This article was downloaded by: [New York University] On: 31 May 2015, At: 01:29 Publisher: Taylor & Francis Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Autophagy Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/kaup20
Autophagy researchers Published online: 02 Dec 2013.
Click for updates To cite this article: (2014) Autophagy researchers, Autophagy, 10:2, 188-191, DOI: 10.4161/auto.27182 To link to this article: http://dx.doi.org/10.4161/auto.27182
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
autophagy community
cell cycle news & views
Autophagy 10:1, 188–191; February 2014; © 2014 Landes Bioscience
Autophagy researchers Serena Carra Email: [email protected]
Research focus Molecular chaperones, protein homeostasis, and neurodegeneration.
Model system Mammalian cells, Drosophila Schneider 2 (S2) cells and Drosophila melanogaster transgenic lines overexpressing or downregulating molecular chaperones.
Education and career 1998, master’s degree, chemical and pharmaceutical sciences, University of Modena, Modena, Italy; advisor: Prof. Nicoletta Brunello. 2000–2004, PhD, neurobiology, University of Catania, Roma and Pavia, Italy; advisors: Prof Roberto Federico Villa and Prof Nicoletta Brunello; 2000–2001, research fellow, Centre de Recherche Hospitalier Université Laval (CHUL), Québec, Canada; advisor: Prof Nicholas Barden; 2004–2007, postdoctoral fellow, Centre de Recherche L’Hôtel-Dieu de Québec, Laval University, Québec, Canada; advisor: Prof Jacques Landry; 2007–2009, postdoctoral fellow, University Medical Center Groningen, The Netherlands; advisor: Prof Harm H Kampinga; 2009–2011, assistant professor, University Medical Center Groningen; 2011–present, assistant professor, University of Modena and Reggio Emilia, Modena, Italy.
188
What do you think is a key question in the autophagy field? Nowadays thanks to the efforts of a number of research groups, we know that several molecular chaperone complexes, including the HSPB8-HSPA8-BAG3 complex, can work in concert with the so-called autophagy receptors (e.g. SQSTM1/p62) and can directly interact with motor proteins to specifically deliver misfolded aggregate-prone substrates to the autophagic vacuoles for degradation. However, how such specificity is achieved is still largely unknown. Understanding at the molecular level how protein quality control and autophagy cooperate to ensure such specificity and to maintain protein homeostasis is crucial and will have a great impact on a number of pathological conditions where autophagy is needed/defective or even “hijacked” (e.g., viral infection).
Why is the field of autophagy important to you? Autophagy-mediated degradation of specific misfolded clients is a crucial step for the maintenance of proteostasis, whose deregulation is associated with
pathological conditions as diverse as neurodegenerative diseases, motor neuron diseases, and aging.
Is there a key experiment/finding that stands out in your mind with regard to autophagy? The discovery of the autophagic receptor proteins such as SQSTM1 has challenged the concept of autophagy as a bulk degradation process and has provided mechanistic insight into the high degree of specificity of cargo delivery to, and degradation by, the autophagic pathway.
Which paper(s) in your research field represents seminal work on autophagy? Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R, Yokoyama M, Mishima K, Saito I, Okano H, Mizushima N. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 2006; 441, 885–9 Komatsu M, Waguri S, Chiba T, Murata S, Iwata JI, Tanida I, Ueno T, Koike M, Uchiyama Y, Kominami E, Tanaka K. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 2006; 441, 880–4
Personal comments In my free time I like to sit on my sofa and listen to jazz and classical music. I also enjoy playing violin (I studied at the music school when I was a teenager). I have been oil painting on and off since nearly 20 years and I still love it. My paintings have no particular style: they differ so much in subject, and colors and they more reflect an impression, a mood. At present, I mainly enjoy being a mum and seeing my 2 lovely sons growing and learning new things every day (they are 1 and 3 years old, respectively). But soon there will be time to enjoy my hobbies together with them, playing music and painting together. And all of this will be even more joyful!
Autophagy Volume 10 Issue 2
©2014 Landes Bioscience. Do not distribute.
Autophagy 2014.10:188-191.
Why do you study autophagy? During my first postdoc, I discovered the HSPB8-HSPA8/Hsc70-BAG3 complex and its role in autophagy-mediated clearance of aggregate-prone proteins. At that time the knowledge about the interplay between the protein quality control system and autophagy was still limited, while the potential therapeutic application of autophagy stimulation to combat aggregate-prone neurodegenerative diseases was becoming more and more evident (e.g., the work of Prof D Rubinsztein, University of Cambridge). Besides, mutations in HSPB8 and BAG3 cause muscular and neuromuscular diseases and deregulated autophagy, and altered client targeting and clearance may contribute to these diseases.
autophagy community
cell cycle news & views
Davide Malagoli Email: [email protected]
Model system Currently working on insect cell cultures (from the fruit fly Drosophila melanogaster and the gypsy moth Lymantria dispar) and molluscan hemocytes (from the apple snail Pomacea canaliculata)
Autophagy 2014.10:188-191.
Education and career 1999, degree in biology, University of Modena and Reggio Emilia, Modena, Italy. 2004, PhD, evolutionary biology, University of Modena and Reggio Emilia; advisor: Prof E Ottaviani. 2005–present, assistant professor, Department of Life Sciences, University of Modena and Reggio Emilia.
Why do you study autophagy? Life is based on adaptation, and adaptation relies on the capability to evolve new functions from existing components and pathways. In these respects, I find autophagy to be a paradigmatic process for a biologist. It involves several components and pathways, which may be involved also in functions totally distinct from autophagy. The balancing between cell survival and death is the extreme example of the potentialities of autophagy.
What do you hope to achieve in your scientific career? That’s a difficult question for an Italian researcher, right now. My lab has not the size or the grants to compete with the majority of the groups working on autophagy. I work in order to provide an original and high profile contribution to the field of autophagy, but I have to be realistic in terms of the scientific achievements I can reach. However, I do hope to give the opportunity to talented students to grow scientifically in my lab and soon
www.landesbioscience.com
become independent and good candidates for PhD or postdoctoral positions in larger and more competitive research groups. This has already happened and represented a gratifying achievement.
Which paper in your research field represents seminal work on autophagy? Berry DL, Baehrecke EH. Growth arrest and autophagy are required for salivary gland cell degradation in Drosophila. Cell 2007; 131:1137–48. Working on insect programmed cell death in lepidopteran larval cells, in 2006 we encountered for the first time autophagy in our model. We started to work in the direction to understand the overlap between autophagy and programmed cell death, and that represented a highly inspiring paper.
If you could meet any scientist, currently living or from the past, who would it be and why? I wish I could have met Stephen Jay Gould, and talk with him about development and evolution.
If you could start over and choose a different career, what would it be? Jazz guitar player and songwriter. I have been studying jazz guitar for more than 10 years. After my degree in biology I had to decide between focusing my energies on science or music. I have opted for a scientific career. There is a great similarity between biology and music. In both of them, starting from a few constant elements, numberless variations on a main theme can be developed.
What one scientific discovery do you wish you had made? Oh, there are several! If I have to choose one, however, I’d say it is the one that I feel I have not fully understood, yet: the uncertainty (or Heisenberg) principle.
Is teaching a substantial part of your current position? If so, what do you teach? Does it benefit your research, or benefit from your research? I am currently teaching comparative anatomy for biology students (one semester per year). Apparently it only marginally benefits from my research and vice versa, but I feel that teaching increases your knowledge and your potentialities as a researcher. At the same time, a researcher usually is at the cutting edge of knowledge, and teaching benefits from this situation.
Personal comments As with many other colleagues, I like my job and I dedicate a lot of time to the lab and manuscript writing. I nonetheless consider the remaining little spare time fundamental. I am the lucky father of 2 children and they require time and attention giving back smiles, hugs, fun, and a good reason to get up singing in the morning. Probably the best pleasure for me is to stay alone spending time on books, comics, aquariology, playing the guitar, walking, and fishing. However, I do not consider myself as a solitary person, and I am always ready for a barbecue or a dinner with friends and those I love.
Autophagy 189
©2014 Landes Bioscience. Do not distribute.
Research focus Soluble factors in invertebrate immunity and cell death
Paul A Ney Jude Children’s Research Hospital, Memphis, TN, USA. 2011–present, member, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.
Why do you study autophagy?
Research focus
Autophagy 2014.10:188-191.
Red blood cell development
Model systems Erythroid cells from mouse fetal liver and blood, Friend virus-infected splenic erythroblasts, and human cord blood CD34+ cells
Education and career 1978–1982, MD, University of WisconsinMadison, WI, USA. 1982–1985, resident, Internal Medicine, Case Western Reserve University, Cleveland, OH, USA. 1985–1988, fellow, Hematology-Oncology, University of Minnesota, Minneapolis, MN, USA. 1988–1994, postdoctoral fellow, Clinical Hematology Branch, NHLBI, NIH, Bethesda, MD, USA. 1994–2011, Assistant and Associate Member, Department of Biochemistry, St.
190
My research interest is red blood cell development and differentiation. Broadly, I am interested in cellular differentiation. I want to know how cells differentiate. Also, I want to know the reason why some types of cells survive for many years and others do not. Every specialized cell type can be thought of as its own model organism. For example, to optimize gas transport, red blood cells jettison their entire cohort of mitochondria at the penultimate stage of erythroid maturation. Thus, red blood cells can be used to study how cells identify, isolate, and eliminate unwanted subcellular organelles, a process about which little is known. Ultrastructurally, this process has features of autophagy, but genetically, in mammalian cells at least, it is more complex. We think this phenomenon is just one manifestation of a general cellular quality control mechanism. By studying mitochondrial clearance in red blood cells, we hope to gain insight into this generic process.
What do you think is a key question in the autophagy field?
to the canonical autophagy pathways defined in yeast. I think such pathways are involved in cellular remodeling during differentiation and the response to intracellular pathogens. Regarding the latter, it would be interesting to know if autophagy or autophagy-related processes are involved in establishing a symbiotic relationship between Wolbachia and filarial species.
If you could start over and choose a different career, what would it be? That is hard to say, but I enjoy manual activity. In this regard, being a scientist is like belonging to a trade. It requires that you master a certain set of skills and then be able to introduce something new into your product. Also, I like the idea of a naturalist—exploring the world with an eye for patterns and an open mind. Actually, there isn’t anything else I’d rather do than to be a scientist.
Personal comments My family and I moved from Memphis, TN to New York City 2 years ago. We enjoy exploring “the city,” and our teenage son and daughter are taking full advantage of their newfound freedom here. We return to the Mississippi River valley periodically, mostly Memphis and New Orleans. We also go skiing, whenever possible, in New England or the Rockies.
It will be important to elucidate autophagy-related processes that operate in parallel
Autophagy Volume 10 Issue 2
©2014 Landes Bioscience. Do not distribute.
Email: [email protected]
Joan S Steffan Research focus To find a treatment for Huntington disease
Model systems Mammalian cells in culture, transgenic flies, and mice
Autophagy 2014.10:188-191.
Education and career 1980, PhD, physiology and pharmacology, University of California, San Diego, La Jolla, CA, USA; advisor: Kurt Benirschke. 1980–2005, postgraduate researcher/specialist series, University of California, Irvine (UCI), USA; advisors: Lee McAlister-Henn, Masayasu Nomura, Leslie M Thompson. 2005–2011, assistant professor in residence, UCI. 2011–present, associate professor in residence, Department of Psychiatry and Human Behavior; fellow, Institute for Memory Impairments and Neurological Disorders, UCI.
Why do you study autophagy? The career path I have taken resulting in my study of autophagy has been circuitous. After receiving a BS in chemistry from Stanford University with undergraduate research in the laboratory of Leonard Hayflick, an authority on cellular aging, I entered graduate school at UCSD and became a reproductive endocrinologist in an attempt to emulate my father, Charles H Sawyer, a groundbreaking pioneer in the field of neuroendocrinology. With my PhD I moved to UCI where my husband, a UCSD-trained MD, matched for his internship/ residency in family medicine. We had 2 sons, and I became a postdoctoral fellow for Lee McAlister-Henn, a wonderful mentor who taught me yeast molecular genetics, protein chemistry, and molecular biology, and I knew I had found my scientific home and discipline— I had fallen in love with Saccharomyces cerevisiae as a model organism. Before the yeast genome was sequenced our group cloned, purified, and characterized the yeast isozymes of malate dehydrogenase and studied metabolism. In 1992 I was hired by Masayasu Nomura, famous for his work on the ribosome, to characterize the genes/proteins involved in RNA polymerase I transcription that his lab had isolated using yeast genetics; I analyzed
www.landesbioscience.com
protein structure/function to help define the yeast RNA polymerase I preinitiation complex, and embraced the field of transcription. In 1998 I left yeast genetics and I joined the UCI laboratory of my longtime dear friend Leslie Thompson. In 1993 Leslie was part of the collaborative group of human geneticists that cloned the gene mutated in Huntington disease (HD). HD is caused by expansion of a polyglutamine (polyQ) repeat within the protein HTT (Huntingtin) resulting in selective neurodegeneration of medium spiny neurons in the striatum and an accumulation of insoluble protein aggregates. Leslie recruited me to her laboratory to investigate my hypothesis that mutant HTT might have an impact on transcription. We began by demonstrating that mutant HTT could cause transcriptional dysregulation and that histone deacetylase inhibitors could slow neurodegeneration in transgenic fly and mouse models of HD, in collaboration with Larry Marsh and Gillian Bates. We then went on to demonstrate that HTT could be SUMO modified and that SUMOylation pathways could regulate HTT toxicity in flies. I received my own faculty position in the UCI Department of Psychiatry and Human Behavior at the age of 50 with tenure at 56, investigating how phosphorylation of the amino-terminal domain of HTT by the inflammatory kinase IKBKB/IKK could regulate its SUMOylation, ubiquitination, acetylation, cellular localization, and toxicity in cell culture. With the help of autophagy expert Ana Maria Cuervo we found that this phosphorylation event activated HTT clearance by the lysosome and the proteasome, and with X William Yang we showed that mimicking this phosphorylation in the context of full-length mutant HTT in mice could abolish HD pathogenesis in vivo. Experience from my varied career path led me to hypothesize that the HTT protein itself might play a role in autophagy that becomes impaired with expansion of the polyQ repeat, declines with aging, and is activated by its phosphorylation under nutrient-rich conditions. I started aligning the HTT protein with yeast autophagy proteins and found weak
similarity between domains of HTT and Atg23, Vac8 and Atg11, 3 yeast proteins involved in nutrient-rich selective autophagy. My research is now focused on defining a selective autophagic role for the HTT protein in striatum, and how this role may be modulated by HTT posttranslational modification/metabolism and with HTT mutation. My life has come full circle, where my experience in aging research, endocrinology, yeast genetics, metabolism, transcription, and neurobiology has united to focus on a possible role for wild-type HTT protein in autophagy that may be relevant to aging, neurodegeneration, and cancer and be a useful therapeutic target in the treatment of all these conditions.
What do you think is a key question in the autophagy field? Are functional homologs of the yeast selective autophagy scaffold protein Atg11 present in mammalian cells?
Personal comments In my free time I like to run outside in the fresh air. I realized back in graduate school that my brain worked better and I just felt better in general after an hour of daily running while listening to my favorite music. Despite all the demands of life, my daily run became and continues to be a priority—it is my time to sort things out and de-stress. I have planned my best experiments while running in beautiful Laguna Beach, CA, where I live, 15 min away from my UCI laboratory.
Autophagy 191
©2014 Landes Bioscience. Do not distribute.
Email: [email protected]
Autophagy Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/kaup20
Autophagy researchers Published online: 02 Dec 2013.
Click for updates To cite this article: (2014) Autophagy researchers, Autophagy, 10:2, 188-191, DOI: 10.4161/auto.27182 To link to this article: http://dx.doi.org/10.4161/auto.27182
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
autophagy community
cell cycle news & views
Autophagy 10:1, 188–191; February 2014; © 2014 Landes Bioscience
Autophagy researchers Serena Carra Email: [email protected]
Research focus Molecular chaperones, protein homeostasis, and neurodegeneration.
Model system Mammalian cells, Drosophila Schneider 2 (S2) cells and Drosophila melanogaster transgenic lines overexpressing or downregulating molecular chaperones.
Education and career 1998, master’s degree, chemical and pharmaceutical sciences, University of Modena, Modena, Italy; advisor: Prof. Nicoletta Brunello. 2000–2004, PhD, neurobiology, University of Catania, Roma and Pavia, Italy; advisors: Prof Roberto Federico Villa and Prof Nicoletta Brunello; 2000–2001, research fellow, Centre de Recherche Hospitalier Université Laval (CHUL), Québec, Canada; advisor: Prof Nicholas Barden; 2004–2007, postdoctoral fellow, Centre de Recherche L’Hôtel-Dieu de Québec, Laval University, Québec, Canada; advisor: Prof Jacques Landry; 2007–2009, postdoctoral fellow, University Medical Center Groningen, The Netherlands; advisor: Prof Harm H Kampinga; 2009–2011, assistant professor, University Medical Center Groningen; 2011–present, assistant professor, University of Modena and Reggio Emilia, Modena, Italy.
188
What do you think is a key question in the autophagy field? Nowadays thanks to the efforts of a number of research groups, we know that several molecular chaperone complexes, including the HSPB8-HSPA8-BAG3 complex, can work in concert with the so-called autophagy receptors (e.g. SQSTM1/p62) and can directly interact with motor proteins to specifically deliver misfolded aggregate-prone substrates to the autophagic vacuoles for degradation. However, how such specificity is achieved is still largely unknown. Understanding at the molecular level how protein quality control and autophagy cooperate to ensure such specificity and to maintain protein homeostasis is crucial and will have a great impact on a number of pathological conditions where autophagy is needed/defective or even “hijacked” (e.g., viral infection).
Why is the field of autophagy important to you? Autophagy-mediated degradation of specific misfolded clients is a crucial step for the maintenance of proteostasis, whose deregulation is associated with
pathological conditions as diverse as neurodegenerative diseases, motor neuron diseases, and aging.
Is there a key experiment/finding that stands out in your mind with regard to autophagy? The discovery of the autophagic receptor proteins such as SQSTM1 has challenged the concept of autophagy as a bulk degradation process and has provided mechanistic insight into the high degree of specificity of cargo delivery to, and degradation by, the autophagic pathway.
Which paper(s) in your research field represents seminal work on autophagy? Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R, Yokoyama M, Mishima K, Saito I, Okano H, Mizushima N. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 2006; 441, 885–9 Komatsu M, Waguri S, Chiba T, Murata S, Iwata JI, Tanida I, Ueno T, Koike M, Uchiyama Y, Kominami E, Tanaka K. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 2006; 441, 880–4
Personal comments In my free time I like to sit on my sofa and listen to jazz and classical music. I also enjoy playing violin (I studied at the music school when I was a teenager). I have been oil painting on and off since nearly 20 years and I still love it. My paintings have no particular style: they differ so much in subject, and colors and they more reflect an impression, a mood. At present, I mainly enjoy being a mum and seeing my 2 lovely sons growing and learning new things every day (they are 1 and 3 years old, respectively). But soon there will be time to enjoy my hobbies together with them, playing music and painting together. And all of this will be even more joyful!
Autophagy Volume 10 Issue 2
©2014 Landes Bioscience. Do not distribute.
Autophagy 2014.10:188-191.
Why do you study autophagy? During my first postdoc, I discovered the HSPB8-HSPA8/Hsc70-BAG3 complex and its role in autophagy-mediated clearance of aggregate-prone proteins. At that time the knowledge about the interplay between the protein quality control system and autophagy was still limited, while the potential therapeutic application of autophagy stimulation to combat aggregate-prone neurodegenerative diseases was becoming more and more evident (e.g., the work of Prof D Rubinsztein, University of Cambridge). Besides, mutations in HSPB8 and BAG3 cause muscular and neuromuscular diseases and deregulated autophagy, and altered client targeting and clearance may contribute to these diseases.
autophagy community
cell cycle news & views
Davide Malagoli Email: [email protected]
Model system Currently working on insect cell cultures (from the fruit fly Drosophila melanogaster and the gypsy moth Lymantria dispar) and molluscan hemocytes (from the apple snail Pomacea canaliculata)
Autophagy 2014.10:188-191.
Education and career 1999, degree in biology, University of Modena and Reggio Emilia, Modena, Italy. 2004, PhD, evolutionary biology, University of Modena and Reggio Emilia; advisor: Prof E Ottaviani. 2005–present, assistant professor, Department of Life Sciences, University of Modena and Reggio Emilia.
Why do you study autophagy? Life is based on adaptation, and adaptation relies on the capability to evolve new functions from existing components and pathways. In these respects, I find autophagy to be a paradigmatic process for a biologist. It involves several components and pathways, which may be involved also in functions totally distinct from autophagy. The balancing between cell survival and death is the extreme example of the potentialities of autophagy.
What do you hope to achieve in your scientific career? That’s a difficult question for an Italian researcher, right now. My lab has not the size or the grants to compete with the majority of the groups working on autophagy. I work in order to provide an original and high profile contribution to the field of autophagy, but I have to be realistic in terms of the scientific achievements I can reach. However, I do hope to give the opportunity to talented students to grow scientifically in my lab and soon
www.landesbioscience.com
become independent and good candidates for PhD or postdoctoral positions in larger and more competitive research groups. This has already happened and represented a gratifying achievement.
Which paper in your research field represents seminal work on autophagy? Berry DL, Baehrecke EH. Growth arrest and autophagy are required for salivary gland cell degradation in Drosophila. Cell 2007; 131:1137–48. Working on insect programmed cell death in lepidopteran larval cells, in 2006 we encountered for the first time autophagy in our model. We started to work in the direction to understand the overlap between autophagy and programmed cell death, and that represented a highly inspiring paper.
If you could meet any scientist, currently living or from the past, who would it be and why? I wish I could have met Stephen Jay Gould, and talk with him about development and evolution.
If you could start over and choose a different career, what would it be? Jazz guitar player and songwriter. I have been studying jazz guitar for more than 10 years. After my degree in biology I had to decide between focusing my energies on science or music. I have opted for a scientific career. There is a great similarity between biology and music. In both of them, starting from a few constant elements, numberless variations on a main theme can be developed.
What one scientific discovery do you wish you had made? Oh, there are several! If I have to choose one, however, I’d say it is the one that I feel I have not fully understood, yet: the uncertainty (or Heisenberg) principle.
Is teaching a substantial part of your current position? If so, what do you teach? Does it benefit your research, or benefit from your research? I am currently teaching comparative anatomy for biology students (one semester per year). Apparently it only marginally benefits from my research and vice versa, but I feel that teaching increases your knowledge and your potentialities as a researcher. At the same time, a researcher usually is at the cutting edge of knowledge, and teaching benefits from this situation.
Personal comments As with many other colleagues, I like my job and I dedicate a lot of time to the lab and manuscript writing. I nonetheless consider the remaining little spare time fundamental. I am the lucky father of 2 children and they require time and attention giving back smiles, hugs, fun, and a good reason to get up singing in the morning. Probably the best pleasure for me is to stay alone spending time on books, comics, aquariology, playing the guitar, walking, and fishing. However, I do not consider myself as a solitary person, and I am always ready for a barbecue or a dinner with friends and those I love.
Autophagy 189
©2014 Landes Bioscience. Do not distribute.
Research focus Soluble factors in invertebrate immunity and cell death
Paul A Ney Jude Children’s Research Hospital, Memphis, TN, USA. 2011–present, member, Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.
Why do you study autophagy?
Research focus
Autophagy 2014.10:188-191.
Red blood cell development
Model systems Erythroid cells from mouse fetal liver and blood, Friend virus-infected splenic erythroblasts, and human cord blood CD34+ cells
Education and career 1978–1982, MD, University of WisconsinMadison, WI, USA. 1982–1985, resident, Internal Medicine, Case Western Reserve University, Cleveland, OH, USA. 1985–1988, fellow, Hematology-Oncology, University of Minnesota, Minneapolis, MN, USA. 1988–1994, postdoctoral fellow, Clinical Hematology Branch, NHLBI, NIH, Bethesda, MD, USA. 1994–2011, Assistant and Associate Member, Department of Biochemistry, St.
190
My research interest is red blood cell development and differentiation. Broadly, I am interested in cellular differentiation. I want to know how cells differentiate. Also, I want to know the reason why some types of cells survive for many years and others do not. Every specialized cell type can be thought of as its own model organism. For example, to optimize gas transport, red blood cells jettison their entire cohort of mitochondria at the penultimate stage of erythroid maturation. Thus, red blood cells can be used to study how cells identify, isolate, and eliminate unwanted subcellular organelles, a process about which little is known. Ultrastructurally, this process has features of autophagy, but genetically, in mammalian cells at least, it is more complex. We think this phenomenon is just one manifestation of a general cellular quality control mechanism. By studying mitochondrial clearance in red blood cells, we hope to gain insight into this generic process.
What do you think is a key question in the autophagy field?
to the canonical autophagy pathways defined in yeast. I think such pathways are involved in cellular remodeling during differentiation and the response to intracellular pathogens. Regarding the latter, it would be interesting to know if autophagy or autophagy-related processes are involved in establishing a symbiotic relationship between Wolbachia and filarial species.
If you could start over and choose a different career, what would it be? That is hard to say, but I enjoy manual activity. In this regard, being a scientist is like belonging to a trade. It requires that you master a certain set of skills and then be able to introduce something new into your product. Also, I like the idea of a naturalist—exploring the world with an eye for patterns and an open mind. Actually, there isn’t anything else I’d rather do than to be a scientist.
Personal comments My family and I moved from Memphis, TN to New York City 2 years ago. We enjoy exploring “the city,” and our teenage son and daughter are taking full advantage of their newfound freedom here. We return to the Mississippi River valley periodically, mostly Memphis and New Orleans. We also go skiing, whenever possible, in New England or the Rockies.
It will be important to elucidate autophagy-related processes that operate in parallel
Autophagy Volume 10 Issue 2
©2014 Landes Bioscience. Do not distribute.
Email: [email protected]
Joan S Steffan Research focus To find a treatment for Huntington disease
Model systems Mammalian cells in culture, transgenic flies, and mice
Autophagy 2014.10:188-191.
Education and career 1980, PhD, physiology and pharmacology, University of California, San Diego, La Jolla, CA, USA; advisor: Kurt Benirschke. 1980–2005, postgraduate researcher/specialist series, University of California, Irvine (UCI), USA; advisors: Lee McAlister-Henn, Masayasu Nomura, Leslie M Thompson. 2005–2011, assistant professor in residence, UCI. 2011–present, associate professor in residence, Department of Psychiatry and Human Behavior; fellow, Institute for Memory Impairments and Neurological Disorders, UCI.
Why do you study autophagy? The career path I have taken resulting in my study of autophagy has been circuitous. After receiving a BS in chemistry from Stanford University with undergraduate research in the laboratory of Leonard Hayflick, an authority on cellular aging, I entered graduate school at UCSD and became a reproductive endocrinologist in an attempt to emulate my father, Charles H Sawyer, a groundbreaking pioneer in the field of neuroendocrinology. With my PhD I moved to UCI where my husband, a UCSD-trained MD, matched for his internship/ residency in family medicine. We had 2 sons, and I became a postdoctoral fellow for Lee McAlister-Henn, a wonderful mentor who taught me yeast molecular genetics, protein chemistry, and molecular biology, and I knew I had found my scientific home and discipline— I had fallen in love with Saccharomyces cerevisiae as a model organism. Before the yeast genome was sequenced our group cloned, purified, and characterized the yeast isozymes of malate dehydrogenase and studied metabolism. In 1992 I was hired by Masayasu Nomura, famous for his work on the ribosome, to characterize the genes/proteins involved in RNA polymerase I transcription that his lab had isolated using yeast genetics; I analyzed
www.landesbioscience.com
protein structure/function to help define the yeast RNA polymerase I preinitiation complex, and embraced the field of transcription. In 1998 I left yeast genetics and I joined the UCI laboratory of my longtime dear friend Leslie Thompson. In 1993 Leslie was part of the collaborative group of human geneticists that cloned the gene mutated in Huntington disease (HD). HD is caused by expansion of a polyglutamine (polyQ) repeat within the protein HTT (Huntingtin) resulting in selective neurodegeneration of medium spiny neurons in the striatum and an accumulation of insoluble protein aggregates. Leslie recruited me to her laboratory to investigate my hypothesis that mutant HTT might have an impact on transcription. We began by demonstrating that mutant HTT could cause transcriptional dysregulation and that histone deacetylase inhibitors could slow neurodegeneration in transgenic fly and mouse models of HD, in collaboration with Larry Marsh and Gillian Bates. We then went on to demonstrate that HTT could be SUMO modified and that SUMOylation pathways could regulate HTT toxicity in flies. I received my own faculty position in the UCI Department of Psychiatry and Human Behavior at the age of 50 with tenure at 56, investigating how phosphorylation of the amino-terminal domain of HTT by the inflammatory kinase IKBKB/IKK could regulate its SUMOylation, ubiquitination, acetylation, cellular localization, and toxicity in cell culture. With the help of autophagy expert Ana Maria Cuervo we found that this phosphorylation event activated HTT clearance by the lysosome and the proteasome, and with X William Yang we showed that mimicking this phosphorylation in the context of full-length mutant HTT in mice could abolish HD pathogenesis in vivo. Experience from my varied career path led me to hypothesize that the HTT protein itself might play a role in autophagy that becomes impaired with expansion of the polyQ repeat, declines with aging, and is activated by its phosphorylation under nutrient-rich conditions. I started aligning the HTT protein with yeast autophagy proteins and found weak
similarity between domains of HTT and Atg23, Vac8 and Atg11, 3 yeast proteins involved in nutrient-rich selective autophagy. My research is now focused on defining a selective autophagic role for the HTT protein in striatum, and how this role may be modulated by HTT posttranslational modification/metabolism and with HTT mutation. My life has come full circle, where my experience in aging research, endocrinology, yeast genetics, metabolism, transcription, and neurobiology has united to focus on a possible role for wild-type HTT protein in autophagy that may be relevant to aging, neurodegeneration, and cancer and be a useful therapeutic target in the treatment of all these conditions.
What do you think is a key question in the autophagy field? Are functional homologs of the yeast selective autophagy scaffold protein Atg11 present in mammalian cells?
Personal comments In my free time I like to run outside in the fresh air. I realized back in graduate school that my brain worked better and I just felt better in general after an hour of daily running while listening to my favorite music. Despite all the demands of life, my daily run became and continues to be a priority—it is my time to sort things out and de-stress. I have planned my best experiments while running in beautiful Laguna Beach, CA, where I live, 15 min away from my UCI laboratory.
Autophagy 191
©2014 Landes Bioscience. Do not distribute.
Email: [email protected]
