Chris Fromme
Professor, Molecular Biology and Genetics
Chris Fromme is an Professor in the Weill Institute for Cell and Molecular Biology and the Department of Molecular Biology and Genetics. After graduating from Cornell with a B.A. in Biology in 1999, Chris did his graduate studies with Greg Verdine at Harvard University, receiving a Ph.D. in Biochemistry in 2004. He then did postdoctoral work as a Miller Institute Fellow with Randy Schekman at UC Berkeley. He joined the Cornell faculty in 2008.
Research Focus
The Golgi complex is the “Grand Central Station” within our cells, serving as the primary sorting organelle at the nexus of the secretory and endocytic trafficking pathways. For example, virtually all proteins that eukaryotic cells display on their surface at the plasma membrane are first synthesized at the endoplasmic reticulum and then trafficked to the Golgi complex. Once at the Golgi, proteins find themselves at a crossroads: they may be trafficked to the plasma membrane, to endocytic organelles, to lysosomal organelles, back to the endoplasmic reticulum, or they may remain within the Golgi complex. We view the Golgi as an excellent model for investigating how decisions are made at the level of an organelle: How does the Golgi maintain homeostasis in the face of constant flux? How does the Golgi respond to changes in cargo load? Does the Golgi communicate with other organelles?
The regulators for all incoming and outgoing Golgi traffic are GTPases of the Rab and Arf families. Arf and Rab proteins are activated by GEFs (guanine nucleotide exchange factors), which are master regulators of trafficking pathways. Despite knowing the identity of many of these regulators, the molecular and atomic basis for their regulation remains poorly defined.
Our lab has discovered that GTPase activation is regulated at the Golgi through GEF autoinhibition, positive feedback, and GTPase crosstalk mechanisms. Our findings lead to a model for regulation of the Golgi in which multiple GTPases pathways, previously considered to act in isolation, are intimately connected. By investigating how the GEFs are regulated using biochemical, structural, and cell biological approaches, we aim to uncover the molecular logic governing regulation of the Golgi at a mechanistic level.
Teaching Focus
Chris currently teaches BioMG 1350, "Cell and Developmental Biology", and participates in BMCB graduate courses. He previously taught BioMG 3350 "Principles of Biochemistry" for 10 years.
Recent Research
The Golgi complex is the “Grand Central Station” within our cells, serving as the primary sorting organelle at the nexus of the secretory and endocytic trafficking pathways. For example, virtually all proteins that eukaryotic cells display on their surface at the plasma membrane are first synthesized at the endoplasmic reticulum and then trafficked to the Golgi complex. Once at the Golgi, proteins find themselves at a crossroads: they may be trafficked to the plasma membrane, to endocytic organelles, to lysosomal organelles, back to the endoplasmic reticulum, or they may remain within the Golgi complex. We view the Golgi as an excellent model for investigating how decisions are made at the level of an organelle: How does the Golgi maintain homeostasis in the face of constant flux? How does the Golgi respond to changes in cargo load? Does the Golgi communicate with other organelles?
The regulators for all incoming and outgoing Golgi traffic are GTPases of the Rab and Arf families. Our lab has discovered that GTPase activation is regulated at the Golgi through autoinhibition, positive feedback, and GTPase crosstalk mechanisms. Our findings lead to a model for regulation of the Golgi in which multiple GTPases pathways, previously considered to act in isolation, are intimately connected. By investigating how the GTPases and their effectors are regulated using biochemical, structural, and cell biological approaches, we aim to uncover the molecular logic governing regulation of the Golgi at a mechanistic level.
Selected Publications:
- Joiner, A.M.N., Phillips, B.P., Yugandhar, K., Sanford, E.J., Smolka, M.B., Yu, H., Miller, E.A., and Fromme, J.C., “Structural basis of TRAPPIII-mediated Rab1 activation.” The EMBO Journal. 40 (2021) e107607.
- Highland, C.M. and Fromme, J.C., “Arf1 directly recruits the Pik1-Frq1 PI4K complex to regulate the final stages of Golgi maturation.” Molecular Biology of the Cell. 32 (2021) 1064-1080.
- Thomas, L.L., Highland, C.M., and Fromme, J.C., “Arf1 orchestrates Rab conversion at the trans-Golgi network.” Molecular Biology of the Cell. 32 (2021) 1104-1120.
- Joiner, A.M.N. and Fromme, J.C., “Structural basis for initiation of COPII vesicle biogenesis.” Structure. 29 (2021) 859-872.
- Feathers, J.R., Spoth, K.A., Fromme, J.C. “Experimental evaluation of super-resolution imaging and magnification choice in single-particle cryo-EM.” Journal of Structural Biology: X. 5 (2021) e100047.
Awards & Honors
- 2021 Robert H. Foote Mid-Career Teaching Award
- 2018 Mentor of the Year, Southern Regional Education Board
- 2018 Faculty Champion Award
- 2016 Fellow, John Simon Guggenheim Memorial Foundation
Courses Taught
- BIOMG 3350: Principles of Biochemistry: Proteins, Metabolism, and Molecular Biology
- BIOMG 8300: Biochemistry Seminar
- BIOG 4990: Independent Undergraduate Research in Biology
Contact Information
457 Weill Hall
Ithaca, NY 14853
jcf14 [at] cornell.edu
Additional Links
Chris in the news
News
The new findings published in Science capture never-before-recorded stages of a molecular construction process, with implications for future pharmaceutical development.
- Molecular Biology and Genetics
- Biology
- Genetics
News
And while scientists have identified enzymes that remove a chemical modification known as lysine myristoylation – a “code” used for cell signaling – the enzymes that add such modifications have proved elusive. Knowledge of such modifications...
- Biology
- Microbiology