Center at Dallas and since April 2011 he is holding the Carl J. and Hortense M. Thomsen Chair in Alzheimer’s Disease Research. His main research interests are focused on understanding the role of deranged calcium signaling in pathogenesis of neurodegenerative disorders such as Alzheimer’s disease, Huntington’s disease and spinocerebellar ataxias.
- Malene Brohus
- (Aalborg University)
Coffee Break [10:15 ～ 10:30]
Session 7: Ca2+ and Mitochondria [10:30 ～ 12:10]
- Tito Calì
- (University of Padova, Italy)
- 2015-Today: Assistant Professor, Department of Biomedical Sciences, University of Padova. The main projects are focused on Parkinson’s Disease, mitochondrial Ca2+ handling with a focus on the MCU complex components and PMCA3-related ataxias.
2013-2015: Senior Research Associate, University of Padova. Molecular contribution of PINK1 and Parkin to pathogenesis of Parkinson’s disease and their relationship in mitochondrial physiology.
2009-2013: Junior Research Associate, University of Padova. Calcium homeostasis and mitochondrial metabolism in neurodegenerative diseases.
2008: PhD Degree “in signi cum laude”, Biochemistry/Molecular Biology, Theodor Kocher institute, University of Bern (CH) and Institute for Research in Biomedicine (IRB), Bellinzona (CH). Thesis title: Tuning Endoplasmic Reticulum Associated Degradation. I describe post-translational mechanisms defined as ERAD tuning that selectively remove ERAD operators from the ER folding compartment.
2005: Doctor in Biological Sciences 110/110 “Cum Laude”, Biochemistry/Molecular Biology, University of L’Aquila and Centre d’Immunologie Marseille Luminy (CIML).
Scientific Independence of young Researchers grant (SIR) from the Italian Ministry of Education, University and Research (MIUR) (2015-2018). Grant No RBSI14C65Z: ER-mitochondria crosstalk in Parkinson’s disease: role of PINK1/Parkin in Ca2+ handling and organelles tethering
Research Grant, University of Padova, Progetto di Ateneo (2016-208). Grant No CALI_SID16_01. Calcium mishandling in the pathogenesis of Congenital Ataxias: structural and functional characterization of novel disease-related human mutations of the neuronal restricted plasma membrane Ca2+ ATPases.
Young Researcher Award, Research Grant, University of Padova (Bando Giovani studiosi 2013-2015). Grant No GRIC128SP0. Spatio-temporally regulated checkpoints for mitochondrial wellness in Familial forms of Parkinson disease: from early defense to mitochondrial clearance
Vicario M, Calì T, et al. A novel PMCA3 mutation in an ataxic patient with hypomorphic phosphomannomutase 2 (PMM2) heterozygote mutations: Biochemical characterization of the pump defect. BBA. 2017
Calì T, et al. The ataxia related G1107D mutation of the plasma membrane Ca2+ ATPase isoform 3 affects its interplay with calmodulin and the autoinhibition process. BBA. 2017
Calì T, et al. A new split-GFP-based probe reveals DJ-1 translocation into the mitochondrial matrix to sustain ATP synthesis upon nutrient deprivation. HMG. 2015.
Calì T, et al. A Novel Mutation in Isoform 3 of the Plasma Membrane Ca2+ Pump Impairs Cellular Ca2+ Homeostasis in a Patient with Cerebellar Ataxia and Laminin Subunit 1α Mutations. JBC 2015.
Calì T, et al. Enhanced parkin levels favor ER-mitochondria crosstalk and guarantee Ca2+ transfer to sustain cell bioenergetics. BBA. 2013
Calì T, et al. α-Synuclein controls mitochondrial calcium homeostasis by enhancing endoplasmic reticulum-mitochondria interactions. JBC. 2012
Zanni G, Calì T, et al. Mutation of plasma membrane Ca2+ ATPase isoform 3 in a family with X-linked congenital cerebellar ataxia impairs Ca2+ homeostasis. PNAS. 2012
- Kevin Foskett
- (University of Pennsylvania, USA)
- Dr. Kevin Foskett is a Professor of Physiology at the University of Pennsylvania, with a cross appointment in the Department of Cellular and Developmental Biology, and a member of the Mahoney Institute of Neurosciences and the Abramson Cancer Center. His research for over 30 years has had as its focus the mechanisms and regulation of ion transport and signal transduction, with significant contributions to a number of fundamental areas of research, including cell volume regulation, mechanisms of osmoregulation by marine fish, mechanisms of intracellular Ca2+ signaling in epithelial cells, mechanisms and regulation of exocrine secretion, the cell biology of cystic fibrosis, and the molecular physiologies of the InsP3R Ca2+ release channel, the mitochondrial Ca2+ uniporter MCU ion channel, and CALHM ion channels. His work has provided insights into the molecular mechanisms of the genetically-inherited forms of Alzheimer’s disease, cellular bioenergetics with relevance for neurodegenerative diseases and cancer, and the molecular physiology of taste perception.
- György Hajnóczky
- (Thomas Jefferson University, USA)
- I am currently a Professor and Director of the MitoCare Center for Mitochondrial Imaging Research and Diagnostics at the Department of Pathology, Anatomy and Cell Biology at Thomas Jefferson University.
The long term objective of my group is to reveal critical roles mitochondria play in integrating cell and tissue function through their dynamics and interactions with other cell structures, coordinating calcium homeostasis, integrating cell metabolism, exerting cellular quality control, and driving cell life/death decisions. To elucidate the mechanisms of mitochondrial signaling and dynamics our group develops microscopic imaging techniques.
Lunch [12:10 ～ 13:50]
Claude B. Klee Memorial Session
Calcineurin and Calmodulin - Past, Present, and Future [13:50 ～ 16:00]
- Mitsuhiko Ikura
- (University of Toronto, Canada)
- Dr. Ikura received his Ph.D. in macromolecular biophysics at the Hokkaido University, Japan, followed by his postdoctoral training at the National Institutes of Health, USA. Dr. Ikura joined the Ontario Cancer Institute/University of Toronto as Senior Scientist/Professor. Dr. Ikura is a world-renowned structural biologist who studies biologically important molecules at Princess Margaret Cancer Centre (formally known as OCI). He has been supported by external individual awards over the past 25 years: MRC Scholarship (1993-1998), CIHR Investigator Award (1998-2003), CHIR Senior Investigator (2003-3004), CRC Tier I Chair in Cancer Structural Biology (2004-present). He also won the HHMI International Research Scholar Award, the CCS William E. Rawls Prize and Robert L. Noble Prize. Internationally, he organized two major meetings in the field of NMR and structural biology: International Conference on Magnetic Resonance on Biological Systems (2002) and the Keystone Symposium on Frontiers of NMR in Biology (2007). He has been serving a number of scientific advisory boards of international organizations including ICMRBS, Asia-Pacific NMR Symposium, and BioMagResBank. In the past five years, he has spoken at 40 international and national scientific meetings including, most recently, plenary Speaker at the 2016 ICMRBS, and has been invited to 61 seminars at various universities and research institutes worldwide. Dr. Ikura hold a Canada Research Chair in Cancer Structural Biology.
- Trisha Davis
- (University of Washington, USA)
- Dr. Trisha N. Davis received her Bachelor’s degree in Biology and Computer Science at the University of California at Santa Cruz. As a National Science Foundation Predoctoral Fellow, she obtained a Ph.D. in Molecular Biophysics and Biochemistry from Yale University, followed by a postdoctoral fellowship from the Anna Fuller Fund to study Biochemistry at the University of California at Berkeley. As a Searle Scholar she joined the University of Washington as Assistant Professor of Biochemistry. There she has risen through the ranks to Professor. In 2005, Dr. Davis was awarded the UW School of Medicine Mentoring Award. In 2008, she won a Humboldt Research Award to study at the Max Planck for Cell Biology in Dresden, Germany for 10 months. In 2012, she became a fellow of the American Association for the Advancement of Science and in 2015, a member of the Washington Academy of Sciences. In 2013, she was awarded the Earl W. Davie/Zymogenetics Endowed Chair in Biochemistry. Dr. Davis has held two key leadership positions, including 15 years as director of a $10 million dollar technology development center funded by the NIH and is currently chair of the Department of Biochemistry in the University of Washington School of Medicine.
- Martha Cyert
- (Stanford University, USA)
- Martha S. Cyert is Professor and Associate Chair of the Department of Biology at Stanford University. She received her Ph.D. from the University of California at San Francisco and carried out postdoctoral training at the University of California Berkeley, where she pioneered studies of calcineurin, the highly conserved Ca2+/calmodulin-regulated protein phosphatase, in Saccharomyces cerevisiae. Dr. Cyert’s research established conserved aspects of substrate recognition by calcineurin, and the mechanism by which the immunosuppressant drugs, cyclosporin A and FK506, inhibit this enzyme. Current studies focus on systems level analyses of the calcineurin signaling network in humans. Professor Cyert is organizer of the 2018 FASEB Protein Phosphatase conference and serves on the Public Affairs Advisory Council for ASBMB. She has been awarded fellowships from the American Cancer Society, the Life Sciences Research Foundation and the Lucille P. Markey Charitable Trust, and was named by Stanford University as a Gabilan Fellow, a Terman Fellow and the Thomas W. and Susan B. Ford University Fellow.
- Jacques Haiech
- (University of Strasbourg, France)
- Equipe de Chimie Thérapeutique Laboratoire d’Innovation Thérapeutique, UMR CNRS 7200 Faculté de Pharmacie 74, route du Rhin, 67401 ILLKIRCH FRANCE; Phone: 33 390244270, e-mail: firstname.lastname@example.org
Date of birth: November 27, 1954
1973 Ecole Normale Supérieure de l'Enseignement Technique, section Mathématiques et Informatique , Cachan.
1975 Master in Mathematics (Potential Theory) (Higher grade)
1976 Agrégation de Mathématiques
1977 Master in Biochemistry (Higher grade)
1978 PhD in Biochemistry (Higher grade)
1981 State Doctorate in Biochemistry (higher grade)
NIH post-doc training C13NMR
Languages: fluent in French and English
1979 CNRS research assistant, Montpellier
1980 post-doc NIH (Foggarty Fellow)
1981 Team Leader « Biochemistry and Pharmacology of arterial vessels », Montpellier
1988 CNRS research director, Marseille
1989 Team leader « Protein engineering », Marseille
1991 Full professor University Aix-Marseille II
1997 Full professor School of Pharmacy, Strasbourg I
1998 Team leader « Biophysics of second messengers », Strasboug
1999 Director of the Research Institute Gilbert laustriat « Biomolecules and Therapeutic Innovations », Strasbourg
2005 Team Leader « Chemical genetics and Pharmacogenomics », Strasbourg.
2009 Professor exceptional class University of Strasbourg
2014 Director School of Innovation PACRI (Paris alliance cancer research institute)
Bibliographic indexes using Publish or Perish software and google scholar as database
Years since first published paper:37,
1986 Prix Mannesman-Kiezsle (Informatique-Intelligence artificielle) avec Jean Sallantin
2001 Chevalier de l’ordre national du mérite
2005 Chevalier des palmes académiques
Experiences in research evaluation
Expert for scientific programs in Belgium and for different European program and in USA (NSF)
1999-2003: Director of the national genomic program (French minister of research)
2010-2014 : Scientific delegate at AERES (French National Agency for Research)
2010-2014 : National Delegate in COST Program
- Ernesto Carafoli
- (Venetian lnst. of Mol. Medicine, Padova, Italy)
- Current position
Emeritus Professor (Biochemistry), Swiss Federal Institute of Technology (ETH), Zurich, Emeritus Faculty Member, Venetian Institute of Molecular Medicine, Padova Italy , Senior Scholar, University of Padova.
M. D., (1957) University of Modena, Italy. Abilitation (Biochemistry) 1968
as an adolescent, for a number of Summers I hitchhiked across war-ravaged Europe as an hitchhiker. Well into middle age I kept climbing mountains, mostly in the rocky Dolomites. Poetry and art, including music, have been my main intellectual non scientific lifelong interests.
When I entered Medical School at the University of Modena I had in mind to become a practicing Doctor, following the footsteps of my father and grandfather. But I soon shifted my interests toward science: which in this case was bioenergetics, as the Institute in which I was working as an internal student was one of the first to work on mitochondria in Italy. And so, after graduation and a brief stint in psychiatry, I ended up as a postdoc in the Laboratory of Albert L. Lehninger at Johns Hopkins. There, the transport of calcium by mitochondria had just been discovered, and Lehninger recommended it to me as the topic of work. It was a turning point in my life, as calcium was to remain my lifelong companion. Our work at at Johns Hopkins on mitochondrial calcium transport provided fundamental support for the revolutionary chemiosmotic theory of Peter Mitchell. After my return to Europe and my appointment at the ETH in Zurich I gradually shifted my interests away from mitochondria, and started working on the calcium transporting ATPase of the plasma membrane. We have worked on it for over three decades, providing fundamental information on the properties and the ATPase and its role in the regulation of cellular calcium signaling. In 2001, having reached retirement age at the ETH in Zurich, I moved back to Padova as a Professor of Biochemistry: two years later, I co-founded the Venetian Institute if Molecular Medicine (VIMM) , where I presently work. In the last ten years or so at the VIMM I have gradually extended my interests to the pathological deviations of the process of calcium signaling, particularly to the genetic mutations of the plasma membrane calcium ATPases in neuronal pathologies.
Nishizuka Lecture [16:10 ～ 17:10]
- Anjana Rao
- (Lajolla Institute, USA)
- Dr. Anjana Rao obtained her Ph.D. in Biophysics from Harvard University and was a Professor at Harvard Medical School until 2010, when she moved to the La Jolla Institute and UCSD (University of California in San Diego). Her research is focused on the regulation of gene expression, using primarily immune cells as a model system. Her lab purified and molecularly characterized the calcium/ calcineurin-regulated transcription factor NFAT; defined diverse transcriptional programs regulated by NFAT proteins in T cells; identified the pore subunit of the store-operated Ca2+ channel, ORAI1; and discovered that proteins of the TET family are enzymes that alter DNA methylation status and regulate gene expression by oxidizing 5-methylcytosine. In recent studies, she has defined the role of NFAT in the hyporesponsive state termed exhaustion in tumor-infiltrating T cells, and explored the roles of TET proteins and oxidized methylcytosines in the immune, haematopoietic and nervous systems as well as in embryonic development and oncogenesis. Dr. Rao has received numerous awards throughout her career. She is an elected member/fellow of the US National Academy of Sciences, the American Academy of Arts and Sciences and the American Association for the Advancement of Science.
GALA Dinner [18:00 ～ 21:00]
Session 9: New Tools of Ca2+ Research [8:30 ～ 10:15]
- Robert Campbell
- (University of Alberta, USA)
- Dr. Robert E. Campbell is a Professor in the Department of Chemistry, University of Alberta (2003 - present). He earned his Ph.D. in Chemistry with Martin Tanner at the University of British Columbia in 2000 and undertook postdoctoral research at the University of California San Diego in the lab of the late Roger Y. Tsien (2008 Nobel Prize). His research is focussed on the development of genetically encoded Ca2+ indicators and optogenetic tools for cell biology applications. His contributions have been recognized with numerous awards including the Teva Canada Limited Biological and Medicinal Chemistry Lectureship Award (2016), the Rutherford Memorial Medal in Chemistry from the Royal Society of Canada (2015), and a Canada Research Chair (2004-2014).
- Tomoki Matsuda
- (Osaka University, Japan)
- Name: Tomoki, MATSUDA, Ph.D.
Position Title: Associate Professor
Affiliation: Institute of Scientific and Industrial Research, Osaka University
Research and professional experience:
2003 Dec. Ph. D., Graduate School of Science, Osaka University 2004-2005 Research Associate, Genome Science Center, RIKEN 2005-2007 Part-Time Research Worker, Research Institute for Electronic Science, Hokkaido University 2007-2008 Research Fellow, Japan Association for the Advancement of Medical Equipment 2008-2012 Assistant Professor, Research Institute for Electronic Science, Hokkaido University 2012-2013 Assistant Professor, The Institute of Scientific and Industrial Research, Osaka University 2013-present Associate Professor, The Institute of Scientific and Industrial Research, Osaka University
- Won Do Heo
- (KAIST, Korea)
- Won Do Heo received his Ph.D. from Gyeongsang National University in Korea in 1999 and moved to Duke University and then to Stanford University for post-doc training. During his postdoctoral training, he investigated the roles of human small GTPases by cloning 125 human small GTPases. His work was published in Cell, Science, and Molecular Cell as the first author. After post-doctoral training he moved to KAIST as a professor. As a PI he continued to study the roles of diverse signaling proteins in mammalian cells by using various bio-imaging technologies. His group has developed novel optogenetic and bio-imaging technologies using the resources of ~20,000 human proteins. He joined the Center for Cognition and Sociality at IBS in 2013 as a group leader and established Bio-Imaging Group and a core Bio-Imaging facility possessing various optical microscopies. His group has focused on developing various bio-imaging and optogenetic tools that are useful for research in neuroscience, including LARIAT, IM-LARIAT, optoSTIM1, optoFGFR and optoTrk receptors. His group is currently applying the novel technologies to the study of spatiotemporal roles of receptors, signaling proteins, second messengers and local mRNA translation in synaptic plasticity and learning and memory in normal and disease mouse models.
- Cassandra L Miller
- (Georgia State University)
- Junji Suzuki
- (University of California, San Francisco)
Coffee Break [10:15 ～ 10:35]
Session 10: Store-operated Ca2+ entry [10:35 ～ 12:20]
- Murali Prakriya
- (Northwestern University, USA)
- Murali Prakriya is a Professor of Pharmacology, Northwestern University, Chicago, USA. His research examines the mechanisms and functions of store-operated calcium channels (SOCs). SOCs are expressed in most animal cells and regulate diverse cellular functions ranging from gene expression, motility and secretion to tissue and organ development, and the immune response. The best-described SOCs are made of the Orai proteins, which form the calcium-selective pores of the channels, and are activated by the ER calcium sensors, STIM1 and STIM2. Prakriya’s work examines the biophysical and structural mechanisms of Orai channel gating, and their physiological roles in neurons, glia, and immune cells.
- Anant Parekh
- (Oxford University, UK)
- Anant Parekh studied Medicine at Oxford University, where he obtained his undergraduate and doctoral degrees. His postdoctoral research was carried out at the Max Planck Institute for biophysical Chemistry in Goettingen, Germany, where he worked in Professor Erwin Neher’s department with Professor Walter Stuehmer and then Professor Reinhold Penner. He moved back to Oxford (Physiology) as a Wellcome Trust Career Development Fellow and Sir Edward Abraham Research Fellow at Keble College. He was subsequently awarded a Lister Institute Senior Research Fellowship, Amersham Medical Fellowship (Keble College) and then Monsanto Senior Research Fellowship (Exeter College, Oxford). He was then appointed to the faculty in the Physiology Department and a Tutorial Fellowship at Lady Margaret Hall. In the same year, he was promoted to Professor of Physiology. Since 2016, he has been Director of the Centre of Physiology and a Fellow of Merton College, Oxford. Anant Parekh’s research interests are on intracellular calcium signalling and how changes in calcium can engender a wide range of cellular responses. In particular, his work has focussed on store-operated calcium channels in the plasma membrane, how these channels interact with intracellular organelles like mitochondria and how these fundamental elements go awry in human disease. He was awarded the Wellcome Prize in Physiology (2002), India International Foundation Prize (2009), GL Brown Prize from the UK Physiological Society (2012). He is an elected member of Academia Europaea and is a Fellow of the Academy of Medical Sciences.
- Donald Gill
- (Pennsylvania State University, USA)
- POSITION TITLE
Professor and Chair, Department of Cellular and Molecular Physiology The Pennsylvania State University College of Medicine
My lab has been studying the molecular mechanisms mediating Ca2+ signals for the last 30 years. We have de-fined many novel parameters of the structure, function and control of the Ca2+ signaling machinery, focusing on smooth muscle and immune cell models to understand the extraordinary molecular cross-talk and functional integration that exists between Ca2+ sensors and Ca2+ channel proteins. My lab has maintained two complemen-tary research projects for many years, one on Ca2+ signaling by STIM proteins in smooth muscle (GM 109279), and the other on control of Orai Ca2+ entry channels in B cells (GM 120783). In recent years, we have focused on the ubiquitously expressed STIM and Orai proteins that mediate essential but quite distinct Ca2+ signals in these two cell types. The MIRA application is an opportunity to combine these studies into a comprehensive program to understand the fundamental “coupling interface” between the STIM protein ER Ca2+ sensors and the ubiquitously expressed Orai family of highly Ca2+-selective Ca2+ entry channels. This tightly regulated STIM-Orai coupling process functions to mediate and integrate Ca2+ signals crucial in controlling transcription, proliferation, motility, and growth remodeling, with broad implications for all cell types.
Over the last 20 years, my lab has maintained a leading role in understanding how “store-operated” Ca2+ signals are generated and how the STIM-Orai Ca2+ signaling pathway operates. Our initial work revealed the process involves reversible ER-PM junctional interactions. Subsequently, we designed the screen used to first identify STIM proteins, and revealed that STIM and Orai proteins reconstitute the authentic Ca2+ release-activated Ca2+ (CRAC) current, the classical hall-mark of store-operated Ca2+ entry (SOCE) in all cells. More recently, we developed a spectrum of molecular probes and cell imaging approaches with which we have mapped the molecular interactions, dynamics and mechanism of the STIM-Orai coupling pathway. These studies utilize a combination of high-resolution imaging technology, real-time FRET analyses, functional channel studies, protein structural analyses, CRISPR/Cas9 gene editing approaches, and design of a spectrum of genetically-encoded single molecule and concatenated molecular probes. Our probes and reagents are rigorously authenticated and key studies are controlled and blinded to avoid misinterpretation or bias. We share our probes and assist others in their use and interpretation; we present findings widely at meetings including the highly subscribed Calcium Signaling Gordon Research Conference I founded in 1993.
This cadre of tools and approaches has allowed my lab to make some critical advances over the last three years that provide an important basis for the MIRA-supported studies we propose. These advances (refs 1-4) fundamentally change our understanding of the STIM-Orai signaling pathway, revealing: (1) the crucial locus on STIM proteins for Orai channel interaction which defines important functional distinctions between STIM1 and STIM2; (2) that the dimeric STIM proteins undergo a surprising unimolecular coupling interaction with Orai channel subunits with important implications for channel cross-talk and clustering; (3) that the Orai1 channel functions as a hexamer (not a tetramer as widely reported) ; (4) that gating of Orai channels is mediated by a remote STIM-induced allosteric control mechanism and not a direct pore-displacement mechanism suggested earlier. The studies proposed build upon this new base of information to determine: (a) how the STIM protein subtypes activate and unfold to interact with Orai channels, (b) what constitutes the molecular basis of STIM-binding to the Orai channel subtypes and how this binding is transduced into channel gating, and (c) how the spatially organized STIM-Orai complexes formed within ER-PM junctions generate coded oscillatory Ca2+ signals to control transcription factor activation and altered growth phenotype.
As Chair of the Department of Cellular and Molecular Physiology at Penn State University College of Medicine, we have assembled a highly interactive group of cellular signaling investigators. We have developed some important collaborations in our study of STIM and Orai proteins. There are three Key Personnel associated with the MIRA project: (a) Dr. Yandong Zhou has worked in my lab for several years and is an extraordinarily talented expert in FRET imaging, super-resolution imaging, electrophysiology, and designing our tagged/ concatenated probes; (b) My lab now works closely with the lab of Dr. Mo Trebak who joined the Department in 2015. His direction is toward translational understanding of the role of Ca2+ entry channels (TRP, Orai and CaV subtypes) in endothelial cell function, and changes during vascular and pulmonary remodeling; (c) We undertake NMR structural analysis on STIM and Orai fragments with Dr. Fang Tian, in the Department of Biochemistry here at Hershey. Penn State is investing in two FEI Krios Cryo-EM transmission electron microscopes, and in collaboration with Dr. Susan Hafenstein (Penn State) and Dr. Vera Moiseenkova-Bell (Case Western), we are using the molecular constructs we have developed to solve structures of the STIM1-Orai1 complex and the Orai1 open channel. In the last 2 years we initiated an important collaboration with Dr. Barbara Niemeyer in Homburg, on the function of the STIM2.1 splice variant of STIM2. This is crucial work in the MIRA project and she has helped us much with examining its expression and allowing us to make dimer constructs of SOAR2.1. We also share resources with another recent Department recruit, Dr. Shengyu Yang, a cancer cell biologist studying the role of Orai channels and actin-bundling proteins in metastatic progression and the invasive properties of melanoma cells. We also have a strong collaboration with Dr. Michael Cahalan at UC Irvine, on analysis of the nature of the ER-PM junctional complex and visualization of the organization of STIM and Orai channels into clusters within the junction.
My lab will continue to train new researchers: I have mentored 15 Ph.D. students, and 21 postdoctoral fellows, and served as Graduate Program Director at U. Maryland for 12 years. At Hershey, we built the new Cellular and Integrative Physiology training program that interfaces with the strong Biomedical Sciences Program.
- Wang, X., Wang, Y., Zhou, Y., Hendron, E., Mancarella, S., Andrake, M.D., Rothberg, B.S., Soboloff, J., and Gill, D.L. (2014). Distinct Orai-coupling domains in STIM1 and STIM2 define the Orai-activating site. Nature Commun. 5:3183 (1-11) DOI:10.1038/ncomms4183 (Feb 4, 2014) PMCID: PMC3995141
- Zhou, Y., Wang, X., Wang, X., Loktionova, N.A., Cai, X., Nwokonko, R.M., Vrana, E., Wang, Y., Rothberg, B.S., and Gill, D.L. (2015). STIM1 dimers undergo unimolecular coupling to activate Orai1 channels. Nature Commun. 6:8395 (1-10) DOI:10.1038/ncomms9395 (Sep 24, 2015) PMCID: PMC4598629.
- Cai, X., Zhou, Y., Nwokonko, R.M., Loktionova, N.A., Wang, X., Xin, P., Trebak, M., Wang Y., and Gill, D.L. (2016). The Orai1 store-operated calcium channel functions as a hexamer. J. Biol. Chem. 291:50, 25764-25775 (Dec 9, 2016) PMCID PMC5207053
- Zhou, Y., Cai, X., Loktionova, N.A., Wang, X., Nwokonko, R.M., Wang, Y., Rothberg, B,S., Trebak, M., and Gill, D.L. (2016) “The STIM1 binding site nexus remotely controls Orai1 channel gating” Nature Commun. 7:13725, 1-13; doi:10.1038/ncomms13725; 1-13 (Dec 5, 2016) PMCID PMC5155162
- Magdalena Czeredys
- (International Institute of Molecular and Cell Biology in Warsaw)
- Wei Zhang
- (Nagoya University)