About

Jan Grimm, MD, PhD, is a member and professor in the Molecular Pharmacology Program at Memorial Sloan Kettering Cancer Center. His research focuses on developing novel and innovative approaches for cancer diagnostics and therapy, utilizing nanotechnology, chemistry, physics, and modern imaging methods to evaluate underlying biology. His lab currently explores several avenues, including the utilization of nanoparticles for cancer therapy, novel imaging approaches such as Cerenkov and optoacoustic imaging, and the biology of PSMA in prostate cancer and neovasculature using a tumor-on-chip microfluidic system. Dr. Grimm develops approaches aimed at improving diagnosis, monitoring, and treatment of prostate and other cancers, contributing to advancements in cancer imaging and targeted therapies.

Research topics

• Computer Science
• Medicine
• Pathology
• Internal medicine
• Political Science
• Radiology
• Nuclear medicine
• Law
• Medical physics
• Cardiology
• Materials science
• Immunology
• Biomedical engineering
• Nanotechnology
• Gastroenterology
• Biology

Selected publications

• Multiplexed imaging of radionuclides

  Nature Biomedical Engineering · 2025-06-20 · 9 citations

  review
  PublisherDOI

• Development of [89Zr]Zr-DFO-CD11b for monitoring myeloid dynamics in response to ferroptosis-mediated TME remodeling

  Nuclear Medicine and Biology · 2025-11-01

  articleOpen accessSenior author
  PublisherDOI

• What a coincidence – overhauling PET imaging with multiplexed PET

  Nuclear Medicine and Biology · 2025-11-01

  articleOpen access1st authorCorresponding
  PublisherDOI

• Radiances of Cerenkov-Emitting Radionuclides on the In Vivo Imaging System

  Journal of Nuclear Medicine · 2025-03-13 · 2 citations

  articleOpen accessSenior author

  Cerenkov (or Cherenkov) luminescence occurs when charged particles exceed the phase velocity of a given medium. Cerenkov as a modality has gained interest for visualization of numerous radionuclides. However, reported Cerenkov intensities are limited or provided as theoretic fluence estimates. Here, we present the largest experimental dataset of Cerenkov-emitting radionuclides using the in vivo imaging system (IVIS Spectrum). We report Cerenkov radiances for 23 Cerenkov-emitting radionuclides, covering electrons, α-particles, and β-particles purified and in equilibrium where appropriate. Radionuclides measured include ¹¹C, ¹⁸F, ³²P, ⁴⁷Sc, ⁵²Mn, ⁶⁴Cu, ⁶⁷Cu, ⁶⁸Ga, ⁷²As, ⁷⁶Br, ⁸⁶Y, ⁸⁹Zr, ⁹⁰Y, ¹²⁴I, ¹³¹I, ¹³⁴Ce, ¹⁶¹Tb, ¹⁷⁷Lu, ²⁰³Pb, ²¹²Pb, ²²³Ra, ²²⁵Ac, and ²²⁷Th. These radiances allow experimental comparisons of radionuclides in Cerenkov luminescence imaging studies in the visible emission window, alongside minimum detectable activity concentrations. Lastly, these values greatly agree with prior theoretic modeling estimates.

  PublisherOA PDFDOI

• A tissue-informed deep learning-based method for positron range correction in preclinical 68Ga PET imaging

  ArXiv.org · 2025-04-27

  preprintOpen access

  Positron range (PR) limits spatial resolution and quantitative accuracy in PET imaging, particularly for high-energy positron-emitting radionuclides like 68Ga. We propose a deep learning method using 3D residual encoder-decoder convolutional neural networks (3D RED-CNNs), incorporating tissue-dependent anatomical information through a u-map-dependent loss function. Models were trained with realistic simulations and, using initial PET and CT data, generated positron range corrected images. We validated the models in simulations and real acquisitions. Three 3D RED-CNN architectures, Single-channel, Two-channel, and DualEncoder, were trained on simulated PET datasets and evaluated on synthetic and real PET acquisitions from 68Ga-FH and 68Ga-PSMA-617 mouse studies. Performance was compared to a standard Richardson-Lucy-based positron range correction (RL-PRC) method using metrics such as mean absolute error (MAE), structural similarity index (SSIM), contrast recovery (CR), and contrast-to-noise ratio (CNR). CNN-based methods achieved up to 19 percent SSIM improvement and 13 percent MAE reduction compared to RL-PRC. The Two-Channel model achieved the highest CR and CNR, recovering lung activity with 97 percent agreement to ground truth versus 77 percent for RL-PRC. Noise levels remained stable for CNN models (approximately 5.9 percent), while RL-PRC increased noise by 5.8 percent. In preclinical acquisitions, the Two-Channel model achieved the highest CNR across tissues while maintaining the lowest noise level (9.6 percent). Although no ground truth was available for real data, tumor delineation and spillover artifacts improved with the Two-Channel model. These findings highlight the potential of CNN-based PRC to enhance quantitative PET imaging, particularly for 68Ga. Future work will improve model generalization through domain adaptation and hybrid training strategies.

  PublisherOA PDFDOI

• 64Cu-radiolabelled Nanoparticles for Cancer RadioTheranostics: Enhancing Multimodal Imaging and Targeted Therapy

  Nuclear Medicine and Biology · 2025-11-01

  articleSenior author
  PublisherDOI

• Abstract A045: Imaging ferroptosis-mediated TME remodeling that sensitize cold tumors for immunotherapy

  Cancer Immunology Research · 2025-02-23

  articleSenior author

  Abstract Background: Immune checkpoint inhibitors (ICIs) harness the power of the immune system to fight against systemic cancers. Despite being one of the most promising current therapeutic strategies, response rates remain heterogeneous. Immunologically cold tumors, such as triple-negative breast cancer (TNBC), are among those that do not respond well to checkpoint inhibition. Ferroptosis-related therapies are emerging as a new class of therapeutics for chemo-resistant and metastatic cancers, as they exploit the antioxidant dependence of cancer cells, circumventing most resistance mechanisms. However, the relationship between ferroptosis and the tumor microenvironment (TME) is not well characterized. Here, we leverage ferroptosis-inducing therapies as an adjuvant for immunotherapy and monitor the myeloid dynamics in response with immuno-Positron Emission Tomography (immuno-PET). Methods: A myeloid-heavy TNBC model was used to study myeloid dynamics in response to ferroptosis therapy. The immunogenicity of ferroptotic cancer cells was investigated through in vitro quantification of damage-associated molecular patterns (DAMPs). The impact of ferroptosis therapies on macrophages was also evaluated. Furthermore, the synergy of ferroptosis-inducing therapy (using IKE) and ICB (with aPD-1) was assessed in vivo, and immune infiltration changes were quantified via flow cytometry and tissue staining. To facilitate this investigation, a pan-myeloid radioimmunoconjugate, 89Zr-DFO-CD11b, was developed as an immunoPET agent to quantitatively monitor spatiotemporal dynamics of tumor myeloid cells during ferroptosis-based therapy. Results: TNBC cells undergoing ferroptosis exhibit an immunogenic phenotype, characterized by increased DAMP production, which can contribute to TME reprogramming. Macrophages exposed to cells undergoing ferroptosis were polarized to an anti-tumor phenotype, exhibited increased tumor spheroid infiltration, and increased phagocytosis signaling. In vivo combination of IKE with aPD-1 suppressed tumor growth. The combination therapy increased tumor infiltration of lymphocyte populations, particularly CD8+ T cells, as well as anti-tumor macrophages, into the tumor core. After confirming 89Zr-DFO-CD11b showed high radiochemical conversion, stability in serum, and specific binding to myeloid cells both in vitro and in vivo, 89Zr-DFO-CD11b was injected IV into tumor-bearing mice receiving therapy. Tumor uptake was significantly less in the combination therapy group, with a distinct pocket of myeloid cells in the center of treated tumors, compared to control tumors with myeloid cells around the tumor periphery. Conclusions: This study underscores the potential of ferroptosis as an adjuvant to immunotherapy, with spatiotemporal immune cell dynamics highlighted by 89Zr-DFO-CD11b myeloid imaging. Future studies will multiplex PET imaging with T cell and ferroptosis markers to further elucidate TME dynamics. Citation Format: Elana Apfelbaum, Nermin Mostafa, Edwin C Pratt, Jan Grimm. Imaging ferroptosis-mediated TME remodeling that sensitize cold tumors for immunotherapy [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr A045.

  PublisherDOI

• Syntheses, Biological and Preclinical Evaluations, and Nanoparticle Formulations of the ROS-Activatable Prodrugs of Doxazolidine for Drug-Resistant Cancer Therapy

  Molecular Pharmaceutics · 2025-12-10

  articleOpen accessSenior authorCorresponding

  Doxorubicin (dox) has been used for the treatments of many cancers for more than 50 years since its discovery. Currently, the treatment with dox is often limited by cardiotoxicity and the development of drug resistance. Doxazolidine (doxaz) is a dox-formaldehyde conjugate discovered in the 1990s. It bears an extra carbon, linking its daunosamine hydroxyl to that adjacent amino substituent to create an oxazolidine ring. In contrast to dox, which is a topoisomerase inhibitor, doxaz cross-links DNA to nonspecifically inhibit cell growth. Doxaz is significantly more cytotoxic than dox, even against the dox-resistant cancer cells, and in spite of its 3-minute half-life for hydrolysis to dox. Doxaz has been studied since its discovery, but not clinically, due to its cytotoxicity and unsuccessful attempts to generate the prodrugs of doxaz that are activated solely in cancer cells without damaging healthy normal cells. Here, we report an ROS-activatable prodrug of doxaz, named Doxaz-BA, formulated as a nanoparticle. We synthesized Doxaz-BA and its derivatives and tested them as nanoparticle formulations in vitro in cell cultures and in vivo in mouse xenografts. This technology provides a highly sought-after cancer therapy that kills only cancer cells, while toxicity to normal tissues is minimal. Doxaz-BA is effective against drug-resistant cancer cells, and the safety assessments showed no toxicity in mouse models. Therefore, this technology offers a possible solution for the clinical translation of Doxaz in treating drug-resistant cancers, which are often incurable in standard clinical settings.

  PublisherOA PDFDOI

• Deciphering the spectra of breast cancer in multispectral optoacoustic tomography

  2025-03-20

  article

  Multispectral optoacoustic tomography (MSOT) has been utilized to non-invasively resolve morphological changes like angiogenesis and metabolic parameters like hemoglobin concentration and oxygenation in breast tumors. Compared to other optical methods, MSOT provides higher spatial resolution, higher penetration depth and does not require the use of contrast agents. Thus, MSOT could aid the non-invasive diagnosis and treatment monitoring of breast cancer. Because MSOT illuminates tissue at multiple wavelengths, the acquired data contains spectral information about the chromophores contained in tissue. This spectral data may serve as additional dimension to infer cancer biomarkers. Recent advances in data processing and image reconstruction enable the spectroscopic analysis of MSOT data. However, effects like fluence attenuation and spectral coloring alter the spectral data hampering the identification of chromophores. Hence, it is necessary to analyze and understand spectral MSOT data—"MSOT spectra”—to not draw wrong conclusions. <br/> <br/> In this work, we showcase MSOT spectra of healthy and cancerous breast tissue in four patients between 680 nm and 1100 nm for the first time. We investigate trends and variations in MSOT spectra of tumor, tumor core, tumor rim, tumor perimeter and healthy background tissue with respect to different regions of interest and with respect to the tumors’ molecular subtypes. Moreover, we showcase effects of spectral coloring which are observed in the in-vivo MSOT spectra. <br/> <br/> Our work provides a new perspective on MSOT imaging of breast cancer. We lay the foundation to derive novel, spectral MSOT biomarkers of breast cancer aiding the clinical translation.

  PublisherDOI

• Interferon regulatory factor 8 induces intrinsic functional changes in mature neutrophils

  Journal of Leukocyte Biology · 2025-06-01 · 2 citations

  articleOpen access

  Neutrophils are the first line of host defense. Neutrophils target invading pathogens by phagocytosis, generation of reactive oxygen species (ROS), neutrophil extracellular trap formation (NETosis), and cytokine production. Interferon regulatory factor 8 (IRF8) plays a central role in the regulation of myeloid cells fate, promoting monocyte and dendritic cell development while inhibiting neutrophil production. The global IRF8 deficiency leads to an accumulation of immature myeloid cells, mostly neutrophils, while IRF8 deficiency restricted to myeloid cells has no effect on myeloid cell differentiation. However, the role of IRF8 in regulating neutrophil function remains to be fully elucidated, especially due to the fact that IRF8 is not expressed in mature neutrophils. This study aims to investigate the impact of IRF8 on effector functions of neutrophils. The absence of IRF8 resulted in a diminished response of neutrophils to inflammatory challenge by lipopolysaccharide (LPS), as evidenced by reduced expression of inflammatory cytokines. This effect was intrinsic to IRF8-/- neutrophils and not driven by extrinsic factors, as assessed comparing bone marrow-derived and estrogen receptor-regulated homeobox B8-derived IRF8-/- neutrophils and was accompanied by reduced p38, extracellular signal-regulated kinase 1/2, and mitogen-activated protein kinase-activated protein kinase 2 activation. It is noteworthy that not all effector functions were affected by IRF8 deficiency. The mechanisms of pathogen elimination, such as phagocytosis and ROS production, were impaired in IRF8-/- neutrophils, whereas processes like NETosis remained entirely intact. In conclusion, our findings suggest that IRF8 shapes the neutrophil response to LPS and modulates neutrophil function, and this process is independent of external factors.

  PublisherOA PDFDOI

Recent grants

• Smart and self-reporting clinical nano carriers for drug delivery

  NIH · $3.5M · 2017–2022

• Exploiting ferroportin for cancer imaging and therapy

  NIH · $2.7M · 2017–2022

• Cerenkov-emission based nanosensors to detect biologic activities in vivo

  NIH · $1.6M · 2012–2017

• Exploring PSMA Biology in Tumor neovasculature

  NIH · $3.5M · 2017–2022

• Cerenkov luminescence imaging for image-guided cancer surgery

  NIH · $474k · 2015–2020

Frequent coauthors

• Ralph Weissleder

  Center for Systems Biology

  172 shared

• Moritz F. Kircher

  Memorial Sloan Kettering Cancer Center

  70 shared

• Travis M. Shaffer

  69 shared

• Vasilis Ntziachristos

  Helmholtz Zentrum München

  67 shared

• David G. Kirsch

  University of Toronto

  60 shared

• Tyler Jacks

  Massachusetts Institute of Technology

  54 shared

• Filip K. Świrski

  Allen Institute for Brain Science

  53 shared

• Edwin C. Pratt

  50 shared

Labs

• The Jan Grimm LabPI

Education

• Nuclear Medicine residency, Radiology

  Memorial Sloan-Kettering Cancer Center

  2009

• PhD

  Universitätsklinikum Schleswig-Holstein

  2005

• MD

  Universität Hamburg

  1995

Awards & honors

• 2014- NIH Nagy New Investigator Award
• 2018- The American Society for Clinical Investigation (ASCI)…