Kathryn E. Wellen, Ph.D.

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Assistant Professor of Cancer Biology
Department: Cancer Biology

Contact information
421 Curie Blvd.
611 BRB II/III
Philadelphia, PA 19104-6160
Office: (215) 746-8599
Fax: 215-573-6725
Lab: (215) 746-4956
Education:
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.
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Description of Research Expertise

Research 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

Research Details:

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:

Rotation projects are available in each area of interest in the lab. Please contact Dr. Wellen for details.

Lab Personnel:

Alessandro Carrer, Postdoctoral Researcher
Ellen Jackson, Research Specialist
Joyce Lee, Graduate Student
Peter Lodato, Research Specialist
Supriya Shah, Postdoctoral Researcher
Sarah Tse, Undergraduate Researcher
Carrie Kitzmiller, Administrative Coordinator

Selected Publications

Wellen KE, Thompson CB: A two-way street: reciprocal regulation of metabolism and signaling. Nature Reviews Molecular Cell Biology 13(4): 270-6, March 2012.

Lu C, Ward PS, Kapoor GS, Rohle D, Turcan S, Abdel-Wahab O, Edwards CR, Khanin R, Figueroa ME, Melnick A, Wellen KE, O'Rourke DM, Berger SL, Chan TA, Levine RL, Mellinghoff IK, Thompson CB: IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature 483(7390): 474-8, February 2012.

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.

Wellen KE, Thompson CB: Cellular Metabolic Stress: Considering how cells respond to nutrient excess. Molecular Cell 40(2): 323-32, October 2010.

*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, 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, Hotamisligil GS: Inflammation, stress, and diabetes. Journal of Clinical Investigation 115: 1111-1119, May 2005.

Wellen KE, Uysal KT, Wiesbrock S, Yang Q, Chen H, Hotamisligil GS: Interaction of tumor necrosis factor-alpha- and thiazolidinedione-regulated pathways in obesity Endocrinology 145(5): 2214-20, May 2004.

Wellen KE, Hotamisligil GS: Obesity-induced inflammatory changes in adipose tissue. Journal of Clinical Investigation 112(12): 1785-8, December 2003.

Emanuelli B, Peraldi P, Filloux C, Chavey C, Freidinger K, Hilton DJ, Hotamisligil GS, Van Obberghen E: SOCS-3 inhibits insulin signaling and is up-regulated in response to tumor necrosis factor-alpha in the adipose tissue of obese mice. Journal of Biological Chemistry 276(51): 47944-9, December 2001.

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Last updated: 01/08/2014
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