# Marc Montminy
Marc R. Montminy is an American biochemist and physiologist known for discovering and characterizing CREB, a transcription factor whose activation by phosphorylation (adding a phosphate group to switch proteins on) controls gene expression in response to hormones and metabolic signals; his laboratory's work on CREB and its coactivators has led to therapeutic insights for diabetes, obesity, and insulin resistance.[1](https://www.salk.edu/scientist/marc-montminy/) CREB, the cAMP response element-binding protein, was the first example of a transcription factor whose activity is modulated by phosphorylation, according to his National Academy of Sciences entry.[2](https://www.nasonline.org/directory-entry/marc-r-montminy-q7bomn/)
| Key facts | Detail |
|---|---|
| Field | Molecular biology: gene regulation, metabolism, endocrinology |
| Principal discovery | CREB and its phosphorylation-dependent activation; the CREB coactivators CBP and CRTC[2](https://www.nasonline.org/directory-entry/marc-r-montminy-q7bomn/) • [3](https://www.nature.com/articles/35085068) |
| Education | BS in biochemistry, Harvard University, 1978; MD and PhD in physiology, Tufts University, 1984[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC3358882/) |
| Training | PhD under Richard H. Goodman at Massachusetts General Hospital and Tufts University[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC3358882/) |
| Career | Harvard Medical School and Joslin Diabetes Center, 1996–1999; Salk Institute after that period[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC3358882/) |
| Honors | National Academy of Sciences, 2009; Richard E. Weitzman Award, 1990; McKnight Neuroscience Development Award[2](https://www.nasonline.org/directory-entry/marc-r-montminy-q7bomn/) • [4](https://pmc.ncbi.nlm.nih.gov/articles/PMC3358882/) • [1](https://www.salk.edu/scientist/marc-montminy/) |
| Recent work | Med14 phosphorylation in the genomic response to GLP-1 agonists (PNAS, 2026)[5](https://doi.org/10.1073/pnas.2536772123) |
| Signature work | ["Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133"](https://doi.org/10.1016/0092-8674(89)90013-5), *Cell*, 1989; ["The CREB Coactivator TORC2 Functions as a Calcium- and cAMP-Sensitive Coincidence Detector"](https://doi.org/10.1016/j.cell.2004.09.015), *Cell*, 2004; ["PGC-1 promotes insulin resistance in liver through PPAR-α-dependent induction of TRB-3"](https://doi.org/10.1038/nm1044), *Nature Medicine*, 2004 |
## Training and early career
According to a PNAS biographical profile, Montminy graduated from Harvard University cum laude with a bachelor's degree in biochemistry in 1978 and enrolled at Tufts University School of Medicine, switching into the dual MD/PhD program in his third year.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC3358882/) He carried out his PhD work under [Richard H. Goodman](https://www.edgepedia.org/richard-h-goodman), then a research fellow at [Massachusetts General Hospital](https://www.edgepedia.org/massachusetts-general-hospital), characterizing the gene that encodes the neuropeptide hormone somatostatin; he stayed in Goodman's laboratory when it moved to [Tufts University](https://www.edgepedia.org/tufts-university) in 1983 and received his MD and his PhD in physiology in 1984.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC3358882/)
As a postdoctoral fellow in Goodman's laboratory, he found that somatostatin mRNA rose when cells were treated with forskolin, which stimulates production of cyclic AMP (cAMP), a common intracellular signaling molecule. That observation led to his seminal discovery of the cAMP response element (CRE), an 8-base-pair DNA sequence upstream of the somatostatin gene that is required for the gene's response to cAMP, and to the purification of a nuclear protein that binds it.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC3358882/) • [1](https://www.salk.edu/scientist/marc-montminy/) He named the protein CREB.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC3358882/)
## Career at Harvard and the Salk Institute
Montminy was a professor of cell biology at Harvard Medical School and director of the Laboratory of Advanced Genetic Technologies and section head of Molecular Biology at the Joslin Diabetes Center; between 1996 and 1999 his focus there turned to CREB's role in energy metabolism and diabetes.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC3358882/) • [1](https://www.salk.edu/scientist/marc-montminy/) After the Joslin period he returned to the Salk Institute.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC3358882/) Screening work during the Joslin period uncovered the CREB-regulated transcription coactivators (CRTCs), which stimulate gene expression after dephosphorylation.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC3358882/) He is now a distinguished professor emeritus at Salk.[6](https://www.salk.edu/news-release/how-do-glp-1-agonists-affect-gene-expression/)
## Representative work
- **Characterization of CREB (Nature, 1987).** His paper with the 43,000-molecular-mass nuclear protein CREB showed that it binds selectively to the cAMP response element of the somatostatin gene and is phosphorylated in vitro by the catalytic subunit of PKA; forskolin stimulation of [PC12](https://www.edgepedia.org/pc12) cells raised phosphorylation of this protein 3- to 4-fold ([10.1038/328175a0](https://europepmc.org/article/MED/2885756)).[7](https://europepmc.org/article/MED/2885756)
- **Ser133 phosphorylation (Cell, 1989).** "Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133" established that PKA phosphorylates CREB at a single amino acid and that this phosphorylation is required for CREB's activation ([10.1016/0092-8674(89)90013-5](https://doi.org/10.1016/0092-8674(89)90013-5)).[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC3358882/)
- **TORC2 and fasting glucose (Nature, 2005).** The paper showed that hormonal and energy-sensing pathways converge on the coactivator TORC2 to modulate hepatic glucose output ([10.1038/nature03967](https://www.nature.com/articles/nature03967)).[8](https://www.nature.com/articles/nature03967)
## CREB, fasting metabolism and diabetes
CREB is phosphorylated in response to a wide variety of signals, yet target gene transcription increases in only a subset of cases; the explanation lies in the CRTCs, latent cytoplasmic coactivators that are activated through dephosphorylation.[9](https://pmc.ncbi.nlm.nih.gov/articles/PMC4324555/) In the fed state TORC2 (now called CRTC2) is sequestered in the cytoplasm; during fasting it is dephosphorylated and moves to the nucleus, where it enhances CREB-dependent transcription of gluconeogenic genes, the program that produces glucose in the liver. Signals that activate AMPK attenuate this program by promoting TORC2 phosphorylation and blocking its nuclear accumulation.[8](https://www.nature.com/articles/nature03967) Insulin shuts down glucose production by inhibiting CRTC2, and the 2005 paper proposed that compounds enhancing TORC2 phosphorylation may benefit fasting hyperglycaemia in type 2 diabetes.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC3358882/) • [8](https://www.nature.com/articles/nature03967)
The other CRTC family members govern whole-body physiology. Mice lacking CRTC3 resist obesity, and human CRTC3 mutations that increase its activity are associated with obesity; mice lacking [CRTC1](https://www.edgepedia.org/crtc1), which is expressed in the brain, have increased appetite, become obese, and are infertile.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC3358882/) Downstream of CREB, phosphorylation recruits the coactivator [CREB-binding protein](https://www.edgepedia.org/creb-binding-protein) (CBP) and its paralogue p300; CREB functions in glucose homeostasis and growth-factor-dependent cell survival and has been implicated in learning and memory.[3](https://www.nature.com/articles/35085068)
## Honors and recognition
Montminy was elected to the National Academy of Sciences in 2009 in Section 42, Medical Physiology and [Metabolism](https://www.edgepedia.org/metabolism).[2](https://www.nasonline.org/directory-entry/marc-r-montminy-q7bomn/) The Endocrine Society awarded him the Richard E. Weitzman Award in 1990, and he has received the McKnight Neuroscience Development Award.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC3358882/) • [1](https://www.salk.edu/scientist/marc-montminy/)
## Recent developments
The lab's output continues in two directions. A 2024 Cell Reports paper described the nutrient sensor CRTC and Sarcalumenin as an alternate pathway in cardiac hypertrophy.[10](https://montminy.salk.edu/publications/) In 2026 the lab published "Med14 phosphorylation shapes genomic response to GLP-1 agonists" in PNAS, contributed by Montminy, examining how GLP-1 drugs act on gene expression in diabetes, cardiovascular disease, and obesity.[5](https://doi.org/10.1073/pnas.2536772123) A Salk news release describes the study as led by senior author Montminy, distinguished professor emeritus, asking "How are GLP-1s causing these effects?"[6](https://www.salk.edu/news-release/how-do-glp-1-agonists-affect-gene-expression/)
## References
1. [Marc Montminy, MD, PhD – Salk Institute](https://www.salk.edu/scientist/marc-montminy/)
2. [Marc R. Montminy – National Academy of Sciences directory](https://www.nasonline.org/directory-entry/marc-r-montminy-q7bomn/)
3. [Transcriptional regulation by the phosphorylation-dependent factor CREB (Nature Reviews Molecular Cell Biology, 2000)](https://www.nature.com/articles/35085068)
4. [Profile of Marc R. Montminy – PNAS biographical profile](https://pmc.ncbi.nlm.nih.gov/articles/PMC3358882/)
5. [Med14 phosphorylation shapes genomic response to GLP-1 agonists (PNAS, 2026)](https://doi.org/10.1073/pnas.2536772123)
6. [How do GLP-1 agonists affect gene expression? – Salk Institute news release](https://www.salk.edu/news-release/how-do-glp-1-agonists-affect-gene-expression/)
7. [Binding of a nuclear protein to the cyclic-AMP response element of the somatostatin gene (Nature, 1987)](https://europepmc.org/article/MED/2885756)
8. [The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism (Nature, 2005)](https://www.nature.com/articles/nature03967)
9. [CREB and the CRTC co-activators: sensors for hormonal and metabolic signals](https://pmc.ncbi.nlm.nih.gov/articles/PMC4324555/)
10. [Publications – Montminy Lab, Salk Institute](https://montminy.salk.edu/publications/)
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*Topic: Encyclopedia › Life and health › Life and health scientists › Life scientists › Researchers in endocrinology and metabolism › Molecular endocrinology researchers*
*Initially written Sep 20, 2026 · Reviewed: Sep 25, 2026 · Edited: Sep 25, 2026; Oct 11, 2026; Oct 15, 2026 · Last review: Sep 25, 2026*
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