Kathryn E. Wellen, Ph.D.
653 BRB II/III
Philadelphia, PA 19104-6160
Lab: (215) 746-4956
B.S. (Biological Psychology, summa cum laude)
The College of William and Mary, 2000.
Ph.D. (Biological Sciences, Genetics & Complex Diseases)
Harvard University, School of Public Health, 2006.
Description of Research ExpertiseResearch Interests: My lab is studying cellular metabolism, particularly how metabolic pathways regulate signal transduction and gene expression in cancer and metabolic disease.
Key Words: metabolism, cancer, diabetes, acetylation, glycosylation, nutrient-sensing
Cancer cells depend on altered nutrient uptake and metabolism to grow and divide. In order to appropriately regulate energy-intensive processes such as growth and proliferation, cells must be able to gauge their metabolic resources. My lab is interested in understanding how cells sense nutrient availability and integrate this information with signaling and transcriptional networks in order to modulate activities such as growth, proliferation, and differentiation. Current research focuses on elucidating the roles of nutrient-sensitive protein modifications in regulating signaling and gene expression in the contexts of cancer and metabolic disease.
We have recently demonstrated that acetylation of histones, and associated changes in gene expression, are responsive to glucose availability in a manner dependent on ATP-citrate lyase (ACL), a metabolic enzyme that cleaves mitochondria-derived citrate to produce acetyl-CoA in the nucleus and cytoplasm. Hence, histones can be modified in a manner responsive to nutrient availability, potentially influencing multiple chromatin-dependent processes. A major current focus of the lab is to elucidate the mechanisms through which ACL regulates acetylation and its impact on signaling and gene expression, using cancer and metabolic cell types and mouse models.
A second area of interest is in understanding the role of the hexosamine biosynthetic pathway in regulating metabolism and growth. The hexosamine pathway is a branch of glucose metabolism that produces UDP-N-acetylglucosamine (UDP-GlcNAc), a donor substrate used in the production of several types of glycans, including N-linked glycans. Many cell surface and secreted proteins are modified co-translationally by N-linked glycosylation, and these glycoproteins can be influenced by metabolic state through glucose flux into the hexosamine pathway. Changes in the function and surface expression of glycoproteins can impact tumor growth by altering cancer cells’ interactions with their environment, including their ability to respond to growth factors and acquire nutrients. We are currently investigating how the hexosamine biosynthetic pathway is regulated in cancer cells and its impact on cancer cell growth and proliferation.
Rotation projects are available in each area of interest in the lab. Please contact Dr. Wellen for details.
Sydney Campbell, Graduate Student
Luke Izzo, Graduate Student
Hayley Affronti, Postdoctoral Researcher
Sully Fernandez, Postdoctoral Researcher
Alessandro Carrer, Postdoctoral Researcher
Lyndsey Makinen, Administrative Assistant
Sophie Trefely, Postdoctoral Researcher
Steven Zhao, Graduate Student
Selected PublicationsWellen KE, Fucho R, Gregor MF, Furuhashi M, Morgan C, Lindstad T, Vaillancourt E, Gorgun CZ, Saatcioglu F, Hotamisligil GS: Coordinated regulation of nutrient and inflammatory responses by STAMP2 is essential for metabolic homeostasis. Cell 129(3): 537-48, May 2007.
*Wellen KE, *Hatzivassiliou G, Sachdeva UM, Bui TV, Cross JR, Thompson CB: ATP-citrate lyase links cellular metabolism to histone acetylation. Science 324(5930): 1076-80, May 2009. Notes: *both authors contributed equally to this work.
Wellen KE, Thompson CB: Cellular Metabolic Stress: Considering how cells respond to nutrient excess. Molecular Cell 40(2): 323-32, October 2010.
Wellen KE, Lu C, Mancuso A, Lemons JM, Ryczko M, Dennis JW, Rabinowitz JD, Coller HA, Thompson CB: The hexosamine biosynthetic pathway couples growth factor-induced glutamine uptake to glucose metabolism. Genes & Development 24(24): 2784-99, December 2010.
Carrer A, Wellen KE: Metabolism and epigenetics: a link cancer cells exploit. Current opinion in biotechnology 34: 23-9, August 2015.
Lee JV, Shah SA, Wellen KE: Obesity, cancer, and acetyl-CoA metabolism. Drug Discovery Today: Disease Mechanisms 10(1-2): e55-e61, June 2013.
Londono Gentile T, Lu C, Lodato, PM, Tse S, Olejniczak S, Witze, ES, Thompson CB, and Wellen KE: DNMT1 is regulated by ATP-citrate lyase and maintains methylation patterns during adipocyte differentiation. Molecular and Cellular Biology 33(19): 3864-78, October 2013.
Lee JV, Carrer A, Shah S, Snyder NW, Wei S, Venneti S, Worth AJ, Yuan Z, Lim HW, Liu S, Jackson E, Aiello NM, Haas NB, Rebbeck TR, Judkins A, Won KJ Chodosh LA, Garcia BA, Stanger BZ, Feldman MD, Blair IA, Wellen KE: Akt-dependent metabolic reprogramming regulates tumor cell histone acetylation. Cell Metabolism 20(2): 306-19, Aug 2014.
Shah S, Carriveau WJ, Li J, Campbell SL, Kopinski P, Lim HW, Daurio N, Trefely S, Won KJ, Wallace DC, Koumenis C, Mancuso A, Wellen KE: Targeting ACLY sensitizes castration-resistant prostate cancer cells to AR antagonism by impinging on an ACLY-AMPK-AR feedback mechanism. Oncotarget 7(28): 43713-43730, July 2016.