Chris Fromme is a Professor in the Department of Molecular Biology and Genetics and the Weill Institute for Cell and Molecular Biology. After graduating from Cornell with a B.A. in Biology in 1999, Chris carried out his graduate studies with Greg Verdine at Harvard University, receiving a Ph.D. in Biochemistry in 2004. He then received postdoctoral training 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. These GTPases serve many critical functions and are themselves tightly regulated. Despite knowing the identity of many of the key GTPase regulators, the molecular and atomic basis for their function 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 are intimately connected through physical interactions. By investigating how the GTPases 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
Much of our recent work has been directed at understanding the biochemical and structural basis for the activation of GTPase proteins at the Golgi. We have used crystallography and cryoEM approaches to visualize the nucleotide exchange reactions that trigger activation of each of the major Golgi trafficking pathways.
Selected Publications:
- Brownfield, B.A., Richardson, B.C., Halaby, S.L., and Fromme, J.C. Sec7 regulatory domains scaffold autoinhibited and active conformations. PNAS. 2024;121:e2318615121
- Manzer, K.M. and Fromme, J.C. The Arf-GAP Age2 localizes to the late-Golgi via a conserved amphipathic helix. Molecular Biology of the Cell. 2023; 34:ar119,1-16.
- Muccini, A.M., Gustafson, M.A., Fromme, J.C. Structural basis for activation of Arf1 at the Golgi complex. Cell Reports. 2022 Aug. 30;40(111282).
- Bagde, S.R., Fromme, J.C. Structure of a TRAPPII-Rab11 activation intermediate reveals GTPase substrate selection mechanisms. Science Advances. 2022 May 13;8(19).
- Bagde, S.R., Mathews, I.I., Fromme, J.C., Kim, C-Y. Modular polyketide synthase contains two reaction chambers that operate asynchronously. Science. 2021 Nov 4;374(6568): 723-729.. 8 (2022) eabn7446.
