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Autophagy 8:11, 15531556; November 2012; 2012 Landes Bioscience

Autophagy researchers
Charleen T. Chu
Email: ctc4@pitt.edu
Research focus
Mitochondrial homeostasis and cell signaling in neurodegeneration

What do you think is a key question(s) in the autophagy field? Or, where do you think the field is heading?

Cortical and midbrain neurons, SH-SY5Y cells, mutant mice

Education and career

1993, Ph.D. in pathology-biochemistry, Duke University School of Medicine; advisor: Salvatore V. Pizzo. 1994, M.D., Duke University School of Medicine. 19941998, anatomic pathology and neuropathology residency with postdoctoral fellowship in neuro-oncology, Duke University; research advisor: Darell D. Bigner. 1998present, assistant professor, associate professor and currently professor of pathology, University of Pittsburgh School of Medicine.

What one scientific discovery do you wish you had made?

The discovery of adapter proteins such as SQSTM1/p62 that target ubiquitinated cargo for autophagy. This work has really opened up the field for envisioning mechanisms of selective autophagy in mammals. We have been working on and off on another hypothesis concerning cargo recognition since 2004, following the report of the LC3 crystal structure and a chance meeting with a previously unknown Pittsburgh colleague in St. Thomas. So there really is a good reason to attend smaller scientific conferences in beautiful locations.

Why do you study autophagy?

One of the joys of science is that you never know exactly where the data will lead you. My journey into the world of autophagy began with a $5 bet and the discovery that instead of trafficking to the nucleus, the kinase we were studying decorated mitochondria undergoing autophagy in degenerating Parkinson disease neurons. At that time, the Atg8/LC3 conjugation system had been discovered, and the potential research implications resonated with both the biochemist and the morphologist in me (derived from my Ph.D. in covalent protein modifications and my training as a diagnostic pathologist, respectively). I predicted that autophagy was going to comprise the next big wave for human disease research, and signed up for the first Gordon Research Conference in 2003 to learn more about its basic regulation. The people in the field have turned out to be generous and fantastic colleagues, and it has been highly rewarding to be part of this growing community.

Personal comments
I enjoy hiking, eating (and thinking about food), vacation travels with my husband and children, reading (mostly science fiction/fantasy), snorkeling, and chow chows (a furry dog breed that, according to legend, was allowed to lick up pieces of the sky that fell during creation). One of my favorite places is a tiny projection of land near Monterey, CA, the Point Lobos State Natural Reserve. This is where I discovered hiking on a family trip away from the concrete world of Los Angeles, gaining an appreciation for trees as well as tide pools, and decades later heard, then saw, a sea otter eating in the wild.

If you could start over and choose a different career, what would it be?
If I were brave enough to jump off the well-lit path up the medical ivory tower, I would be a food anthropologist or photojournalist, traveling the world to study the interplay of culture and cuisine, or poking around in the secret lives of obscure animals and plants.

www.landesbioscience.com Autophagy

1553

2012 Landes Bioscience. Do not distribute.

Model system

Key questions include mechanisms underlying cell type-, stimulus- or cargo-specific responses and how these interact with or modulate the classical autophagy pathways. It is likely that the regulation of autophagy is not a linear process, but rather involves integration of a network of signaling inputs. My first exposure to autophagy was during my clinical training, years before I rediscovered it as a researcher. I was taught that despite its striking ultrastructure, it was not diagnostically useful as it represented a nonspecific cellular response to many kinds of stress. Of course, the concept of selective autophagy has now moved to the forefront in fields such as Parkinson disease, given growing molecular evidence that cargo sequestration may play a pivotal role in familial neurodegenerative diseases. A second emerging theme reflects mechanisms that balance and cross-regulate autophagic degradation and biosynthetic/ regenerative responses to cellular injury. For example, our recent study in chronic MPP+ toxicity suggests that the capacity for aging or diseased neurons to upregulate mitochondrial biogenesis may determine the overall outcome of mitophagy-inducing injuries. As a cellular recycling response, impairment at any step of the processautophagy induction, cargo targeting, maturation/degradation or reutilization of liberated moleculesmay represent a potential future target for diseasemodulating therapies.