autophagy community
cell cycle news & views
Autophagy 10:1, 3–6; January 2014; © 2014 Landes Bioscience
Autophagy researchers Ian G Ganley
Research focus The signaling pathways that regulate autophagy
Model system Mammalian tissue culture
Education and career 1997, master’s degree, biochemistry, University of Oxford, UK; advisor: Lynne Cox. 2002, PhD, University of Cambridge, UK; advisor: Nicholas Ktistakis. 2002–2005, postdoctoral fellow, Stanford University, Stanford, CA, USA; advisor: Suzanne Pfeffer. 2007– 2010, research fellow, Memorial SloanKettering Cancer Center, New York, NY, USA; advisor: Xuejun Jiang. 2010–present, program leader, MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, UK.
Why do you study autophagy? Growing up I always wanted to be an astronaut (I still do) and visit new planets. However, given the practicalities and lack of opportunities in this field, I decided to pursue other career options. It was during the
latter stages of high school that I remember reading biology textbooks showing images of scanning and transmission election micrographs. These detailed weird and wondrous membrane structures inside the cell captured my imagination and brought to mind the extra-terrestrial. So, I decided I might indeed have a career exploring “alien” worlds, but subcellular ones rather than those in the cosmos. I am fascinated as to how these intracellular membrane compartments form and communicate with each other and was therefore attracted to autophagy as the membranous autophagosome can apparently form de novo. This gives us a great system to look at the fundamentals behind compartment formation within the cell. So here I am, trying to look at the signals that lead to autophagosome formation.
What do you think is a key question in the autophagy field? Is autophagy modulation going to be beneficial in disease therapy? Autophagy dysregulation, be it increased or impaired, has been linked to many different human diseases though whether this is a cause or consequence is not clear in the vast majority of cases. In order to answer this question I think it is essential to develop better chemicals that are specific autophagy inhibitors. Currently we rely on compounds such as chloroquine or bafilomycin A1 that, while inhibiting autophagy, block lysosomal function (and other things)—an end point of many intracellular trafficking pathways. This makes it very difficult to validate autophagy as a viable approach in treating disease.
Which paper in your research field represents seminal work on autophagy? For me, I think one of the most important papers was from the Ohsumi laboratory
concerning the mechanism of autophagy inhibition by TOR kinase (Kamada et al., JCB 2000). This paper was the first to show that a signaling pathway directly interacts with the core autophagy machinery to control autophagosome formation. This work placed the Atg1 complex at the apex of autophagy induction, and how TOR phosphorylates and regulates the Atg1Atg13 interaction is still the best-understood mechanism of autophagy induction (which is largely conserved in mammalian cells). It is possible that removal of these inhibitory TOR/ MTOR modifications is a fundamental requirement for all forms of autophagy, or alternate, overriding mechanisms may exist: these are some of the possibilities we are interested in exploring.
If you could meet any scientist, currently living or from the past, who would it be and why? I think this would be a close call between George Palade and Christian de Duve who shared the Nobel Prize with Albert Claude in 1974. Not only did they pioneer electron microscopy, but also cell fractionation, and with this they established the importance of cellular compartmentalization. They are the grandfathers of our field. Palade’s series of papers elucidating the secretory pathway are some my favorites.
Personal comments I used to have an active personal life ranging from hiking and snowboarding to scuba diving and motorcycle riding. However, my wife and I decided this was not enough and so had 2 lovely daughters (5 and 3 years old). They run us both ragged, but are without a doubt the most precious things in our lives. What little time I have left is spent with family exploring the beautiful Scottish countryside that is right on our doorstep.
www.landesbioscience.com Autophagy
3
©2014 Landes Bioscience. Do not distribute.
Email: [email protected]
cell cycle news & views
Nathalie M Mazure Email: [email protected]
Model system Human cancer and normal cell lines, spheroids, mice
Education and career 1993, PhD, applied biology and genetics, University of Technology of Compiegne, France; advisor: Dr N Truffaut. 1994–1997, postdoctoral fellow, hypoxia and radiation oncology, Stanford University, CA, USA; advisor: Dr A Giaccia. 1997–2001, postdoctoral fellow, Centre National de la Recherche Scientifique (CNRS), Meudon, France; advisor: Dr JL Danan. 2001–2010, postdoctoral fellow, CNRS, Nice, France; advisor: Dr J Pouysségur. 2010– present, senior scientist, CNRS, Nice, France.
How did you get into the autophagy field? Simply by chance. I worked in the field of hypoxia for nearly 20 years and became interested in BNIP3, a target gene of HIF1A [hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)]. At this time BNIP3 was characterized as a proapoptotic protein; however, we noted that BNIP3 is expressed in tissues in areas of no cell death. Expression occurs very early along the gradient of hypoxia, which forms between the blood vessel and necrotic zones. Thus, we questioned the real role/function of BNIP3 under hypoxic conditions in cancer cells. In our cellular models (LS174 colon adenocarcinoma and HeLa cervix cancer cell lines), overexpression of BNIP3 does not bring about apoptosis. Moreover, invalidation (siRNA) in hypoxia results in cell death. We therefore deduced that BNIP3 and its close cousin BNIP3L possess
4
a “protective” role in tumor cells. It was at this time that we became interested in autophagy. It was a real challenge to understand the molecular mechanisms involved. Have we really understood? I’m not sure.
Why do you study autophagy? In recent years, I became interested in the resistance to cell death of hypoxic cells. Too often, people think that hypoxia kills cells. However, hypoxia stimulates survival of tumor cells by promoting autophagy. Yet, blocking autophagy in hypoxia does not lead to massive killing of tumor cells—it kills only 10–20% of the cells, at least over short times. It is this insidious side (that autophagy can kill cells or help them survive) that fascinates me. Like it or not, we have to deal with autophagy.
Why is the field of autophagy important to you? The last few years of trying to understand the inner workings of autophagy in hypoxia have opened other doors to other subjects. Although I became less attached to autophagy, it is still important to me, because whatever you do, autophagy influences all your experimental data. I used to work without paying attention to autophagy, but now I cannot work the same way. Especially when you are interested in cell survival. The duality of autophagy also interests me a lot. Should we block autophagy and its “survival” side or should we push it to the extreme and provoke cell death? The answer is still not clear to me and the action window for one or the other solution is probably not very large.
surface of the Earth. However, if by the end of my career I discover a tumor marker that can direct patients to a particular treatment, saving them time in the fight against the disease, then I think I would have fulfilled my role as a researcher. Finding time...always…a little more...and push the limits!
Personal comments I am a wife and a mother of a 17-year-old teenager. We have a dog, a cat, and a goldfish. When my son was a baby and I could not remember stories in the evening to send him to sleep, so I told him stories about hypoxia and mitochondria, of nice cells and nasty cells. My son is not a scientist—I wonder why!! I need challenges, even in my everyday life. This is why I decided to go horseback riding, even though I had never mounted a horse before. Though, learning to remount a horse after a bad fall is a bit like doing research, right?
What do you hope to achieve in your scientific career? I do not pretend that I alone will find the answer that eradicates cancer from the
Autophagy Volume 10 Issue 1
©2014 Landes Bioscience. Do not distribute.
Research focus Resistance to cell death of hypoxic tumor cells
Takeshi Noda
Research focus The regulatory mechanisms of autophagy and their application to dentistry
Model system Yeast (Saccharomyces cerevisiae) and mammalian cultured cells
Education and career 1996, PhD in science, University of Tokyo, Tokyo, Japan; advisor: Yoshinori Ohsumi. 1996– 2006, assistant professor, National Institute for Basic Biology, Okazaki, Japan. 2003–2005, visiting scientist, University of California, San Diego, La Jolla, California; advisor: Scott Emr. 2006– 2010, associate professor, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan. 2010–2012, associate professor, Graduate School of Frontier Biosciences, Osaka University. 2012–present, professor, Graduate School of Dentistry, Osaka University.
Why do you study autophagy? Just before I entered graduate school, my advisor, Yoshinori Ohsumi, had discovered
www.landesbioscience.com
autophagy in yeast, and I and another graduate student, Miki Tsukada, started to work on the topic. The first yeast autophagy paper was published the following year (Takeshige et al., J Cell Biol. 1992). Since then, I have spent most of my scientific career exploring autophagy.
without starvation. This experiment uncovered not only the critical role of TOR in the regulation of autophagy, but also the more basic idea that protein synthesis and protein degradation are controlled like the two sides of a coin by a single regulator.
What do you think is a key question in the autophagy field?
Which paper in your research field represents seminal work on autophagy?
As I became involved in the study of autophagy, I suspected that the degradation mechanism must be elucidated to fully understand life. My idea was correct, and today there is no doubt regarding the importance of autophagy in a number of physiological aspects. I am currently interested in how other cellular processes regulate autophagy and, in turn, how autophagy regulates other cellular processes.
Although I was involved with it, I consider the first yeast autophagy paper (Takeshige et al., J Cell Biol. 1992) to be a seminal paper. It is mostly limited to a description of the phenomenon. Today journals often request a great deal of data regarding molecular mechanisms and their physiological importance, especially if the journal is highly ranked. I would like to stress, however, that the first descriptions of novel phenomena are quite critical, especially in the early days of a new field in science.
Why is the field of autophagy important to you? As a basic life scientist, it is quite valuable that I have been closely involved in the expansion of the autophagy field. In 1991, only a limited number of groups were investigating autophagy, but nowadays many researchers are addressing the many issues related to autophagy. It’s quite exciting, and I propose that we need to evaluate the science using a long-term view. I would also like to develop, or at least be involved in the development of, another field similar to autophagy as the next challenge.
What one scientific discovery do you wish you had made? When I solve a puzzle hidden in nature, I experience the true pleasure and excitement of science. There is often beauty to be found in a hidden answer, and that is the supreme satisfaction. In that sense, I like Jacob and Monod’s operon theory.
Personal comments Besides science, it is truly exciting to me when I imagine how my 6-year-old boy looks at the world and how he feels about everything.
Is there a key experiment/finding that stands out in your mind with regard to autophagy? One simple but important experiment is that in which rapamycin was added to the yeast medium, and autophagy was induced
Autophagy 5
©2014 Landes Bioscience. Do not distribute.
Email: [email protected]
Jianhua Zhang Email: [email protected]
Model system Cells and animals
If you could meet any scientist, currently living or from the past, who would it be and why? I would like to meet Charles Darwin. It must be a fascinating experience to observe and study the behaviors and morphologies of so many species of animals.
Education and career 1991, PhD, University of Texas Southwestern Medical Center at Dallas, TX, USA; advisor: Joseph Sambrook. 1991–1995, postdoc, Whitehead Institute for Biomedical Research, Cambridge, MA, USA; advisor: Richard Young. 1996–2005, research assistant professor, University of Cincinnati College of Medicine, Cincinnati, OH, USA; 2005–present, assistant and associate professor, University of Alabama at Birmingham, AL, USA.
If you could start over and choose a different career, what would it be? Biomedical research still would rank at the top. I might see myself being interested in seismology.
What one scientific discovery do you wish you had made? I wish I had discovered oxygen. It is such an important molecule and the first simple experiments clearly showed it was essential for life.
Why do you study autophagy? I started to work on autophagy due to an interest in Parkinson disease and an accidental finding from a collaborative study on a role of lysosomal CTSD/cathepsin D in the degradation of SNCA/α-synuclein. The study led us to asking more specific questions regarding the checkpoints of autophagy regulation in response to distinctive signals, and in degrading excessive, unwanted, or toxic species of lipids, proteins, and organelles.
Which paper in your research field represents seminal work on autophagy? Two back-to-back papers come to mind: Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice By Hara et al., Nature 2006; and Loss of autophagy in the central nervous system causes neurodegeneration in mice by Komatsu et al., Nature 2006. They established an important role of autophagy in clearance of protein aggregates in the brain and in neuronal survival.
6
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? Teaching occupies a substantial part of my current position. First, I give lectures on cell death in neurodevelopment, cell death in cancer, neuronal bioenergetics, evolution of the brain, and Parkinson disease whenever a graduate course needs me. These lectures force me, in a good way, to think about autophagy, cell death, and the brain from different perspectives. Second, I am co-course director with a few other faculty members on a seminar practice in neuroscience course that helps students give 45 min presentations on their work. We also ask each student to ask questions in every class. This class is great in that it not only helps the students and the faculty members to discuss their respective work, but also drastically improves the students’ understanding of the literature, critical thinking, and oral presentation skills. In addition, it reminds the faculty members how not to do a poor job
when we give presentations. Third, I co-direct a journal club on autophagy that helps both the students and myself to keep up with the current literature and discuss where the field is headed. I also direct an autophagy in health and diseases class to cover the key concepts and signaling pathways in autophagy, which gives a broader overview of the history and landmarks in autophagy research. Last, but not least, I have been mentoring graduate students and postdocs in my lab, working on various aspects of autophagy and this helps make the research interesting.
Personal comments I am married to a scientist working on the mitochondrion. We enjoy traveling, interacting with people of different cultural backgrounds, visiting historical sites, observing animals in diverse living conditions, and savoring ethnic food. We take piano lessons and practice daily. On weekends, we take short walks, go to concerts and movies, grow many different vegetables in the garden, and entertain friends. I also take weekly Indian dance lessons, and sometimes participate in performances. I have an obsession on keeping the house clean and tidy, which might be a byproduct of studying autophagy.
Autophagy Volume 10 Issue 1
©2014 Landes Bioscience. Do not distribute.
Research focus Autophagy in neuronal survival, function, and redox bioenergetics
cell cycle news & views
Autophagy 10:1, 3–6; January 2014; © 2014 Landes Bioscience
Autophagy researchers Ian G Ganley
Research focus The signaling pathways that regulate autophagy
Model system Mammalian tissue culture
Education and career 1997, master’s degree, biochemistry, University of Oxford, UK; advisor: Lynne Cox. 2002, PhD, University of Cambridge, UK; advisor: Nicholas Ktistakis. 2002–2005, postdoctoral fellow, Stanford University, Stanford, CA, USA; advisor: Suzanne Pfeffer. 2007– 2010, research fellow, Memorial SloanKettering Cancer Center, New York, NY, USA; advisor: Xuejun Jiang. 2010–present, program leader, MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, UK.
Why do you study autophagy? Growing up I always wanted to be an astronaut (I still do) and visit new planets. However, given the practicalities and lack of opportunities in this field, I decided to pursue other career options. It was during the
latter stages of high school that I remember reading biology textbooks showing images of scanning and transmission election micrographs. These detailed weird and wondrous membrane structures inside the cell captured my imagination and brought to mind the extra-terrestrial. So, I decided I might indeed have a career exploring “alien” worlds, but subcellular ones rather than those in the cosmos. I am fascinated as to how these intracellular membrane compartments form and communicate with each other and was therefore attracted to autophagy as the membranous autophagosome can apparently form de novo. This gives us a great system to look at the fundamentals behind compartment formation within the cell. So here I am, trying to look at the signals that lead to autophagosome formation.
What do you think is a key question in the autophagy field? Is autophagy modulation going to be beneficial in disease therapy? Autophagy dysregulation, be it increased or impaired, has been linked to many different human diseases though whether this is a cause or consequence is not clear in the vast majority of cases. In order to answer this question I think it is essential to develop better chemicals that are specific autophagy inhibitors. Currently we rely on compounds such as chloroquine or bafilomycin A1 that, while inhibiting autophagy, block lysosomal function (and other things)—an end point of many intracellular trafficking pathways. This makes it very difficult to validate autophagy as a viable approach in treating disease.
Which paper in your research field represents seminal work on autophagy? For me, I think one of the most important papers was from the Ohsumi laboratory
concerning the mechanism of autophagy inhibition by TOR kinase (Kamada et al., JCB 2000). This paper was the first to show that a signaling pathway directly interacts with the core autophagy machinery to control autophagosome formation. This work placed the Atg1 complex at the apex of autophagy induction, and how TOR phosphorylates and regulates the Atg1Atg13 interaction is still the best-understood mechanism of autophagy induction (which is largely conserved in mammalian cells). It is possible that removal of these inhibitory TOR/ MTOR modifications is a fundamental requirement for all forms of autophagy, or alternate, overriding mechanisms may exist: these are some of the possibilities we are interested in exploring.
If you could meet any scientist, currently living or from the past, who would it be and why? I think this would be a close call between George Palade and Christian de Duve who shared the Nobel Prize with Albert Claude in 1974. Not only did they pioneer electron microscopy, but also cell fractionation, and with this they established the importance of cellular compartmentalization. They are the grandfathers of our field. Palade’s series of papers elucidating the secretory pathway are some my favorites.
Personal comments I used to have an active personal life ranging from hiking and snowboarding to scuba diving and motorcycle riding. However, my wife and I decided this was not enough and so had 2 lovely daughters (5 and 3 years old). They run us both ragged, but are without a doubt the most precious things in our lives. What little time I have left is spent with family exploring the beautiful Scottish countryside that is right on our doorstep.
www.landesbioscience.com Autophagy
3
©2014 Landes Bioscience. Do not distribute.
Email: [email protected]
cell cycle news & views
Nathalie M Mazure Email: [email protected]
Model system Human cancer and normal cell lines, spheroids, mice
Education and career 1993, PhD, applied biology and genetics, University of Technology of Compiegne, France; advisor: Dr N Truffaut. 1994–1997, postdoctoral fellow, hypoxia and radiation oncology, Stanford University, CA, USA; advisor: Dr A Giaccia. 1997–2001, postdoctoral fellow, Centre National de la Recherche Scientifique (CNRS), Meudon, France; advisor: Dr JL Danan. 2001–2010, postdoctoral fellow, CNRS, Nice, France; advisor: Dr J Pouysségur. 2010– present, senior scientist, CNRS, Nice, France.
How did you get into the autophagy field? Simply by chance. I worked in the field of hypoxia for nearly 20 years and became interested in BNIP3, a target gene of HIF1A [hypoxia inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)]. At this time BNIP3 was characterized as a proapoptotic protein; however, we noted that BNIP3 is expressed in tissues in areas of no cell death. Expression occurs very early along the gradient of hypoxia, which forms between the blood vessel and necrotic zones. Thus, we questioned the real role/function of BNIP3 under hypoxic conditions in cancer cells. In our cellular models (LS174 colon adenocarcinoma and HeLa cervix cancer cell lines), overexpression of BNIP3 does not bring about apoptosis. Moreover, invalidation (siRNA) in hypoxia results in cell death. We therefore deduced that BNIP3 and its close cousin BNIP3L possess
4
a “protective” role in tumor cells. It was at this time that we became interested in autophagy. It was a real challenge to understand the molecular mechanisms involved. Have we really understood? I’m not sure.
Why do you study autophagy? In recent years, I became interested in the resistance to cell death of hypoxic cells. Too often, people think that hypoxia kills cells. However, hypoxia stimulates survival of tumor cells by promoting autophagy. Yet, blocking autophagy in hypoxia does not lead to massive killing of tumor cells—it kills only 10–20% of the cells, at least over short times. It is this insidious side (that autophagy can kill cells or help them survive) that fascinates me. Like it or not, we have to deal with autophagy.
Why is the field of autophagy important to you? The last few years of trying to understand the inner workings of autophagy in hypoxia have opened other doors to other subjects. Although I became less attached to autophagy, it is still important to me, because whatever you do, autophagy influences all your experimental data. I used to work without paying attention to autophagy, but now I cannot work the same way. Especially when you are interested in cell survival. The duality of autophagy also interests me a lot. Should we block autophagy and its “survival” side or should we push it to the extreme and provoke cell death? The answer is still not clear to me and the action window for one or the other solution is probably not very large.
surface of the Earth. However, if by the end of my career I discover a tumor marker that can direct patients to a particular treatment, saving them time in the fight against the disease, then I think I would have fulfilled my role as a researcher. Finding time...always…a little more...and push the limits!
Personal comments I am a wife and a mother of a 17-year-old teenager. We have a dog, a cat, and a goldfish. When my son was a baby and I could not remember stories in the evening to send him to sleep, so I told him stories about hypoxia and mitochondria, of nice cells and nasty cells. My son is not a scientist—I wonder why!! I need challenges, even in my everyday life. This is why I decided to go horseback riding, even though I had never mounted a horse before. Though, learning to remount a horse after a bad fall is a bit like doing research, right?
What do you hope to achieve in your scientific career? I do not pretend that I alone will find the answer that eradicates cancer from the
Autophagy Volume 10 Issue 1
©2014 Landes Bioscience. Do not distribute.
Research focus Resistance to cell death of hypoxic tumor cells
Takeshi Noda
Research focus The regulatory mechanisms of autophagy and their application to dentistry
Model system Yeast (Saccharomyces cerevisiae) and mammalian cultured cells
Education and career 1996, PhD in science, University of Tokyo, Tokyo, Japan; advisor: Yoshinori Ohsumi. 1996– 2006, assistant professor, National Institute for Basic Biology, Okazaki, Japan. 2003–2005, visiting scientist, University of California, San Diego, La Jolla, California; advisor: Scott Emr. 2006– 2010, associate professor, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan. 2010–2012, associate professor, Graduate School of Frontier Biosciences, Osaka University. 2012–present, professor, Graduate School of Dentistry, Osaka University.
Why do you study autophagy? Just before I entered graduate school, my advisor, Yoshinori Ohsumi, had discovered
www.landesbioscience.com
autophagy in yeast, and I and another graduate student, Miki Tsukada, started to work on the topic. The first yeast autophagy paper was published the following year (Takeshige et al., J Cell Biol. 1992). Since then, I have spent most of my scientific career exploring autophagy.
without starvation. This experiment uncovered not only the critical role of TOR in the regulation of autophagy, but also the more basic idea that protein synthesis and protein degradation are controlled like the two sides of a coin by a single regulator.
What do you think is a key question in the autophagy field?
Which paper in your research field represents seminal work on autophagy?
As I became involved in the study of autophagy, I suspected that the degradation mechanism must be elucidated to fully understand life. My idea was correct, and today there is no doubt regarding the importance of autophagy in a number of physiological aspects. I am currently interested in how other cellular processes regulate autophagy and, in turn, how autophagy regulates other cellular processes.
Although I was involved with it, I consider the first yeast autophagy paper (Takeshige et al., J Cell Biol. 1992) to be a seminal paper. It is mostly limited to a description of the phenomenon. Today journals often request a great deal of data regarding molecular mechanisms and their physiological importance, especially if the journal is highly ranked. I would like to stress, however, that the first descriptions of novel phenomena are quite critical, especially in the early days of a new field in science.
Why is the field of autophagy important to you? As a basic life scientist, it is quite valuable that I have been closely involved in the expansion of the autophagy field. In 1991, only a limited number of groups were investigating autophagy, but nowadays many researchers are addressing the many issues related to autophagy. It’s quite exciting, and I propose that we need to evaluate the science using a long-term view. I would also like to develop, or at least be involved in the development of, another field similar to autophagy as the next challenge.
What one scientific discovery do you wish you had made? When I solve a puzzle hidden in nature, I experience the true pleasure and excitement of science. There is often beauty to be found in a hidden answer, and that is the supreme satisfaction. In that sense, I like Jacob and Monod’s operon theory.
Personal comments Besides science, it is truly exciting to me when I imagine how my 6-year-old boy looks at the world and how he feels about everything.
Is there a key experiment/finding that stands out in your mind with regard to autophagy? One simple but important experiment is that in which rapamycin was added to the yeast medium, and autophagy was induced
Autophagy 5
©2014 Landes Bioscience. Do not distribute.
Email: [email protected]
Jianhua Zhang Email: [email protected]
Model system Cells and animals
If you could meet any scientist, currently living or from the past, who would it be and why? I would like to meet Charles Darwin. It must be a fascinating experience to observe and study the behaviors and morphologies of so many species of animals.
Education and career 1991, PhD, University of Texas Southwestern Medical Center at Dallas, TX, USA; advisor: Joseph Sambrook. 1991–1995, postdoc, Whitehead Institute for Biomedical Research, Cambridge, MA, USA; advisor: Richard Young. 1996–2005, research assistant professor, University of Cincinnati College of Medicine, Cincinnati, OH, USA; 2005–present, assistant and associate professor, University of Alabama at Birmingham, AL, USA.
If you could start over and choose a different career, what would it be? Biomedical research still would rank at the top. I might see myself being interested in seismology.
What one scientific discovery do you wish you had made? I wish I had discovered oxygen. It is such an important molecule and the first simple experiments clearly showed it was essential for life.
Why do you study autophagy? I started to work on autophagy due to an interest in Parkinson disease and an accidental finding from a collaborative study on a role of lysosomal CTSD/cathepsin D in the degradation of SNCA/α-synuclein. The study led us to asking more specific questions regarding the checkpoints of autophagy regulation in response to distinctive signals, and in degrading excessive, unwanted, or toxic species of lipids, proteins, and organelles.
Which paper in your research field represents seminal work on autophagy? Two back-to-back papers come to mind: Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice By Hara et al., Nature 2006; and Loss of autophagy in the central nervous system causes neurodegeneration in mice by Komatsu et al., Nature 2006. They established an important role of autophagy in clearance of protein aggregates in the brain and in neuronal survival.
6
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? Teaching occupies a substantial part of my current position. First, I give lectures on cell death in neurodevelopment, cell death in cancer, neuronal bioenergetics, evolution of the brain, and Parkinson disease whenever a graduate course needs me. These lectures force me, in a good way, to think about autophagy, cell death, and the brain from different perspectives. Second, I am co-course director with a few other faculty members on a seminar practice in neuroscience course that helps students give 45 min presentations on their work. We also ask each student to ask questions in every class. This class is great in that it not only helps the students and the faculty members to discuss their respective work, but also drastically improves the students’ understanding of the literature, critical thinking, and oral presentation skills. In addition, it reminds the faculty members how not to do a poor job
when we give presentations. Third, I co-direct a journal club on autophagy that helps both the students and myself to keep up with the current literature and discuss where the field is headed. I also direct an autophagy in health and diseases class to cover the key concepts and signaling pathways in autophagy, which gives a broader overview of the history and landmarks in autophagy research. Last, but not least, I have been mentoring graduate students and postdocs in my lab, working on various aspects of autophagy and this helps make the research interesting.
Personal comments I am married to a scientist working on the mitochondrion. We enjoy traveling, interacting with people of different cultural backgrounds, visiting historical sites, observing animals in diverse living conditions, and savoring ethnic food. We take piano lessons and practice daily. On weekends, we take short walks, go to concerts and movies, grow many different vegetables in the garden, and entertain friends. I also take weekly Indian dance lessons, and sometimes participate in performances. I have an obsession on keeping the house clean and tidy, which might be a byproduct of studying autophagy.
Autophagy Volume 10 Issue 1
©2014 Landes Bioscience. Do not distribute.
Research focus Autophagy in neuronal survival, function, and redox bioenergetics
