Scott B. Selleck

About Me

Dr. Selleck earned his Bachelors Degree in Zoology from the University of Washington, and his MD and PhD degrees at Washington University School of Medicine in St. Louis.

He was a postdoctoral fellow at both the Massachussets Institute of Technology and Brandeis University after which he was appointed as Assistant Professor at the University of Arizona, Department of Molecular and Cellular Biology. Following tenure and promotion to Associate Professor he was recruited to serve as the Director of the Developmental Biology Center, Professor of Pediatrics and Genetics, Cell Biology and Development at the University of Minnesota, where he held the Martin Lenz Harrison Endowed Chair. Professor Selleck served in this capacity from 2002-2009.  In 2009 Dr. Selleck accepted the position of Head of the Department of the Biochemistry & Molecular Biology Department at The Pennsylvania State University, where he served until 2017. Currently, as a Professor at Penn State he continues his work on signaling networks affecting developmental and age-dependent neurodegenerative disorders, including Alzheimer's and Parkinson's disease.

Research Summary

The Selleck lab has a longstanding interest in a class of cell surface of proteins that serve as growth factor co-receptors, heparan sulfate modified proteins or proteoglycans (HSPGs). These molecules modulate the signaling and distribution of many important protein growth factors, including FGFs, Wnts, Hh, and BMPs. A few years ago, we determined that these co-receptors play an important role in suppressing autophagy, a critical cell repair and catabolic process that delivers materials to the lysosome. In retrospect, this makes complete sense since the promotion of growth factor signaling is fundamentally an anabolic process and this is accompanied by suppression of catabolic breakdown. Autophagy also promotes release of lipid stores (lipophagy), removal of damaged organelles, including mitochondria (mitophagy), and transfers materials to the lysosome for breakdown to molecular building blocks. In many neurodegenerative diseases, autophagy is compromised, affecting lipid metabolism, and mitochondrial function. There is considerable data to support the contention that autophagy deficits are an early and critical pathology that leads to cell loss and molecular changes that produce neurodegenerative disease. We have been interested in whether activating autophagy by compromising HSPG function can elevate autophagy and restore cell repair in neurodegenerative disease. Our work in Drosophila, mouse astrocytes, and human cells has demonstrated that modest changes in heparan sulfate structure can activate autophagy and suppress cell loss in models of Parkinson's, Alzheimer's, and amyotrophic lateral sclerosis. We are working on developing therapeutic applications of this biology.

Honors and Awards

• Phi Beta Kappa, University of Washington, 1979.
   
• Medical Scientist Training Program (M.D./Ph.D.) NIH Fellowship, Washington University School of Medicine, 1981-1988.
   
• Spencer T. and Ann W. Olin Medical Scientist Fellow, Washington University School of Medicine, 1989.
   
• Life Sciences Research Foundation Postdoctoral Fellowship, 1989-1992.
   
• Alfred P. Sloane Foundation Research Fellowship for Young Investigators, 1994-96.
   
• Martin Lenz Harrison Land Grant Chair in Pediatrics, University of Minnesota, 2002-2009.
   

Selected Publications

• Nakato, H., Futch, T., and Selleck, S.B. (1995).  The  division abnormally delayed (dally) gene: a putative integral membrane proteoglycan required for cell division patterning during post-embryonic development of the nervous system in Drosophila.  Development 121:3687-3702.
   
• Tsuda, M., Kamimura, K., Nakato, H., Archer, M., Staatz, W., Fox, B., Humphrey, M., Olson, S. Siegfried, E., Stam, L., and Selleck, S.B. (1999).  A cell surface proteoglycan, Dally, regulates Wingless signaling in Drosophila. Nature 400:276-280.
   
• Balciuniene*, J. Feng*, N-P., Iyadurai, K. , Hirsch, B., Charnas, L., Bill, B., Staaf, J., Oseth L., Roberts, W., Avramopoulos, D., Borg Å, Valle, D., Schimmenti, L., Selleck,, S.B. (2007). Recurrent 10q22-23 deletions: a genomic disorder on 10q associated with Cognitive and Behavioral Abnormalities AJHG 80(5):938-47. * contributed equally
   
• Girirajan, S, RL Johnson, , F Tassone, J Balciuniene, N Katiyar, K Fox, C Baker, A Srikanth, K-H Yeoh, SJ Khoo, TB Nauth, R Hansen, M Ritchie, I Hertz-Picciotto, EE Eichler, IN Pessah, SB Selleck (2012).  Global increases in both common and rare copy number load associated with autism. Hum Mol Genet. 2013 Jul 15;22(14):2870-80. doi: 10.1093/hmg/ddt136. Epub 2013 Mar 27.
   
• Kim, D.,  Volk, Girirajan, S., Pendergrass, S., Hall, M., Verma,, S.S., Schmidt, R.J., Hansen, R.., Ghoshf, D., Hertz-Picciotto, I., Ritchie, M.D., and Selleck, S.B. (2017).  Interactions between air pollution exposure and copy number variation confer significant risk for autism. Autism Research. Apr 27. doi: 10.1002/aur.1799.
   
• Reynolds-Peterson, C.E., Zhao†, N. Xu, J. Serman, T.M. Xu, J-l., and Selleck, S.B. (2017). Heparan Sulfate Proteoglycans Regulate Autophagy in Drosophila. Autophagy. Apr 12:1-18. doi: 10.1080/15548627.2017.1304867.
   
• Reynolds-Peterson, C., Xu, J., Zhao, N., Cruse, C., Yonel, B., Trasorras, C., Toyoda, H., Kinoshita-Toyoda, A., Dobson, J., Schultheis, N., Jiang, M., and Selleck, S.B. (2020).  Heparan sulfate structure affects autophagy, lifespan, responses to oxidative stress, and cell degeneration in Drosophila parkin mutants.  G3: Genes Genomes Genetics 10: 129-141.
   
• Schultheis, N., Jiang, M., and Selleck, S.B. (2021).  Putting the brakes on autophagy: The role of heparan sulfate modified proteins in the balance of anabolic and catabolic pathways and intracellular quality control.  Matrix Biol. 100: 173-181.
   
• Schultheis N, Connell A, Kapral A, Becker RJ, Mueller R, Shah S, O'Donnell M, Roseman M, Wang W, Yin F, Weiss R.J., Selleck SB. Altering heparan sulfate suppresses cell abnormalities and neuron loss in Drosophila presenilin model of Alzheimer's. iScience (2024) 27: 110256. doi: 10.1016/j.isci.2024.110256