Martin Bergö, Vice President

I am the Vice President of Karolinska Institutet (KI) from 1 March, 2023.
As vice president, I will support our new President, Annika Östman Wernerson, to implement Strategy 2030 and develop at KI a strong, attractive, and sustainable academic environment grounded in common ethics and values. To accomplish this, I would like to listen to our entire organization and identify and channel its collective ideas and resourcefulness.

Martin Bergö
Martin Bergö. Photo: Martin Stenmark

I come directly from a role as Academic Vice President for Research and chair of the Committee for Research at KI—a job that allowed me to widen my communications channels within the university and region and expand my national and international networks. It also taught me about the enormous strength and flexibility of our world-leading institution as well as its urgent and long-term challenges.

In my early career I studied chemistry and medicine at Umeå University and obtained a PhD in medical biochemistry and followed this up with postdoctoral studies at the University of California, San Francisco. I then started my own research group at the Sahlgrenska Academy, University of Gothenburg in 2004 and was recruited to Karolinska Institutet in 2015.

As a researcher I am a professor of molecular medicine with a long-standing interest in basic science and disease mechanisms. My group has primarily studied cancer including lung cancer, malignant melanoma, leukemia, and lymphoma, but also inflammatory disorders including atherosclerosis and rheumatoid arthritis, and the accelerated aging disorder Hutchinson-Gilford Progeria Syndrome (HGPS). We have been fortunate to be able to perform curiosity-driven research and well positioned to capitalize on unexpected findings.

All our current research areas stem from a basic interest in an intracellular biochemical signaling pathway that is present in most eukaryotic organisms. See Research description for more information.

Research description

My research group defines the biochemical and medical importance of the five enzymes that post-translationally modify so-called CAAX proteins. CAAX proteins, including K-RAS, RAC1, and prelamin A, are involved in the pathogenesis of both common and rare diseases such as cancer, inflammatory disorders, and accelerated aging syndromes (progeria). Over the past 20 years, we have defined the role of the five enzymes; studied how their activities influence disease development; and evaluated their suitability as targets for new therapies.

To accomplish this, we have used a broad spectrum of research platforms of molecular, translational, and epidemiologic character. With support from US, European, and Swedish grant agencies—and by us highly appreciated awards and recognition—we have been given unique opportunities to perform curiosity-driven basic research and resources to capitalize on unexpected results—both within and outside the CAAX-protein field. Here are two examples:

First, our group discovered—contrary to popular belief—that antioxidants including vitamin E and beta-carotene accelerate the progression and metastasis of lung cancer and malignant melanoma—driven by the CAAX-protein oncoproteins KRAS and NRAS. Molecular analyses led to the identification of a new mechanism that drives metastasis: the transcription factor BACH1 is activated in response to dietary antioxidants and by endogenous cellular antioxidants; BACH1 switches on the expression of glycolytic genes, which stimulates aerobic glycolysis which in turn fuels cancer cell invasion and metastasis.

Overall, these results provide a potential explanation for the varying outcomes of clinical trials with antioxidants and a therapeutic opportunity to prevent lung cancer metastasis. They have also led to interesting discussions on cancer prevention and nutritional recommendations for cancer patients.

Second, we identified a new potential therapy for children with Hutchinson-Gilford Progeria Syndrome (HGPS). A mutation in the CAAX-protein prelamin A (LMNA) causes HGPS which is associated with rapid aging (hair loss, muscle weakness, arthritis, and osteoporosis) and death in teenage years from cardiovascular disease. We found that targeting prelamin A methylation by inhibiting the enzyme ICMT markedly improves disease phenotypes and survival in mice with progeria and overcomes senescence of cultured cells from children with HGPS.

Our main challenge for the future is to synthesize potent and specific ICMT inhibitors which will form the basis for further development and clinical trials.

10 Selected publications

'ROS-lowering doses of vitamins C and A accelerate malignant melanoma metastasis.
Kashif M, Yao H, Schmidt S, Chen X, Truong M, Tüksammel E, Liu Y, Bergo MO
Redox Biol 2023 Apr;60():102619

A small-molecule ICMT inhibitor delays senescence of Hutchinson-Gilford progeria syndrome cells.
Chen X, Yao H, Kashif M, Revêchon G, Eriksson M, Hu J, Wang T, Liu Y, Tüksammel E, Strömblad S, Ahearn IM, Philips MR, Wiel C, Ibrahim MX, Bergo MO
Elife 2021 Feb;10():

Knockout of the RAS endoprotease RCE1 accelerates myeloid leukemia by downregulating GADD45b.
Karlsson C, Akula MK, Staffas A, Cisowski J, Sayin VI, Ibrahim MX, Lindahl P, Bergo MO
Leukemia 2021 Feb;35(2):606-609

Targeting RAS-converting enzyme 1 overcomes senescence and improves progeria-like phenotypes of ZMPSTE24 deficiency.
Yao H, Chen X, Kashif M, Wang T, Ibrahim MX, Tüksammel E, Revêchon G, Eriksson M, Wiel C, Bergo MO
Aging Cell 2020 Aug;19(8):e13200

BACH1 Stabilization by Antioxidants Stimulates Lung Cancer Metastasis.
Wiel C, Le Gal K, Ibrahim MX, Jahangir CA, Kashif M, Yao H, Ziegler DV, Xu X, Ghosh T, Mondal T, Kanduri C, Lindahl P, Sayin VI, Bergo MO
Cell 2019 Jul;178(2):330-345.e22

Protein prenylation restrains innate immunity by inhibiting Rac1 effector interactions.
Akula MK, Ibrahim MX, Ivarsson EG, Khan OM, Kumar IT, Erlandsson M, Karlsson C, Xu X, Brisslert M, Brakebusch C, Wang D, Bokarewa M, Sayin VI, Bergo MO
Nat Commun 2019 Sep;10(1):3975

Antioxidants can increase melanoma metastasis in mice.
Le Gal K, Ibrahim MX, Wiel C, Sayin VI, Akula MK, Karlsson C, Dalin MG, Akyürek LM, Lindahl P, Nilsson J, Bergo MO
Sci Transl Med 2015 Oct;7(308):308re8

Antioxidants accelerate lung cancer progression in mice.
Sayin VI, Ibrahim MX, Larsson E, Nilsson JA, Lindahl P, Bergo MO
Sci Transl Med 2014 Jan;6(221):221ra15

Targeting isoprenylcysteine methylation ameliorates disease in a mouse model of progeria.
Ibrahim MX, Sayin VI, Akula MK, Liu M, Fong LG, Young SG, Bergo MO
Science 2013 Jun;340(6138):1330-3

Targeting GGTase-I activates RHOA, increases macrophage reverse cholesterol transport, and reduces atherosclerosis in mice.
Khan OM, Akula MK, Skålen K, Karlsson C, Ståhlman M, Young SG, Borén J, Bergo MO
Circulation 2013 Feb;127(7):782-90

Teaching portfolio

I taught in the dental and medical programs as an “amanuens” and PhD student at Umeå University. At the University of Gothenburg, I taught cell biology at the BMA program and also served in the Committee for Research Education at the University of Gothenburg during a period of extensive reorganization of the eligibility, scope, topics, courses, and financing of research education at the Sahlgrenska Academy. As a docent and professor, I mainly focused on teaching at masters and doctoral levels and have been main supervisor for 9 completed PhD students.

Another rewarding education-related experience is as a popular science lecturer to patient organizations, oncologists, nutritionists, dieticians, and the general public. Finally, I have 10 years of experience as chairman of the board for Folkuniversitetet väst where we focus on life-long learning and educational activities for all ages (such as folkbildning, schools for art, dance, and acting, and SFI, Komvux, Korta vägen, folkhögskolor, and gymnasier). I have thus gained a broad experience with education in Swedish society.

Education

Education
2023-2024 SUHF:s Higher academic leadership program (HeLP15)
2015 Professor, Karolinska Institutet
2010 Professor, University of Gothenburg
2005 Docent, University of Gothenburg
1998-2004 Postdoc, the University of California, San Francisco (UCSF)
1993-1998 PhD in medical biochemistry and biophysics
1995-1998 Medical school, Umeå University
1992-1993 Dental school, Umeå University
1991-1992 Chemistry and biology studies, Umeå University, Sweden
1990-1991 Military service

Academic honours, awards and prizes

Academic honours, awards and prizes
2022 Adjunct member of the Nobel Committee
2018 The Sjöberg Foundation
2018 The Nobel Assembly at Karolinska Institutet
2014 Project Grant, Knut & Alice Wallenberg Foundation, main applicant
2012 Göran Gustafsson’s Prize in Medicine, the Royal Swedish Academy of Sciences
2010 Albert Wallin’s Science Prize, the Royal Academy of Science and Arts in Gothenburg
2009 Senior Research Fellow, the Swedish Research Council
2008 Erik K. Fernströms prize for young scientists in medicine
2008 Senior Investigator Award, the Swedish Cancer Society
2007 ERC Starting Investigator Grant
2006 JoséCarreras Young Investigator Award, European Hematology Association
2005 KVA Akademiforskare”, the Royal Swedish Academy of Sciences
2004 National Institutes of Health (NIH) R21 grant, Principal investigator

Contact

Martin Bergö

Vice President

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BW
Content reviewer:
16-01-2024