BS (Microbiology): The University of Michigan; Ann Arbor, MI; 1984
PhD (Pharmacology): The University of Michigan; 1990
MD (Medicine): Wayne State University; Detroit, MI; 1994
Intern (Pediatrics): Johns Hopkins Children’s Hospital; Baltimore, MD; 1994-1995
Resident: (Pediatrics): Johns Hopkins Children’s Hospital; 1994-1995
Clinical Fellow (Pediatric Hematology/Oncology): Fred Hutchinson Cancer Research Center (FHCRC)/University of Washington Medical Center and Children’s Hospital; Seattle, WA; 1997-2000
Research Associate: FHCRC; 2000- 2002
Dr. Meshinchi is a pediatric hematologist/oncologist who treats children with high-risk leukemias. He is a widely regarded expert in stem cell transplantation for pediatric leukemia patients, management of post-transplant relapse and targeted therapies for acute myeloid leukemia patients. He splays national roles as the Chairman of the Children’s Oncology Group (COG) Myeloid Disease Biology Committee, Director of the COG Integrated Translational Research Center and Vice Chair of the COG Myeloid Disease Committee.
Dr. Meshinchi’s laboratory is focused on the identification and functional evaluation of molecular alterations in leukemias, in order to advance novel “biomarkers” for clinical risk assessment and to be used as therapeutic targets. He is recognized worldwide as an expert in large-scale studies of the many genes (the genome), “RNA” molecules that are made from genes (the transcriptome), and small chemical changes that can substantially change gene, RNA and protein activities (the epigenome) to promote leukemia formation and progression.
In close collaboration with COG and Southwest Oncology Group (SWOG) Myeloid Disease Committees, Meshinchi and colleagues use pediatric and adult patient biospecimens from multi-institutional trials to define potential biomarkers of disease state and/or therapeutic sensitivity and test their real-world utility in clinical trials. They have shown that persistence small numbers of “residual” leukemic cells carrying leukemia-associated aberrations after initial therapy (minimal residual disease; MRD) is highly associated with eventual relapse. This early and sensitive method of detection of persistent disease can help identify those destined for eventual relapse and augment their therapy to improve outcome.
State-of-the-art molecular techniques are being used to identify putative markers of especially high-risk cases, which can be validated in a large cohort of specimens from pediatric and adult AML patients for whom clinical outcome data is also available. This information will be used to create patient-specific risk profiles that can help identify optimal treatment(s) for individual patients. It is also very helpful in clarifying the role of particular mutations in the evolution of AML and other myeloid malignancies, so that new targeted therapies can be developed.
The Meshinchi team also uses robotic high-throughput profiling to screen well-annotated patient specimens of sensitivities to hundreds of novel therapeutics to identify agents that may have efficacy in patients with specific genomic profile. In considering genomic alterations in AML, they clarified the prevalence and clinical significance of mutations in the FLT3 gene and other, related “receptor tyrosine kinases” (RTKs) that have recently been implicated by the Meshinchi group and others. Dr. Meshinchi showed that FLT3 activating mutations are associated with particularly aggressive cases of pediatric AML. Drug inhibitors of FLT3 and certain other RTKs are being tested in the clinic.
Dr. Meshinchi leads the national Therapeutically Applicable Research to Generate Effective Treatments (TARGET) AML Initiative, which seeks to identify valid therapeutic targets so that new, more effective treatments can be developed for children with cancer. AML is one of the 5 diseases selected for comprehensive mutli-platform genomic and epigenomic evaluation to identify biomarkers associated with disease outcome as well those who are viable candidates for targeted therapy. As part of this initiative, whole genomes, whole transcriptomes and whole RNA-encoding gene “exomes” are being sequenced in several hundred specimens from children with AML, in order to identify disease-associated alterations. Transcriptomics, epigenomics, and profiling of non-protein coding “microRNA” is also being performed. Certain biomarkers will be rapidly validated and translated into clinical applications.