Adrienne Wang , PhD

I study aging and neurodegenerative disease using fruit flies. My scientific path included a lot of exploration of "non-traditional" science careers and contemplation of the meaning of life. I don't know that I've made much progress on some of those bigger questions, but along the way, I have learned so much about the world around us and the scientific principals that govern cellular function. My interest in biology really began with a drive to understand people and behavior. I attended UC Berkeley as an undergraduate and after initial flirtation with cognitive science as a major, I ultimately found more satisfaction in the answers available from experimental systems and molecular research. I ended up getting a degree in Molecular and Cell Biology with an emphasis in neurobiology. After several years working in labs and at a small biotech startup in the SF Bay Area, I decided to go back to school, ultimately moving to Ann Arbor to pursue a PhD in Neuroscience at the University of Michigan. My work there melded much of what fascinated me as an undergraduate, the connection between structure and function, both at the anatomical level and the molecular level. My dissertation focused on the neurodegenerative disease Spinal Bulbar Muscular Atrophy and ways to harness the cell's innate protein quality control pathways to treat the disease. Although I entered graduate school on the premise that I was looking for expertise, not necessarily a career in academia, it was during this time that I started rethinking my initial bias against becoming a professor. I had grown up in the Seattle area, and my two best friends from high-school attended Western. When my thinking in graduate school began to shift, I have clear memories of saying "Maybe I could stay in academics. Maybe I could see myself as a professor at a place like Western".

After completing my PhD, and having spent about 14 years living somewhere other than the PNW, I was eager to move back. I found a postdoctoral position at the University of Washington in Matt Kaeberlein's lab where I began to learn more about the biological mechanisms of aging and how those mechanisms might affect susceptibility to neurodegenerative disease.

Research in my lab uses the fruit fly as a model organism to understand pathological mechanisms of neurodegenerative disease and how these might interact with molecular changes seen with age. Genetic studies from many model organisms have identified a number of pathways that modulate aging and lifespan across species, and we are interested in investigating how modifying these pathways influence the onset and progression of neurodegenerative diseases such as Alzheimer’s disease and mitochondrial disease.

• B.A. in Molecular Cell Biology with an emphasis in Neurobiology from the University of California, Berkeley, 2001.
• Ph.D. in Neuroscience from the University of Michigan, 2011. Dissertation title: Targeting Protein Quality Control Pathways in Spinal Bulbar Muscular Atrophy.
• Postdoctoral Fellow at the University of Washington in the Promislow and Kaeberlein labs 2012-2017.

Selected Publications

1. Urfer SR, Latimer CS, Ladiges W, Keene CD, Benbow S, Harrison B, Promislow DEL, Kaeberlein M, Kraemer BC, Wang A, Guscetti F, Darvas M. Cross species application of quantitative neuropathology assays developed for clinical Alzheimer's disease samples. Pathobiol Aging Age Relat Dis. 2019;9(1):1657768. doi: 10.1080/20010001.2019.1657768. eCollection 2019. PubMed PMID: 31528297; PubMed Central PMCID: PMC6735310.
2. Wang A.M., Mouser J., Pitt J., Promislow D., Kaeberlein M. Rapamycin enhances survival in a Drosophila model of mitochondrial disease. Oncotarget. 2016 May 10;7(19):27787-801. doi: 10.18632/oncotarget.8497
3. Bitto A, Wang AM, Bennett CF, Kaeberlein M. Biochemical Genetic Pathways that Modulate Aging in Multiple Species. Cold Spring Harb Perspect Med. 2015 Nov 2;5(11). pii: a025114. doi: 10.1101/cshperspect.a025114. Review. PubMed PMID: 26525455; PubMed Central PMCID: PMC4632857
4. Wang AM, Promislow DE, Kaeberlein M. Fertile waters for aging research. Cell. 2015 Feb 26;160(5):814-5. PMID:25723160.
5. Burman JL, Itsara LS, Kayser EB, Suthammarak W, Wang AM, Kaeberlein M, Sedensky MM, Morgan PG, Pallanck LJ. A Drosophila model of mitochondrial disease caused by a complex I mutation that uncouples proton pumping from electron transfer. Dis Model Mech. 2014 Oct;7(10):1165-74. PMCID: PMC4174527.
6. Wang AM, Lessons from Drosophila in Neurodegeneration: Mechanisms of Toxicity and Therapeutic Targets in Spinal and Bulbar Muscular Atrophy, In: Drosophila Melanogaster Models of Motor Neuron Disease, edited by R. Cauchi, Nova Science Publishers, 2013
7. Wang AM, Miyata Y, Klinedinst S, Peng HM, Chua JC, Komiyama T, Merry DE, Pratt WB, Osawa Y, Collins CA, Gestwicki JE, Lieberman AP. Activation of Hsp70 reduces neurotoxicity by promoting polyglutamine protein degradation. Nat Chem Biol. 2013 Feb;9(2):112-8. PMCID: PMC3552084

- Featured as a Research Highlight in Nature Reviews Drug Discovery 12, 102 (February 2013)

1. Yu Z, *Wang AM, Adachi H, Katsuno M, Sobue G, Yue Z, Robins DM, Lieberman AP. Macroautophagy is regulated by the UPR-mediator CHOP and accentuates the phenotype of SBMA mice. PLoS Genet 2011;7(10). PMCID: PMC3192827.
2. *Wang AM, Morishima Y, Clapp KM, Peng HM, Pratt WB, Gestwicki JE, Lieberman AP.  Inhibition of Hsp70 by methylene blue affects signaling protein function and ubiquitination and modulates polyglutamine protein degradation.  J Biol Chem, 285:15714-15723, 2010. PMCID: PMC2871437.
3. Yu Z, Wang A, Robbins DM, Lieberman AP.  Altered RNA splicing contributes to skeletal muscle pathology in Kennedy disease knock-in mice.  Dis Model Mech, 2:500-507, 2009.  (Highlighted in “In This Issue”.)  PMCID: PMC2737058
4. Morishima Y, Wang AM, Yu Z, Pratt WB, Osawa Y, Lieberman AP.  CHIP deletion reveals functional redundancy of E3 ligases in promoting degradation of both signaling proteins and expanded glutamine proteins. Hum Mol Genet, 17:3942-3952, 2008. PMCID: PMC2605787
5. Bergman C.M., Pfeiffer B.D., Rincoln-Limas D.E., Hoskins R.A.,Gnirke A.,
   Mungall C.J., Wang A.M., Kronmiller B., Pacleb J., Park S., Stapleton M., Wan K., George R.A., Jong P.J., Botas J., Rubin G.M., Celniker S.E.
   (2002) Assessing the Impact of Comparative Genomic Sequence Data on the Functional Annotation of the Drosophila Genome. Genome Biol. 2002;3(12). PMCID: PM12537575

* denotes co-first authorship