Novotny Tumor Glycomics Laboratory
Principal Investigator: Milos Novotny, Ph.D.
Institution: Indiana University, Bloomington, IN
Dr. Novotny leads a group that has been involved for 10 years in the development of glycomic and glycoproteomic molecular profiling techniques and their applications to disease biomarkers. The laboratory is expertly equipped with the latest mass-spectrometric instrumentation and separation technologies.
Collaborating with clinical investigators at the Simon Cancer Center (Indiana University Medical School, Indianapolis) and Georgetown University, the group has applied glycomic and glycoproteomic screening procedures based on mass spectrometry and capillary electrophoresis to find glycans and glycoproteins that distinguish sera from patients with breast, ovarian, prostate, hepatocellular, esophageal, and pancreatic cancers. While these translational science studies are relatively recent, several cancer-related investigations have been published that indicate considerable potential of analytical glycobiology in the early diagnosis and prognosis of cancer and its related conditions. Evaluations of quantitative glycomic patterns involve principal component analysis and statistical methods routinely accepted in the clinical laboratories. The chemical structures of putative glycan biomarkers are being primarily determined through tandem mass spectrometry.
The glycomic analyses used in this research laboratory environment are relatively fast, so that the investigators have been able to analyze hundreds of serum samples from diverse patient populations. In collaboration with Dr. Stephen Jacobson (microchip technologies) and Dr. Haixu Tang (bioinformatics) at Indiana University , the laboratory is working to transfer the knowledge obtained through biomarker mass-spectrometric identification to capillary electrophoresis microchip profiling with two objectives: faster acquisition of glycomic profiles for diagnostic and prognostic measurements; and resolution of certain glycan isomers that may be pertinent to cancer.
It is also essential that bioanalytical procedures utilize very small samples of human physiological fluids (e.g., microliter volumes of blood serum or pancreatic cyst fluids). The analytical results are correlated with the clinical information obtained through collaborations at the Simon Cancer Center and Hoosier Oncology Group in the Indiana University School of Medicine.
During the last 2 years, their studies have been supported by a Tumor Glycomics Laboratory grant from NCI and a center grant from the National Center for Research Resources. As a part of the Tumor Glycomics Laboratory grant, they have developed collaborations with Professor William Hancock (Northeastern University, Boston, MA) on the structural characterization of breast cancer glycoprotein biomarkers, as well as the application of glycomic profiling to lung cancer sera obtained from the patients before and after a surgical removal of tumors (Drs. Harvey Pass and Margaret Huflejt, New York University Medical School).
Publications:
- Mann BF, Goetz JA, House MG, Schmidt CM, Novotny MV. Glycomic and proteomic profiling of pancreatic cyst fluids identifies hyperfucosylated lactosamines on the N-linked glycans of overexpressed glycoproteins. Mol Cell Proteomics. 2012; (in press).
- Svoboda M, Mann B, Goetz JA, Novotny MV. Examination of Glycan Profiles from IgG-Depleted Human Immunoglobulins Facilitated by Microscale Affinity Chromatography. Anal Chem. 2012; (in press).
- Alley WR, Vasseur JA, Goetz JA, Svoboda M, Mann BF, Matei DE, Menning N, Hussein A, Mechref Y, Novotny MV. N-linked Glycan Structures and Their Expressions Change in the Blood Sera of Ovarian Cancer Patients. J Proteome Res. 2012; (in press)
- Zhuang Z, Mitra I, Hussein A, Novotny MV, Mechref Y, Jacobson S. Microchip Electrophoresis of N-Glycans on Serpentine Separation Channels with Asymmetrically Tapered Turns. Electrophoresis 2011; 32(2):246-53.
- Mann B, Madera M, Klouckova I, Dobrolecki LE, Hickey RJ, Hammoud ZT, Novotny MV. A Quantitative Investigation of Fucosylated Serum Glycoproteins with Application to Esophageal Adenocarcinoma. Electrophoresis 2010; 31(11):1833-1841.
- Alley WR Jr, Madera M, Mechref Y, Novotny MV. Chip-based reversed-phase liquid chromatography-mass spectrometry of permethylated N-linked glycans: a potential methodology for cancer-biomarker discovery. Anal Chem. 2010; 82(12):5095-106.
- Alley WR, Novotny MV. Glycomic analysis of sialic acid linkages in glycans derived from blood serum glycoproteins. J Proteome Res. 2010; 9(6): 3062-72
- Mann B, Madera M, Klouckova I, Mechref Y, Dobrolecki LE, Hickey RJ, Hammoud ZT, Novotny MV. A quantitative investigation of fucosylated serum glycoproteins with application to esophageal adenocarcinoma. Electrophoresis. 2010; 31(11):1833-41.
- Goetz JA, Mechref Y, Kang P, Jeng MH, Novotny, MV. Glycomic profiling of invasive and non-invasive breast cancer cells. Glycoconj J. 2009; 26(2):117-31.
- Goldman R, Ressom HW, Varghese RS, Goldman L, Bascug G, Loffredo CA, Abdel-Hamid M, Gouda I, Ezzat S, Kyselova Z, Mechref Y, Novotny M.V. Detection of hepatocellular carcinoma using glycomic analysis. Clinical Cancer Res. 2009; 15(5):1808-13.
- Mechref Y, Hussein A, Bekesova S, Pungpapong V, Zhang M, Dobrolecki LE, Hickey RJ, Hammoud ZT, Novotny MV. Quantitative serum glycomics of esophageal adenocarcinoma and other esophageal disease onsets. J Proteome Res. 2009; 8(6):2656-66.
- Isailovic D, Kurulugama RT, Plasencia MD, Stokes ST, Kyselova Z, Goldman R, Mechref Y, Novotny MV, Clemmer DE. Profiling of human serum glycans associated with liver cancer and cirrhosis by IMS-MS. J Proteome Res. 2008; 7:1109-1117.
- Kyselova Z, Mechref Y, Kang P, Goetz JA, Dobrolecki LE, Sledge GW, Schnaper L, Hickey RJ, Malkas LH, Novotny, MV. Breast cancer diagnosis and prognosis through quantitative measurements of serum glycan profiles. Clin Chem. 2008; 54:1166-1175.
- Ressom HW, Varghese RS, Goldman L, An Y, Loffredo CA, Abdel-Hamid M, Kyselova Z, Mechref Y, Novotny M, Drake SK, Goldman R. Analysis of MALDI-TOF mass spectrometry data for discovery of peptide and glycan biomarkers of hepatocellular carcinoma. J Proteome Res. 2008; 7:603-610.
- Kyselova Z, Mechref Y, Al Bataineh M, Dobrolecki L E, Hickey RJ, Sweeney CJ, Novotny MV. Alterations in the serum glycome due to metastatic prostate cancer. J Proteome Res. 2007; 6:1822-1832.
- Zhuang Z, Starkey JA, Mechref Y, Novotny MV, Jacobson SC. Electrophoretic analysis of n-glycans on microfluidic devices. Anal Chem. 2007; 79:7170-7175.
In the Media:
"Sweet Science," by Roberta Kwok, Food, Volume 30 Number 1, Fall 2007.
Patents
Provisional application: Application of Macroporous Silica Synthesized by a Salt-Templated Aerosol Method for Chromatography. Inventors: Mann, B.F., Mann, A.K.P., Skrabalak, S.E., and Novotny, M.V. Filed: January 11, 2012. #61/585,445
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