Dr. Emmett has a diverse research background, ranging from a Master's in Microbiology/Molecular Biology to a Ph.D. in Biochemistry/Neuropharmacology and subsequent training and extensive hands-on research experience in mass spectrometry allows me to undertake wide range biologically oriented projects and to initiate numerous successful interdisciplinary collaborations. My research in the pharmaceutical industry in neuroscience drug discovery groups (Ciba-Geigy and G.D. Searle) provided extensive in vivo pharmacology animal experience, that includes surgical procedures, drug delivery, microdialysis, in vivo and in vitro biochemical assays (ELISA and mass spectrometry based), receptor binding and robotic automation that clearly distinguish me from other mass spectrometry experts
I have extensive mass spectrometry experience with emphasis on ultra-high sensitivity analysis of biological samples using Nano-scale Liquid Chromatography, Microelectrospray Mass Spectrometry, which I specifically developed for my Ph.D. research. At the NHMFL, I developed biological applications for high-resolution Fourier Transform Ion Cyclotron Resonance (FT-ICR) Mass Spectrometry with emphasis on identification of novel therapeutic targets and biomarkers in oncology (esp. neuro-oncology). All biological projects were under my direction.
In the field of cancer research, I have established multiple collaborations that focus on neuro-oncology, breast, prostate and gastro-intestinal stromal tumors (GIST). Together with my primary collaborators at M.D. Anderson Cancer Center-Houston, we identified Galectin 1 as a novel therapeutic target for glioblastoma multiforme. I organized a multi-disciplinary, “integrated omics” research team with multiple capabilities that includes genomics, transcriptomics, proteomics, glycomics, lipidomics, metabolomics and phenomics targeted at the molecular analysis of human cancer. In contrast to the “shotgun approach”, I have developed an information rich method that permits a hypothesis driven, carefully planned experimental design leading to the data that enables identification of novel therapeutic targets and biomarkers.
The glycobiology of glioblastoma and glioblastoma stem cells is another area of research that holds great interest to me. Preliminary data of glucose and mannose metabolism in cell culture and their effect on N-glycosylation of proteins shows correlation to data gathered in in vivo brain tumor models, ER stress proteins and ADP/ATP ratios. Of interest is the direct incorporation of mannose into N-glycans in glioblastoma derived cancer stems cells and ependymoma cell lines, but the inability of glioblastoma cells to utilize mannose to build N-glycans. Tracing the glycans through the pathways was made possible through development of a novel analytical method to assay total N-glycans (Anal. Chem, 2010, 24: 2386-2392) and through the design of unique isotopically labeled substrates and inhibitors that previously were unavailable. This research holds great promise to better understand the impact of the metabolism of glucose and mannose on cancer progression and survival. Additional potential of this research is in determination of the molecular mode of action of certain chemotherapeutic agents, design of new agents and in the identification of novel therapeutic targets.
My integrated omics approach has been applied to the study of High-Charge, High-Energy (HZE) Irradiation induced Hepatocellular Carcinoma (HCC). This work is funded by NASA’s Land-Based Radiations Study Section, January, 2015 and again in a NASA Multi-institutional NSCOR, April, 2015.
My lab is also working on methodologies for the early noninvasive detection of cancer with the focus of early personalized treatment of IDH mutant cancers (glioma, cholangiocarcinoma, chondrosarcoma and AML) which occur in younger patients (20-40 years of age) who are in the prime of their lives. The target is the oncometabolite metabolite (R)-2HG produced in IDH mutant cancers that plays an active role in the growth and formation of tumors. Early detection will direct personalized treatment, enhance therapy progress, save lives and millions of dollars in health care of these patients. New method development is necessary to advance new therapeutic treatments and diagnostics and my lab works on these advancements at both the bench level and in the development of new instrumentation for detection and discovery for treatment of human disease.
Finally, I have a well-documented publication/citation/presentation record which I am continually amending. I have published in a wide range of journals in several scientific disciplines (e.g. molecular biology, neuroscience, analytical chemistry, oncology, etc.). My publications (111) are highly cited: 26% cited over 50 times, 14% cited over 100 times, 4% cited over 200 times and 2% cited over 400 times. My Hirsch Index is 38.
Selected Publications (demonstrating research diversity):
- In Vivo Modulation of the N-Methyl-D-Aspartate Receptor Complex by D-Serine: Potentiation of on Going Neuronal Activity as Evidenced by Increased Cerebellar Cyclic GMP. Paul L. Wood, Mark R. Emmett, Tadimenti S. Rao, Steve Mick, Julie Cler, and Smrity Iyengar, in J. Neurochem. (1989) 53:979-981.
- Actions of D-Cycloserine at the N-Methyl-D-Aspartate Associated Glycine Receptor Site In vivo. Mark R. Emmett, Steve J. Mick, Julie A. Cler, Tadimeti S. Rao, Smriti Iyengar and Paul L. Wood, in Neuropharmacology (1991) 30 (11):1167-1171.
- Micro-Electrospray MS: Ultra-High-Sensitivity Analysis of Peptides and Proteins. Mark R. Emmett and Richard M. Caprioli, in J. Am. Soc. Mass Spectrom. (1994) 5:605-613.
- Method for Lipidomic Analysis: p53 Expression Modulation of Sulfatide, Ganglioside and Phospholipid Composition of U87 MG Glioblastoma Cells, Huan He, Charles A. Conrad, Carol L. Nilsson, Yongjie Ji, Tanner M. Schaub, Alan G. Marshall and Mark R. Emmett, Analytical Chemistry, 2007, 79: 8423-8430.
- Integrative Biological Analysis For Neuropsychopharmacology, Mark R. Emmett, Roger A. Kroes, Joseph R. Moskal, Charles A. Conrad, Waldemar Priebe, Fernanda Laezza, Anke Meyer-Baese and Carol L. Nilsson, Neuropsychopharmacology REVIEWS, 2014, 39: 5-23.
Complete List of Published Work in My Bibliography:
Standing in front of the Bruker 12T FT-ICR MS. From left to right: Mark R. Emmett, Ph.D., Cheryl F. Lichti, Ph.D. (now at Washington University, St. Louis, MO), Brooke L. Barnette (Ph.D. Candidate) and Shinji K. Strain (MD/Ph.D. Candidate).