M.D., University of Michigan, 1997.
Ph.D., University of Michigan, Cellular and Molecular Biology, 1997.
B.A., Case Western Reserve University, Biochemistry, 1990.
My laboratory draws on perspectives from systems biology and complexity science to address important problems in basic and applied cancer research.
More specifically, we are investigating microRNAs, which are 22 nt non-protein-encoding RNA molecules that function to repress messenger RNA targets to modulate gene expression networks. We have three ongoing projects (see below) and several others in development.
(1) MicroRNA regulatory networks in cancer.
We are using computational and experimental methods to understand the mechanisms of regulation of microRNAs, at both the transcriptional and post-transcriptional levels. We are especially interested in understanding how this regulation is altered in cancer.
(2) Blood-based detection and monitoring of cancer.
We reported in 2008 that microRNAs are released from tumors and circulate in a highly stable form in the bloodstream (Mitchell, Parkin and Kroh et al., PNAS, 2008), providing a new class of blood-based biomarkers for cancer. We are currently investigating the potential of this approach for cancer diagnosis, monitoring and prediction of therapeutic response in a number of cancer types.
(3) RNA as a hormone.
Our discovery of microRNAs in the circulation have led us to hypothesize that RNA may have a long-range cell-cell communication role, akin to steroid hormones and protein cytokines. We are currently investigating this hypothesis.
We use both reductionist and integrative perspectives, and work at the intersection of several disciplines:
* Cancer Biology: with a particular interest in what makes tumors robust to perturbation.
* Network Biology: with a particular interest in integration of biological network data to develop testable hypotheses relevant to cancer biology.
* Bioinformatics and Computational Biology: as tools for addressing biological questions relevant to microRNA networks and cancer.
* Genetics and Functional Genomics: as a rich source of perturbation experiments that can help us infer the functional organization of biological systems.
* Clinical Oncology: to help chose relevant questions to address in the laboratory.
We believe a more system level perspective, grounded in the framework of molecular networks, will be useful for understanding and targeting the regulatory networks that underlie the cancer phenotype.
(Reading, Writing, Speaking)
English: (Fluent, Fluent, Fluent)
Honors and Awards
2009, Prostate Cancer Foundation Creativity Award, Prostate Cancer Foundation
2009, Damon Runyon-Rachleff Innovation Award, Damon Runyon Cancer Research Foundation
2008, Jaconnette L. Tietze Young Scientist Award, Fred Hutchinson Cancer Research Center
2007, Roger Moe Award for Translational Research, Fred Hutchinson Cancer Research Center
1997, George R. DeMuth Medical Scientist Training Program Award, University of Michigan Medical Scientist Training Program
1997, William F. Dodd Robinson Award in Internal Medicine, University of Michigan
1990, Summa Cum Laude (graduated 1st in class), Case Western Reserve University
1990, Longway Scholarship (top student in class), University of Michigan Medical School
2003-2005, Affiliate Physician, Massachusetts General Hospital
2002-2005, Instructor, Harvard University
2002-2005, Staff Physician, Dana-Farber Cancer Institute
2002-2005, Associate Physician (Affiliate), Brigham and Women's Hospital
2002-2003, Clinical and Research Fellow, Massachusetts General Hospital, Medicine Service
2000-2005, Research Fellow, Dana-Farber Cancer Institute and Harvard University, Primary Mentor: Marc Vidal, Ph.D. / Co-Mentor: Gary Ruvkun, Ph.D.
1999-2002, Clinical Fellow in Medicine, Harvard University
1999-2002, Fellow - Adult Oncology, Dana-Farber Cancer Institute
1997-1999, Intern & Resident, University of Michigan, Medical School, Internal Medicine
Systematic design and functional analysis of artificial microRNAs.. Nucleic acids research.. 2014.
Intact MicroRNA Analysis Using High Resolution Mass Spectrometry.. Journal of the American Society for Mass Spectrometry.. 2013.
Systematic Screen Identifies miRNAs that Target RAD51 and RAD51D to Enhance Chemosensitivity.. Molecular cancer research : MCR.. 2013.
Absolute quantification by droplet digital PCR versus analog real-time PCR.. Nature methods. 10(10):1003-5.. 2013.
Digital genomic quantification of tumor-infiltrating lymphocytes.. Science translational medicine. 5(214):214ra169.. 2013.
The human TUT1 nucleotidyl transferase as a global regulator of microRNA abundance.. PloS one. 8(7):e69630.. 2013.
Plasma processing conditions substantially influence circulating microRNA biomarker levels.. PloS one. 8(6):e64795.. 2013.
The accessible chromatin landscape of the human genome.. Nature. 489(7414):75-82.. 2012.
MicroRNA profiling: approaches and considerations.. Nature reviews. Genetics. 13(5):358-69.. 2012.
Blood cell origin of circulating microRNAs: a cautionary note for cancer biomarker studies.. Cancer prevention research (Philadelphia, Pa.). 5(3):492-497.. 2012.
An integrative genomic approach identifies p73 and p63 as activators of miR-200 microRNA family transcription.. Nucleic acids research. 40(2):499-510.. 2012.
Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma.. Proceedings of the National Academy of Sciences of the United States of America. 108(12):5003-8.. 2011.
HIF induces human embryonic stem cell markers in cancer cells.. Cancer research. 71(13):4640-52.. 2011.
Metastatic progression of prostate cancer and e-cadherin regulation by zeb1 and SRC family kinases.. The American journal of pathology. 179(1):400-10.. 2011.
MicroRNA-138 Modulates DNA Damage Response by Repressing Histone H2AX Expression.. Molecular cancer research : MCR. 9(8):1100-11.. 2011.
Utilization of plasmonic and photonic crystal nanostructures for enhanced micro- and nanoparticle manipulation.. Journal of visualized experiments : JoVE. (55). 2011.
Nanostructure-enhanced laser tweezers for efficient trapping and alignment of particles.. Optics express. 18(15):16005-13.. 2010.
MiR-221 and MiR-222 alterations in sporadic ovarian carcinoma: Relationship to CDKN1B, CDKNIC and overall survival.. Genes, chromosomes & cancer. 49(7):577-84.. 2010.
Regulation of miR-200 family microRNAs and ZEB transcription factors in ovarian cancer: evidence supporting a mesothelial-to-epithelial transition.. Gynecologic oncology. 116(1):117-25.. 2010.
Activation of the MEK-S6 pathway in high-grade ovarian cancers.. Applied immunohistochemistry & molecular morphology : AIMM / official publication of the Society for Applied Immunohistochemistry. 18(6):499-508.. 2010.