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Marikki K. Laiho, M.D., Ph.D.

Photo of Dr. Marikki K. Laiho, M.D., Ph.D.
  • Director, Division of Molecular Radiation Sciences
  • Professor of Radiation Oncology and Molecular Radiation Sciences

Research Interests

DNA damage biology; Regulation and targeting of RNA polymerase I transcription; Nucleolar stress response

Background

Dr. Marikki K. Laiho is a Professor of Radiation Oncology and Molecular Radiation Sciences and Oncology at the Johns Hopkins University School of Medicine. Her laboratory has made several important findings on the regulation of p53 tumor suppressor protein in DNA damage and applied these to discovery screens and development of cancer therapeutic molecules.

Dr. Laiho serves as the Willard and Lillian Hackerman Professor of Radiation Oncology and director of the Division of Molecular Radiation Sciences. She co-directs the Cancer Chemical and Structural Biology Program and the Experimental Irradiators Core at the Johns Hopkins University Sidney Kimmel Cancer Center.

She received her bachelor of medicine, licentiate of medicine (M.D.), and Ph.D. degrees at the University of Helsinki. She performed a postdoctoral fellowship in biochemistry at the University of Massachusetts Medical Center and Sloan-Kettering Institute. Dr. Laiho joined the Johns Hopkins faculty in 2007.

Prior to joining Johns Hopkins, Dr. Laiho was a research associate in the Cell Biology and Genetics Program at Memorial Sloan-Kettering Cancer Center. She was also Director of the Molecular Cancer Biology Program at the University of Helsinki.

Her research interests include cancer biology and DNA damage biology.

Dr. Laiho serves on the School of Medicine Research Council at Johns Hopkins and several other institutional committees. Her work has been recognized by national and international awards, including the 2015 Harrington Scholar-Innovator Award. She has published over 100 peer-reviewed articles on cancer biology and the relevance and implications of cellular DNA damage response in cancer. Dr. Laiho holds a part-time position as Professor of Pharmaceutical Cell and Molecular Biology at the University of Helsinki, Finland.

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Titles

  • Director, Division of Molecular Radiation Sciences
  • Vice Chair for Research, Department of Radiation Oncology and Molecular Radiation Sciences
  • Co-Director, Cancer Chemical and Structural Biology Program, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
  • Willard and Lillian Hackerman Professor of Radiation Oncology
  • Professor of Radiation Oncology and Molecular Radiation Sciences
  • Professor of Oncology

Departments / Divisions

Centers & Institutes

Education

Additional Training

University of Massachusetts Medical Center, Worcester, MA, 1989, Postdoctoral Fellow

Research & Publications

Research Summary

Application of new cancer therapeutic strategies requires precise understanding of the drug mechanism of action and vulnerability of the cancer to the strategy. Remarkably, cancers have continuous demands for new protein synthesis to supply their growth and proliferation. The first and rate-limiting step in ribosome biosynthesis is RNA polymerase I (Pol I) transcription, and in most cancers this process is highly activated. These findings reveal a therapeutic vulnerability.

Despite the established connections between ribosome biosynthesis and cancer growth, attempts to exploit Pol I as a clinically relevant drug target have been limited. Dr. Laiho and her team have discovered and characterized a family of novel small-molecules that potently and selectively inhibit Pol I transcription. The mechanism of action of the molecules is unique and dependent on the Pol I enzyme. These new molecular entities directly and specifically inhibit Pol I transcription. There are no comparators as other molecules classified as Pol I inhibitors act by targeting cellular topoisomerases. The highly innovative revelations by Dr. Laiho’s team affirm that tumor cells are more dependent on ribosome biogenesis than normal cells and that therapeutic index is attainable. 

The team uses unbiased, broad genomic and cancer cell line vulnerability screens and detailed mechanistic analyses to uncover biomarkers denoting sensitivity. These approaches facilitate the therapeutic use of Pol I inhibitors in the clinic and aid in identifying patients benefiting from this strategy. Their work is built on interdisciplinary expertise in cancer biology, drug discovery, development, and preclinical modeling and aims at clinical translation of these advances.

Lab

Dr. Laiho’s lab seeks to understand the regulatory events that prevail in cancer cells, and detect and exploit cancer cell characteristics that could be used as basis of new cancer therapies.

The approaches used in the laboratory are aimed to provide novel information on the regulation of cellular DNA damage and tumorigenesis pathways, to identify new targets for therapy, and to apply this knowledge to therapy efforts. The studies aim at a rapid transfer of findings arising from focused mechanistic studies into translational cancer research.

Lab Website: Marikki Laiho Lab

Clinical Trials

Learn more about clinical trials at the Johns Hopkins Kimmel Cancer Center.

Selected Publications

View all on Pubmed

Peltonen K, Colis L, Liu H, Trivedi R, Moubarek MS, Moore HM, Bai B, Rudek MA, Bieberich CJ, Laiho, M. A targeting modality for destruction of RNA polymerase I that possesses anticancer activity. Cancer Cell 25(1):77-90, 2014

Peltonen K, Colis L, Liu H, Jaamaa S, Zhang Z, af Hallstrom T, Moore HM, Sirajuddin P, Laiho M. Small molecule BMH-compounds that inhibit RNA polymerase I and cause nucleolar stress. Mol. Cancer Ther. 13(11): 2537-2546, 2014

Wei T, Najmi SM, Liu H, Peltonen K, Kucerova A, Schneider DA, Laiho M. Small-molecule Targeting of RNA Polymerase I Activates a Novel, Conserved Transcription Elongation Checkpoint. Cell Reports 23: 404-414, 2018

Low JI*, Sirajuddin P*, Moubarek M, Agarwal S, Rege A, Liu H, Yang Z, De Marzo AM, Bieberich C, Laiho M. Effective targeting of RNA polymerase I in treatment-resistant prostate cancer. The Prostate 79(16):1837-1851, 2019

Low JY, Brennen WN, Meeker AK, Ikonen E, Simons BW, Laiho M. Stromal CAVIN1 controls prostate cancer microenvironment and metastasis by modulating lipid distribution and inflammatory signaling. Mol. Cancer Res. 18(9):1414-1426,2020

Contact for Research Inquiries

Phone: 410-502-9748

Academic Affiliations & Courses

Graduate Program Affiliation

Cellular and Molecular Medicine

Pathobiology

Courses and Syllabi

  • Radiobiology (Course Director)

Activities & Honors

Honors

  • Helsinki City Science Prize, 2003
  • The Finnish Academy of Science and Letters, Member, The Finnish Academy of Science and Letters, 2008
  • Prostate Cancer Foundation Global Challenge Award, Prostate Cancer Foundation, 2014
  • Harrington Scholar-Innovator Award, Harrington Institute, 2014
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