Dr. Kaplan is a physician scientist who developed the concept of the pre-metastatic niche describing the changes in distant microenvironments in response to a growing tumor that create a niche environment conducive to disseminating tumor cell survival and growth resulting in clinically relevant metastasis. Dr Kaplan has an active translational research program focusing on developing novel biomarkers and targets of the metastatic microenvironment by understanding the commonalities in mechanisms employed by a cancer cell to generate an entire heterogenous tumor at distant sites and stem cells and their niche to repopulate tissues.
Phase I/II Trial of PLX3397 in Children and Young Adults with Refractory Leukemias and Refractory Solid Tumors Including Neurofibromatosis Type 1 (NF1) Associated Plexiform Neurofibromas (PN)Referral Contacts
Contact Name Phone Number Melissa Amaya 301.451.9036
Comprehensive Omics Analysis of Pediatric Solid Tumors and Establishment of a Repository for Related Biological StudiesReferral Contacts
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The research focuses on understanding how cancer spreads and how it develops its own blood supply. The work aims not only to understand these fundamental processes of cancer progression but also to develop novel therapies that target a tumor's ability to grow blood vessels and spread to distant sites. One of the research program's main aims is to detail the earliest microenvironmental events in the metastatic cascade and translate these findings into the clinical setting. This work led to the development of a novel paradigm demonstrating that even localized tumors have systemic effects to prepare distant tissue sites for metastases. This is based on our discoveries that bone marrow-derived cells are recruited to future sites of metastasis and establish a receptive microenvironment for incoming circulating tumor cells, termed the 'pre-metastatic niche'. We have determined that these specialized bone marrow-derived cells are present in the circulation as well as in metastatic tissue of patients with pediatric and adult cancers. These cells may serve not only as useful biomarkers for metastatic propensity, but also as fundamental mediators of the metastatic process and therefore a potential useful target for the prevention of metastatic spread. The role of these bone marrow-derived cells in tumor progression, neo-angiogenesis and promoting immune evasion, and the specific regulation of gene expression in the pre-metastatic niche are current areas of focus.
The laboratory is focused on translation of these preclinical findings into the development of clinical studies aimed at targeting the tumor microenvironment. Performing gene expression profiling of the cells in the tumor microenvironment in patient samples can support a personalized approach to treatment of how that tumor impacts its host. We are currently performing several correlational studies to determine the timing of mobilization of the bone marrow-derived cells, changes that occur with chemotherapy, radiation and surgery as well as differences in these cells in circulation and specific tissue sites. These studies will hopefully lay the ground work for design of targeted therapies to be administered at specific time points to thwart the critical interaction of a tumor and its microenvironment.
- Sci Transl Med. 6: 237ra67, 2014. [ Journal Article ]
- Blood. 122: 1105-13, 2013. [ Journal Article ]
- Neoplasia. 15: 848-62, 2013. [ Journal Article ]
Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET.Nature Med. 18: 883-91, 2012. [ Journal Article ]
- Blood. 117: 2484-93, 2011. [ Journal Article ]
Dr Kaplan received her medical degree from Dartmouth Medical School in Hanover, NH. She completed her pediatric residency training at Harvard Children's Hospital Boston and Boston Medical Center. Following residency Dr Kaplan pursued a fellowship in Pediatric Hematology and Oncology at Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical Center, where she served as Chief Fellow. She did her postdoctoral research work in the laboratory of Dr. David Lyden. She was appointed Assistant Professor at Weill Cornell Medical College and Assistant Member at Memorial Sloan Kettering Cancer Center in 2006. In the fall of 2010 she joined the Pediatric Oncology Branch of the NCI. She is a clinician and physician scientist with active translational and clinical research interests focused on the mechanism of cancer spread. Dr Kaplan has been the recipient of several grants including the Charles, Lillian and Betty Neuwirth Clinical Scholar in Pediatric Oncology, Doris Duke Charitable Career Development Award, a co-investigator in the Komen Foundation Investigator-Initiated Award, Hope Street Kids grant award, ASCO young investigator award, and the Association for Research of Childhood Cancer.
|Fidelia Acevedo||Program Assistant|
|Daniel Beury Ph.D.||Postdoctoral Fellow (CRTA)|
|Kush Bhatt B.S.||Postbaccalaureate Fellow|
|Lauren Hittson M.D.||Clinical Fellow|
|Wei Ju Ph.D.||Research Biologist (Contr)|
|Sabina Kaczanowska Ph.D.||Postdoctoral Fellow (CRTA)|
|Meera Murgai, Ph.D.||Postdoctoral Fellow (CRTA)|
|Jennifer Zhu B.S.||Postbaccalaureate Fellow|