About

Peter L. Olson is a Research Professor in the Department of Earth & Planetary Sciences at Johns Hopkins University. His research focuses on understanding the dynamics of Earth's interior, including the mantle and the core. Olson is especially interested in how these major parts of the Earth interact to produce plate tectonics, deep mantle plumes, and the geomagnetic field, as well as the formation of the Earth's core. His approach combines theory, numerical models, and laboratory fluid dynamics models to interpret global geophysical data related to the Earth's deep interior and other planets. Olson specializes in the dynamics of Earth's core, particularly the magnetohydrodynamic processes responsible for generating the geomagnetic field in the fluid outer core, and how this process is influenced by the solid inner core and the lower mantle. Recently, he has begun a systematic investigation of the slow carbon cycle, focusing on the cycling of carbon through the components of the Earth system that control climate on geologic timescales. This work is conducted in collaboration with colleagues in EPS and other U.S. institutions, involving graduate students and postdoctoral researchers at Johns Hopkins.

Research topics

• Medicine
• Biology
• Geology
• Physics
• Astronomy
• Astrobiology
• Geochemistry
• Paleontology
• General surgery
• Thermodynamics
• Traditional medicine
• Intensive care medicine
• Oncology
• Cancer research
• Geophysics
• Astrophysics
• Surgery
• Family medicine
• Internal medicine

Selected publications

• Depletion of moderately volatile elements by pebble accretion in Earth-like planets

  Icarus · 2026-04-18

  article1st authorCorresponding
  PublisherDOI

• Chondritic component pebbles as sources of Earth’s composition and water

  2025-01-01

  article
  PublisherDOI

• Abstract 5637: A novel KIF18A inhibitor for targeting chromosomal instability in cancer

  Cancer Research · 2025-04-21

  article

  Abstract Anti-mitotic drugs are frequently used to treat cancer and many work by targeting microtubules and disrupting the mitotic phase of the cell cycle. However, dose-limiting toxicity associated with inhibition of cell division in normal cells limits the clinical benefit of this drug class. The spindle assembly checkpoint (SAC) has emerged as a vulnerability for cancer cells with chromosomal instability due to their increased dependence on proper chromosome alignment. KIF18A is a kinesin family motor protein that promotes chromosome alignment by dampening chromosome oscillation. Targeting KIF18A provides an opportunity for cancer-specific dysregulation of the SAC and therefore a significantly improved therapeutic window. Here we describe a novel series of potent KIF18A inhibitors (IC50 < 30 nM) in both KIF18A ATPase biochemical and OVCAR-3 cell growth inhibition assays. These KIF18A inhibitors demonstrated >300-fold selectivity against other kinesins that are essential for various cellular functions. The high selectivity of these inhibitors is reflected in the lack of in vitro toxicity in normal dividing cells and bone marrow hematopoietic progenitor cells. Furthermore, the anti-proliferative activity is highly correlated with biochemical activity, with increased levels of the mitotic phase biomarker pHH3, and with increased arrest of cells in the mitotic phase. Utilizing the predictive power of Iambic’s AI-driven platform, compounds in this series were optimized to exhibit a favorable ADME profile, low risk of drug-drug interaction liabilities and good bioavailability across multiple rodent and non-rodent preclinical species. The lead molecule IAM-K1 in this series is negative in the mini Ames genotoxicity test and has favorable predicted human pharmacokinetics and metabolism. IAM-K1 displays >10 uM direct IC50 inhibition against the major human cytochrome P450 enzymes, including 2C9, 2C19 and 3A4, reducing the risk to alter the metabolism of co-administered drugs. IAM-K1 has robust anti-proliferation activity in a number of cell lines, representing different cancer indications, and is approximately 2-3 fold more potent than a reference compound AMG650. Furthermore, IAM-K1 achieves similar PD and TGI efficacy as AMG650 in vivo at much lower systemic exposure. Repeat oral dosing of IAM-K1 led to durable tumor regression in the OVCAR-3 xenograft mouse model without impacting body weight. The anti-tumor activity is correlated with an increase in pHH3 in xenograft tumors, consistent with the on-target mechanism of mitotic arrest. Together with a predictive biomarker approach, targeting KIF18A with IAM-K1 and other compounds in this series is expected to provide a novel anti-cancer treatment to patients with a wide therapeutic window. Citation Format: Lana Kulyk, Shawn Wright, Jill Hallin, Michael Maestre, Joseph Dennis, Iriny Botrous, Anders S. Christensen, Jan Pencik, Craig Gutierrez, Afsheen Banisadr, Jeeyoung Park, Abby Adams, Chang Zhao, Kelly Chen, Stephen Munoz, Shane Yost, Marcelo Lacerda, Angus Voice, Mary L. Anderson, Bo Liu, Matt Welborn, Chao Zhang, Jeff Hager, Fred Manby, Tom Miller, Hui Zhang, Laurent Gomez, Peter Olson, Zhongdong Huang, Chunmei Zhao. A novel KIF18A inhibitor for targeting chromosomal instability in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5637.

  PublisherDOI

• Abstract 3786: Combination of MTA-cooperative PRMT5 inhibitor BMS-986504 and KRAS inhibitors for the treatment of <i>MTAP</i>-deleted <i>KRAS</i>-mutant pancreatic cancer

  Cancer Research · 2025-04-21 · 2 citations

  article

  Abstract Protein arginine methyltransferase 5 (PRMT5) is a synthetic lethal target in cancers harboring genomic deletions of the MTAP gene, which encodes the enzyme methylthioadenosine phosphorylase. Approximately one in four pancreatic ductal adenocarcinoma (PDAC) cases harbor homozygous deletion of the MTAP gene (MTAP-del), providing a promising novel targeted therapy for PDAC. The methylthioadenosine (MTA)-cooperative PRMT5 inhibitor BMS-986504 (previously known as MRTX1719) leverages the elevated MTA levels present in MTAP-del tumors to selectively block PRMT5 function in cancer but not normal cells and tissues. BMS-986504 demonstrated clinical activity in MTAP-del cancers without the dose-limiting hematological toxicity associated with previous first-generation PRMT5 inhibitors, however the utility of this approach has not been thoroughly investigated in PDAC. Here, we demonstrated that BMS-986504 suppressed PRMT5 function and cell growth in MTAP-del PDAC cells in vitro and in established cell line- and patient-derived xenograft mouse models. Furthermore, CRISPR/Cas9 screens were performed using the MTAP-del, KRAS-mutant MIA PaCa-2 cell line in vitro and in vivo to identify genes that modulated sensitivity to BMS-986504. We identified KRAS as one of the top depleted target genes in both screens (in the top 50 in vitro and the top 20 in vivo). We validated co-targeting KRAS as a combination strategy and found that combined small molecule inhibition of PRMT5 and G12C/D-mutant KRAS (using adagrasib and MRTX1133, respectively) effectively suppressed MTAP-del PDAC growth in vitro and in vivo. We also performed RNA-Seq analysis and determined that PRMT5 inhibition disrupts RNA splicing of genes that are essential for PDAC growth. Further, we determined that, while PRMT5 and KRAS regulate distinct transcriptomes, they converge on common pathways governing cancer cell growth and combined inhibition of PRMT5 and KRAS caused marked downregulation of PDAC-essential genes. These findings provide a rationale for combined inhibition of PRMT5 and KRAS to maximize targeted therapies for MTAP-del and KRAS-mutant biomarker-positive PDAC. Citation Format: Kristina Drizyte-Miller, Lars D. Engstrom, Jeffrey A. Klomp, Clint A. Stalnecker, Laura Waters, Andrew Calinisan, Ryan Robb, Khalilah E. Taylor, Mallory K. Roach, Addison G. Stamey, Seamus Degan, Wen-Hsuan Chang, Xousaen M. Helu, David Nguyen, Laura D. Hover, Elisa Baldelli, Mariaelena Pierobon, Emanuel F. Petricoin, Kirsten L. Bryant, David M. Briere, James G. Christensen, Jill Hallin, Adrienne D. Cox, Peter Olson, Channing J. Der. Combination of MTA-cooperative PRMT5 inhibitor BMS-986504 and KRAS inhibitors for the treatment of MTAP-deleted KRAS-mutant pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3786.

  PublisherDOI

• Abstract CT079: Pharmacodynamic (PD) and exploratory biomarker (BM) analysis of the PRMT5 inhibitor BMS-986504 in patients (pts) with advanced solid tumors with homozygous MTAP deletion (<i>MTAP</i>-del)

  Cancer Research · 2025-04-25 · 1 citations

  article

  Abstract Background: Effective treatments (Tx) are needed for MTAP-del cancers (10-15% of all cancers). BMS-986504 (formerly MRTX1719) is a potential first-in-class MTA-cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor that selectively binds to the PRMT5-MTA complex, a synthetic lethal target in MTAP-del but not MTAP-wild-type cells. In the first-in-human phase 1/2 CA240-0007 study, BMS-986504 was well tolerated and showed clinical activity in heavily pretreated pts across multiple advanced solid tumors with homozygous MTAP-del. Here, we report results of exploratory PD analyses of PRMT5 inhibition with BMS-986504 in CA240-0007. Methods: Pts with advanced, unresectable or metastatic solid tumors with homozygous MTAP-del received BMS-986504 (50 to 800 mg) in 3-wk cycles. Symmetric dimethylarginine (SDMA) and intron retention are known PD BMs of PRMT5 inhibition. Therefore, PD effects of BMS-986504 were assessed via changes in plasma and tumor SDMA levels (mass spec and IHC), intron retention, and gene expression (RNASeq) based on samples collected at baseline (BL) and cycle 2 day 1 (C2D1). Additional analyses correlating efficacy outcomes with PD results and select mutations at BL were performed in clinically evaluable pts as of 19-SEP-24. Results: Robust PD modulation of the PRMT5 pathway was observed with BMS-986504. Among pts with matched samples (n = 63), median plasma SDMA levels were reduced by 56% from BL (122.6 ng/mL) to C2D1 (53.8 ng/mL). There were dose-dependent reductions in median plasma SDMA with the greatest reductions at 400 mg QD (59.7% [n = 20]), 400 mg BID (61.9% [n = 9]) and 600 mg QD (59.1% [n = 14]). These PD effects were corroborated in the tumor. Median tumor SDMA levels decreased from an HScore of 285 at BL to 0 at C2D1. Consistent with the SDMA decreases, increased intron retention was observed in 9/11 pts with matched samples. BMS-986504 led to downregulation of several gene pathways including DNA repair and mitotic spindle formation, and MYC and E2F targets, as assessed by RNASeq. There was no significant change in expression of MAT2A, PRMT5, or other PRMT genes, suggesting a lack of compensation for PRMT5 inhibition through these genes. Responses were observed with BMS-986504 across EGFR, KRAS, and TP53 mutation subgroups. Additional correlative analyses among BMs and efficacy outcomes will be presented. Conclusions: BMS-986504 demonstrated robust PD effects across multiple doses and solid tumors which is consistent with the proposed mechanism of action. There was a trend of increasing plasma SDMA reduction across doses, with the greatest reductions observed at 400 mg QD and above. Together these results support further investigation of BMS-986504 at 400 mg QD and higher doses as a potential first-in-class synthetic lethal Tx option in pts with advanced solid tumors with MTAP-del. Citation Format: Jordi Rodón, Tyler Simpson, Ben George, Pasi A. Jänne, Kathryn C. Arbour, Konstantinos Leventakos, Kyriakos P. Papadopoulos, Melissa L. Johnson, Alexander I. Spira, Cesar A. Perez, Hani M. Babiker, Richard Zuniga, Candace L. Haddox, Tapsi Kumar, Yidi Qin, Wen-Chi Chou, Peter Olson, Kenna Anderes, Alice Wozniak, Curtis Chin, Ming Lei, Jason T. Henry. Pharmacodynamic (PD) and exploratory biomarker (BM) analysis of the PRMT5 inhibitor BMS-986504 in patients (pts) with advanced solid tumors with homozygous MTAP deletion (MTAP-del) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT079.

  PublisherDOI

• P3.03.29 IAM1363 Is a Potent, Selective, and Irreversible HER2 and Pan-HER2 Mutant Small Molecule Inhibitor for the Treatment of HER2-Driven NSCLC

  Journal of Thoracic Oncology · 2025-10-01

  article
  PublisherDOI

• Adeno-to-squamous transition drives resistance to KRAS inhibition in LKB1 mutant lung cancer

  Cancer Cell · 2024 · 108 citations

  • Cancer research
  • Biology
  • Medicine

  lung cancer mouse models and organoids treated with KRAS inhibitors reveal tumors invoke a lineage plasticity program, adeno-to-squamous transition (AST), that enables resistance to KRAS inhibition. Transcriptomic and epigenomic analyses reveal ΔNp63 drives AST and modulates response to KRAS inhibition. We identify an intermediate high-plastic cell state marked by expression of an AST plasticity signature and Krt6a. Notably, expression of the AST plasticity signature and KRT6A at baseline correlates with poor adagrasib responses. These data indicate the role of AST in KRAS inhibitor resistance and provide predictive biomarkers for KRAS-targeted therapies in lung cancer.

  PublisherDOI

• Pebble accretion and siderophile element partitioning between Earth's mantle and core

  Physics of The Earth and Planetary Interiors · 2024-12-10 · 4 citations

  article1st authorCorresponding
  PublisherDOI

• Building Earth with pebbles made of chondritic components

  Geochimica et Cosmochimica Acta · 2024-11-24 · 6 citations

  articleOpen access
  PublisherOA PDFDOI

• Comment on "Did the terrestrial planets of the Solar System form by pebble accretion?"

  arXiv (Cornell University) · 2024-11-26 · 1 citations

  preprintOpen access

  Morbidelli, Kleine &amp; Nimmo (2024) (MKN) recently published a critical analysis on whether the terrestrial planets in the Solar System formed by rapid pebble accretion or by the classical route of multiple giant impacts between planetary embryos after the dissipation of the protoplanetary disc. They arrive at the conclusion that the terrestrial planets did not form by pebble accretion. Although we welcome debate on this topic, we want to emphasize here several points that we disagree on. We will not address in detail every claim made in MKN, but rather stick to four main points. Our conclusion is that pebble accretion remains a viable mechanism to drive significant growth of protoplanets in the protoplanetary disc, with as much as 70% of Earth formed by pebble accretion. This rapid growth phase must nevertheless have been followed by an extended period of collisional growth after the end of the protoplanetary disc phase, likely culminating with the moon-forming giant impact. We emphasize here an important recent result from Olson &amp; Sharp (2023), namely that significant growth by pebble accretion can be reconciled with the Hf-W decay system even for a canonical moon-forming giant impact with a Mars-mass protoplanet and a low equilibration efficiency - a more massive impactor, as proposed in Johansen et al. (2023), is not necessary. Given that terrestrial planet formation naturally involves both pebble accretion and a combination of small and large impactors, this challenges the very notion of making an either/or distinction between the classical collision model and the pebble accretion model.

  PublisherOA PDFDOI

Recent grants

• FESD Proposal,Type I: Open Earth Systems: Whole planet models for global processes and major events in Earth's history

  NSF · $4.8M · 2011–2018

• Investigation of the Causes of Geomagnetic Dipole Moment Change

  NSF · $330k · 2006–2010

• Core-Mantle Interaction and Evolution of the Geodynamo

  NSF · $413k · 2009–2013

• Fluid Dynamics Experiments on Core Formation

  NSF · $233k · 2011–2015

• Collaborative Research: CSEDI--Interdisciplinary Investigation of Geodynamo Reversal Mechanisms

  NSF · $104k · 2007–2010

Frequent coauthors

• Fred Furtner

  International Rescue Committee

  173 shared

• Juliet Orellana

  173 shared

• Teresa Omiotek

  Advisory Board Company (United States)

  173 shared

• James Madara

  St. Louis County Missouri

  173 shared

• Sasha Grossman

  Johns Hopkins University

  173 shared

• Michael Ryder

  Advisory Board Company (United States)

  173 shared

• Doug Brandt

  Johns Hopkins University

  173 shared

• Patricia Panek

  Perspectives Charter School

  173 shared

Education

• Ph.D>, Geology and Geophysics

  University of California Berkeley