Laura Baranello
About me
Chromatin Biology, Topoisomerases and Cancer
I received my PhD from the University of Bologna, Italy. During my PhD training with Prof. Capranico, I became fascinated by the mechanism of topoisomerases in regulating the topology of DNA during transcription and replication, a truly fundamental processes in life.As a postdoctoral fellow, I joined the laboratory of Dr. Levens at the National Institutes of Health (NIH). During my postdoctoral training I developed a variety of new protocols for next generation sequencing that opened new horizons for the study of DNA topology. Specifically, I discovered a new mechanism that synchronizes the activity of topoisomerase 1 with the state of RNA polymerase.
In 2016, I became Assistant Professor–Group Leader and Wallenberg Academy Fellow at ̽ѡ, Department of Cell and Molecular Biology, Stockholm (Sweden). My research program aims to define the still unknown mechanisms of topoisomerase regulation that sustain the proliferation of cancer cells. My long-term goal is to target the regulation of topoisomerases to halt cancer progression.
2021 Cancerfonden-Project Grant
2021 Vetenskapsrådet-Project Grant (MH)
2020 EMBO
2019 NBIS
2018 Cancerfonden-Project Grant
2018 KID Funding
2018 KI Fonder
2016 Wallenberg Academy Fellow in Medicine
2016 KI Faculty Funded Position as Assistant Professor
2016 Vetenskapsrådet-Starting Grant (MH)
2016 VINNOVA Marie Sklodowska-Curie Fellowship
2012 FARE (Fellows Award for Research Excellence), NIH (USA)
2010–2017 Postdoctoral Fellow with Dr. Levens, National Institutes of Health (NIH, USA)
2007–2010 PhD in Cellular, Molecular and Industrial Biology, with Prof. Capranico, University of Bologna (Italy)
Research
Mechanism and targeting of topoisomerase regulation
Cancer is a biologically complex disease that causes significant deaths in the human population. Pharmaceuticals that inhibit enzymes called topoisomerases are effective at killing many types of cancer cells. Unfortunately, the body’s healthy cells are also damaged by this treatment.
Development of tumor-specific topoisomerase inhibitor-based therapies will require better knowledge of the mechanism of topoisomerase activity.
Topoisomerases are important cellular enzymes; they are involved in processes in which genes are copied, or when DNA is replicated prior to cell division. They unwind the DNA double helix, so that the enzymes that are going to transcribe genes or replicate DNA strands are able to do so. Although conventionally considered to be constitutively active enzymes, recent evidence show that topoisomerases execute their function through regulatory interactions with partner proteins that modulate their activity to affect the transcriptional outcome. Understanding the mechanism of this regulation might provide a new strategy to affect topoisomerase activity in cancer cells.
Our ongoing and future investigations are based on these findings. We use a variety of approaches including biochemical assays, next-generation sequencing techniques, genome editing and drug screens to:
- Identify new proteins regulating topoisomerase 1 and topoisomerase 2 activity. Among the potential partners we focus on transcription and chromatin factors.
- Understand the molecular details of how topoisomerases are regulated by their protein partners during transcription.
- Identify drugs targeting the stimulation of topoisomerase activity in cancer cells.
Conference organiser
- Cold Spring Harbor meeting 2024 ""
- EMBO workshop
- Cell and Molecular Biology seminar series
Teaching
Medical Program courses
"The healthy human"PhD courses
"The epigenome: a platform for the integration of metabolic and signaling pathways in development and on the path to diseases""Cell cycle, cancer and anti-cancer targets"
Articles
- Article: NATURE COMMUNICATIONS. 2025;16(1):7458Lee T-H; Qiao CX; Kuzin V; Shi Y; Farkas M; Zhao Z; Ramanarayanan V; Wu T; Guan T; Zhou X; Corujo D; Buschbeck M; Baranello L; Oberdoerffer P
- Article: SCIENCE ADVANCES. 2023;9(41):eadg5109Cameron DP; Grosser J; Ladigan S; Kuzin V; Iliopoulou E; Wiegard A; Benredjem H; Jackson K; Liffers ST; Lueong S; Cheung PF; Vangala D; Pohl M; Viebahn R; Teschendorf C; Wolters H; Usta S; Geng K; Kutter C; Arsenian-Henriksson M; Siveke JT; Tannapfel A; Schmiegel W; Hahn SA; Baranello L
- Article: SCIENCE ADVANCES. 2023;9(30):eadg1805Pederiva C; Trevisan DM; Peirasmaki D; Chen S; Savage SA; Larsson O; Ule J; Baranello L; Agostini F; Farnebo M
- Article: SCIENCE ADVANCES. 2022;8(49):eabq0648Meroni A; Grosser J; Agashe S; Ramakrishnan N; Jackson J; Verma P; Baranello L; Vindigni A
- Article: STAR PROTOCOLS. 2022;3(3):101581Kuzin V; Wiegard A; Cameron DP; Baranello L
- Article: CANCER RESEARCH COMMUNICATIONS. 2022;2(3):182-201Castell A; Yan Q; Fawkner K; Bazzar W; Zhang F; Wickstrom M; Alzrigat M; Franco M; Krona C; Cameron DP; Dyberg C; Olsen TK; Verschut V; Schmidt L; Lim SY; Mahmoud L; Hydbring P; Lehmann S; Baranello L; Nelander S; Johnsen JI; Larsson L-G
- Article: MOLECULAR CELL. 2022;82(1):140-158.e12Das SK; Kuzin V; Cameron DP; Sanford S; Jha RK; Nie Z; Rosello MT; Holewinski R; Andresson T; Wisniewski J; Natsume T; Price DH; Lewis BA; Kouzine F; Levens D; Baranello L
- Article: MOLECULAR CELL. 2021;81(24):5007-5024.e9Wiegard A; Kuzin V; Cameron DP; Grosser J; Ceribelli M; Mehmood R; Ballarino R; Valant F; Grochowski R; Karabogdan I; Crosetto N; Lindqvist A; Bizard AH; Kouzine F; Natsume T; Baranello L
- Article: PLOS PATHOGENS. 2021;17(9):e1009954Li J; Nagy N; Liu J; Gupta S; Frisan T; Hennig T; Cameron DP; Baranello L; Masucci MG
- Article: PLOS GENETICS. 2021;17(9):e1009763Wu P-S; Grosser J; Cameron DP; Baranello L; Strom L
- Article: LIFE SCIENCE ALLIANCE. 2021;4(3):e202000980Cascales HS; Burdova K; Middleton A; Kuzin V; Mullers E; Stoy H; Baranello L; Macurek L; Lindqvist A
- Article: METHODS IN MOLECULAR BIOLOGY. 2021;2318:161-185Cameron DP; Kuzin V; Baranello L
- Article: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2020;117(24):13457-13467Devaiah BN; Mu J; Akman B; Uppal S; Weissman JD; Cheng D; Baranello L; Nie Z; Levens D; Singer DS
- Article: MOLECULAR CELL. 2019;75(2):267-283.e12Gothe HJ; Bouwman BAM; Gusmao EG; Piccinno R; Petrosino G; Sayols S; Drechsel O; Minneker V; Josipovic N; Mizi A; Nielsen CF; Wagner E-M; Takeda S; Sasanuma H; Hudson DF; Kindler T; Baranello L; Papantonis A; Crosetto N; Roukos V
- Article: CELL. 2018;173(5):1165-1178.e20Vian L; Pekowska A; Rao SSP; Kieffer-Kwon K-R; Jung S; Baranello L; Huang S-C; El Khattabi L; Dose M; Pruett N; Sanborn AL; Canela A; Maman Y; Oksanen A; Resch W; Li X; Lee B; Kovalchuk AL; Tang Z; Nelson S; Di Pierro M; Cheng RR; Machol I; St Hilaire BG; Durand NC; Shamim MS; Stamenova EK; Onuchic JN; Ruan Y; Nussenzweig A; Levens D; Aiden EL; Casellas R
- Article: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 2018;19(3):E884-884Bjorkegren C; Baranello L
- Article: METHODS IN MOLECULAR BIOLOGY. 2018;1672:155-166Baranello L; Kouzine F; Wojtowicz D; Cui K; Zhao K; Przytycka TM; Capranico G; Levens D
- Article: METHODS IN MOLECULAR BIOLOGY. 2018;1703:95-108Kouzine F; Baranello L; Levens D
- Article: MOLECULAR CELL. 2017;67(6):1013-1025.e9Porter JR; Fisher BE; Baranello L; Liu JC; Kambach DM; Nie Z; Koh WS; Luo J; Stommel JM; Levens D; Batchelor E
- Article: MOLECULAR CELL. 2017;67(4):566-578.e10Kieffer-Kwon K-R; Nimura K; Rao SSP; Xu J; Jung S; Pekowska A; Dose M; Stevens E; Mathe E; Dong P; Huang S-C; Ricci MA; Baranello L; Zheng Y; Ardori FT; Resch W; Stavreva D; Nelson S; McAndrew M; Casellas A; Finn E; Gregory C; St Hilaire BG; Johnson SM; Dubois W; Cosma MP; Batchelor E; Levens D; Phair RD; Misteli T; Tessarollo L; Hager G; Lakadamyali M; Liu Z; Floer M; Shroff H; Aiden EL; Casellas R
- Article: CELL SYSTEMS. 2017;4(3):344-356.e7Kouzine F; Wojtowicz D; Baranello L; Yamane A; Nelson S; Resch W; Kieffer-Kwon K-R; Benham CJ; Casellas R; Przytycka TM; Levens D
- Journal article: BIOPHYSICAL REVIEWS. 2016;8(3):259-268Levens D; Baranello L; Kouzine F
- Article: CHROMOSOME RESEARCH. 2016;24(2):175-181Baranello L; Kouzine F; Sanford S; Levens D
- Article: CELL. 2016;165(2):357-371Baranello L; Wojtowicz D; Cui K; Devaiah BN; Chung H-J; Chan-Salis KY; Guha R; Wilson K; Zhang X; Zhang H; Piotrowski J; Thomas CJ; Singer DS; Pugh BF; Pommier Y; Przytycka TM; Kouzine F; Lewis BA; Zhao K; Levens D
- Article: AMERICAN JOURNAL OF HUMAN GENETICS. 2016;98(4):627-642Kuschal C; Botta E; Orioli D; Digiovanna JJ; Seneca S; Keymolen K; Tamura D; Heller E; Khan SG; Caligiuri G; Lanzafame M; Nardo T; Ricotti R; Peverali FA; Stephens R; Zhao Y; Lehmann AR; Baranello L; Levens D; Kraemer KH; Stefanini M
- Article: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 2014;15(7):13111-13122Baranello L; Kouzine F; Wojtowicz D; Cui K; Przytycka TM; Zhao K; Levens D
- Article: NUCLEUS. 2014;5(3):195-202Kouzine F; Levens D; Baranello L
- Article: NATURE STRUCTURAL & MOLECULAR BIOLOGY. 2013;20(3):396-403Kouzine F; Gupta A; Baranello L; Wojtowicz D; Ben-Aissa K; Liu J; Przytycka TM; Levens D
- Article: NUCLEIC ACIDS RESEARCH. 2010;38(1):159-171Baranello L; Bertozzi D; Fogli MV; Pommier Y; Capranico G
- Article: BIOCHIMIE. 2007;89(4):482-489Capranico G; Ferri F; Fogli MV; Russo A; Lotito L; Baranello L
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All other publications
- Review: ANNUAL REVIEW OF BIOCHEMISTRY. 2025;94(1):333-359Baranello L; Kouzine F; Levens D
- Preprint: BIORXIV. 2024;BIORXIVLee T-H; Qiao CX; Kuzin V; Shi Y; Ramanaranayan V; Wu T; Zhou X; Corujo D; Buschbeck M; Baranello L; Oberdoerffer P
- Conference publication: BIOPHYSICAL JOURNAL. 2018;114(3):13ALevens D; Kouzine F; Baranello LF
- Book chapter: NUCLEAR ARCHITECTURE AND DYNAMICS. 2018;p. 81-99Baranello L; Levens D; Kouzine F
- Preprint: BIORXIV. 2017Cascales HS; Burdova K; Middleton A; Kuzin V; Müllers E; Stoy H; Baranello L; Macurek L; Lindqvist A
- Review: BIOPHYSICAL REVIEWS. 2016;8(Suppl 1):23-32Levens D; Baranello L; Kouzine F
- Editorial comment: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2014;111(3):889-890Baranello L; Kouzine F; Levens D
- Review: TRANSCRIPTION. 2013;4(5):232-237Baranello L; Kouzine F; Levens D
- Review: BIOCHIMICA ET BIOPHYSICA ACTA: INTERNATIONAL JOURNAL OF BIOCHEMISTRY AND BIOPHYSICS. 2012;1819(7):632-638Baranello L; Levens D; Gupta A; Kouzine F
- Book chapter: DNA TOPOISOMERASES AND CANCER: CANCER DRUG DISCOVERY AND DEVELOPMENT. 2012;p. 309-324Capranico G; Baranello L; Bertozzi D; Marinello J
- Review: BIOCHIMICA ET BIOPHYSICA ACTA: INTERNATIONAL JOURNAL OF BIOCHEMISTRY AND BIOPHYSICS. 2010;1806(2):240-250Capranico G; Marinello J; Baranello L
Grants
- Swedish Research Council1 January 2025 - 31 December 2029Inhibitors of Topoisomerases (TOPs, TOP1, TOP2) are mainstays of anticancer therapy. While they have proven effective, the toxicity of current TOP drugs in non-cancer cells, limits their use. Development of tumour-specific TOP inhibitors will require a better knowledge of TOPs. This project will define how TOP are regulated and target these regulatory mechanisms with drugs. TOPs promote transcription and replication by cleaving/resealing DNA strands, removing supercoils generated during polymerase elongation. In my works published in Cell and Mol Cell, I discovered that the activity of TOPs is regulated. The oncoprotein MYC joins TOP1 and TOP2 in a topoisome complex and stimulates their activities to boost cell proliferation. Targeting the mechanism of the topoisome instead of the single TOPs might selectively halt MYC while preserving physiological TOP activity, avoiding DNA damage associated to current TOP drugs.By using genomics, biochemical and microscopy approaches, as well as drug screens, I will define the mechanism of MYC-driven cellular proliferation via regulation of the topoisome and develop drugs blocking the topoisome to arrest tumor growth. This project is feasible based on compelling preliminary data and collaborations. The work will identify novel drugs to target TOPs that can be put forward in clinical trials for the benefit of the society. This new way of targeting TOPs to affect MYC is a beyond the state-of-the-art approach to the field of cancer biology.
- Swedish Research Council1 January 2023 - 31 December 2027Inhibitors of DNA topoisomerases (TOPs, TOP1 and TOP2) are mainstays of anticancer therapy. While they have proven effective, the toxicity of current TOP drugs in non-cancer cells, limits their use. Development of tumour-specific TOP inhibitors will require a better knowledge of the mechanisms of TOP. This proposal will define how TOP are regulated and will target these regulatory mechanisms with drugs.My works published in Cell and Molecular Cell have shown that the DNA cleavage-religation activity of TOPs is regulated. The oncoprotein MYC joins TOP1 and TOP2 in a “topoisome” complex and stimulates their activities to remove the supercoiling produced during transcription and replication, thus boosting cellular proliferation. Therefore, targeting the mechanism of the topoisome instead of the single TOPs, will selectively halt MYC oncogenic function while preserving physiological TOP activity, avoiding the generation of DNA damage associated to current TOP drugs.By using new genomic tools to study TOPs, biochemical and microscopy approaches, as well as drug screens, I will define the mechanism of MYC-driven transcriptional amplification via topoisome assembly and develop drugs blocking topoisome activity to arrest tumour growth. This proposal is highly feasible based on my background, compelling preliminary data, and strong collaborations with KI and NIH. My work will identify novel ways to target TOPs that can be put forward in clinical trials for the benefit of society.
- Swedish Research Council1 January 2022 - 31 December 2024
- Swedish Cancer Society1 January 2022Cancer is a biologically complex disease and is today one of the most common causes of death. Blocking topoisomerase enzymes (TOP1 and TOP2) is one of the cornerstones of today's cancer treatment, and is used against several common tumor types, such as breast, colon, lung, and ovarian cancer. Despite their good anticancer effect, the use of today's topoisomerase-inhibiting drugs is limited by their toxic effect on healthy cells. Developing new -topoisomerase inhibitors that only inhibit tumor cells is therefore of great importance, but to achieve this goal, in-depth knowledge of the mechanisms that regulate the cellular activity of topoisomerases is required. This project aims to define the molecular mechanisms that regulate the role of topoisomerases in RNA transcription. In my work, published in the prestigious journal Cell, I show that TOP1 is controlled by other enzymes and is not constantly active as previously thought. In my recent work, which is under review in Cell, I show that the oncoprotein MYC interacts with topoisomerases and stimulates their activity to promote rapid cellular growth. Our findings make the MYC/TOP system an attractive candidate for the development of drugs that target the activation of topoisomerases in the treatment of MYC-driving tumors. Using biochemical analysis, sequencing methods and drug screening, I will characterize how MYC regulates topoisomerases and identify drugs that target the MYC/TOP interaction. In fact, I have already developed a drug cocktail that has high anticancer potential but reduced toxicity. I now want to test this cocktail in preclinical models of colon and pancreatic cancer. The work will lead to the identification of a new strategy for gentler cancer treatments that can be tested in future clinical trials to improve both survival and quality of life in cancer patients.
- Functional characterization of topoisomerase regulatory interactions, for targeted anticancer therapySwedish Cancer Society1 January 2018Cancer is a biologically complex disease and one of the most common causes of death. Inhibition of the enzymes topoisomerase (TOP) TOP1 and TOP2 are one of the cornerstones of today's cancer treatment, and are used against several common tumor diseases in both men and women, such as breast, colon, lung, ovarian cancer. Despite their good anticancer effect, the use of current TOP inhibitory drugs is limited by their toxic effect on healthy cells. Developing new TOP inhibitors that only inhibit tumor cells is therefore of great importance, but in order to achieve this goal, in-depth knowledge of the mechanisms regulating the cellular activity of the topoisomerases is required. This project aims to map the molecular mechanisms that control the role of TOP enzymes in gene regulation and, based on this, find new targets to fight for specifically killing cancer cells. In my latest publication in the well-reputed Cell, I present the groundbreaking discovery that the TOP activity is stimulated by the enzyme RNA polymerase II. Because rapidly dividing cancer cells require higher gene expression than normal cells, they are also expected to require higher TOP activity. My hypothesis is therefore that specific inhibition of growing cancer cells can be achieved by blocking the proteins that stimulate TOP over its basic level of activity. By using biochemical and sequencing methods and screening of drug candidates, in this project I will identify new proteins that regulate TOP and the mechanisms for how they regulate TOP. Furthermore, based on these discoveries, I will explore new potential drugs that specifically target the proteins that regulate TOP. The work will lead to the identification of new cancer drugs that can be evaluated in future clinical trials to directly improve the survival and quality of life of cancer patients.
- Swedish Research Council1 January 2017 - 31 December 2020
- VINNOVA1 August 2016 - 30 December 2019