Jan Grimm - Researcher Profile | Memorial Sloan-Kettering Cancer Center

Office phone:

646-888-3095

Laboratory phone:

646-888-3101

E-mail:

grimmj@mskcc.org

Affiliations:

Molecular Pharmacology & Chemistry Program; Nanotechnology Center; Radiology

Research topics:

Cell Death; Molecular Imaging; Radiation Sciences & Radiochemistry; Tumor Growth & Metastasis

Lab Head CV

The Grimm Lab in the Molecular Pharmacology and Chemistry Program focuses on the development of novel and innovative molecular imaging approaches for cancer diagnostics, predominantly based on activatable iamging agents. These approaches combine and utilize modern biology, nanotechnology, chemistry and physics with modern imaging methods (MRI, optical imaging, PET and lately Cerenkov) to create novel imaging agents that allow much earlier detection and improved therapy monitoring of cancer. The lab strives to develop completely novel concepts how to image biological events, keeping clinical translatability of the projects within sight. We are aiming at translational research but are also interested in preclinical research, where one main aspect is the biology of PSMA as it pertains to new imaging and therapy approaches. The lab is housed in the Zuckerman Research Building (20th floor).

Probe concepts in Molecular Imaging Nonspecific probes are non-directed. Most of the MR and CT contrast agents belong into this group. Targeted agents are binding to specific targets, mediated by ligands attached to their surface. Smart probes are activated by enzymatic conversion. Cell tracking is added here as a fourth option since cells comprise a special, living kind of probe that seeks its target actively unlike any other probe.

While novel biologic therapies use biological mechanisms such as blockage of specific kinases (e.g bcr-abl), current imaging methods to evaluate molecular endpoints of therapies with CT or MRI rely mainly on the administration of nonspecific contrast agents. Imaging agents capable of revealing the biological functions of their targets would significantly improve our ability to diagnose disease and monitor novel therapies. Such activatable or “smart” imaging agents are transformed to their active, signal-producing state only upon interacting with their target.

Molecular Imaging Conventional imaging provides anatomical information while molecular imaging allows detecting changes on a molecular level. These changes occur many years before the actual manifestation on the anatomical level. (Grimm J and Hricak H (2008) Curr Opinion Urol 18:61)

This considerably reduces nonspecific background signal and represents a higher level of probe sophistication compared to targeted agents alone, which indicate the presence of their target but do not deliver any information about the biologic activity. Multimodality imaging allows us to utilize the same imaging agent with different imaging modalities, which increases the versatility of such agents.

Interdisciplinary approach Molecular Imaging is at the intersection of various disciplines and thrives by their inteactions

Molecular Imaging not only aims to detect diseases earlier and more specifically, it also aids in drug development. Novel drugs are increasingly geared towards affecting only specific proteins, e.g. to inhibit activated oncogenic kinases (biologicals). An imaging agent based on such a biological drug has the potential to indicate non-invasively if the target protein is actually present and, once therapy is initiated, to monitor the therapy with the very same imaging agent. This provides is an important step towards Personalized Medicine, tailoring towards the specific needs of the patient. This is also relevant in pharmaceutical development of drugs as such approaches allow better evaluation of the potentials of a drug candidate.

The Grimm Lab is interested in molecular iamging approaches for oncology, using various modalities (e.g. optical, PET, MRI).

Since the lab is situated at the intersection of various disciplines — such as Molecular Biology, Chemistry (organic and inorganic), Physics, Radiopharmacy, and Imaging — the lab is open to a wide variety of specialists interested in interdisciplinary research. We understand Molecular Imaging as an interdisciplinary approach that combines the knowledge of different fields to create innovative and unique new agents for various imaging applications. Consequently, several collaborations with other laboratories in the US and abroad exist.